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Sample records for metallothionein reduces central

  1. Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures

    DEFF Research Database (Denmark)

    Penkowa, Milena; Florit, Sergi; Giralt, Mercedes

    2005-01-01

    We examined metallothionein (MT)-induced neuroprotection during kainic acid (KA)-induced excitotoxicity by studying transgenic mice with MT-I overexpression (TgMT mice). KA induces epileptic seizures and hippocampal excitotoxicity, followed by inflammation and delayed brain damage. We show for th...

  2. Role of metallothionein-III following central nervous system damage

    DEFF Research Database (Denmark)

    Carrasco, Javier; Penkowa, Milena; Giralt, Mercedes

    2003-01-01

    We evaluated the physiological relevance of metallothionein-III (MT-III) in the central nervous system following damage caused by a focal cryolesion onto the cortex by studying Mt3-null mice. In normal mice, dramatic astrogliosis and microgliosis and T-cell infiltration were observed in the area...... the inflammatory response elicited in the central nervous system by a cryoinjury, nor does it serve an important antioxidant role, but it may influence neuronal regeneration during the recovery process....

  3. Metallothionein expression in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Ortega-Aznar, A

    2003-01-01

    Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS...... by tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show...

  4. Ptaquiloside reduces NK cell activities by enhancing metallothionein expression, which is prevented by selenium.

    Science.gov (United States)

    Latorre, Andreia O; Caniceiro, Beatriz D; Fukumasu, Heidge; Gardner, Dale R; Lopes, Fabricio M; Wysochi, Harry L; da Silva, Tereza C; Haraguchi, Mitsue; Bressan, Fabiana F; Górniak, Silvana L

    2013-02-08

    Pteridium aquilinum, one of the most important poisonous plants in the world, is known to be carcinogenic to animals and humans. Moreover, our previous studies showed that the immunosuppressive effects of ptaquiloside, its main toxic agent, were prevented by selenium in mouse natural killer (NK) cells. We also verified that this immunosuppression facilitated development of cancer. Here, we performed gene expression microarray analysis in splenic NK cells from mice treated for 14 days with ptaquiloside (5.3 mg/kg) and/or selenium (1.3 mg/kg) to identify gene transcripts altered by ptaquiloside that could be linked to the immunosuppression and that would be prevented by selenium. Transcriptome analysis of ptaquiloside samples revealed that 872 transcripts were expressed differentially (fold change>2 and p<0.05), including 77 up-regulated and 795 down-regulated transcripts. Gene ontology analysis mapped these up-regulated transcripts to three main biological processes (cellular ion homeostasis, negative regulation of apoptosis and regulation of transcription). Considering the immunosuppressive effect of ptaquiloside, we hypothesized that two genes involved in cellular ion homeostasis, metallothionein 1 (Mt1) and metallothionein 2 (Mt2), could be implicated because Mt1 and Mt2 are responsible for zinc homeostasis, and a reduction of free intracellular zinc impairs NK functions. We confirm these hypotheses and show increased expression of metallothionein in splenic NK cells and reduction in free intracellular zinc following treatment with ptaquiloside that were completely prevented by selenium co-treatment. These findings could help avoid the higher susceptibility to cancer that is induced by P. aquilinum-mediated immunosuppressive effects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Metallothionein in Brain Disorders

    Directory of Open Access Journals (Sweden)

    Daniel Juárez-Rebollar

    2017-01-01

    Full Text Available Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV, three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

  6. Reduced central blood volume in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Sørensen, T I

    1989-01-01

    was inversely correlated to the systemic vascular resistance (r = -0.49, p less than 0.001), the latter being significantly reduced in the patient group. Patients with cirrhosis apparently are unable to maintain a normal central blood volume. This may be due to arteriolar vasodilation, portosystemic collateral......The pathogenesis of ascites formation in cirrhosis is uncertain. It is still under debate whether the effective blood volume is reduced (underfilling theory) or whether the intravascular compartment is expanded (overflow theory). This problem has not yet been solved because of insufficient tools...... for measuring the central blood volume. We have developed a method that enables us to determine directly the central blood volume, i.e., the blood volume in the heart cavities, lungs, and central arterial tree. In 60 patients with cirrhosis and 16 control subjects the central blood volume was assessed according...

  7. Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-alpha and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE)

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2001-01-01

    . However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We herewith demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-alpha during EAE. Zn-MT-II treatment could also significantly reduce...... apoptotic cell death of neurons and oligodendrocytes during EAE, as judged by using TUNEL and immunoreactivity for cytochrome c and caspases 1 and 3. In contrast, the number of apoptotic lymphocytes and macrophages was less affected by Zn-MT-II treatment. The Zn-MT-II-induced decrease in proinflammatory...... cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE...

  8. Metallothionein-I+II in neuroprotection

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Jensen, Rikke; Pedersen, Dan S

    2009-01-01

    Metallothionein (MT)-I+II synthesis is induced in the central nervous system (CNS) in response to practically any pathogen or disorder, where it is increased mainly in reactive glia. MT-I+II are involved in host defence reactions and neuroprotection during neuropathological conditions, in which MT...... and scavenging of reactive oxygen species (ROS) leading to cellular redox control. By regulating metal ions, MT-I+II can control metal-containing transcription factors, zinc-finger proteins and p53. However, the neuroprotective functions of MT-I+II also involve an extracellular component. MT-I+II protects...

  9. Does Central Bank Transparancy Reduce Interest Rates?

    NARCIS (Netherlands)

    Geraats, P.; Eijffinger, S.C.W.; van der Cruijsen, C.A.B.

    2006-01-01

    Central banks have become increasingly transparent during the last decade. One of the main bene ts of transparency predicted by theoreticalmodels is that it enhances the credibility, reputation, and exibility of monetary policy, which suggests that increased transparency should result in lower

  10. Effects of buthionine sulfoximine nifurtimox and benznidazole upon trypanothione and metallothionein proteins in Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    JUAN DIEGO MAYA

    2004-01-01

    Full Text Available Proteins rich in sulfhydryl groups, such as metallothionein, are present in several strains of the parasite Trypanosoma cruzi, the etiological agent of Chagas' disease. Metallothionein-like protein concentrations ranged from 5.1 to 13.2 pmol/mg protein depending on the parasite strain and growth phase. Nifurtimox and benznidazole, used in the treatment of Chagas' disease, decreased metallothionein activity by approximately 70%. T. cruzi metallothionein was induced by ZnCl2. Metallothionein from T. cruzi was partially purified and its monobromobimane derivative showed a molecular weight of approximately 10,000 Da by SDS-PAGE analysis. The concentration of trypanothione, the major glutathione conjugate in T. cruzi, ranged from 3.8 to 10.8 nmol/mg protein, depending on the culture phase. The addition of buthionine sulfoximine to the protozoal culture considerably reduced the concentration of trypanothione and had no effect upon the metallothionein concentration. The possible contribution of metallothionein-like proteins to drug resistance in T. cruzi is discussed.

  11. Assessment of metallothionein and antibodies to metallothionein in normal and autistic children having exposure to vaccine-derived thimerosal.

    Science.gov (United States)

    Singh, Vijendra K; Hanson, Jeff

    2006-06-01

    Allergic autoimmune reaction after exposure to heavy metals such as mercury may play a causal role in autism, a developmental disorder of the central nervous system. As metallothionein (MT) is the primary metal-detoxifying protein in the body, we conducted a study of the MT protein and antibodies to metallothionein (anti-MT) in normal and autistic children whose exposure to mercury was only from thimerosal-containing vaccines. Laboratory analysis by immunoassays revealed that the serum level of MT did not significantly differ between normal and autistic children. Furthermore, autistic children harboured normal levels of anti-MT, including antibodies to isoform MT-I (anti-MT-I) and MT-II (anti-MT-II), without any significant difference between normal and autistic children. Our findings indicate that because autistic children have a normal profile of MT and anti-MT, the mercury-induced autoimmunity to MT may not be implicated in the pathogenesis of autism.

  12. Arsenic Induction of Metallothionein and Metallothionein Induction Against Arsenic Cytotoxicity.

    Science.gov (United States)

    Rahman, Mohammad Tariqur; De Ley, Marc

    Human exposure to arsenic (As) can lead to oxidative stress that can become evident in organs such as the skin, liver, kidneys and lungs. Several intracellular antioxidant defense mechanisms including glutathione (GSH) and metallothionein (MT) have been shown to minimize As cytotoxicity. The current review summarizes the involvement of MT as an intracellular defense mechanism against As cytotoxicity, mostly in blood. Zinc (Zn) and selenium (Se) supplements are also proposed as a possible remediation of As cytotoxicity. In vivo and in vitro studies on As toxicity were reviewed to summarize cytotoxic mechanisms of As. Intracellular antioxidant defense mechanisms of MT are linked in relation to As cytotoxicity. Arsenic uses a different route, compared to major metal MT inducers such as Zn, to enter/exit blood cells. A number of in vivo and in vitro studies showed that upregulated MT biosynthesis in blood components are related to toxic levels of As. Despite the cysteine residues in MT that aid to bind As, MT is not the preferred binding protein for As. Nonetheless, intracellular oxidative stress due to As toxicity can be minimized, if not eliminated, by MT. Thus MT induction by essential metals such as Zn and Se supplementation could be beneficial to fight against As toxicity.

  13. Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes

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    Lee Sook-Jeong

    2010-10-01

    Full Text Available Abstract Zinc dyshomeostasis has been recognized as an important mechanism for cell death in acute brain injury. An increase in the level of free or histochemically reactive zinc in astrocytes and neurons is considered one of the major causes of death of these cells in ischemia and trauma. Although zinc dyshomeostasis can lead to cell death via diverse routes, the major pathway appears to involve oxidative stress. Recently, we found that a rise of zinc in autophagic vacuoles, including autolysosomes, is a prerequisite for lysosomal membrane permeabilization and cell death in cultured brain cells exposed to oxidative stress conditions. The source of zinc in this process is likely redox-sensitive zinc-binding proteins such as metallothioneins, which release zinc under oxidative conditions. Of the metallothioneins, metallothionein-3 is especially enriched in the central nervous system, but its physiologic role in this tissue is not well established. Like other metallothioneins, metallothionein-3 may function as metal detoxicant, but is also known to inhibit neurite outgrowth and, sometimes, promote neuronal death, likely by serving as a source of toxic zinc release. In addition, metallothionein-3 regulates lysosomal functions. In the absence of metallothionein-3, there are changes in lysosome-associated membrane protein-1 and -2, and reductions in certain lysosomal enzymes that result in decreased autophagic flux. This may have dual effects on cell survival. In acute oxidative injury, zinc dyshomeostasis and lysosomal membrane permeabilization are diminished in metallothionein-3 null cells, resulting in less cell death. But over the longer term, diminished lysosomal function may lead to the accumulation of abnormal proteins and cause cytotoxicity. The roles of zinc and metallothionein-3 in autophagy and/or lysosomal function have just begun to be investigated. In light of evidence that autophagy and lysosomes may play significant roles in the

  14. Does central fatigue explain reduced cycling after complete sleep deprivation?

    Science.gov (United States)

    Temesi, John; Arnal, Pierrick J; Davranche, Karen; Bonnefoy, Régis; Levy, Patrick; Verges, Samuel; Millet, Guillaume Y

    2013-12-01

    Sleep deprivation (SD) is characterized by reduced cognitive capabilities and endurance exercise performance and increased perceived exertion (RPE) during exercise. The combined effects of SD and exercise-induced changes in neuromuscular function and cognition are unknown. This study aimed to determine whether central fatigue is greater with SD, and if so, whether this corresponds to diminished cognitive and physical responses. Twelve active males performed two 2-d conditions (SD and control (CO)). On day 1, subjects performed baseline cognitive and neuromuscular testing. After one night of SD or normal sleep, subjects repeated day 1 testing and then performed 40-min submaximal cycling and a cycling test to task failure. Neuromuscular and cognitive functions were evaluated during the cycling protocol and at task failure. After SD, exercise time to task failure was shorter (1137 ± 253 vs 1236 ± 282 s, P = 0.013) and RPE during 40 min submaximal cycling was greater (P = 0.009) than that in CO. Maximal peripheral voluntary activation decreased by 7% (P = 0.003) and cortical voluntary activation tended to decrease by 5% (P = 0.059) with exercise. No other differences in neuromuscular function or cognitive control were observed between conditions. After SD, mean reaction time was 8% longer (P = 0.011) and cognitive response omission rate before cycling was higher (P cognitive performance deterioration in SD. One night of complete SD resulted in decreased time to task failure and cognitive performance and higher RPE compared with the control condition. The lack of difference in neuromuscular function between CO and SD indicates that decreased SD exercise performance was probably not caused by increased muscular or central fatigue.

  15. Metallothionein protection of cadmium toxicity

    International Nuclear Information System (INIS)

    Klaassen, Curtis D.; Liu, Jie; Diwan, Bhalchandra A.

    2009-01-01

    The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research on this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tissues and dramatically decreases biliary excretion of Cd. Cd-bound to MT is responsible for Cd accumulation in tissues and the long biological half-life of Cd in the body. Induction of MT protects against acute Cd-induced lethality, as well as acute toxicity to the liver and lung. Intracellular MT also plays important roles in ameliorating Cd toxicity following prolonged exposures, particularly chronic Cd-induced nephrotoxicity, osteotoxicity, and toxicity to the lung, liver, and immune system. There is an association between human and rodent Cd exposure and prostate cancers, especially in the portions where MT is poorly expressed. MT expression in Cd-induced tumors varies depending on the type and the stage of tumor development. For instance, high levels of MT are detected in Cd-induced sarcomas at the injection site, whereas the sarcoma metastases are devoid of MT. The use of MT-transgenic and MT-null mice has greatly helped define the role of MT in Cd toxicology, with the MT-null mice being hypersensitive and MT-transgenic mice resistant to Cd toxicity. Thus, MT is critical for protecting human health from Cd toxicity. There are large individual variations in MT expression, which might in turn predispose some people to Cd toxicity.

  16. Structure and Function of Vertebrate Metallothioneins

    DEFF Research Database (Denmark)

    Penkowa, Milena; Vasak, Milan; Hidalgo, Juan

    2009-01-01

    In 1957, Margoshes and Vallee reported on the isolation of a protein from horse kidney, which showed a high affinity for cadmium, and soon thereafter the protein was named metallothionein (MT) by the leading scientists Ka¨ gi and Vallee. Fifty years of intense research has dissected out many of t...

  17. Metallothionein responses of mangrove crab, Sesarma huzardi ...

    African Journals Online (AJOL)

    The call to incorporate biomarker studies in biomonitoring and ecotoxicological programmes has gained immense support in recent times prompting studies at the sub organismal levels with the aim of developing protocols that will aid to safeguard the whole ecosystem from pollution effect. Metallothioneins (MTs) are low ...

  18. Recent Developments in Quantification Methods for Metallothionein

    Czech Academy of Sciences Publication Activity Database

    Dabrio, M.; Rodriquez, A. R.; Bordin, G.; Bebiano, M. J.; De Ley, M.; Šestáková, Ivana; Vašák, M.; Nordberg, M.

    2002-01-01

    Roč. 88, č. 2 (2002), s. 123-134 ISSN 0162-0134 R&D Projects: GA MŠk OC D21.002; GA MŠk OC D8.10 Institutional research plan: CEZ:AV0Z4040901 Keywords : electrochemistry * metallothionein * mass spectrometry Subject RIV: CG - Electrochemistry Impact factor: 2.204, year: 2002

  19. Metallothioneins are multipurpose neuroprotectants during brain pathology

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2006-01-01

    Metallothioneins (MTs) constitute a family of cysteine-rich metalloproteins involved in cytoprotection during pathology. In mammals there are four isoforms (MT-I - IV), of which MT-I and -II (MT-I + II) are the best characterized MT proteins in the brain. Accumulating studies have demonstrated MT...

  20. Microfinance and reducing poverty in Central Africa | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    In spite of an abundance of natural resources, including oil and minerals, poverty is increasing in Central Africa. About 40% of the people in Cameroon live below the poverty threshold, 55% in Chad, 50% in Congo and 43% in Gabon. A considerable amount of research has attempted to generate insight into the factors that ...

  1. Youth employment to reduce violence in Central America | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    According to 2014 statistics, four out of the 10 countries with the highest homicide rates in the world are in Central America. The vast majority of victims of violence are young men between the ages of 15 and 24, some of whom also risk becoming perpetrators of violence. Access to jobs, in both formal and informal labour ...

  2. Tetrahymena metallothioneins fall into two discrete subfamilies.

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    Silvia Díaz

    2007-03-01

    Full Text Available Metallothioneins are ubiquitous small, cysteine-rich, multifunctional proteins which can bind heavy metals.We report the results of phylogenetic and gene expression analyses that include two new Tetrahymena thermophila metallothionein genes (MTT3 and MTT5. Sequence alignments of all known Tetrahymena metallothioneins have allowed us to rationalize the structure of these proteins. We now formally subdivide the known metallothioneins from the ciliate genus Tetrahymena into two well defined subfamilies, 7a and 7b, based on phylogenetic analysis, on the pattern of clustering of Cys residues, and on the pattern of inducibility by the heavy metals Cd and Cu. Sequence alignment also reveals a remarkably regular, conserved and hierarchical modular structure of all five subfamily 7a MTs, which include MTT3 and MTT5. The former has three modules, while the latter has only two. Induction levels of the three T. thermophila genes were determined using quantitative real time RT-PCR. Various stressors (including heavy metals brought about dramatically different fold-inductions for each gene; MTT5 showed the highest fold-induction. Conserved DNA motifs with potential regulatory significance were identified, in an unbiased way, upstream of the start codons of subfamily 7a MTs. EST evidence for alternative splicing in the 3' UTR of the MTT5 mRNA with potential regulatory activity is reported.The small number and remarkably regular structure of Tetrahymena MTs, coupled with the experimental tractability of this model organism for studies of in vivo function, make it an attractive system for the experimental dissection of the roles, structure/function relationships, regulation of gene expression, and adaptive evolution of these proteins, as well as for the development of biotechnological applications for the environmental monitoring of toxic substances.

  3. Centralized contracting an imperative for reducing health system costs.

    Science.gov (United States)

    Baskel, Christopher

    2014-03-01

    As a health system expands, there is a concomitant need for its leaders to take steps to ensure that redundancies in purchasing processes do not drive up costs to unsustainable levels. Spectrum Health in Grand Rapids, Mich., tackled this challenge by instituting a revenue-driven, patient-care-focused value analysis process that centralized contracting processes in several areas of nonsalary expense. Spectrum went on to uncover opportunities for cutting costs in its decentralized, non-purchase order expenses, saving 24 percent in the first of four arenas.

  4. Relationship of hypoxia to metallothionein expression in murine tumors

    International Nuclear Information System (INIS)

    Raleigh, James A.; Chou, S.-C.; Tables, Lakesha; Suchindran, Sunil; Varia, Mahesh A.; Horsman, Michael R.

    1998-01-01

    Purpose: To investigate if metallothionein, an endogenous chemo- and radioprotectant, is expressed in hypoxic cells in mouse C3H mammary carcinomas and if that expression responds to acute changes in tumor hypoxia. Methods and Materials: C3H mammary tumors were established in the hind legs of female CDF 1 mice. The mice were then subjected to air breathing (chronic hypoxia), carbogen breathing (acute decrease in hypoxia), or hydralazine injection (acute increase in hypoxia). Ninety minutes after the start of the experiment, tumors were excised, fixed in formalin, and sectioned. Hypoxic cells and metallothionein-containing cells were quantitated by image analysis. Pimonidazole hydrochloride and an IgG 1 mouse monoclonal antibody were used to detect hypoxia, and a mouse antimetallothionein monoclonal antibody (DAKO) was used to detect Type I and II metallothionein in sets of contiguous tissue sections. Results: The distribution of immunostaining intensity for metallothionein was the same in all three groups--heavy in hypoxic cells and light in other regions of the tumors. The acute increase in hypoxia caused by hydralazine injection was accompanied by an increase in metallothionein expression (p = 0.04). Carbogen breathing largely eliminated pimonidazole binding, but metallothionein expression persisted in the tumors of carbogen-breathing mice. Conclusions: Hypoxic cells in C3H mammary carcinomas strongly express metallothionein. Metallothionein expression is responsive to acute increases in hypoxia brought about by hydralazine injection. The effectiveness of hydralazine in enhancing the activation of bioreductive cytotoxins might be offset by the increased expression of metallothionein. The persistence of metallothionein in tumors of carbogen-breathing mice might contribute to a residual radioresistance in the tumors

  5. Effect of interleukin-6 neutralization on CYP3A11 and metallothionein-1/2 expressions in arthritic mouse liver.

    Science.gov (United States)

    Ashino, Takashi; Arima, Yoshiko; Shioda, Seiji; Iwakura, Yoichiro; Numazawa, Satoshi; Yoshida, Takemi

    2007-03-08

    Rheumatoid arthritis is characterized by chronic inflammation of the synovial tissue. We examined the effect of interleukin (IL)-6 neutralization on the expression of cytochrome P450 or metallothionein-1/2 (metallothionein) during chronic phase inflammatory disease using rheumatoid arthritis model mice, human T-cell leukemia virus type I (HTLV-I) transgenic mice. Serum IL-6 concentrations of arthritis-developed HTLV-I transgenic mice were 129.9+/-26.1 pg/ml. Moreover, signal transducer and activator of transcription (STAT) 1/3 phosphorylations was observed in arthritic HTLV-I transgenic mouse livers. CYP3A11 mRNA was more strongly reduced by the development of arthritis in HTLV-I transgenic mouse livers as compared with CYP2C29 or CYP2E1 mRNAs. CYP3A protein and testosterone 6beta-hydroxylation activity also changed in a similar manner to the corresponding CYP3A11 mRNA level. On the other hand, metallothionein mRNA was significantly induced as compared with that of wild-type or non-arthritic mice. CYP3A suppression and metallothionein mRNA overexpression activity seen in the developed arthritic mice returned to the gene conditions of the non-arthritic HTLV-I transgenic mice by IL-6 antibody at 48 h after treatment. The present study has revealed that CYP3A11 and metallothionein expressions are affected by the release of IL-6 by arthritis and its systemic circulation, and neutralization of IL-6 recovered from the down-regulation of CYP3A11 mRNA and the induction of metallothionein mRNA in arthritic HTLV-I transgenic mice.

  6. Association of metabolic syndrome with reduced central serotonergic activity.

    Science.gov (United States)

    Herrera-Marquez, Rocio; Hernandez-Rodriguez, Jorge; Medina-Serrano, Julio; Boyzo-Montes de Oca, Alfonso; Manjarrez-Gutierrez, Gabriel

    2011-03-01

    The aim of this study was to determine the differences between two groups of adolescents with metabolic syndrome (MetS) and normal controls in relation to brain serotonergic activity through intensity-dependent auditory-evoked potentials (IDAEPs) and plasma free fraction of L-tryptophan. Eighteen adolescents with MetS and thirteen controls were studied. Free fraction, bound and total plasma L-tryptophan, glucose, cholesterol, triglycerides, HDL-cholesterol, albumin and IDAEPs were determined. Glycemia, triglycerides were significantly elevated, and HDL-cholesterol in plasma was significantly reduced. Free fraction and free fraction/total L-tryptophan ratio were decreased. The slope of the amplitude/stimulus intensity function of the N1/P2 component significantly increased in adolescents with MetS. Decrease of free fraction of L-tryptophan in plasma and increase of the slope of the N1/P2 component suggest a low brain serotonin tone. Cortex responses are regulated by serotonergic innervations and may show a different behavior in young patients with MetS. Therefore, the slope of the N1/P2 component along with the free fraction of L-tryptophan in plasma, indicate that in adolescents with MetS the state of serotonergic brain activity is depressed and possibly related to psychiatric disorders.

  7. Advantages and disadvantages of voltammetric method in studying cadmium-metallothionein interactions.

    Science.gov (United States)

    Erk, M; Raspor, B

    2000-03-01

    A sensitive and chemical species-selective technique of differential pulse anodic stripping voltammetry (DPASV) was applied in studying the cadmium-metallothionein (Cd-MT) interaction. The amperometric titrations of the purified MT20 and MT10 fractions, isolated by verified biochemical procedures from the digestive gland of cadmium-exposed mussels Mytilus galloprovincialis, with Cd2+ ions were performed in the buffered sodium chloride solution of 0.59 M ionic strength, pH 7.9 and 25 degrees C. Applying the DPASV method at various cadmium to metallothionein ratio several groups of chemical species were recorded. The data on the available ligand concentration to complex cadmium ions (CL), the apparent concentration stability constants (K,) of the respective complexes and the reliability of the determined complexing parameters are discussed. In quantifying the Cd-MT interaction the interference of dithiotreitol (DTT), which is used as the reducing agent in isolation and purification of MTs, is documented.

  8. Smoking specifically induces metallothionein-2 isoform in human placenta at term

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Garrido, Fernando; Llanos, Miguel N.

    2006-01-01

    Recently, we reported the presence of higher levels of metallothionein (MT) in placentas of smokers compared to non-smokers. In the present study, we designed experiments to separate and evaluate two isoforms of MT (MT-1 and MT-2) in placentas of smokers and non-smokers. Metallothionein was extracted and separated by ion-exchange high performance liquid chromatography (HPLC), previous saturation with cadmium chloride. Two peaks eluting at 6 and 12.5 min, corresponding to MT-1 and MT-2, respectively, were obtained. Metallothionein present in both peaks was identified by Western blot analysis using a monoclonal antibody directed against MT-1 and MT-2. Each isoform concentration was calculated after measuring its cadmium content by atomic absorption spectrometry with inductively coupled-plasma. In placentas of smokers, MT-2 levels increased by seven-fold compared to non-smokers, whereas MT-1 was not changed. Total placental cadmium and zinc concentrations, determined by atomic absorption spectrometry and neutron activation analysis, respectively, were higher in smokers. Metallothioneins levels were clearly in excess to bind all cadmium ions present in placentas. However, most of placental zinc remains unbound to MTs, although as much as twice zinc ions could be bound to MT in smokers. In conclusion, MT-2 is the main isoform induced by smoking, suggesting that this isoform could be involved in placental cadmium and zinc retention. This fact, which could contribute to reduce the transference of zinc to the fetus, may be associated to detrimental effects on fetal growth and development

  9. The role of metallothionein in oncogenesis and cancer treatment

    Directory of Open Access Journals (Sweden)

    Anna Bizoń

    2017-02-01

    Full Text Available Metallothionein is cysteine-rich low molecular mass protein. The involvement of MT in many physiological and pathophysiological processes such as apoptosis, proliferation, angiogenesis, and the detoxification of heavy metals suggested participation of this protein in carcinogenesis and tumor therapy.Depending on the type of tissue and classification of carcinoma various it was observed relation between MT expression and tumor type, stage, grade, poor prognosis and body resistance to radiotherapy and chemotherapy. MT in tumor cell plays important role in defense mechanism against the effect of radiation by inhibiting the processes that lead to the apoptosis. A number of studies have shown an increased expression of MT in various human tumors of larynx, pancreas, kidney, uterus and breast, whereas lower MT expression was detected in liver tumors. Variable MT expression was detected in case of thyroid, prostate, lung, stomach and central nervous system tumors.Also MT plays crucial role in the cytostatics treatment. MT can bind cis-platinum compounds and removes them from the cells, which may lead to multidrug resistance. However, the same functions of MT protect against the negative effects of chemotherapeutic treatment. It is especially important in case of heart cells.Analysis of MT expression in tumor cells may be useful in choosing method of treatment. It is difficult to determine whether increased expression of MT is only a inducing factor of the development of the carcinogenesis, its malignances and multidrug resistance, or it is a factor inhibiting the induction and development of cancer.

  10. Clinical significance of metallothioneins in cell therapy and nanomedicine

    Directory of Open Access Journals (Sweden)

    Sharma S

    2013-04-01

    Full Text Available Sushil Sharma,1 Afsha Rais,1 Ranbir Sandhu,1 Wynand Nel,1 Manuchair Ebadi21Saint James School of Medicine, Bonaire, The Netherlands; 2Department of Pharmacology, Physiology, and Therapeutics, Center of Excellence in Neuroscience, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USAAbstract: Mammalian metallothioneins (MTs are low molecular weight (6–7 kDa cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs. MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide–ubiquinone oxidoreductase (complex-1, a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs

  11. Metallothioneins: Emerging Modulators in Immunity and Infection

    Directory of Open Access Journals (Sweden)

    Kavitha Subramanian Vignesh

    2017-10-01

    Full Text Available Metallothioneins (MTs are a family of metal-binding proteins virtually expressed in all organisms including prokaryotes, lower eukaryotes, invertebrates and mammals. These proteins regulate homeostasis of zinc (Zn and copper (Cu, mitigate heavy metal poisoning, and alleviate superoxide stress. In recent years, MTs have emerged as an important, yet largely underappreciated, component of the immune system. Innate and adaptive immune cells regulate MTs in response to stress stimuli, cytokine signals and microbial challenge. Modulation of MTs in these cells in turn regulates metal ion release, transport and distribution, cellular redox status, enzyme function and cell signaling. While it is well established that the host strictly regulates availability of metal ions during microbial pathogenesis, we are only recently beginning to unravel the interplay between metal-regulatory pathways and immunological defenses. In this perspective, investigation of mechanisms that leverage the potential of MTs to orchestrate inflammatory responses and antimicrobial defenses has gained momentum. The purpose of this review, therefore, is to illumine the role of MTs in immune regulation. We discuss the mechanisms of MT induction and signaling in immune cells and explore the therapeutic potential of the MT-Zn axis in bolstering immune defenses against pathogens.

  12. Expression of metallothionein 3 in ductal breast cancer.

    Science.gov (United States)

    Gomulkiewicz, Agnieszka; Jablonska, Karolina; Pula, Bartosz; Grzegrzolka, Jedrzej; Borska, Sylwia; Podhorska-Okolow, Marzenna; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Ugorski, Maciej; Zabel, Maciej; Dziegiel, Piotr

    2016-12-01

    Metallothionein 3 (MT-3) has the ability to regulate the growth of nerve cells, but the significance of MT-3 expression outside the central nervous system and its participation in carcinogenesis have not yet been clarified. The aim of our study was to investigate the expression of MT-3 in ductal breast cancer and to determine its relationship with well-defined clinicopathological factors in this type of tumor. The study was conducted on 134 cases of invasive ductal breast carcinoma (IDC), 42 samples of non-malignant breast tissue (NMBT), and 26 cases of mastopathy. Moreover, selected breast cancer cell lines (MCF-7, SKBR-3, MDA-MB-231, BO2) and normal human breast epithelial cells (hTERT-HME1) were used. The expression of MT-3 was examined on the protein level using immunohistochemistry and on the mRNA level using real-time PCR. It was shown that the MT-3 protein in cells of IDC and mastopathy appeared in the cytoplasm as well as in the cell nuclei. Both the cytoplasmic and nuclear expression of MT-3 was significantly lower in IDC than in the mastopathies (p<0.0001 and p<0.001). However, no significant correlation was demonstrated between the level of MT-3 protein and the studied clinicopathological factors. The mRNA expression of MT-3 in IDC was also lower than in non‑malignant breast tissue (p<0.0001). Furthermore, in the cases of IDC with lymph node metastasis, the level of MT-3 mRNA was significantly lower than in the cases without metastasis (p=0.0199). The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line (p<0.001). These results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression.

  13. Redefining the role of metallothionein within the injured brain: extracellular metallothioneins play an important role in the astrocyte-neuron response to injury

    DEFF Research Database (Denmark)

    Chung, Roger S; Penkowa, Milena; Dittmann, Justin

    2008-01-01

    A number of intracellular proteins that are protective after brain injury are classically thought to exert their effect within the expressing cell. The astrocytic metallothioneins (MT) are one example and are thought to act via intracellular free radical scavenging and heavy metal regulation...... regeneration. First, we show that MT can be detected within the extracellular fluid of the injured brain, and that cultured astrocytes are capable of actively secreting MT in a regulatable manner. Second, we identify a receptor, megalin, that mediates MT transport into neurons. Third, we directly demonstrate...... severed mature optic nerve. Our work suggests that the protective functions of MT in the central nervous system should be widened from a purely astrocytic focus to include extracellular and intra-neuronal roles. This unsuspected action of MT represents a novel paradigm of astrocyte-neuronal interaction...

  14. Metallothionein isoform expression by breast cancer cells.

    Science.gov (United States)

    Barnes, N L; Ackland, M L; Cornish, E J

    2000-08-01

    Expression of metallothionein (MT) isoforms by a human breast cancer cell line, PMC42, which retains many characteristics of normal breast epithelial cells and expresses functional estrogen receptors, was examined because it has been proposed that human breast cancer cells which are estrogen receptor positive can be differentiated from those which are estrogen receptor negative, by failure to express MT-1E [J.A. Friedline, S.H. Garrett, S. Somji, J.H. Todd, D. A. Sens, Differential expression of the MT-1E gene in estrogen-receptor positive and -negative breast cancer cell lines, Am. J. Pathol. 152 (1998) 23-27]. Using RT-PCR, PMC42 cells were found to transcribe genes for the MT isoforms IE, IX and 2A but not 1A or 1H. In order to examine which of the expressed isoforms might protect against metal toxicity, the cells were challenged with high concentrations of zinc and copper. Using competitive RT-PCR, cells resistant to 500 microM zinc showed 7+/-2 fold (SD, n=3) increases in expression of MT-1X and 6+/-3 fold increases in expression of MT-2A compared to control cells in normal media. For cells resistant to 250 microM copper the corresponding increases were 37+/-13 and 60+/-20 fold, whilst for control cells treated with 250 microM copper for only 6 h, increases were 10+/-3 and 6+/-3 fold. There was only a low level of expression of MT-1E in untreated cells and but a >120 fold increase in copper- resistant cells. Thus estrogen receptor positive cells cannot, in general, be differentiated from estrogen receptor negative cells by failure to express MT-1E, as suggested by Friedline et al. (1998). Increased expression of MT-1E, as well as MT-1X and MT-2A, protects against metal toxicity in PMC42 breast cancer cells.

  15. Responses of Aquatic Saproxylic Macroinvertebrates to Reduced-Impact Logging in Central Amazonia.

    Science.gov (United States)

    Roque, F O; Escarpinati, S C; Valente-Neto, F; Hamada, N

    2015-08-01

    Reduced-impact logging (RIL) is an alternative land use because it reduces damage to forest cover in comparison with clear-cut practices. However, management practices adopted in RIL can affect wood availability and, consequently, fauna associated with dead wood during part of their life cycle (saproxylic). In this study, we evaluated whether aquatic saproxylic macroinvertebrates are affected by reduced-impact logging in Central Amazonia. We selected six streams in areas under reduced-impacted logging and six in primary forest areas and collected submerged woody debris. We did not find any differences in water pH, conductivity, and wood availability between reduced-impacted forest and primary forest streams. We found 248 saproxylic aquatic macroinvertebrates belonging to 37 taxa. We found five wood specialist (Dryops, Lutrochus, Stenochironomus, Oukuriella, and Endotribelos) and 32 generalists, totalling 98 and 150 individuals, respectively. In general, our results show that reduced-impact logging does not affect richness, abundance, and composition of saproxylic macroinvertebrates. The main explanation for this pattern is that management practices do not change important macroinvertebrate niche dimensions, including wood availability and the water's chemical and physical variables. Thus, controlled logging, such as applied in the area of the Central Amazonian streams studied, opens a new prospect for insect conservation and commercial exploitation of wood, which is not possible when clear-cut practices are adopted.

  16. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    OpenAIRE

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2013-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random or...

  17. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  18. Clinical intervention to reduce central obesity and menopausal symptoms in women aged 35 to 55 years.

    Science.gov (United States)

    Bitner, Diana L; Wild, Robert A

    2014-09-01

    Central obesity is a risk factor for cardiovascular disease and diabetes. Women commonly increase central fat deposition during the menopausal transition. The purpose of this demonstration project was to determine whether a personalized sex-specific intervention, WAIPointes (WAI stands for Who Am I), could reduce central obesity in women undergoing perimenopausal transition. Eighty-three of 103 women aged 35 to 55 years and experiencing symptoms of the menopausal transition completed a 6-month WAIPointes demonstration project; 75 consented to data review.Sex-specific history was obtained on visit 1; directed physical examination for body mass index, body fat percentage, waist circumference, and blood pressure were performed at each of four or five subsequent monthly visits. Other tests were ordered as necessary to determine risk stratification.Participants were assessed for menopause status, and they reported activity and menopausal symptoms at each visit. Personalized strategies for health improvement were developed in partnership. Women served as their own controls. Data from visit 2 were compared with data from visit 4. The intervention reduced waist circumference and diastolic blood pressure and improved self-reported menopausal symptoms and physical activity levels. Although further study is needed, findings suggest that the WAIPointes program offers potential as an effective office-based clinical intervention to reduce cardiovascular risk factors and symptoms of menopause in women during the menopausal transition.

  19. The role of metallothionein II in neuronal differentiation and survival

    DEFF Research Database (Denmark)

    Køhler, Lene B; Berezin, Vladimir; Bock, Elisabeth

    2003-01-01

    Metallothionein I and II (MT-I+II) are antioxidant and tissue protective factors. We have previously shown that MT-I+II prevent oxidative stress and apoptotic cell death and are of therapeutic value in brain inflammation. However, MT-I+II are expressed in glia and it remains to be elucidated if MT...

  20. Effect of lead on metallothionein concentration in leadresistant ...

    African Journals Online (AJOL)

    Metallothioneins (MTs) are cysteine-rich metal-binding proteins found in a wide variety of organisms including bacteria, fungi as well as all eukaryotic plant and animal species. MTs bind essential and nonessential heavy metals. MTs production was evaluated by a simple spectrophotometry methodology. The study ...

  1. Metallothionein as a useful marker in Hodgkin lymphoma subclassification

    DEFF Research Database (Denmark)

    Penkowa, Milena; Sørensen, Brit Ladegaard; Nielsen, Signe Lidou

    2009-01-01

    Metallothionein (MT) expression is considered to be a prognostic factor that promotes tumor resistance to apoptosis. In non-Hodgkin lymphomas, MT is differentially expressed and constitutes a risk factor. We have characterised MT in lymph nodes of Hodgkin lymphoma (HL) [patients with nodular...

  2. Barley metallothioneins differ in ontogenetic pattern and response to metals

    DEFF Research Database (Denmark)

    Schiller, Michaela; Hegelund, Josefine Nymark; Pedas, Pai

    2014-01-01

    The barley genome encodes a family of 10 metallothioneins (MTs) that have not previously been subject to extensive gene expression profiling. We show here that expression of MT1a, MT2b1, MT2b2 and MT3 in barley leaves increased more than 50-fold during the first 10 d after germination. Concurrent...

  3. Cadmium modulates adipocyte functions in metallothionein-null mice

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Takashige; Nishiyama, Kaori; Kadota, Yoshito; Sato, Masao; Inoue, Masahisa; Suzuki, Shinya, E-mail: suzukis@ph.bunri-u.ac.jp

    2013-11-01

    Our previous study has demonstrated that exposure to cadmium (Cd), a toxic heavy metal, causes a reduction of adipocyte size and the modulation of adipokine expression. To further investigate the significance of the Cd action, we studied the effect of Cd on the white adipose tissue (WAT) of metallothionein null (MT{sup −/−}) mice, which cannot form atoxic Cd–MT complexes and are used for evaluating Cd as free ions, and wild type (MT{sup +/+}) mice. Cd administration more significantly reduced the adipocyte size of MT{sup −/−} mice than that of MT{sup +/+} mice. Cd exposure also induced macrophage recruitment to WAT with an increase in the expression level of Ccl2 (MCP-1) in the MT{sup −/−} mice. The in vitro exposure of Cd to adipocytes induce triglyceride release into culture medium, decrease in the expression levels of genes involved in fatty acid synthesis and lipid hydrolysis at 24 h, and at 48 h increase in phosphorylation of the lipid-droplet-associated protein perilipin, which facilitates the degradation of stored lipids in adipocytes. Therefore, the reduction in adipocyte size by Cd may arise from an imbalance between lipid synthesis and lipolysis. In addition, the expression levels of leptin, adiponectin and resistin decreased in adipocytes. Taken together, exposure to Cd may induce unusually small adipocytes and modulate the expression of adipokines differently from the case of physiologically small adipocytes, and may accelerate the risk of developing insulin resistance and type 2 diabetes. - Highlights: • Cd causes a marked reduction in adipocyte size in MT-null mice. • Cd enhances macrophage migration into adipose tissue and disrupt adipokine secretion. • MT gene alleviates Cd-induced adipocyte dysfunctions. • Cd enhances the degradation of stored lipids in adipocytes, mediated by perilipin. • Cd induces unusually small adipocytes and the abnormal expression of adipokines.

  4. [Trace elements storage peculiarities and metallothionein content in human thyroid gland under iodine deficiency euthyroid nodular goiter].

    Science.gov (United States)

    Fal'fushins'ka, H I; Hnatyshyna, L L; Osadchuk, O Ĭ; Shydlovs'kyĭ, V O; Stoliar, O B

    2014-01-01

    Accumulation of iodine and copper in the node, paranodular and contralateral (not affected tissue by node) tissues of thyroid gland in relation to the level of metal-binding proteins, potential antioxidants and oxidative changes in tissue was investigated. To assess the severity of the pathological process the molecular markers of cytotoxicity were used. The reduction of total iodine (by 19.5%), increase of inorganic iodine fraction (by 82.4%) and total copper content (twice) in paranodular and nodular tissues compared with contrlateral part have been established. Excess of copper in goitrous-changes tissue was partially accumulated in the metallothioneins. The level of metal-binding form of metallothioneins and reserve of free thiols of these proteins was higher two-three times and lower content of reduced glutathione in node-affected tissue compared to the contralateral part. Signs of cytotoxicity among them: higher cathepsine D free activity (up to 84.6% and 134.4% in paranodular tissue and node respectively) and higher level of DNA strand breaks in the node (up to 22.6%) were observed. In paranodular tissue the range of indices variability compared with parenchyma of contralateral part is shorter than in the node. Thus, under low level of iodine organification and high copper level in goitrous-modified tissue of thyroid gland metallothionein may provide a partial compensatory effect on prooxidative processes.

  5. Transcutaneous electrical nerve stimulation reduces pain, fatigue and hyperalgesia while restoring central inhibition in primary fibromyalgia.

    Science.gov (United States)

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol G T; Liebano, Richard E; Amrit, Anand S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2013-11-01

    Because transcutaneous electrical nerve stimulation (TENS) works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo-controlled cross-over design to test the effects of a single treatment of TENS with people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS and no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and in movement; pressure pain thresholds, 6-m walk test, range of motion; 5-time sit-to-stand test, and single-leg stance. Conditioned pain modulation was completed at the end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. Pressure pain thresholds increased at the site of TENS (spine) and outside the site of TENS (leg) when compared to placebo TENS or no TENS. During active TENS, conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to the way in which TENS is used clinically on pain, fatigue, function, and quality of life in individuals with fibromyalgia. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

    International Nuclear Information System (INIS)

    Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P.

    1990-01-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions

  7. Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein.

    Science.gov (United States)

    Chin, Wei-Chih; Lin, Kuo-Hsing; Chang, Jui-Jen; Huang, Chieh-Chen

    2013-09-11

    Though n-butanol has been proposed as a potential transportation biofuel, its toxicity often causes oxidative stress in the host microorganism and is considered one of the bottlenecks preventing its efficient mass production. To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengers for reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT), mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed the greatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, and nickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress. Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging but also regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion protein could contribute in an enhancement of the host microorganism's growth rate. The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli were examined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein, OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These results presented indicate potential novel approaches for engineering stress tolerant microorganism strains.

  8. Dietary Supplementation of Blueberry Juice Enhances Hepatic Expression of Metallothionein and Attenuates Liver Fibrosis in Rats

    Science.gov (United States)

    Wang, Yuping; Cheng, Mingliang; Zhang, Baofang; Nie, Fei; Jiang, Hongmei

    2013-01-01

    Aim To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense. Methods Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques. Results Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver. Conclusion Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis. PMID:23554912

  9. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents

    Energy Technology Data Exchange (ETDEWEB)

    Kaina, B.; Lohrer, H.; Karin, M.; Herrlich, P. (Kernforschungszentrum Karlsruhe, Karlsruhe (Germany, F.R.))

    1990-04-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions.

  10. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents.

    Science.gov (United States)

    Kaina, B; Lohrer, H; Karin, M; Herrlich, P

    1990-01-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of reduced glutathione synthesis, the transfectants were not more resistant to the lethal effects of ionizing radiation and bleomycin than the parent cells. Thus free radicals generated by these agents cannot be scavenged efficiently by MT in vivo. The hMT-IIA transfectants, however, but not control transfectants harboring a BPV-MT promoter-neo construct, tolerated significantly higher doses of the alkylating agents N-methyl-N-nitrosourea and N-methyl-N'-nitro-N-nitrosoguanidine. Resistance and MT overexpression occurred irrespective of selection and cultivation in cadmium and zinc. There was no increase in resistance to methyl methanesulfonate and N-hydroxyethyl-N-chloroethylnitrosourea. MT did not affect the degree of overall DNA methylation after N-methyl-N-nitrosourea treatment nor the level of O6-methylguanine-DNA methyltransferase. The results suggest that MT participates as a cofactor or regulatory element in repair or tolerance of toxic alkylation lesions. Images PMID:2320583

  11. Effects of heavy metals on Drosophila larvae and a metallothionein cDNA

    Energy Technology Data Exchange (ETDEWEB)

    Maroni, G.; Lastowski-Perry, D.; Otto, E.; Watson, D.

    1986-03-01

    Drosophila melanogaster larvae reared on food containing radioactive cadmium retained over 80% of it, mostly in the intestinal epithelium. The majority of this radioactivity was associated with a soluble protein of less than 10,000 molecular weight. Synthesis of this cadmium-binding protein was induced by the metal as demonstrated by incorporation of radioactive cysteine. Most copper ingested by larvae was also found to associate with a low molecular weight, inducible protein, but some of it was found in an insoluble fraction. A D. melanogaster cDNA clone was isolated based on its more intense hybridization to copies of RNA sequences from copper-fed larvae than from control larvae. This clone showed strong hybridization to mouse metallothionein-I cDNA at reduced stringency. Its nucleotide sequence includes an open-reading segment which codes for a 40 amino acid protein; this protein was identified as metallothionein based on its similarity to the amino-terminal portion of mammalian and crab metalloproteins. The ten cysteine residues present occur in five pairs of near-vicinal cysteines (Cys-X-Cys). This cDNA sequence hybridized to a 400-nucleotide polyadenylated RNA whose presence in the cells of the alimentary canal of larvae was stimulated by ingestion of cadmium or copper; in other tissues this RNA was present at much lower levels.

  12. Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    We examined the expression and roles of neuroprotective metallothionein-I+II (MT-I+II) in the rat CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for the human autoimmune disease, multiple sclerosis (MS). EAE caused significant macrophage activation, T-lymphocyte infiltrat......We examined the expression and roles of neuroprotective metallothionein-I+II (MT-I+II) in the rat CNS in experimental autoimmune encephalomyelitis (EAE), an animal model for the human autoimmune disease, multiple sclerosis (MS). EAE caused significant macrophage activation, T...... to study the effects of increased MT levels, we administered Zn-MT-II intraperitoneally (i.p.) to rats during EAE. Clinically, Zn-MT-II treatment reduced the severity of EAE symptoms and mortality in a time- and dose-dependent manner. Histopathologically, Zn-MT-II increased reactive astrogliosis...... of action on macrophages, while T lymphocytes are affected locally in the CNS. During EAE, oxidative stress was decreased by Zn-MT-II, which could contribute to the diminished clinical scores observed. None of the effects caused by Zn-MT-II could be attributable to the zinc content. These results suggest MT...

  13. Peptides modeled after the alpha-domain of metallothionein induce neurite outgrowth and promote survival of cerebellar granule neurons

    DEFF Research Database (Denmark)

    Asmussen, Johanne Wirenfeldt; Ambjørn, Malene; Bock, Elisabeth

    2009-01-01

    Metallothionein (MT) is a metal-binding protein capable of preventing oxidative stress and apoptotic cell death in the central nervous system of mammals, and hence is of putative therapeutic value in the treatment of neurodegenerative disorders. Recently, we demonstrated that a peptide modeled...... amino acids, as potent stimulators of neuronal differentiation and survival of primary neurons. In addition, we show that a peptide derived from the N-terminus of the MT beta-domain, EmtinBn, promotes neuronal survival. The neuritogenic and survival promoting effects of EmtinAc, similar to MT and Emtin...

  14. Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jaromir Gumulec

    Full Text Available Metallothionein (MT has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013 and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls. A significantly positive association between MT staining and tumors (vs. healthy tissues was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03 and ovarian tumors (OR 7.83; 1.09-56.29, and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30. No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30. In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46, particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81. However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of

  15. Metallothionein as biomarker of mussel exposure to heavy metals

    International Nuclear Information System (INIS)

    Raspor, B.; Erk, M.; Pavicic, J.; Juric, D.; Kwokal, Z.; Odzak, N.

    1999-01-01

    The biological effect of marine pollution with heavy metals is followed in bivalves by means of the induced amount of metallothioneins (MTs), determined in different tissue types. The biological effect of the available toxic metals, cadmium and mercury, are related to the amount of MTs in the whole edible part, gills and the digestive gland of Mytilus galloprovincialis. For that purpose highly sensitive chemical and biochemical methods for metal and metallothionein content determination were developed and applied. The study was conducted in the Kastela Bay, which is the urban and industrial center of Dalmatia, Croatia, with two groups of mussels, indigenous and the transplanted. In accordance with the objective of the Symposium the results on monitoring the marine pollution by means of MTs as a biomarker, isolated from the edible, sessile and filter-feeding bivalves are discussed. (author)

  16. Exercise-induced metallothionein expression in human skeletal muscle fibres

    DEFF Research Database (Denmark)

    Penkowa, Milena; Keller, Pernille; Keller, Charlotte

    2005-01-01

    in both type I and II muscle fibres. This is the first report demonstrating that MT-I + II are significantly induced in human skeletal muscle fibres following exercise. As MT-I + II are antioxidant factors that protect various tissues during pathological conditions, the MT-I + II increases post exercise......Exercise induces free oxygen radicals that cause oxidative stress, and metallothioneins (MTs) are increased in states of oxidative stress and possess anti-apoptotic effects. We therefore studied expression of the antioxidant factors metallothionein I and II (MT-I + II) in muscle biopsies obtained...... in response to 3 h of bicycle exercise performed by healthy men and in resting controls. Both MT-I + II proteins and MT-II mRNA expression increased significantly in both type I and II muscle fibres after exercise. Moreover, 24 h after exercise the levels of MT-II mRNA and MT-I + II proteins were still highly...

  17. Renoprotection From Diabetic Complications in OVE Transgenic Mice by Endothelial Cell Specific Overexpression of Metallothionein: A TEM Stereological Analysis.

    Science.gov (United States)

    Carlson, Edward C; Chhoun, Jennifer M; Grove, Bryon D; Laturnus, Donna I; Zheng, Shirong; Epstein, Paul N; Tan, Yi

    2017-03-01

    We previously demonstrated that OVE transgenic diabetic mice are susceptible to chronic complications of diabetic nephropathy (DN) including substantial oxidative damage to the renal glomerular filtration barrier (GFB). Importantly, the damage was mitigated significantly by overexpression of the powerful antioxidant, metallothionein (MT) in podocytes. To test our hypothesis that GFB damage in OVE mice is the result of endothelial oxidative insult, a new JTMT transgenic mouse was designed in which MT overexpression was targeted specifically to endothelial cells. At 60 days of age, JTMT mice were crossed with age-matched OVE diabetic mice to produce bi-transgenic OVE-JTMT diabetic progeny that carried the endothelial targeted JTMT transgene. Renal tissues from the OVE-JTMT progeny were examined by unbiased TEM stereometry for possible GFB damage and other alterations from chronic complications of DN. In 150 day-old OVE-JTMT mice, blood glucose and HbA1c were indistinguishable from age-matched OVE mice. However, endothelial-specific MT overexpression in OVE-JTMT mice mitigated several DN complications including significantly increased non-fenestrated glomerular endothelial area, and elimination of glomerular basement membrane thickening. Significant renoprotection was also observed outside of endothelial cells, including reduced podocyte effacement, and increased podocyte and total glomerular cell densities. Moreover, when compared to OVE diabetic animals, OVE-JTMT mice showed significant mitigation of nephromegaly, glomerular hypertrophy, increased mesangial cell numbers and increased total glomerular cell numbers. These results confirm the importance of oxidative stress to glomerular damage in DN, and show the central role of endothelial cell injury to the pathogenesis of chronic complications of diabetes. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:560-576, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Advisibility of excavating an additional central shaft to reduce duration of mine construction. [USSR

    Energy Technology Data Exchange (ETDEWEB)

    Durov, E.M.

    1981-09-01

    This paper evaluates methods of reducing duration and cost of underground black coal mine construction. A proposed scheme of coal deposit opening by a system of three mine shafts is critically analyzed. In comparison to the conventional scheme, the proposed one has one additional mine shaft in the central mine zone. The shaft, equipped with a cage hoisting system, permits the rate of mine drivage in the center of the mine to be increased. The cage hoisting system in the additional shaft is activated before the main skip shaft has been equipped and is in operation. Duration of mine construction is reduced by 6 to 10 months. Exacavation of the additional shaft costs from 2.5 to 3.5 million rubles. A further system of mine construction is also analyzed. The main shaft in the mine center is temporarily equipped with a cage hoisting system. The cage system is used for hoisting rocks removed from mine headings and main workings constructed at the bottom of the main shaft. The main shaft is equipped with skips and hoisting tower at a later stage when construction of main roadways and structures at its bottom has been completed. The proposed system permits mine construction to be reduced by 4 to 5 months without a major increase in investment.

  19. Metallothionein deficiency aggravates depleted uranium-induced nephrotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Yuhui; Huang, Jiawei; Gu, Ying; Liu, Cong; Li, Hong; Liu, Jing; Ren, Jiong; Yang, Zhangyou [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China); Peng, Shuangqing [Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Science, 20 Dongdajie Street, Fengtai District, Beijing 100071 (China); Wang, Weidong, E-mail: wwdwyl@sina.com [Department of Radiation Oncology, Shanghai Jiao Tong University Affiliated Sixth People' s Hospital, Shanghai 200233 (China); Li, Rong, E-mail: yuhui_hao@126.com [State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing 400038 (China)

    2015-09-15

    Depleted uranium (DU) has been widely used in both civilian and military activities, and the kidney is the main target organ of DU during acute high-dose exposures. In this study, the nephrotoxicity caused by DU in metallothionein-1/2-null mice (MT −/−) and corresponding wild-type (MT +/+) mice was investigated to determine any associations with MT. Each MT −/− or MT +/+ mouse was pretreated with a single dose of DU (10 mg/kg, intraperitoneal injection) or an equivalent volume of saline. After 4 days of DU administration, kidney changes were assessed. After DU exposure, serum creatinine and serum urea nitrogen in MT −/− mice significantly increased than in MT +/+ mice, with more severe kidney pathological damage. Moreover, catalase and superoxide dismutase (SOD) decreased, and generation of reactive oxygen species and malondialdehyde increased in MT −/− mice. The apoptosis rate in MT −/− mice significantly increased, with a significant increase in both Bax and caspase 3 and a decrease in Bcl-2. Furthermore, sodium-glucose cotransporter (SGLT) and sodium-phosphate cotransporter (NaPi-II) were significantly reduced after DU exposure, and the change of SGLT was more evident in MT −/− mice. Finally, exogenous MT was used to evaluate the correlation between kidney changes induced by DU and MT doses in MT −/− mice. The results showed that, the pathological damage and cell apoptosis decreased, and SOD and SGLT levels increased with increasing dose of MT. In conclusion, MT deficiency aggravated DU-induced nephrotoxicity, and the molecular mechanisms appeared to be related to the increased oxidative stress and apoptosis, and decreased SGLT expression. - Highlights: • MT −/− and MT +/+ mice were used to evaluate nephrotoxicity of DU. • Renal damage was more evident in the MT −/− mice after exposure to DU. • Exogenous MT also protects against DU-induced nephrotoxicity. • MT deficiency induced more ROS and apoptosis after exposure to

  20. Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults

    Directory of Open Access Journals (Sweden)

    Chih-Hsiang Yang

    2015-01-01

    Full Text Available Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258 completed a brief web survey in October–November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction.

  1. Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

    Directory of Open Access Journals (Sweden)

    Mario Rivera-Meza

    2017-07-01

    Full Text Available We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde or there might be additional effects at central level. High drinker rats (UChB were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day or vehicle (as control was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day did not develop ethanol-conditioned place preference (CPP.In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol

  2. Fenofibrate Administration Reduces Alcohol and Saccharin Intake in Rats: Possible Effects at Peripheral and Central Levels

    Science.gov (United States)

    Rivera-Meza, Mario; Muñoz, Daniel; Jerez, Erik; Quintanilla, María E.; Salinas-Luypaert, Catalina; Fernandez, Katia; Karahanian, Eduardo

    2017-01-01

    We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde) or there might be additional effects at central level. High drinker rats (UChB) were allowed to voluntary drink 10% ethanol for 2 months. Afterward, a daily dose of fenofibrate (25, 50 or 100 mg/kg/day) or vehicle (as control) was administered orally for 14 days. Voluntary ethanol intake was recorded daily. After that time, animals were deprived of ethanol access for 24 h and administered with an oral dose of ethanol (1 g/kg) for acetaldehyde determination in blood. Fenofibrate reduced ethanol voluntary intake by 60%, in chronically drinking rats, at the three doses tested. Acetaldehyde in the blood rose up to between 80 μM and 100 μM. Considering the reduction of ethanol consumption, blood acetaldehyde levels and body weight evolution, the better results were obtained at a dose of 50 mg fenofibrate/kg/day. This dose of fenofibrate also reduced the voluntary intake of 0.2% saccharin by 35% and increased catalase levels 2.5-fold in the liver but showed no effects on catalase levels in the brain. To further study if fenofibrate administration changes the motivational properties of ethanol, a conditioned-place preference experiment was carried out. Animals treated with fenofibrate (50 mg/kg/day) did not develop ethanol-conditioned place preference (CPP).In an additional experiment, chronically ethanol-drinking rats underwent two cycles of ethanol deprivation

  3. METALLOTHIONEIN GENE TRANSCRIPTION AS AN INDICATOR OF METAL EXPOSURE IN FATHEAD MINNOWS

    Science.gov (United States)

    Metallothionein is a cysteine rich, low molecular weight, metal binding protein. Basal levels of endogenous metallothioneins (MT) have been reported in all eucaryotes. MT has been shown to play an essential role in regulating physiological requirements of essential metals such a...

  4. Cadmium induces a novel metallothionein and phytochelatin 2 in an aquatic fungus

    International Nuclear Information System (INIS)

    Jaeckel, Petra; Krauss, Gudrun; Menge, Sieglinde; Schierhorn, Angelika; Ruecknagel, Peter; Krauss, Gerd-Joachim

    2005-01-01

    Cadmium stress response was measured at the thiol peptide level in an aquatic hyphomycete (Heliscus lugdunensis). In liquid culture, 0.1mM cadmium increased the glutathione (GSH) content and induced the synthesis of additional thiol peptides. HPLC, electrospray ionization mass spectrometry, and Edman degradation confirmed that a novel small metallothionein as well as phytochelatin (PC2) were synthesized. The metallothionein has a high homology to family 8 metallothioneins (http://www.expasy.ch/cgi-bin/lists?metallo.txt). The bonding of at least two cadmium ions to the metallothionein was demonstrated by mass spectrometry (MALDI MS). This is the first time that simultaneous induction of metallothionein and phytochelatin accompanied by an increase in GSH level has been shown in a fungus under cadmium stress, indicating a potential function of these complexing agents for in vivo heavy metal detoxification. The method presented here should be applicable as biomarker tool. ol

  5. Blockade of Metallothioneins 1 and 2 Increases Skeletal Muscle Mass and Strength

    Science.gov (United States)

    Summermatter, Serge; Bouzan, Anais; Pierrel, Eliane; Melly, Stefan; Stauffer, Daniela; Gutzwiller, Sabine; Nolin, Erin; Dornelas, Christina; Fryer, Christy; Leighton-Davies, Juliet; Glass, David J.

    2016-01-01

    ABSTRACT Metallothioneins are proteins that are involved in intracellular zinc storage and transport. Their expression levels have been reported to be elevated in several settings of skeletal muscle atrophy. We therefore investigated the effect of metallothionein blockade on skeletal muscle anabolism in vitro and in vivo. We found that concomitant abrogation of metallothioneins 1 and 2 results in activation of the Akt pathway and increases in myotube size, in type IIb fiber hypertrophy, and ultimately in muscle strength. Importantly, the beneficial effects of metallothionein blockade on muscle mass and function was also observed in the setting of glucocorticoid addition, which is a strong atrophy-inducing stimulus. Given the blockade of atrophy and the preservation of strength in atrophy-inducing settings, these results suggest that blockade of metallothioneins 1 and 2 constitutes a promising approach for the treatment of conditions which result in muscle atrophy. PMID:27956698

  6. Metallothionein expression during liver regeneration after partial hepatectomy in cadmium-pretreated rats

    Energy Technology Data Exchange (ETDEWEB)

    Margeli, A.P. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Theocharis, S.E. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Yannacou, N.N. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Spiliopoulou, C. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece)); Koutselinis, A. (Dept. of Forensic Medicine and Toxicology, School of Medicine, Univ. of Athens (Greece))

    1994-10-01

    Metallothionein is a low molecular mass protein inducible mainly by heavy metals, having high affinity for binding cadmium, zinc and copper. In the present study we investigated the expression of metallothionein in regenerating liver, at different time intervals, in cadmium pretreated partially hepatectomized rats. Liver metallothionein is highly expressed during regeneration induced by partial hepatectomy in rats, providing zinc within the rapidly growing tissue. Cadmium pretreatment caused inhibition of the first peak of liver regeneration, while metallothionein expression was markedly more prominent in the liver residues of cadmium-pretreated rats. These results demonstrate that although metallothionein able to bind temporarily metal ions as zinc and cadmium has been highly expressed, the liver regenerative process was inhibited possibly due to the effects of cadmium on other pivotal events necessary to the DNA replication. (orig.)

  7. Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C; Carrasco, J; Hidalgo, J

    2001-01-01

    during experimental autoimmune encephalomyelitis in interferon-gamma receptor knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv.Mice with experimental autoimmune encephalomyelitis showed a significant induction of metallothioneins-I+II in the spinal cord white matter......, and to a lower extent in the brain. Interferon-gamma receptor knockout mice suffered from a more severe experimental autoimmune encephalomyelitis, and interestingly showed a higher metallothioneins-I+II induction in both white and grey matter of the spinal cord and in the brain. In contrast...... to the metallothioneins-I+II isoforms, metallothionein-III expression remained essentially unaltered during experimental autoimmune encephalomyelitis; interferon-gamma receptor knockout mice showed an altered metallothionein-III expression (a slight increase in the spinal cord white matter) only in the C57BL/6x129/Sv...

  8. Shaping mechanisms of metal specificity in a family of metazoan metallothioneins: evolutionary differentiation of mollusc metallothioneins

    Directory of Open Access Journals (Sweden)

    Atrian Sílvia

    2011-01-01

    Full Text Available Abstract Background The degree of metal binding specificity in metalloproteins such as metallothioneins (MTs can be crucial for their functional accuracy. Unlike most other animal species, pulmonate molluscs possess homometallic MT isoforms loaded with Cu+ or Cd2+. They have, so far, been obtained as native metal-MT complexes from snail tissues, where they are involved in the metabolism of the metal ion species bound to the respective isoform. However, it has not as yet been discerned if their specific metal occupation is the result of a rigid control of metal availability, or isoform expression programming in the hosting tissues or of structural differences of the respective peptides determining the coordinative options for the different metal ions. In this study, the Roman snail (Helix pomatia Cu-loaded and Cd-loaded isoforms (HpCuMT and HpCdMT were used as model molecules in order to elucidate the biochemical and evolutionary mechanisms permitting pulmonate MTs to achieve specificity for their cognate metal ion. Results HpCuMT and HpCdMT were recombinantly synthesized in the presence of Cd2+, Zn2+ or Cu2+ and corresponding metal complexes analysed by electrospray mass spectrometry and circular dichroism (CD and ultra violet-visible (UV-Vis spectrophotometry. Both MT isoforms were only able to form unique, homometallic and stable complexes (Cd6-HpCdMT and Cu12-HpCuMT with their cognate metal ions. Yeast complementation assays demonstrated that the two isoforms assumed metal-specific functions, in agreement with their binding preferences, in heterologous eukaryotic environments. In the snail organism, the functional metal specificity of HpCdMT and HpCuMT was contributed by metal-specific transcription programming and cell-specific expression. Sequence elucidation and phylogenetic analysis of MT isoforms from a number of snail species revealed that they possess an unspecific and two metal-specific MT isoforms, whose metal specificity was

  9. Central fuel banking to reduce the number of proliferation sensitive enrichment activities

    International Nuclear Information System (INIS)

    Cserhati, A.

    2008-01-01

    Central fuel banking is a complex international political, economic and technical concept that aims to reduce uncontrolled spreading of uranium enrichment technology in the world in order to prevent proliferation of nuclear weapons. This paper first gives an outline of the notions: 'non-proliferation', the 'front-end' of the fuel cycle, the scope of fuel baking, nuclear fuel and the 60 years of enrichment technology. Enrichment technology is highly concentrated in the nuclear weapon states and other developed countries, but this is not exclusive any more. The technology is spreading. The global demand for enrichment services - parallel to massive nuclear investments in the civil sector and the ageing of older facilities - is constantly growing. Proliferation sensitivity calls for an effective and comprehensive non-proliferation regime. The solution may be multilateralizing the nuclear fuel cycle. After a historical overview, the proposals on multilateral nuclear approaches are presented. The assessment of the proposals is complex in the dimensions of: the non-proliferation aim, the assurance of supply aspect and other variables such as legal issues and non-nuclear inducements. A general evaluation and the recommendations of the Expert Panel of the IAEA are introduced outlining a plan on a middle- and long-term basis. The conclusion of the paper stresses the importance and challenge in finding the 'new balance' between obligations and interests of the members of the global community stating that the answers will have a significant impact on the nuclear indus- try, world wide economics and security policy. (orig.)

  10. Metallothionein metabolism in the streptozotocin-diabetic rat

    International Nuclear Information System (INIS)

    Chen, M.L.; Failla, M.L.

    1986-01-01

    Earlier reports from their laboratory showed the induction of the insulin-deficient diabetic state in adult rats was associated with an accumulation of zinc, copper, and a metallothionein-like zinc and copper binding protein in the soluble fraction of liver and kidney. Based upon chromatographic and electrophoretic properties, -SH to metal ratio and amino acid composition, they now report that elevated concentrations of metallothioneins (MT)-I and -II are indeed present in diabetic rat liver and kidney cytosol. The relative rates of MT synthesis in tissues from diabetic and control rats were measured by comparing incorporation of 35 S-cysteine into MT vs. total cytoplasmic proteins at 5 h after injection of the precursor. The relative rates of MT synthesis in livers from rats diabetic for 10 d and fed either chow or purified diet containing 13 or 35 ppm copper were 1.4, 2.3 and 2.8 times greater, respectively, than control rats fed the same diets. Higher relative rates of MT synthesis were also observed in kidneys from diabetic rats fed purified diets compared to controls. Maximal relative rates of MT synthesis in diabetic liver and kidney were observed at 4 and 10 d, respectively, after onset of diabetes. The half-lives of cytoplasmic MT in liver and kidney from diabetic (10 d) rats were 1.3 and 2.6 days, respectively; half-lives of MT in control liver and kidney were 5.0 and 2.1 days, respectively

  11. Increased levels of metallothionein in placenta of smokers

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Arguello, Graciela; Suazo, Myriam; Llanos, Miguel N.

    2005-01-01

    Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 ng/ml were included in the smoking group. Determination of placental MT was performed by western blot analysis after tissue homogenization and saturation with cadmium chloride (1000 ppm). Metallothionein was analyzed with a monoclonal antibody raised against MT-1 and MT-2 and with a second anti mouse antibody conjugated to alkaline phosphatase. Zinc and cadmium were determined by neutron activation analysis and atomic absorption spectrometry respectively. Smokers showed higher placental MT and cadmium levels, together with decreased newborn birth weights, as compared to non-smokers. The semi-quantitative analysis of western blots by band densitometry indicated that darker bands corresponded to MT present in smokers' samples. This study confirms that cigarette smoking increases cadmium accumulation in placental tissue and suggests that this element has a stimulatory effect on placental MT production

  12. Nebivolol reduces central blood pressure in stage I hypertensive patients: experimental single cohort study

    Directory of Open Access Journals (Sweden)

    Renan Oliveira Vaz-de-Melo

    Full Text Available CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients.DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital.METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR, central BP and augmentation index before and after 3 months of using nebivolol.RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2 with large abdominal waist (102.1 ± 7.2 cm. There were significant decreases in peripheral systolic BP (P = 0.0020, diastolic BP (P = 0.0049, HR (P < 0.0001 and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083 after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment.CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP.

  13. Metallothionein-I and -III expression in animal models of Alzheimer disease

    DEFF Research Database (Denmark)

    Carrasco, J; Adlard, P; Cotman, C

    2006-01-01

    Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human...

  14. Contemporary approaches to reducing the risks of central counterparties based on the use of marginal contributions

    Directory of Open Access Journals (Sweden)

    Utkin Viktor Sergeyevich

    2012-07-01

    Full Text Available To protect their own interests central counterparties has developed a number of procedures, including payment of guarantee margin by trading members as a means to ensure their positions. This article discusses a number of approaches, which attempt to simulate the risks of the Central Committee, as well as calculating the amount of margin and other resources in the event of insolvency. These approaches are based on the simulation of the three main types: (a statistical modeling; (b optimization modeling, and (c model of option pricing. The author incorporates the basic provisions of models.

  15. Expression of metallothioneins I and II related to oxidative stress in the liver of aluminium-treated rats.

    Science.gov (United States)

    Ghorbel, Imen; Chaabane, Mariem; Elwej, Awatef; Boudawara, Ons; Abdelhedi, Sameh; Jamoussi, Kamel; Boudawara, Tahya; Zeghal, Najiba

    2016-10-01

    Hepatotoxicity, induced by aluminium chloride (AlCl 3 ), has been well studied but there are no reports about liver metallothionein (MT) genes induction. Therefore, it is of interest to establish the mechanism involving the relation between MT gene expression levels and the oxidative stress status in hepatic cells of aluminium-treated rats. Aluminium (Al) was administered to rats in their drinking water at a dose of 50 mg/kg body weight for three weeks. AlCl 3 provoked hepatotoxicity objectified by an increase in malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), advanced oxidation protein products (AOPP), protein carbonyls (PCO) and a decrease in reduced glutathione (GSH), non-protein thiols (NPSH) and vitamin C. CAT and Glutathione peroxidase (GPx) activities were decreased while Mn-SOD gene expression, total Metallothionein content and MT I and MT II genes induction were increased. There are changes in plasma of some trace elements, albumin levels, transaminases, LDH and ALP activities. All these changes were supported by histopathological observations.

  16. Electrochemical Characterization of Metal-Binding Properties of Metallothioneins Isolated from M. galloprovincialis

    OpenAIRE

    Raspor, Biserka; Pavičić, Jasenka

    1997-01-01

    Amperometric titrations of defined metallothionein concentrations with the standard CdCl2 solution have been performed in seawater samples at pH > 8, in order to define the metal-binding properties of purified mussel metallothionein component. The concentration of the formed Cd-thionein complex has been assessed in the indirect and direct mode. The results on the available ligand concentration CL for complexing Cd2+ ions and the apparent stability constant K, determined by two procedures are ...

  17. Generation and analysis of plasmas with centrally reduced helicity in full-tungsten ASDEX upgrade

    Energy Technology Data Exchange (ETDEWEB)

    Bock, Alexander

    2016-03-01

    The most promising concepts for harnessing nuclear fusion are toroidal devices like tokamaks, where a plasma is confined by helically twisted magnetic field lines. To provide the twisting of the field lines, a tokamak relies on a toroidal current in the plasma, which is largely generated by a transformer. As such, conventional tokamaks are limited to pulsed operation. Moreover, this current makes tokamak plasmas prone to numerous confinement degrading magnetohydrodynamic (MHD) instabilities that can emerge at locations where the field line helicity q takes on rational values like 1/1, 3/2 or 2/1, i.e. sawteeth or neoclassical tearing modes (NTMs). This thesis presents studies of plasmas with centrally elevated q-profiles created by external electron-cyclotron and neutral beam current drive (ECCD/NBCD) under steady-state conditions in the full-tungsten tokamak ASDEX Upgrade. Without the usually monotonic q-profile, instabilities of low helicity disappear, thereby improving the plasma stability. Furthermore, elevating q increases the amount of so-called (toroidal) bootstrap current, which the plasma drives by itself in the presence of pressure gradients, thereby reducing the reliance on the transformer. In the best case, an advanced tokamak (AT) could thus run in steady state. Additionally, an elevated and thus flat/slightly reversed q-profile is thought to improve confinement by impeding turbulent transport. Reconstruction of the tailored q-profile is accomplished with the new integrated data equilibrium (IDE) code and information from a key diagnostic that is based on the Motional Stark Effect (MSE). During the course of this work it was discovered that the MSE diagnostic suffers from interference from polarised background light. A prototype mitigation system was successfully tested. Also, non-linearities in the diagnostic's optical relay system were found and a calibration scheme devised to take them into account. Both the conventional approach of AT

  18. Repair of DNA damage in the human metallothionein gene family

    International Nuclear Information System (INIS)

    Leadon, S.A.; Snowden, M.M.

    1987-01-01

    In order to distinguish enhanced repair of a sequence due to its transcriptional activity from enhanced repair due to chromatin alterations brought about by integration of a sequence into the genome, we have investigated the repair of damage both in endogenous genes and in cell lines that contain an integrated gene with an inducible promoter. The endogenous genes we are studying are the metallothioneins (MTs), a multigene family in man consisting of about 10-12 members. Cultured cells were exposed to 10-J/m 2 uv light and allowed to repair in the presence of bromodeoxyuridine. The DNA was then isolated, digested with Eco RI, and fully hybrid density DNA made by semiconservative synthesis was separated from unreplicated DNA by centrifugation in CsCl density gradients. Unreplicated, parental-density DNA was then reacted with a monoclonal antibody against bromouracil. 1 ref., 1 fig., 1 tab

  19. The involvement of metallothionein in the development of aquatic invertebrate

    Energy Technology Data Exchange (ETDEWEB)

    Mao Huan; Wang Dahui [Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Yang Wanxi, E-mail: wxyang@spermlab.org [Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China)

    2012-04-15

    The many documents on metallothioneins (MTs) in aquatic organisms focus especially on their use as biomarkers in environmental monitoring programs, but there are a few papers that summarize the physiological role of MTs in aquatic organisms especially in their development. The multifaceted role of MTs include involvement in homeostasis, protection against heavy metals and oxidant damage, metabolic regulation, sequestration and/or redox control. MTs could be induced by heavy metals which are able to hinder gametogenesis, suppress embryogenesis, and hamper development. Here we pay more attention on the non-essential metal cadmium, which is the most studied heavy metal regarding MTs, and its effects on the development of aquatic invertebrates. In this paper, we have collected published information on MTs in aquatic organisms - mollusks, crustaceans, etc., and summarize its functions in aquatic invertebrates, especially those related to their development.

  20. Molecular functions of metallothionein and its role in hematological malignancies

    Directory of Open Access Journals (Sweden)

    Takahashi Shinichiro

    2012-07-01

    Full Text Available Abstract Metallothionein (MT was reported to be a potential negative regulator of apoptosis, and various reports have suggested that it may play roles in carcinogenesis and drug resistance, in at least a portion of cancer cells. The author summarizes the current understanding of the molecular functions of MT for tumor cell growth and drug resistance. These activities are regulated through intracellular metal ion modulation and free radical scavenging. Compared with analyses of solid tumors, few studies have analyzed the roles of MT in hematological malignancies. This review mainly describes the functions of MT in hematopoietic cells. Furthermore, through expression analyses of leukemias and lymphomas, the roles of MT in the biology of these diseases are particularly focused upon.

  1. Temporal variations in metallothionein concentration and subcellular distribution of metals in gills and digestive glands of the oyster Crassostrea angulata

    Directory of Open Access Journals (Sweden)

    Chiara Trombini

    2010-11-01

    Full Text Available The metallothionein levels and metal concentrations in whole body, digestive gland and gills of Crassostrea angulata were analyzed in field samples collected from the River Guadalquivir estuary over several years following a mining waste spill upstream. The subcellular distribution of metals was analyzed to determine the mechanisms involved in the detoxification process. The highest metallothionein levels were reported in the digestive gland shortly after the mining contamination event. In this organ, metals are stored preferentially in the non-cytosolic fraction when increased bioaccumulation takes place. In the cytosol of the gills, metals are associated with metallothionein, whereas in the digestive gland, the distribution of metals between metallothioneins and high molecular weight proteins is similar. Metallothionein variation cannot be explained by metals alone; other abiotic factors must be taken into account. In order to use metallothionein as a metal exposure biomarker in field studies, natural variability needs to be taken into account for the correct interpretation of results.

  2. Metallothionein expression in chloroplasts enhances mercury accumulation and phytoremediation capability.

    Science.gov (United States)

    Ruiz, Oscar N; Alvarez, Derry; Torres, Cesar; Roman, Laura; Daniell, Henry

    2011-06-01

    Genetic engineering to enhance mercury phytoremediation has been accomplished by expression of the merAB genes that protects the cell by converting Hg[II] into Hg[0] which volatilizes from the cell. A drawback of this approach is that toxic Hg is released back into the environment. A better phytoremediation strategy would be to accumulate mercury inside plants for subsequent retrieval. We report here the development of a transplastomic approach to express the mouse metallothionein gene (mt1) and accumulate mercury in high concentrations within plant cells. Real-time PCR analysis showed that up to 1284 copies of the mt1 gene were found per cell when compared with 1326 copies of the 16S rrn gene, thereby attaining homoplasmy. Past studies in chloroplast transformation used qualitative Southern blots to evaluate indirectly transgene copy number, whereas we used real-time PCR for the first time to establish homoplasmy and estimate transgene copy number and transcript levels. The mt1 transcript levels were very high with 183,000 copies per ng of RNA or 41% the abundance of the 16S rrn transcripts. The transplastomic lines were resistant up to 20 μm mercury and maintained high chlorophyll content and biomass. Although the transgenic plants accumulated high concentrations of mercury in all tissues, leaves accumulated up to 106 ng, indicating active phytoremediation and translocation of mercury. Such accumulation of mercury in plant tissues facilitates proper disposal or recycling. This study reports, for the first time, the use of metallothioneins in plants for mercury phytoremediation. Chloroplast genetic engineering approach is useful to express metal-scavenging proteins for phytoremediation. © 2011 The Authors. Plant Biotechnology Journal © 2011 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  3. Zn tolerance of novel Colocasia esculenta metallothionein and its domains in Escherichia coli and tobacco.

    Science.gov (United States)

    Kim, Yeon-Ok; Lee, Yoon Gyo; Patel, Darshan H; Kim, Ho Myeong; Ahn, Sung-Ju; Bae, Hyeun-Jong

    2012-11-01

    Contrary to extensive researches on the roles of metallothioneins (MTs) in metal tolerance of animals, the roles of plant MTs in metal tolerance are largely under investigation. In this study, we evaluated the functional role of type 2 MT from Colocasia esculenta (CeMT2b) in Zn tolerance of tobacco and E. coli cells. Under Zn-stress conditions, transgenic tobacco overexpressing CeMT2b displayed much better seedling growth, a significant decrease in the levels of H(2)O(2) and an increase in Zn accumulation compared with the wild type. Overexpression of CeMT2b in E. coli greatly enhanced Zn tolerance and Zn accumulation under Zn stresses compared with control cells. CeMT2b bound 5.38 ± 0.29 atoms of Zn per protein. To identify a structural domain of CeMT2b for Zn binding, we investigated the growth of E. coli expressing each of the N-terminal, C-terminal, and central linker domains or a CNC motif deletion from the C-terminus of full-length CeMT2b. The results showed that the CNC motif is required for Zn tolerance, and the N-terminal domain is more effective in Zn tolerance than the C-terminal domain. Taken together, our results provide direct evidence for functional contributions of CeMT2b in Zn tolerance of tobacco and E. coli cells.

  4. An immunohistochemical study on the tissue-specific localization of metallothionein in dogs.

    Science.gov (United States)

    Shimada, A; Yanagida, M; Umemura, T

    1997-01-01

    To study the tissue specificity of metallothionein (MT) expression, tissues of dogs ranging in age from 1 day to 18 years were examined immunohistochemically. Of the organs examined, liver and kidney showed the strongest immunoreactivity; a comparable intensity of MT immunolabelling was noted in the two organs in adult animals. In the central nervous system, astrocytes and ependymal cells showed MT immunoreactivity. MT labelling was shown in the sustentacular cells of the olfactory epithelium, but immunoreactivity was slight in the epithelium of the respiratory tract. Slight MT immunoreactivity was demonstrated in the epithelium of a variety of glands (sweat, uterine, mammary, olfactory, perianal and thyroid) and in parietal cells of the fundic glands of the stomach. Sporadic MT immunolabelling was demonstrated in the columnar and goblet cells of the small and large intestines, surface mucosal cells of the stomach and epithelial cells of the hair follicles. These findings may help in understanding important features of MT, such as its dynamic induction mechanism, its systemic degradation pathway and the possible biological functions.

  5. Metallothionein Zn(2+)- and Cu(2+)-clusters from first-principles calculations

    DEFF Research Database (Denmark)

    Greisen, Per Junior; Jespersen, Jakob Berg; Kepp, Kasper Planeta

    2012-01-01

    in electron density on bridging sulfurs. Various imposed backbone constraints quantify the sensitivity of cluster electronic structure towards protein conformational changes. The large negative charge densities of the clusters are central to MT function, and the smaller β-clusters are more prone......Detailed electronic structures of Zn(ii) and Cu(ii) clusters from metallothioneins (MT) have been obtained using density functional theory (DFT), in order to investigate how oxidative stress-caused Cu(ii) intermediates affect Zn-binding to MT and cooperatively lead to Cu(i)MT. The inferred accuracy...... is ∼0.02-0.03 Å for metal-thiolate bond lengths for the models that are the most realistic MT models so far studied by DFT. We find terminal Zn-S and Cu-S bond lengths of 2.35-2.38 Å and 2.30-2.34 Å, whereas bridging M-S bonds are 0.05-0.11 Å longer. This electronic effect is also reflected in changes...

  6. Centralized breastmilk handling and bar code scanning improve safety and reduce breastmilk administration errors.

    Science.gov (United States)

    Steele, Caroline; Bixby, Christine

    2014-11-01

    Safe handling and preparation of breastmilk within the hospital setting are often taken for granted, and the process may not be scrutinized until problems arise. Areas of concern focus on both risk of contamination of breastmilk feedings due to handling and fortification and risk of a breastmilk misadministration. In two phases, Children's Hospital of Orange County (Orange, CA) implemented centralized breastmilk handling and breastmilk bar code scanning. As a result of these process changes, reports of breastmilk administration errors decreased to zero. However, bar code scanning allowed for the tracking of near misses. During the first 6 months of breastmilk bar code scanning, 55 attempts to feed the wrong breastmilk to the wrong patient and 127 attempts to feed expired breastmilk were prevented. Our findings are consistent with current practice recommendations that support the use of centralized breastmilk handling and systems for proper identification of breastmilk.

  7. Public accessibility of biomedical articles from PubMed Central reduces journal readership--retrospective cohort analysis.

    Science.gov (United States)

    Davis, Philip M

    2013-07-01

    Does PubMed Central--a government-run digital archive of biomedical articles--compete with scientific society journals? A longitudinal, retrospective cohort analysis of 13,223 articles (5999 treatment, 7224 control) published in 14 society-run biomedical research journals in nutrition, experimental biology, physiology, and radiology between February 2008 and January 2011 reveals a 21.4% reduction in full-text hypertext markup language (HTML) article downloads and a 13.8% reduction in portable document format (PDF) article downloads from the journals' websites when U.S. National Institutes of Health-sponsored articles (treatment) become freely available from the PubMed Central repository. In addition, the effect of PubMed Central on reducing PDF article downloads is increasing over time, growing at a rate of 1.6% per year. There was no longitudinal effect for full-text HTML downloads. While PubMed Central may be providing complementary access to readers traditionally underserved by scientific journals, the loss of article readership from the journal website may weaken the ability of the journal to build communities of interest around research papers, impede the communication of news and events to scientific society members and journal readers, and reduce the perceived value of the journal to institutional subscribers.

  8. Activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

    Science.gov (United States)

    Côté, Isabelle; Green, Sara M; Morgan, Drake; Carter, Christy S; Tümer, Nihal; Scarpace, Philip J

    2018-03-01

    Recent evidence indicate that melanotan II (MTII) reduces body mass independently of caloric reduction. Because MTII induces a transient hypophagia, caloric reduction is still considered a primary mechanism for MTII-mediated body mass loss. To examine the contribution of caloric reduction to long-term body mass loss in response to MTII, we centrally infused MTII or vehicle in ad libitum fed (MTII and Control) animals in comparison with a group of animals that were pair-fed (PF) to the MTII group. Food intake and body mass were recorded daily, and body composition was assessed biweekly. The present study demonstrates that central MTII-mediated body mass loss is only partially mediated by caloric restriction, and the long-term body mass loss is independent of the initial hypophagia. More importantly, central MTII administration induced a rapid but sustained fat mass loss, independently of caloric reduction. MTII-treated animals preserved their lean/fat mass ratio throughout the study, whereas PF animals underwent a transient reduction of lean/fat mass ratio that was only normalized when food intake returned to Control level. In summary, it can be concluded that activation of the central melanocortin system in rats persistently reduces body and fat mass independently of caloric reduction.

  9. Intraductal Cooling via a Nasobiliary Tube During Radiofrequency Ablation of Central Liver Tumors Reduces Biliary Injuries.

    Science.gov (United States)

    Felker, Ely R; Lee-Felker, Stephanie A; Ajwichai, Khobkhoon; Tan, Nelly; Lu, David S; Durazo, Francisco A; Raman, Steven S

    2015-06-01

    The objective of our study was to determine the safety and efficacy of intraductal perfusion of chilled 5% dextrose in water (D5W) via an endoscopic nasobiliary tube (NBT) for the prevention of thermal bile duct injury in patients undergoing percutaneous radiofrequency ablation (RFA) of central liver tumors. We performed a retrospective study comparing outcomes of 32 consecutive patients who underwent percutaneous RFA of central liver tumors without intraductal perfusion of chilled D5W (control cohort) and 14 consecutive patients who underwent temporary intraductal perfusion of chilled D5W at 2 mL/s via endoscopic NBT placement before RFA (endoscopic NBT cohort). The primary and secondary outcomes were the rate of biliary complications and local tumor progression, respectively. All patients tolerated the procedures well. There was a significantly lower rate of biliary complications in the endoscopic NBT cohort (0/14 patients, 0%) than in the control cohort (10/32 patients, 31%) (p NBT cohort (12/14 patients, 86%) compared with the control cohort (20/32 patients, 62%) (p = 0.05). There was no difference in the rate of local tumor progression between the endoscopic NBT cohort (4/19 tumors, 21%) and the control cohort (9/39 tumors, 23%) (p = 1.0). Perfusion of chilled water through an endoscopic NBT helps prevent thermal biliary injury during RFA of central liver tumors without increasing rates of local tumor progression.

  10. Transcutaneous Electrical Nerve Stimulation (TENS) reduces pain, fatigue, and hyperalgesia while restoring central inhibition in primary fibromyalgia

    Science.gov (United States)

    Dailey, Dana L; Rakel, Barbara A; Vance, Carol GT; Liebano, Richard E; Anand, Amrit S; Bush, Heather M; Lee, Kyoung S; Lee, Jennifer E; Sluka, Kathleen A

    2014-01-01

    Because TENS works by reducing central excitability and activating central inhibition pathways, we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition. The current study used a double-blinded randomized, placebo controlled cross-over design to test effects of a single treatment of TENS in people with fibromyalgia. Three treatments were assessed in random order: active TENS, placebo TENS, no TENS. The following measures were assessed before and after each TENS treatment: pain and fatigue at rest and movement, pressure pain thresholds (PPTs), 6 minute walk test (6MWT), range of motion (ROM), five time sit to stand test (FTSTS), and single leg stance (SLS). Conditioned pain modulation (CPM) was completed at end of testing. There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS. PPTs increased at site of TENS (spine) and outside site of TENS (leg) when compared to placebo TENS or no TENS. During Active TENS CPM was significantly stronger compared to placebo TENS and no TENS. No changes in functional tasks were observed with TENS. Thus, the current study suggests TENS has short-term efficacy in relieving symptoms of fibromyalgia while the stimulator is active. Future clinical trials should examine the effects of repeated daily delivery of TENS, similar to how TENS is used clinically, on pain, fatigue, function and quality of life in individuals with fibromyalgia. PMID:23900134

  11. The metabolic syndrome is associated with reduced central serotonergic responsivity in healthy community volunteers.

    Science.gov (United States)

    Muldoon, Matthew F; Mackey, Rachel H; Korytkowski, Mary T; Flory, Janine D; Pollock, Bruce G; Manuck, Stephen B

    2006-02-01

    The pathobiology of the metabolic syndrome remains unclear. The central nervous system is likely to be involved via regulation of eating, physical activity, blood pressure, and metabolism. The objective of this study was to test the hypothesis that low central serotonergic activity is associated with the metabolic syndrome. This was a cross-sectional study of 345 healthy community volunteers, aged 30-55 yr, not taking medications for hypertension, lipid disorders, or diabetes. Central serotonergic responsivity was assessed with the iv citalopram challenge test. The serum prolactin area under the curve (AUC) over 150 min was calculated, and all analyses were adjusted for age, sex, plasma citalopram concentration, and baseline prolactin. The metabolic syndrome was defined according to the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. Insulin resistance was estimated by homeostasis model assessment. Compared with other individuals, persons meeting either NCEP or IDF criteria for the metabolic syndrome had lower mean prolactin responses (P syndrome (NCEP criteria: odds ratio, 2.38; 95% confidence interval, 1.14-4.97; P = 0.02; IDF criteria: odds ratio, 2.80; 95% confidence interval, 1.48-5.30; P = 0.002). Finally, the prolactin AUC was negatively associated with insulin resistance (beta = -0.03, P = 0.02). Corroborating previous evidence, the metabolic syndrome was associated with diminished brain serotonergic activity as reflected in a comparative blunting of the prolactin response to a selective serotonergic challenge. This association may have implications for the etiology, prevention, and treatment of the metabolic syndrome.

  12. Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Penkowa, Milena; Hidalgo, Juan

    2005-01-01

    lower levels of MT-I+II were also detected in the plasma of type 2 diabetic subjects compared with control subjects. These results suggest that, in control subjects, the MT-I+II defense system is active and inducible within skeletal muscle tissue and plasma. In type 2 diabetes, reduced levels of MT......Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine....... Immunohistochemical analysis revealed reduced MT-I+II levels in the skeletal muscle of type 2 diabetic subjects compared with control subjects. Control subjects produced a robust increase of MT-I+II in response to training; however, in type 2 diabetes, MT-I+II levels remained essentially unchanged. Significantly...

  13. REDUCING THE ROLE CONFLICT OF WORKING WOMAN: BETWEEN WORK AND FAMILY CENTRALITY

    Directory of Open Access Journals (Sweden)

    Desty Ranihusna

    2015-09-01

    Full Text Available The aim of this study is to find direct impact of pay satisfaction in WFC and examines direct impact of WFC and FWC for work satisfaction. It also examines impact of moderating variable of work-family centrality moderating variable from relation of WFC and FWC in work satisfaction (case study of married female lecturers in UNNES. This research was done because there were differences between results of WFC and FWC to JS and recommendation to add moderating variable and PS to WFC. It used SPSS to examine hypothesis with CFA, to test validity, classical assumption testing and t test was also used. Moderating variable was tested by value of absolute deviation. The data in this research is primary data in the form of questionnaire and interview.  The result shows that there are strong impacts between PS and WFC. There is no impact between WFC and FWC to JS. Supporting moderating variable is Work Centrality. Although, they prioritize their family, female lecturers are still trying to work professionally

  14. Conference report on tobacco taxes in Central America: current situation and opportunities to reduce prevalence and increase fiscal revenues.

    Science.gov (United States)

    Garcés, Ana; Garcés, Miguel; Barnoya, Joaquin; Cabrera, Maynor; Sandoval, Rosa; Orozco, Juan Guillermo; Chaloupka, Frank J

    2014-01-01

    As stated in Article 6 of Framework Convention on Tobacco Control (FCTC), increasing tobacco prices through higher taxes is one of the most effective interventions to reduce tobacco use and to encourage smokers to quit. The potential for tax increases on tobacco products in Central America is ample. We aim to synthesize the current tobacco taxes situation and highlight research needs to strengthen taxation. In May 2012, a workshop was carried out with representatives from each Central American country to analyze the tobacco tax situation in each country and to identify key research gaps with experts in the field. Tobacco taxes in Central America fall far short of the levels recommended by FCTC. Moreover, the legal framework is complex and creates barriers for higher taxes that require further research and political will. Top research priorities are an in-depth analysis of tobacco tax legislation, impact of tax and price policies, analysis of costs associated to health care of tobacco-related diseases and lost productivity, and the feasibility of approaches to increasing tobacco taxes in certain contexts. An additional area of research is the interrelationship between human rights and tobacco control. Central American countries would benefit from increasing excise taxes on tobacco products. The lack of available data and research to counteract tobacco industry arguments are significant obstacles. Active leadership of civil society in support of the partnership of chronic disease interventions is vital in order to obtain tax increases on tobacco products.

  15. Developing a sustainable agro-system for central Nepal using reduced tillage and straw mulching.

    Science.gov (United States)

    Atreya, Kishor; Sharma, Subodh; Bajracharya, Roshan M; Rajbhandari, Neeranjan P

    2008-08-01

    In Nepal, soil erosion under maize (Zea mays) agro-ecosystems is most critical during the pre-monsoon season. Very few field experiments have been conducted on reduced tillage and rice straw (Oryza sativa) mulching, although these conservation approaches have been recommended. Thus, a five replicate field experiment was established in 2001 at Kathmandu University (1500 m above sea level) on land with 18% slope to evaluate the efficiency of reduced tillage and mulching on soil and nutrient losses and maize yield. The results showed non-significant differences among conservation approaches on runoff and maize yield. Mulching and reduced tillage significantly lowered annual and pre-monsoon soil and nutrient losses compared to conventional tillage. Soil organic matter (SOM) and nitrogen losses associated with eroded sediment were significantly higher in conventional tillage. However, due to limited availability and high opportunity cost of rice straw, reduced tillage would be a better option for soil and nutrient conservation without sacrificing economic yield in upland maize agro-ecosystems.

  16. Control Strategies to Reduce the Energy Consumption of Central Domestic Hot Water Systems

    Energy Technology Data Exchange (ETDEWEB)

    Dentz, Jordan [The Levy Partnership, Inc., New York, NY (United States). Advanced Residential Integrated Energy Solutions; Ansanelli, Eric [The Levy Partnership, Inc., New York, NY (United States). Advanced Residential Integrated Energy Solutions; Henderson, Hugh [The Levy Partnership, Inc., New York, NY (United States). Advanced Residential Integrated Energy Solutions; Varshney, Kapil [The Levy Partnership, Inc., New York, NY (United States). Advanced Residential Integrated Energy Solutions

    2016-06-23

    Domestic hot water (DHW) heating is the second largest energy end use in U.S. buildings, exceeded only by space conditioning. Recirculation systems consisting of a pump and piping loop(s) are commonly used in multifamily buildings to reduce wait time for hot water at faucets; however, constant pumping increases energy consumption by exposing supply and return line piping to continuous heat loss, even during periods when there is no demand for hot water. In this study, ARIES installed and tested two types of recirculation controls in a pair of buildings in order to evaluate their energy savings potential. Demand control, temperature modulation controls, and the simultaneous operation of both were compared to the baseline case of constant recirculation. Additionally, interactive effects between DHW control fuel reductions and space conditioning (heating and cooling) were estimated in order to make more realistic predictions of the payback and financial viability of retrofitting DHW systems with these controls. Results showed that DHW fuel consumption reduced by 7% after implementing the demand control technique, 2% after implementing temperature modulation, and 15% after implementing demand control and temperature modulation techniques simultaneously; recirculation pump runtime was reduced to 14 minutes or less per day. With space heating and cooling interactions included, the estimated annual cost savings were 8%, 1%, and 14% for the respective control techniques. Possible complications in the installation, commissioning and operation of the controls were identified and solutions offered.

  17. Control Strategies to Reduce the Energy Consumption of Central Domestic Hot Water Systems

    Energy Technology Data Exchange (ETDEWEB)

    Dentz, Jordan; Ansanelli, Eric; Henderson, Hugh; Varshney, Kapil

    2016-06-03

    Domestic hot water (DHW) heating is the second largest energy end use in U.S. buildings, exceeded only by space conditioning. Recirculation systems consisting of a pump and piping loop(s) are commonly used in multifamily buildings to reduce wait time for hot water at faucets; however, constant pumping increases energy consumption by exposing supply and return line piping to continuous heat loss, even during periods when there is no demand for hot water. In this study, ARIES installed and tested two types of recirculation controls in a pair of buildings in order to evaluate their energy savings potential. Demand control, temperature modulation controls, and the simultaneous operation of both were compared to the baseline case of constant recirculation. Additionally, interactive effects between DHW control fuel reductions and space conditioning (heating and cooling) were estimated in order to make more realistic predictions of the payback and financial viability of retrofitting DHW systems with these controls. Results showed that DHW fuel consumption reduced by 7% after implementing the demand control technique, 2% after implementing temperature modulation, and 15% after implementing demand control and temperature modulation techniques simultaneously; recirculation pump runtime was reduced to 14 minutes or less per day. With space heating and cooling interactions included, the estimated annual cost savings were 8%, 1%, and 14% for the respective control techniques. Possible complications in the installation, commissioning and operation of the controls were identified and solutions offered.

  18. Combination therapy with lercanidipine and enalapril reduced central blood pressure augmentation in hypertensive patients with metabolic syndrome.

    Science.gov (United States)

    Ghiadoni, Lorenzo; Bruno, Rosa Maria; Cartoni, Giulia; Stea, Francesco; Magagna, Armando; Virdis, Agostino; Grassi, Davide; Ferri, Claudio; Taddei, Stefano

    2017-05-01

    Arterial stiffness and blood pressure (BP) augmentation are independent predictors of cardiovascular events. In a randomized, open, parallel group study we compared the effect on these parameters of combination therapy with an ACE-inhibitor plus calcium channel blocker or thiazide diuretic in 76 hypertensive patients with metabolic syndrome uncontrolled by ACE-inhibitor monotherapy. After 4weeks run-in with enalapril (ENA, 20mg), patients were randomized to a combination therapy with lercanidipine (LER, 10-20mg) or hydrochlorothiazide (HCT, 12.5-25mg) for 24weeks. Aortic stiffness (carotid to femoral pulse wave velocity, PWV), central BP values and augmentation (augmentation index, AIx) were measured by applanation tonometry. The two groups showed similar office and central BP after run-in. Office (ENA/LER: from 149.1±4.9/94.5±1.5 to 131.7±8.1/82.2±5.3; ENA/HCT: from 150.3±4.7/94.7±2.1 to 133.1±7.1/82.8±5.3mmHg) and central BP (ENA/LER 127.4±17.1/85.2±12.1 to 120.5±13.5/80.0±9.5mmHg; ENA/HCT 121.6±13.4/79.3±9.5mmHg) were similarly reduced after 24weeks. PWV was comparable after run-in and not differently reduced by the two treatments (ENA/LER from 8.6±1.5 to 8.1±1.3m/s, pmetabolic syndrome not controlled by ENA alone. These results indicate a positive effect of the combination of ENA/LER on central BP augmentation, suggesting a potential additive role for cardiovascular protection. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Metal contamination in harbours impacts life-history traits and metallothionein levels in snails.

    Directory of Open Access Journals (Sweden)

    Maria Alexandra Bighiu

    Full Text Available Harbours with limited water exchange are hotspots of contaminant accumulation. Antifouling paints (AF contribute to this accumulation by leaching biocides that may affect non-target species. In several leisure boat harbours and reference areas in the Baltic Sea, chronic exposure effects were evaluated using caging experiments with the snail Theodoxus fluviatilis. We analysed variations in ecologically relevant endpoints (mortality, growth and reproduction in concert with variation in metallothionein-like proteins (MTLP levels. The latter is a biomarker of exposure to metals, such as copper (Cu and zinc (Zn, which are used in AF paints as active ingredient and stabilizer, respectively. In addition, environmental samples (water, sediment were analysed for metal (Cu and Zn and nutrient (total phosphorous and nitrogen concentrations. All life-history endpoints were negatively affected by the exposure, with higher mortality, reduced growth and lower fecundity in the harbours compared to the reference sites. Metal concentrations were the key explanatory variables for all observed adverse effects, suggesting that metal-driven toxicity, which is likely to stem from AF paints, is a source of anthropogenic stress for biota in the harbours.

  20. Arbuscular mycorrhiza affects nickel translocation and expression of ABC transporter and metallothionein genes in Festuca arundinacea.

    Science.gov (United States)

    Shabani, Leila; Sabzalian, Mohammad R; Mostafavi pour, Sodabeh

    2016-01-01

    Mycorrhizal fungi are key microorganisms for enhancing phytoremediation of soils contaminated with heavy metals. In this study, the effects of the arbuscular mycorrhizal fungus (AMF) Funneliformis mosseae (=Glomus mosseae) on physiological and molecular mechanisms involved in the nickel (Ni) tolerance of tall fescue (Festuca arundinacea = Schedonorus arundinaceus) were investigated. Nickel addition had a pronounced negative effect on tall fescue growth and photosynthetic pigment contents, as well as on AMF colonization. Phosphorus content increased markedly in mycorrhizal plants (M) compared to non-inoculated (NM) ones. However, no significant difference was observed in root carbohydrate content between AMF-inoculated and non-inoculated plants. For both M and NM plants, Ni concentrations in shoots and roots increased according to the addition of the metal into soil, but inoculation with F. mosseae led to significantly lower Ni translocation from roots to the aboveground parts compared to non-inoculated plants. ABC transporter and metallothionein transcripts accumulated to considerably higher levels in tall fescue plants colonized by F. mosseae than in the corresponding non-mycorrhizal plants. These results highlight the importance of mycorrhizal colonization in alleviating Ni-induced stress by reducing Ni transport from roots to shoots of tall fescue plants.

  1. Plan to Reduce Improper Care of Peripherally-inserted Central Venous Catheters in Outpatient Chemotherapy Patients

    Directory of Open Access Journals (Sweden)

    Shu-Mei Chen

    2014-09-01

    Full Text Available This project aims at improving peripherally-inserted central venous catheter (PICC care in chemotherapy outpatients. From February to March 2011, 16.8% of PICCs were not cared for properly. The main problems encountered were dermatitis, catheter obstruction and catheter slippage. These problems were caused by lack of wound care guidelines for the PICC, the nursing staff's lack of knowledge and skills for PICC nursing care, and patients and their families’ lack of knowledge regarding PICC home care. Improvement plans included: 1. To establish norms for care of normal and abnormal PICC wounds and produce instructional videos; 2. To design correct flushing and butterfly fixation methods of the PICC. 3. To develop the transparent waterproof protective jacket and to produce a home nursing care manual and instructional video. After implementation of this project, the rate of improper PICC care decreased to 6.1% in September to November 2011, thus achieving the goals of this project. This PICC care project not only enhanced the professional knowledge and skills of nurses, but also the knowledge of patients regarding self-care.

  2. Metallothionein expression in mouse immune organ induced by radiation

    International Nuclear Information System (INIS)

    Ju Guizhi; Fan Cai; Liu Shuzheng

    2000-01-01

    To explore the effect of ionizing radiation on the expression of metallothionein (MT) in immune organs, the 109 Cd-haemoglobin affinity assay was employed to measure the content of MT in tissues. The dose effect relationship of the MT expression in mouse thymus and spleen was investigated 16h after exposure to 0.5, 1, 2, 4 and 6 Gy whole body irradiation (WBI). And the time course changes in MT expression in mouse thymus and spleen were also determined at different time intervals after 4 Gy WBI. The results showed that the MT content in mouse thymus was significantly increased 16 h after 4 Gy and 6 Gy irradiation compared with that in sham-irradiated mice (p < 0.05, respectively). And it was found that the MT content in mouse thymus was also increased significantly from 8 h to 48 h after 4 Gy irradiation compared with that in sham-irradiated mice (p < 0.05 - p < 0.001). However, there were no markedly changes for the MT expression in the mouse spleen after exposure to X rays. These results mentioned above suggest that the MT expression in immune organs could be induced by X rays, which may be tissue-specific

  3. The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism.

    Science.gov (United States)

    Krężel, Artur; Maret, Wolfgang

    2017-06-09

    Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn 2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn 2+ , the loading of exocytotic vesicles with zinc species, and the control of Zn 2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn 2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn 2+ and Cu⁺ match the biological requirements for controlling-binding and delivering-these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn 2+ and Cu⁺. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

  4. The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism

    Directory of Open Access Journals (Sweden)

    Artur Krężel

    2017-06-01

    Full Text Available Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn2+, the loading of exocytotic vesicles with zinc species, and the control of Zn2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn2+ and Cu+ match the biological requirements for controlling—binding and delivering—these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn2+ and Cu+. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms.

  5. Hepatic metallothionein turnover in toxic milk mutant mice

    International Nuclear Information System (INIS)

    Rauch, H.; Wells, A.J.

    1989-01-01

    Homozygous toxic milk (tx tx) mice are characterized by extraordinary hepatic copper levels, the excess copper being associated with metallothionein (MT). We have compared MT metabolism in normal and mutant animals. To evaluate MT turnover, animals were injected with 35 S-cysteine, followed in 24 hours by a cold cysteine chase. Animals were sacrificed daily and radioactivity in hepatic MT fractions was used to calculated MT half-life. Based on uptake of label, MT synthesis is very active in tx mice, this MT having a half life of 4-5 days. MT synthesis in normals is much lower, one fourth or less radioactivity. To increase MT synthesis, normals were primed by prior zinc (150 μg) or copper (90 μg) injection; MT label was doubled, the resulting MT showing a slow turnover rate, half-life about 6 days. Another group of normals were primed as above but with metal injections repeated daily so as to measure turnover under conditions of continuous high level MT synthesis, comparable to those prevailing in mutant animals. Although initial label uptake was the same as that of previously primed animals, turnover was hastened, half-life 2-3 days. Thus, copper accumulation in mutants is attributable at least in part to increased rate of synthesis coupled with decreased rate of turnover of MT

  6. A Review of Metallothionein Isoforms and their Role in Pathophysiology

    Directory of Open Access Journals (Sweden)

    Senthil kumar M

    2011-05-01

    Full Text Available Abstract The Metallothionein (MT is a protein which has several interesting biological effects and has been demonstrated increase focus on the role of MT in various biological systems in the past three decades. The studies on the role of MT were limited with few areas like apoptosis and antioxidants in selected organs even fifty years after its discovery. Now acknowledge the exploration of various isoforms of MT such as MT-I, MT-II, MT-III and MT-IV and other isoforms in various biological systems. Strong evidence exists that MT modulates complex diseases and the immune system in the body but the primary function of MT still remains unknown. This review's main objective is to explore the capability to specifically manipulate MT levels in cells and in animals to provide answers regarding how MT could impact those complex disease scenarios. The experimental result mentioned in this review related among MT, zinc, cadmium, diabetic, heart disease, bone retardation, neuro toxicity, kidney dysfunction, cancer, and brain suggest novel method for exploration and contribute significantly to the growing scientist to research further in this field.

  7. Metallothionein 3 expression in normal skin and malignant skin lesions.

    Science.gov (United States)

    Pula, Bartosz; Tazbierski, Tadeusz; Zamirska, Aleksandra; Werynska, Bozena; Bieniek, Andrzej; Szepietowski, Jacek; Rys, Janusz; Dziegiel, Piotr; Podhorska-Okolow, Marzena

    2015-01-01

    Metallothionein-3 (MT-3) has been shown to be expressed in several malignancies and to have an impact on patients' survival in breast and urinary bladder cancer cases. However, its expression has not been determined in normal skin or in its malignant lesions. MT-3 expression was studied using immunohistochemistry in 17 cases of normal skin, 18 of actinic keratosis (AK), 39 of squamous cell carcinoma (SCC), and 23 of basal cell carcinoma (BCC). Low MT-3 expression was observed in normal skin epidermis with faint or no expression in the epidermis basal layer. Significantly higher MT-3 expression was noted in AK (P=0.007) and SCC (P<0.0001), as compared with normal skin epidermis. BCC cases were characterized by the lowest MT-3 expression of all the examined groups, which was significantly lower in comparison to normal skin epidermis, AK, and SCC (P=0.009;P<0.0001 and P<0.0001, respectively). In conclusion, MT-3 may be involved in the development of SCC.

  8. The Functions of Metamorphic Metallothioneins in Zinc and Copper Metabolism

    Science.gov (United States)

    Krężel, Artur; Maret, Wolfgang

    2017-01-01

    Recent discoveries in zinc biology provide a new platform for discussing the primary physiological functions of mammalian metallothioneins (MTs) and their exquisite zinc-dependent regulation. It is now understood that the control of cellular zinc homeostasis includes buffering of Zn2+ ions at picomolar concentrations, extensive subcellular re-distribution of Zn2+, the loading of exocytotic vesicles with zinc species, and the control of Zn2+ ion signalling. In parallel, characteristic features of human MTs became known: their graded affinities for Zn2+ and the redox activity of their thiolate coordination environments. Unlike the single species that structural models of mammalian MTs describe with a set of seven divalent or eight to twelve monovalent metal ions, MTs are metamorphic. In vivo, they exist as many species differing in redox state and load with different metal ions. The functions of mammalian MTs should no longer be considered elusive or enigmatic because it is now evident that the reactivity and coordination dynamics of MTs with Zn2+ and Cu+ match the biological requirements for controlling—binding and delivering—these cellular metal ions, thus completing a 60-year search for their functions. MT represents a unique biological principle for buffering the most competitive essential metal ions Zn2+ and Cu+. How this knowledge translates to the function of other families of MTs awaits further insights into the specifics of how their properties relate to zinc and copper metabolism in other organisms. PMID:28598392

  9. Characteristics, functions and applications of metallothionein in aquatic vertebrates

    Directory of Open Access Journals (Sweden)

    Wei-Chao eWang

    2014-08-01

    Full Text Available The documents on Metallothioneins (MTs in aquatic creatures, especially focusing on their function as biomarkers in environmental monitoring programmes, are vast and increasing. There are, however, few papers to summary the physiological role of MTs in aquatic organisms especially on development. The multifaceted roles of MTs include involvement in homeostasis, protection against heavy metals and oxidant damages, and metabolic regulation, sequestration and/or redox control. In this paper, we have collected published information on MTs in aquatic organisms—pisces, amphibians, mammals etc, and analyzed their function in these aquatic animals. MTs have four main functions in aquatic vertebrate. They are respectively bioaccumulation of toxic metals and detoxification, homeostatic regulation of metals, protection against oxidative stress and neuroprotective mechanism. MTs separate in different tissues and they have various distributions in different tissues of aquatic vertebrate, including liver, gills, kidney, testes and brain. MTs can be induced by a variety of environmental and physiological factors, among which, heavy metals are the main kind of MTs inducers in aquatic vertebrate. Here we pay more attention on the essential metals copper (Cu and zinc (Zn and the non-essential metals cadmium (Cd, silver (Ag, lead (Pb and mercury (Hg.

  10. Prognostic significance of metallothionein in B-cell lymphomas

    DEFF Research Database (Denmark)

    Poulsen, Christian Bjørn; Borup, Rehannah; Borregaard, Niels

    2006-01-01

    We have investigated metallothionein (MT) I and II mRNA and protein in B-cell lymphomas with particular reference to diffuse large B-cell lymphoma (DLBCL). The mRNA profiling was performed on Affymetrix arrays and showed up-regulated MT mRNA in 15 of 48 DLBCLs, including 12 of 23 activated B......-cell (ABC) and 3 of 9 type-3 lesions. In contrast, MT mRNA was low to undetectable in 16 germinal center B-cell (GCB)-type DLBCLs. Only 1 of 15 patients with up-regulated MT mRNA achieved a sustained remission, suggesting that up-regulated MT mRNA constitutes a significant risk factor for treatment failure......, in 115 DLBCLs, MT labeling of more than 20% lymphoma cells was associated with a significantly poorer 5-year survival, independent of the age, stage, or International Prognostic Index. Taken together, it is suggested that both increased MT mRNA and MT protein expression by more than 20% lymphoma cells...

  11. Cadmium/zinc-metallothionein induces DNA strand breaks in vitro.

    Science.gov (United States)

    Müller, T; Schuckelt, R; Jaenicke, L

    1991-01-01

    The in vitro DNA strand breaking activity of metallothionein (MT) containing Cd2+ and Zn2+ in a molar ratio of 5:2 is described. Studies with radical scavengers and electron paramagnetic resonance spectroscopy indicate that the DNA damage might be caused by a radical species formed by the native protein (i.e., MT) charged with the heavy metal ions. No DNA strand breaks are detectable with the heat-denatured MT or with Cd2+ or Zn2+ alone. Inhibition studies using EDTA as a metal ion chelator or N-ethylmaleimide to alkylate sulfhydryl groups suggest that both the bound heavy metal ions as well as the SH groups of the various cysteine residues of MT may be involved in the MT-dependent DNA cleavage. Further characterization showed that the DNA cleavage is more likely random than sequence- or base-specific. These observations may provide a clue in the search for initial events in Cd-related carcinogenicity.

  12. Antiseptic barrier cap effective in reducing central line-associated bloodstream infections: A systematic review and meta-analysis.

    Science.gov (United States)

    Voor In 't Holt, Anne F; Helder, Onno K; Vos, Margreet C; Schafthuizen, Laura; Sülz, Sandra; van den Hoogen, Agnes; Ista, Erwin

    2017-04-01

    Microorganisms can intraluminally access a central venous catheter via the catheter hub. The catheter hub should be appropriately disinfected to prevent central line-associated bloodstream infections (CLABSIs). However, compliance with the time-consuming manual disinfection process is low. An alternative is the use of an antiseptic barrier cap, which cleans the catheter hub by continuous passive disinfection. To compare the effects of antiseptic barrier cap use and manual disinfection on the incidence of CLABSIs. Systematic review and meta-analysis. We systematically searched Embase, Medline Ovid, Web-of-science, CINAHL EBSCO, Cochrane Library, PubMed Publisher and Google Scholar until May 10, 2016. The primary outcome, reduction in CLABSIs per 1000 catheter-days, expressed as an incidence rate ratio (IRR), was analyzed with a random effects meta-analysis. Studies were included if 1) conducted in a hospital setting, 2) used antiseptic barrier caps on hubs of central lines with access to the bloodstream and 3) reported the number of CLABSIs per 1000 catheter-days when using the barrier cap and when using manual disinfection. A total of 1537 articles were identified as potentially relevant and after exclusion of duplicates, 953 articles were screened based on title and abstract; 18 articles were read full text. Eventually, nine studies were included in the systematic review, and seven of these nine in the random effects meta-analysis. The pooled IRR showed that use of the antiseptic barrier cap was effective in reducing CLABSIs (IRR=0.59, 95% CI=0.45-0.77, Pantiseptic barrier cap is associated with a lower incidence CLABSIs and is an intervention worth adding to central-line maintenance bundles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Identification and cloning of first cadmium metallothionein like gene from locally isolated ciliate, Paramecium sp.

    Science.gov (United States)

    Shuja, Rukhsana Nighat; Shakoori, Abdul Rauf

    2009-03-01

    First cadmium metallothionein like gene PMCd1 of a ciliate, Paramecium sp., isolated from industrial wastewater has been cloned and sequenced. PMCd1 is an intronless gene, encoding 612 nucleotides, with TAA coding for glutamine. The coding region of PMCd1 comprises 203 amino acids, including 37 cysteine residues with a conserved structural pattern in the form of recurring structural motifs, arranged in 17 x-cys-x-y-cys-x, 1 x-cys-cys-x and x-cys-x contexts. Both, the deduced amino acids and nucleotide sequence differ, not only from other animal metallothioneins (MTs), but also from the previously characterized Tetrahymena Cu and Cd-MTs. The translated protein of PMCd1 contains conserved cysteine residues, peculiar characteristic of stress inducible metallothionein genes of ciliates and other groups of organisms.

  14. Metal and metallothionein content in tissues from wild and farmed Anguilla anguilla at commercial size.

    Science.gov (United States)

    Ureña, R; Peri, S; del Ramo, J; Torreblanca, A

    2007-05-01

    Metallothionein and metal content (Cd, Zn, Hg, Cu, Fe, Pb and Mn) were determined in various organs of commercially available eel (Anguilla anguilla) of similar size obtained from a local farm and from The Albufera Lake in Valencia (Spain). Farmed fish showed statistically significant higher Cd concentrations in liver and kidney whereas wild individuals had higher levels of Pb in blood and Zn in kidney. Significant positive correlations were found between metallothionein and Cd in kidney of farmed eel and between metallothionein and Cu in liver of wild ones. No statistically significant differences were found between the two populations in the concentration of any of the metals analyzed in muscle and in all instances these levels were lower than the limits established by the Spanish legislation for fish destined for human consumption.

  15. A nightly conditioning method to reduce parasitic power consumption in molten-salt central-receiver solar-power plants

    Energy Technology Data Exchange (ETDEWEB)

    Pacheco, J.E.

    1995-06-01

    A method to reduce nightly parasitic power consumption in a molten salt central receiver is discussed where salt is drained from the piping and heat tracing is turned off to allow the piping to cool to ambient overnight, then in the morning the pipes are filled while they are cold. Since the piping and areas of the receiver in a molten-nitrate salt central-receiver solar power plant must be electrically heated to maintain their temperatures above the nitrate salt freezing point (430{degrees}F, 221{degrees}C), considerable energy could be used to maintain such temperatures during nightly shut down and bad weather. Experiments and analyses have been conducted to investigate cold filling receiver panels and piping as a way of reducing parasitic electrical power consumption and increasing the availability of the plant. The two major concerns with cold filling are: (1) how far can the molten salt penetrate cold piping before freezing closed and (2) what thermal stresses develop during the associated thermal shock. Experiments and analysis are discussed.

  16. A synthetic cadmium metallothionein gene (PMCd1syn) of Paramecium species: expression, purification and characteristics of metallothionein protein.

    Science.gov (United States)

    Dar, Saira; Shuja, Rukhsana N; Shakoori, Abdul Rauf

    2013-02-01

    Metallothioneins (MTs) are metal binding proteins that are rich in cysteine residues constituting 10-30 % of the total protein, and in which the thiol groups bind to the metal ions. The increasing amount of metal ions in the medium have shown increased production of MTs by different organisms such as bacteria, protozoa and mammals like humans. PMCd1 is the first gene ever discovered in Paramecium, a ciliated protozoan, that could produce this MT in response to cadmium. In this study the PMCd1syn gene has been cloned in pET41a expression vector and expressed in an Escherichia coli BL21-codonplus strain for the first time. Since the gene PMCd1 amplified from Paramecium contained 10 codons, which could act as stop codons during expression in E. coli, this gene of 612 bps was synthesized to substitute these (stop) codons for the Paramecium sp. specific amino acids. For stability of the expressed protein, glutathione-S-transferase gene was fused with PMCd1syn gene and coexpressed. The cells expressing PMCd1syn demonstrated increased accumulation of cadmium. This is the first report of cadmium MT protein expressed from Paramecium species, particularly from synthetic MT gene (PMCd1syn). This fusion protein, the molecular weight of which has been confirmed to be 53.03 kDa with MALDI analysis, is rich in cysteine residues, and has been shown for the first time in this ciliate to bind to and sequester Cd(2+)-ions.

  17. Dietary cadmium and benzo(a)pyrene increased intestinal metallothionein expression in the fish Fundulus heteroclitus

    Energy Technology Data Exchange (ETDEWEB)

    Roesijadi, Guritno; Rezvankhah, Saeid; Perez-Matus, Alejandro; Mitelberg, A.; Torruellas, K.; Van Veld, P. A.

    2008-10-17

    To test the effect of dietary exposure to cadmium and benzo(a)pyrene on induction of metallothionein mRNA in the Fundulus heteroclitus, fish were individually fed a pelletized gel food containing cadmium, benzo(a)pyrene, or a combination of the two over a period of seven days, then analyzed for relative levels of metallothionein mRNA in the intestine, liver, and gill using real-time RT-qPCR. An initial experiment with only cadmium exposure showed an apparent 10-fold induction in the intestine, but no induction in liver or gill. Ingestion of contaminated pellets varied in individual fish, and because it was possible to monitor individual ingestion rates with our method, individual cadmium doses were estimated from the amount of ingested cadmium. When the levels of metallothionein mRNA were related to the dose to each fish, a linear dose-response relationship was observed for the intestine, but not the other organs, which showed no induction. In a second experiment, dose was controlled by placing the entire daily cadmium dose into a single contaminated pellet that was fed first (thereby, effectively controlling the effect of variable ingestion rates), and the interaction between cadmium and benzo(a)pyrene was also investigated. The intestine was again the primary organ for metallothionein induction by cadmium, with a 20-fold increase in metallothionein mRNA over control levels. When benzo(a)pyrene was administered together with cadmium, induction of metallothionein was potentiated by the presence of benzo(a)pyrene, with the main effect seen in the intestine, where already high levels of induction by cadmium alone increased by 1.74-fold when benzo(a)pyrene was present.

  18. Glucocorticoids regulate metallothionein-1/2 expression in rat choroid plexus: effects on apoptosis.

    Science.gov (United States)

    Martinho, A; Gonçalves, I; Santos, C R

    2013-04-01

    The choroid plexus (CP) participates in the synthesis, secretion and regulation of the cerebrospinal fluid, in the removal of its toxic compounds and in the regulation of the availability of essential metal ions to the brain. It expresses and secretes metallothioneins 1/2 (MT-1/2) which are key components in the maintenance of the central nervous system metal homeostasis and have anti-apoptotic properties, thereby protecting the brain. Glucocorticoids regulate MT-1/2 expression in several brain regions, but within the choroid plexuses (CPs) it remains unknown. Glucocorticoid levels increase in response to stress with implications in apoptosis. Further, CP expresses glucocorticoid (GR) and mineralocorticoid receptors (MR) turning it into likely glucocorticoid responsive structure. Data prompted us to study the regulation of MT-1/2 expression in response to glucocorticoids in the rat CP, and to investigate its implications in apoptosis. MT-1/2 protein and mRNA expression analysis showed that hydrocortisone up-regulates MT-1/2 expression in rat choroid plexus (RCP) cell line and in primary cultures of choroid plexus epithelial cells (CPEC) cultures via GR and MR. Also, incubation of RCP cells with hydrocortisone significantly diminished apoptosis, an effect eliminated by the addition of a MT-1/2 antibody. Moreover, induction of psychosocial stress, with concomitant rise of corticosterone levels, increased MT-1/2 expression in liver and in CP of male and female rats, with an exception observed in CP from males subjected to acute stress in which down-regulation in MT-1/2 expression occurred. Altogether, the results obtained demonstrated that stress/glucocorticoids regulate MT-1/2 expression in rat CP, with implications on apoptosis.

  19. Overexpressed human metallothionein IIA gene protects Chinese hamster ovary cells from killing by alkylating agents.

    OpenAIRE

    Kaina, B; Lohrer, H; Karin, M; Herrlich, P

    1990-01-01

    Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected with a bovine papillomavirus (BPV)-linked construct carrying the human metallothionein IIA (hMT-IIA) gene. Transfectants survived 40-fold higher levels of cadmium chloride, harbored at least 30 copies of hMT-IIA, and contained 25- to 166-fold more MT than the parent cells. Even under conditions of re...

  20. Sleepiness and activity in heart failure patients with reduced ejection fraction and central sleep-disordered breathing.

    Science.gov (United States)

    Atalla, Angela; Carlisle, Thomas W; Simonds, Anita K; Cowie, Martin R; Morrell, Mary J

    2017-06-01

    Patients with heart failure (HF) and sleep disordered breathing (SDB) are typically not sleepy, unlike patients without heart failure. Previous work in HF patients with obstructive SDB suggested that sleepiness was associated with a reduction in daytime activity. The consequences of predominately central SDB on sleepiness in HF are less well understood. The aim of this study was to test the hypothesis that subjective sleepiness is associated with reduced daytime activity in HF patients with central SDB, compared to those without SDB. The Epworth Sleepiness Scale (ESS), nocturnal polysomnography, and 14 days of wrist watch actigraphy were used to assess subjective daytime sleepiness, nocturnal sleep and breathing, and 24-h activity levels, respectively. A total of 54 patients with HF were studied, nine had obstructive SDB and were removed from further analysis. Of the patients, 23 had HF with predominantly central SDB (HF-CSA; apnea-hypopnea index (AHI) median 20.6 (IQR 12.9-40.2)/h), and 22 had noSDB (HF-noSDB; AHI 3.7 (2.5-5.9)/h). The median patient age was 68 years (range 59-73 years). There were no significant differences either in ESS score (HF-CSA; 8 [4-10] vs. HF-noSDB; 8 (6-12); p = 0.49) or in duration of daytime activity (HF-CSA 14.5 (14.1-15.2) and HF-noSDB 15.1 (14.4-15.3) hours; p = 0.10) between the groups. HF patients with predominately central SDB are not subjectively sleepy compared to those without SDB, despite reduced sleep quality. We speculate that the lack of sleepiness (based on ESS score) may be due to increased sympathetic nerve activity, although further studies are needed due to the small number (n = 5) of sleepy HF-CSA patients. Daytime activity was not different between HF-noSDB and HF-CSA patients. Copyright © 2017. Published by Elsevier B.V.

  1. Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats

    International Nuclear Information System (INIS)

    Morales, Ana I.; Vicente-Sanchez, Cesar; Jerkic, Mirjana; Santiago, Jose M.; Sanchez-Gonzalez, Penelope D.; Perez-Barriocanal, Fernando; Lopez-Novoa, Jose M.

    2006-01-01

    Inflammation can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radical scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and metallothionein expression. The study was performed in Wistar rats that were administered during 9 weeks with either cadmium (1.2 mg Cd/kg/day, s.c.), quercetin (50 mg/kg/day, i.p.) or cadmium + quercetin. Renal toxicity was evaluated by measuring blood urea nitrogen concentration and urinary excretion of enzymes marker of tubular damage. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) renal expression were assessed by Western blot. Renal expression of metallothionein 1 and 2 (MT-1, MT-2) and eNOS mRNA was assessed by Northern blot. Our data demonstrated that Cd-induced renal toxicity was markedly reduced in rats that also received quercetin. MT-1 and MT-2 mRNA levels in kidney were substantially increased during treatment with Cd, being even higher when the animals received Cd and quercetin. Renal eNOS expression was significantly higher in rats receiving Cd and quercetin than in animals receiving Cd alone or in control rats. In the group that received Cd, COX-2 and iNOS expression was markedly higher than in control rats. In the group Cd + quercetin, no changes in COX-2 and iNOS expression were observed compared with the control group. Our results demonstrate that quercetin treatment prevents Cd-induced overexpression of iNOS and COX-2, and increases MT expression. These effects can explain the protection by quercetin of Cd-induced nephrotoxicity

  2. Prognostic significance of metallothionein expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Moraitis Epaminondas

    2005-01-01

    Full Text Available Abstract Background Metallothionein (MT protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. Patients and methods The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival. Results Positive MT staining was present in 21 cases (49%, being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. Conclusions The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic

  3. Role of Metallothionein in Post-Burn Inflammation.

    Science.gov (United States)

    Zhang, Wei; Xie, Yongjun; Liu, Weihua; Xu, Xuefeng; Chen, Xuelian; Liu, Hairong; Liu, Yueming

    2016-04-01

    Metallothioneins (MTs) are a family of low molecular-weight and cysteine-rich metalloproteins that regulate metal metabolism and protect cells from oxygen free radicals. Recent studies suggested that MTs have some anti-inflammatory effects. However, the role of MTs in post-burn inflammation remains unclear. This study is designed to investigate the role of MTs in post-burn inflammation in a mouse burn model. MT-I/II null (-/-) and C57BL/6 wild-type (WT) mice were randomly divided into sham burn, burn, Zn treated, and Zn-MT-2 treated groups. The inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). Myeloperoxidase (MPO) activity was determined by spectrophotometry. In in vitro study, exogenous MT-2 was added to macrophages that were stimulated with burn serum in the presence or absence of a p38 MAPK inhibitor SB203580. The IL-6 and TNF-α messenger RNA (mRNA) expression were detected by quantitative real-time polymerase chain reaction. The levels of p38 expression were determined by Western blot. Burn induced increased inflammatory cytokines such as interleukin (IL)-1β, IL-6, tumor necrosis factors-α, and macrophage chemoattractant protein-1 production in burn wound and serum. The MPO activities in the lung and heart were also increased after burn. These effects were significantly more prominent in MT (-/-) mice than in WT mice. Furthermore, these effects were inhibited by administration of exogenous MT-2 to both WT and MT (-/-) mice. Exogenous MT-2 inhibited the p38 expression and abrogated the increase of IL-6 and TNF-α mRNA expression from macrophages that were stimulated with burn serum. The effect of MT-2 was not further strengthened in the presence of SB203580. MTs may have a protective role against post-burn inflammation and inflammatory organ damage, at least partly through inhibiting the p38 MAPK signaling.

  4. Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

    Science.gov (United States)

    Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G

    2017-06-01

    Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Flux analysis of central metabolic pathways in the Fe(III)-reducing organism Geobacter metallireducens via 13C isotopiclabeling

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yinjie J.; Chakraborty, Romy; Martin, Hector Garcia; Chu,Jeannie; Hazen, Terry C.; Keasling, Jay D.

    2007-08-13

    We analyzed the carbon fluxes in the central metabolism ofGeobacter metallireducens strain GS-15 using 13C isotopomer modeling.Acetate labeled in the 1st or 2nd position was the sole carbon source,and Fe-NTA was the sole terminal electron acceptor. The measured labeledacetate uptake rate was 21 mmol/gdw/h in the exponential growth phase.The resulting isotope labeling pattern of amino acids allowed an accuratedetermination of the in vivo global metabolic reaction rates (fluxes)through the central metabolic pathways using a computational isotopomermodel. The model indicated that over 90 percent of the acetate wascompletely oxidized to CO2 via a complete tricarboxylic acid (TCA) cyclewhile reducing iron. Pyruvate carboxylase and phosphoenolpyruvatecarboxykinase were present under these conditions, but enzymes in theglyoxylate shunt and malic enzyme were absent. Gluconeogenesis and thepentose phosphate pathway were mainly employed for biosynthesis andaccounted for less than 3 percent of total carbon consumption. The modelalso indicated surprisingly high reversibility in the reaction betweenoxoglutarate and succinate. This step operates close to the thermodynamicequilibrium possibly because succinate is synthesized via a transferasereaction, and its product, acetyl-CoA, inhibits the conversion ofoxoglutarate to succinate. These findings enable a better understandingof the relationship between genome annotation and extant metabolicpathways in G. metallireducens.

  6. Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

    Directory of Open Access Journals (Sweden)

    Grazia Fernanda Spitoni

    Full Text Available Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20, in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.

  7. Diazepam treatment reduces inflammatory cells and mediators in the central nervous system of rats with experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Fernández Hurst, Nicolás; Zanetti, Samanta R; Báez, Natalia S; Bibolini, Mario J; Bouzat, Cecilia; Roth, German A

    2017-12-15

    Benzodiazepines are psychoactive drugs and some of them also affect immune cells. We here characterized the inflammatory and infiltrating immune cells in the central nervous system (CNS) during the acute phase of experimental autoimmune encephalomyelitis (EAE) in animals treated with Diazepam. Also, we evaluated the expression of Translocator Protein (18kDa) (TSPO), which is a biomarker of neuroinflammatory diseases. The results indicate that Diazepam exerts protective effects on EAE development, decreasing the incidence of the disease and reducing the number of inflammatory cells in CNS, with a concomitant decrease of TSPO levels in brain tissue and CNS inflammatory CD11b + cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Amount and metal composition of midgut gland metallothionein in shore crabs (Carcinus maenas) after exposure to cadmium in the food

    International Nuclear Information System (INIS)

    Pedersen, Knud Ladegaard; Bach, Louise Thornhøj; Bjerregaard, Poul

    2014-01-01

    Highlights: • Crabs were fed with Cd in concentrations of 1.1–5.1 μg g −1 food. • Metallothionein concentrations only increased at 5.1 μg g −1 . • Cd contents of metallothionein increased linearly with exposure. • A marked influence by the variable Cu contents on metal composition was recorded. • Digestive gland metallothionein is a poor biomarker for Cd exposure. - Abstract: Accumulation of cadmium in aquatic invertebrates may compromise human food safety and anthropogenic additions of cadmium to coastal areas cause concern. Induction of crustacean metallothionein has been suggested as a useful biomarker for contamination of the aquatic environment with cadmium. We investigated how exposure to low concentrations of cadmium in the food affects the subcellular binding of cadmium with the shore crab Carcinus maenas as model organism. Approximately 80% of the assimilated cadmium was bound in the soluble fraction of the midgut gland and of this, 82% was found in the metallothionein fraction. Metallothionein synthesis was only induced at the highest exposure level. However, the number of cadmium atoms bound per molecule of metallothionein increased linearly with exposure, from approximately 0.18 in the control group to 1.4 in a group administered food containing 5.1 μg Cd g −1 . We noted a marked interaction between the presence of copper and zinc in the midgut gland and the binding of cadmium. The usefulness of crustacean midgut gland metallothionein as a biomarker for cadmium exposure at modest levels was questioned since exposures at levels producing significant increases in the tissue contents of the metal did not result in elevated concentrations of metallothionein in the midgut gland

  9. Cytotoxicant-induced trophoblast dysfunction and abnormal pregnancy outcomes: role of zinc and metallothionein.

    Science.gov (United States)

    McAleer, Mary Frances; Tuan, Rocky S

    2004-12-01

    Normal trophoblast function, including implantation, hormone production, and formation of the selectively permeable maternofetal barrier, is essential for the establishment and maintenance of the fetoplacental unit and proper fetal development. Maternal cytotoxicant exposure causes the destruction of these cells, especially the terminally differentiated syncytiotrophoblasts, and results in a myriad of poor pregnancy outcomes. These outcomes range from intrauterine growth retardation and malformation to spontaneous abortion or stillbirth. There is recent evidence that the metal-binding protein, metallothionein, is involved in the protection of human trophoblastic cells from heavy metal-induced and severe oxidative stress-induced apoptosis. Metallothionein, with its unique biochemical structure, can both bind essential metal ions, such as the transcription modulator zinc, and yet allow their ready displacement by toxic nonessential metal ions or damaging free radicals. These properties suggest that metallothionein may be responsible not only for sequestering the cytotoxic agents, but also for altering signal transduction in the affected cells. Here, we review several identified causes of adverse pregnancy outcomes (specifically, prenatal exposure to cigarette smoke and alcohol, gestational infection, and exposure to environmental contaminants), discuss the role of zinc in modulating the cellular response to these toxic insults, and then propose how metallothionein may function to mediate this protective response. Published 2005 Wiley-Liss, Inc.

  10. Expression of the rgMT gene, encoding for a rice metallothionein ...

    Indian Academy of Sciences (India)

    However, the precise function of the metallothionein-like proteins such as the one coded for rgMT gene isolated from rice (Oryza sativa L.) is not completely understood. The whole genome analysis of rice (O. sativa) showed that the rgMT gene is homologue to the Os11g47809 on chromosome 11 of O. sativa sp. japonica ...

  11. Unexpected Interactions of the Cyanobacterial Metallothionein SmtA with Uranium.

    Science.gov (United States)

    Acharya, Celin; Blindauer, Claudia A

    2016-02-15

    Molecules for remediating or recovering uranium from contaminated environmental resources are of high current interest, with protein-based ligands coming into focus recently. Metallothioneins either bind or redox-silence a range of heavy metals, conferring protection against metal stress in many organisms. Here, we report that the cyanobacterial metallothionein SmtA competes with carbonate for uranyl binding, leading to formation of heterometallic (UO2)(n)Zn4SmtA species, without thiol oxidation, zinc loss, or compromising secondary or tertiary structure of SmtA. In turn, only metalated and folded SmtA species were found to be capable of uranyl binding. (1)H NMR studies and molecular modeling identified Glu34/Asp38 and Glu12/C-terminus as likely adventitious, but surprisingly strong, bidentate binding sites. While it is unlikely that these interactions correspond to an evolved biological function of this metallothionein, their occurrence may offer new possibilities for designing novel multipurpose bacterial metallothioneins with dual ability to sequester both soft metal ions including Cu(+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+) and hard, high-oxidation state heavy metals such as U(VI). The concomitant protection from the chemical toxicity of uranium may be valuable for the development of bacterial strains for bio-remediation.

  12. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Shoko, E-mail: satosho@rs.tus.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan); Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp [Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Yonago 683-8503 (Japan); Tohkin, Masahiro, E-mail: tohkin@phar.nagoya-cu.ac.jp [Department of Medical Safety Science, Graduate School of Pharmaceutical Science, Nagoya City University, Nagoya 267-8603 (Japan); Gonzalez, Frank J., E-mail: gonzalef@mail.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Komai, Michio, E-mail: mkomai@m.tohoku.ac.jp [Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555 (Japan)

    2013-11-15

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.

  13. Recombinational micro-evolution of functionally different metallothionein promoter alleles from Orchesella cincta.

    NARCIS (Netherlands)

    Janssens, T.K.S.; Mariën, A.G.H.; Cenijn, P.H.; Legler, J.; van Straalen, N.M.; Roelofs, D.

    2007-01-01

    Background. Metallothionein (mt) transcription is elevated in heavy metal tolerant field populations of Orchesella cincta (Collembola). This suggests that natural selection acts on transcriptional regulation of mt in springtails at sites where cadmium (Cd) levels in soil reach toxic values This

  14. Recombinational micro-evolution of functionally different metallothionein promoter alleles from Orchesella cincta

    NARCIS (Netherlands)

    Janssens, Thierry K S; Mariën, Janine; Cenijn, Peter; Legler, J; van Straalen, Nico M; Roelofs, Dick

    2007-01-01

    BACKGROUND: Metallothionein (mt) transcription is elevated in heavy metal tolerant field populations of Orchesella cincta (Collembola). This suggests that natural selection acts on transcriptional regulation of mt in springtails at sites where cadmium (Cd) levels in soil reach toxic values This

  15. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells...

  16. The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

    International Nuclear Information System (INIS)

    Sato, Shoko; Shirakawa, Hitoshi; Tomita, Shuhei; Tohkin, Masahiro; Gonzalez, Frank J.; Komai, Michio

    2013-01-01

    Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHR or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction

  17. Expression of the rgMT gene, encoding for a rice metallothionein ...

    Indian Academy of Sciences (India)

    ions in the environment is a major problem worldwide. High levels of heavy metal ions such as Cu, Cd and ... for the thiol group of the cysteine (Cys) residues, and thereby protect plants from heavy metal toxicity ( ... Construction of expression vectors and yeast transformation. Previously the metallothionein-like (designed as ...

  18. Determination of content of metallothionein and low molecular mass stress peptides in transgenic tobacco plants

    Czech Academy of Sciences Publication Activity Database

    Diopan, V.; Shestivska, V.; Adam, V.; Macek, Tomáš; Macková, M.; Havel, L.; Kizek, R.

    2008-01-01

    Roč. 94, č. 3 (2008), s. 291-298 ISSN 0167-6857 R&D Projects: GA MŠk 1M06030 Institutional research plan: CEZ:AV0Z40550506 Keywords : metallothionein * Nicotiana tabacum * thiols * phytoremediation Subject RIV: EI - Biotechnology ; Bionics Impact factor: 1.017, year: 2008

  19. Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation

    DEFF Research Database (Denmark)

    Hidalgo, Juan; Penkowa, Milena; Espejo, Carmen

    2006-01-01

    In recent years it has become increasingly clear that the metallothionein (MT) family of proteins is important in neurobiology. MT-I and MT-II are normally dramatically up-regulated by neuroinflammation. Results for MT-III are less clear. MTs could also be relevant in human neuropathology. In Alz......-II, and MT-III in brain physiology....

  20. Characterization of three distinct metallothionein genes of the Ag-hyperaccumulating ectomycorrhizal fungus Amanita strobiliformis

    Czech Academy of Sciences Publication Activity Database

    Hložková, K.; Matěnová, M.; Žáčková, P.; Strnad, Hynek; Hršelová, Hana; Hroudová, Miluše; Kotrba, P.

    2016-01-01

    Roč. 120, č. 3 (2016), s. 358-369 ISSN 1878-6146 R&D Projects: GA ČR(CZ) GAP504/11/0484 Institutional support: RVO:61388971 ; RVO:68378050 Keywords : Ectomycorrhizal fungi * Gene expression * Metal binding * Metallothionein Subject RIV: EB - Genetics ; Molecular Biology ; EE - Microbiology, Virology (MBU-M) Impact factor: 2.184, year: 2016

  1. Protective role of metallothionein during regeneration in Eisenia andrei exposed to cadmium.

    Science.gov (United States)

    Rorat, Agnieszka; Vandenbulcke, Franck; Gałuszka, Adrianna; Klimek, Beata; Plytycz, Barbara

    2017-12-01

    Lumbricid earthworms are often exposed to simultaneous action of various environmental stressors like soil contamination, temperature fluctuation or predators' attacks, which may induce extrusion of coelomocyte-containing coelomic fluid or loss of tail segments. If the injuries are not lethal, renewal of the immune-competent cells and soluble components of coelomic fluid and/or the regeneration of tail segments occurs. The aim of our investigations was to test the hypothesis that exposure of adult earthworms Eisenia andrei to cadmium-polluted soil at room temperature (RT) and/or low temperature (6°C) have adverse effects on restoration of experimentally depleted coelomocytes or on regeneration of amputated posterior segments. Intact control earthworms and their experimental counterparts subjected to electrostimulation-induced coelomocyte depletion or surgical amputation of posterior segments were maintained either in control soil or in soil spiked with cadmium chloride (500mg/kg air-dried soil) at RT or 6°C. Four weeks after the beginning of experiments, cadmium accumulation in earthworm bodies was significantly lower at 6°C than at room temperature. The numbers of restored cells and fluorophore contents were hardly affected by temperature or cadmium. However, cocoon production was reduced by cadmium and completely abolished at 6°C and regeneration of amputated posterior segments was inhibited in cold but was enhanced by cadmium exposure at RT. Independently on the temperature, the 4-week cadmium exposure of adult earthworms was connected with significantly upregulated expression of Cd-metallothionein (but not of catalase, lysenin and phytochelatin) in coelomocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc

    Energy Technology Data Exchange (ETDEWEB)

    Medici, Valentina; Sturniolo, Giacomo Carlo; D' Inca, Renata [Department of Surgical and Gastroenterological Sciences, University of Padua, Padua (Italy); Santon, Alessandro; Giannetto, Sabrina; Albergoni, Vincenzo; Irato, Paola [Department of Biology, University of Padua, via U. Bassi 58/B, 35131 Padua (Italy)

    2002-09-01

    The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh{sup 8}dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week. (orig.)

  3. The teratogenicity of cadmium-metallothionein in the rat

    International Nuclear Information System (INIS)

    Webb, M.; Holt, D.; Brown, N.; Hard, G.C.

    1988-01-01

    A single dose in the range 0.25-1.9 mg metallothionein-bound cadmium (MT-Cd)/kg body weight, when administered parenterally to the rat between day 8 and day 14 of gestation, is teratogenic. In vitro, the development of the isolated rat conceptus is unaffected by the addition of 1.5 μM MT-Cd to the culture medium whereas the same concentration of ionic Cd (as CdCl 2 ) is lethal. At short times after injection of 0.25 mg MT-Cd/kg body weight on gd 12, the maximal foetal and placental contents of Cd are low in comparison with those after a teratogenic dose of CdCl 2 and are of the same order as those in the embryo and placenta + yolk sac of the rat conceptus, cultured in the presence of the highest no-effect concentration of CdCl 2 . From this evidence, it is concluded that the uptake by the conceptus in vivo of either CdMT, or of Cd liberated therefrom, is unlikely to contribute to the teratogenic response. In the pregnant, as in the non-pregnant rat, the kidney appears to be the only organ that is affected directly by the metalloprotein. All doses in the range 0.25-1.0 mg MT-Cd/kg body weight are nephrotoxic and result in prolonged anorexia in the pregnant animal. While some of the foetal deformities that occur in the CdMT-dosed animal seem to be direct consequences of the renal dysfunction, others apparently are secondary to the maternal anorexia. In rats that are injected i.p on gd 12 with 0.25 mg MT-Cd/kg renal uptake of Cd is slower, but the final concentration is higher than in animals that are given the same dose i.v. At this and the higher dose levels structural and/or functional damage to the kidneys also is greater in i.p.-, than in i.v.-dosed animals. The incidence of foetal malformations, however, is similar in the i.p. and i.v. groups and varies little over the dose range. (orig./MG)

  4. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  5. Teratogenicity of cadmium-metallothionein in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Webb, M.; Holt, D.; Brown, N.; Hard, G.C.

    1988-06-01

    A single dose in the range 0.25-1.9 mg metallothionein-bound cadmium (MT-Cd)/kg body weight, when administered parenterally to the rat between day 8 and day 14 of gestation, is teratogenic. In vitro, the development of the isolated rat conceptus is unaffected by the addition of 1.5 ..mu..M MT-Cd to the culture medium whereas the same concentration of ionic Cd (as CdCl/sub 2/) is lethal. At short times after injection of 0.25 mg MT-Cd/kg body weight on gd 12, the maximal foetal and placental contents of Cd are low in comparison with those after a teratogenic dose of CdCl/sub 2/ and are of the same order as those in the embryo and placenta + yolk sac of the rat conceptus, cultured in the presence of the highest no-effect concentration of CdCl/sub 2/. From this evidence, it is concluded that the uptake by the conceptus in vivo of either CdMT, or of Cd liberated therefrom, is unlikely to contribute to the teratogenic response. In the pregnant, as in the non-pregnant rat, the kidney appears to be the only organ that is affected directly by the metalloprotein. All doses in the range 0.25-1.0 mg MT-Cd/kg body weight are nephrotoxic and result in prolonged anorexia in the pregnant animal. While some of the foetal deformities that occur in the CdMT-dosed animal seem to be direct consequences of the renal dysfunction, others apparently are secondary to the maternal anorexia. In rats that are injected i.p on gd 12 with 0.25 mg MT-Cd/kg renal uptake of Cd is slower, but the final concentration is higher than in animals that are given the same dose i.v. At this and the higher dose levels structural and/or functional damage to the kidneys also is greater in i.p.-, than in i.v.-dosed animals. The incidence of foetal malformations, however, is similar in the i.p. and i.v. groups and varies little over the dose range.

  6. Characterization of mercury bioremediation by transgenic bacteria expressing metallothionein and polyphosphate kinase

    Directory of Open Access Journals (Sweden)

    Gonzalez-Ruiz Gloriene

    2011-08-01

    Full Text Available Abstract Background The use of transgenic bacteria has been proposed as a suitable alternative for mercury remediation. Ideally, mercury would be sequestered by metal-scavenging agents inside transgenic bacteria for subsequent retrieval. So far, this approach has produced limited protection and accumulation. We report here the development of a transgenic system that effectively expresses metallothionein (mt-1 and polyphosphate kinase (ppk genes in bacteria in order to provide high mercury resistance and accumulation. Results In this study, bacterial transformation with transcriptional and translational enhanced vectors designed for the expression of metallothionein and polyphosphate kinase provided high transgene transcript levels independent of the gene being expressed. Expression of polyphosphate kinase and metallothionein in transgenic bacteria provided high resistance to mercury, up to 80 μM and 120 μM, respectively. Here we show for the first time that metallothionein can be efficiently expressed in bacteria without being fused to a carrier protein to enhance mercury bioremediation. Cold vapor atomic absorption spectrometry analyzes revealed that the mt-1 transgenic bacteria accumulated up to 100.2 ± 17.6 μM of mercury from media containing 120 μM Hg. The extent of mercury remediation was such that the contaminated media remediated by the mt-1 transgenic bacteria supported the growth of untransformed bacteria. Cell aggregation, precipitation and color changes were visually observed in mt-1 and ppk transgenic bacteria when these cells were grown in high mercury concentrations. Conclusion The transgenic bacterial system described in this study presents a viable technology for mercury bioremediation from liquid matrices because it provides high mercury resistance and accumulation while inhibiting elemental mercury volatilization. This is the first report that shows that metallothionein expression provides mercury resistance and

  7. Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake?

    Science.gov (United States)

    Russell-Jones, D; Danne, T; Hermansen, K; Niswender, K; Robertson, K; Thalange, N; Vasselli, J R; Yildiz, B; Häring, H U

    2015-10-01

    Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  8. Antibiotics at the time of removal of central venous catheter to reduce morbidity and mortality in newborn infants.

    Science.gov (United States)

    McMullan, Rowena L; Gordon, Adrienne

    2018-03-07

    Late-onset sepsis is associated with increased rates of mortality and morbidity in newborn infants, in addition to poorer long-term developmental outcomes and increased length of stay and hospital costs. Central line-associated blood stream infection (CLABSI) is the most common cause of late-onset sepsis in hospitalised infants, and prevention of CLABSI is a key objective in neonatal care. Increased frequency of CLABSI around the time of removal of central venous catheters (CVCs) has been reported, and use of antibiotics at the time of removal may reduce the incidence and impact of late-onset sepsis in vulnerable newborn infants. To determine the efficacy and safety of giving antibiotics at the time of removal of a central venous catheter (CVC) for reduction of morbidity and mortality in newborn infants, in particular effects on late-onset sepsis. We used the standard search strategy of the Cochrane Neonatal Review Group without language restriction to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 3), MEDLINE via PubMed (1966 to 6 April 2017), Embase (1980 to 6 April 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 6 April 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised, quasi-randomised, and cluster-randomised trials considering use of any antibiotic or combination of antibiotics at the time of CVC removal in newborn infants compared with placebo, no antibiotics, or another antibiotic or combination of antibiotics. We extracted data using standard methods of the Cochrane Neonatal Review Group. Two review authors independently selected, assessed the quality of, and extracted data from the included study. Only one randomised controlled trial was eligible for inclusion in this analysis. Forty-four of a total of 88 infants received two doses of cephazolin

  9. Antiseptic barrier cap effective in reducing central line-associated bloodstream infections : A systematic review and meta-analysis

    NARCIS (Netherlands)

    Voor In 't Holt, Anne F; Helder, Onno K; Vos, Margreet C; Schafthuizen, Laura; Sülz, Sandra; van den Hoogen, Agnes; Ista, Erwin

    2017-01-01

    BACKGROUND: Microorganisms can intraluminally access a central venous catheter via the catheter hub. The catheter hub should be appropriately disinfected to prevent central line-associated bloodstream infections (CLABSIs). However, compliance with the time-consuming manual disinfection process is

  10. Metallothionein overexpression of bladder biopsies associated with tissue hypoxia in patients with interstitial cystitis/painful bladder syndrome.

    Science.gov (United States)

    Lee, Jane-Dar; Lee, Ming-Huei

    2014-07-01

    To study the relationship between hypoxia and metallothionein expression in bladder biopsies of interstitial cystitis/painful bladder syndrome patients. The study group consisted of 41 patients with interstitial cystitis/painful bladder syndrome, and the control group consisted of 12 volunteers without any interstitial cystitis/painful bladder syndrome symptoms. All biopsy specimens were analyzed for both proteins of hypoxia-inducible factor-1α and metallothionein expression by immunoblotting, immunostaining and confocal laser scanning microscopy. Data were analyzed using the Mann-Whitney U-test. An increased expression of hypoxia-inducible factor-1α and metallothionein was noted in the study group compared with the control group (P interstitial cystitis suggest that overexpression of metallothionein is associated with the bladder hypoxia related to this disease. © 2014 The Japanese Urological Association.

  11. Zinc chelation: a metallothionein 2A's mechanism of action involved in osteosarcoma cell death and chemotherapy resistance.

    Science.gov (United States)

    Habel, N; Hamidouche, Z; Girault, I; Patiño-García, A; Lecanda, F; Marie, P J; Fromigué, O

    2013-10-24

    Osteosarcoma is the most common primary tumor of bone occurring in children and adolescents. The histological response to chemotherapy represents a key clinical factor related to survival. We previously showed that statins exhibit antitumor effects in vitro, inducing apoptotic cell death, reducing cell migration and invasion capacities and strengthening cytotoxic effects in combination with standard drugs. Comparative transcriptomic analysis between control and statin-treated cells revealed strong expression of several genes, including metallothionein (MT) 2A. MT2A overexpression by lentiviral transduction reduced bioavailable zinc levels, an effect associated with reduced osteosarcoma cell viability and enhanced cell differentiation. In contrast, MT2A silencing did not modify cell viability but strongly inhibited expression of osteoblastic markers and differentiation process. MT2A overexpression induced chemoresistance to cytotoxic drugs through direct chelation of platinum-containing drugs and indirect action on p53 zinc-dependent activity. In contrast, abrogation of MT2A enhanced cytotoxic action of chemotherapeutic drugs on osteosarcoma cells. Finally, clinical samples derived from chemonaive biopsies revealed that tumor cells expressing low MT2A levels correspond to good prognostic (good responder patients with longer survival rate), whereas high MT2A levels were associated with adverse prognosis (poor responder patients). Taken together, these data show that MT2A contributes to chemotherapy resistance in osteosarcoma, an effect partially mediated by zinc chelation. The data also suggest that MT2A may be a potential new prognostic marker for osteosarcoma sensitivity to chemotherapy.

  12. Electronic health record solutions to reduce central line-associated bloodstream infections by enhancing documentation of central line insertion practices, line days, and daily line necessity.

    Science.gov (United States)

    Quan, Kathleen A; Cousins, Sarah M; Porter, Darlene D; O'Brien, Margaret; Rudkin, Scott; Lambertson, Brian; Hoang, Dennis; Dangodara, Amish A; Huang, Susan S

    2016-04-01

    Central line-associated bloodstream infections (CLABSIs) continue to cause preventable morbidity and mortality, but methods for tracking and ensuring consistency of CLABSI-prevention activities remain underdeveloped. We created an integrated electronic health record solution to prompt sterile central venous catheter (CVC) insertion, CVC tracking, and timely line removal. The system embedded central line insertion practices (CLIP) elements in inserter procedure notes, captured line days and new lines, matching each with its CLIP form and feeding back compliance, and enforced daily documentation of line necessity in physician progress notes. We examined changes in CLIP compliance and form submission, number of new line insertions captured, and necessary documentation. Standard reporting of CLIP compliance, which measures compliance per CLIP form received, artificially inflated CLIP compliance relative to compliance measured using CVC placements as the denominator; for example, 99% per CLIP form versus 55% per CVC placement. This system established a higher threshold for CLIP compliance using this denominator. Identification of CVCs increased 35%, resulting in a decrease in CLABSI rates. The system also facilitated full compliance with daily documentation of line necessity. Integrated electronic health records systems can help realize the full benefit of CLABSI prevention strategies by promoting, tracking, and raising the standard for best practices behavior. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  13. Incidence and Outcomes of Central Nervous System Hemophagocytic Lymphohistiocytosis Relapse after Reduced-Intensity Conditioning Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Lounder, Dana T; Khandelwal, Pooja; Chandra, Sharat; Jordan, Michael B; Kumar, Ashish R; Grimley, Michael S; Davies, Stella M; Bleesing, Jack J; Marsh, Rebecca A

    2017-05-01

    Hemophagocytic lymphohistiocytosis (HLH) is an immune regulatory disorder that commonly presents with central nervous system (CNS) involvement. The only cure for genetic HLH is hematopoietic stem cell transplantation (HSCT), typically treated with reduced-intensity conditioning (RIC) regimens. We sought to estimate the incidence of CNS relapse after RIC HSCT, determine risk factors, and evaluate outcomes. We performed a retrospective chart review of 94 consecutive children and young adults with primary HLH who received RIC HSCT. CNS relapse within 1 year after transplantation was diagnosed by review of clinical symptoms, cerebral spinal fluid (CSF), and radiologic findings. Four (4.25%) patients developed symptoms of possible CNS HLH after HSCT and 3 patients were diagnosed. Eight patients underwent screening lumbar puncture because of history of active CNS disease at the onset of the conditioning regimen and 4 had evidence of continued disease. The overall incidence of CNS relapse and continued CNS disease after RIC HSCT was 8%. All patients with CNS disease after HSCT responded to CNS-directed therapy. Whole blood donor chimerism at the time of CNS relapse was low at 1% to 34%, but it remained high at 88% to 100% for patients with continued CNS disease. Overall survival for patients with CNS relapse was 50%, compared with 75% for patients without CNS disease (P = .079). Our data suggest that a low level of donor chimerism or active CNS disease at the time of transplantation increase the risk of CNS HLH after HSCT. Surveillance CSF evaluation after allogeneic RIC HSCT should be considered in patients with risk factors and CNS-directed treatment should be initiated if appropriate. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Effects of organism preparation in metallothionein and metal analysis in marine invertebrates for biomonitoring marine pollution.

    Science.gov (United States)

    Oaten, J F P; Hudson, M D; Jensen, A C; Williams, I D

    2015-06-15

    Metallothionein (MT) is established as a potentially useful biomarker for monitoring aquatic pollution. This paper addresses widespread inconsistencies in storage conditions, tissue type selection and pre-treatment of samples before MT and metal analysis in biomarker studies. This variation hampers comparability and so the widespread implementation of this monitoring approach. Actively sampled Mytilus edulis in Southampton Water, UK were exposed to different storage temperatures, a variety of tissue types were analysed, and various pre-treatments of transportation on ice, transportation in seawater, depuration, and rapid dissection in the field were examined. Storage temperatures of -20 °C were found to be adequate for periods of at least ten weeks, as MT was not reduced by protein degradation compared with samples kept at -80 °C. Whole tissue and digestive gland concentrations of MT and metals were significantly positively correlated and directly relatable. MT in the digestive gland appeared to be more responsive to metals than in whole tissue, where it may be diluted, masking MT responses. However, longer study periods may suffer the effects of mass changes to the digestive gland, which alters MT concentration, and it may therefore be advisable to measure whole tissue. Depuration and transportation in seawater reduced both MT and metal concentrations in the digestive gland, and few correlations between MT and metals were identified for these treatments. It is therefore recommended that: i) samples are transported to the laboratory on ice and dissected as soon as possible thereafter, ii) depuration should not be used when examining MT response to metal exposure until further research clarifying its utility is reported, iii) either whole tissue or the digestive gland can be used to measure MT, though whole tissue may be preferable on long-term studies, and iv) organisms can be stored at -20 °C before analysis for up to ten weeks. These practices can be applied

  15. Metallothionein prevents neurodegeneration and central nervous system cell death after treatment with gliotoxin 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Quintana, Albert; Carrasco, Javier

    2004-01-01

    Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) induces significant inflammation and neurodegeneration but also affords neuroprotection against acute traumatic brain injury. This neuroprotection...

  16. Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein

    OpenAIRE

    Chin, Wei-Chih; Lin, Kuo-Hsing; Chang, Jui-Jen; Huang, Chieh-Chen

    2013-01-01

    Background Though n-butanol has been proposed as a potential transportation biofuel, its toxicity often causes oxidative stress in the host microorganism and is considered one of the bottlenecks preventing its efficient mass production. Results To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengers for reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein ...

  17. Electrochemical study of heavy metals and metallothionein in yeast Yarrowia lipolytica

    Czech Academy of Sciences Publication Activity Database

    Strouhal, M.; Kizek, René; Vacek, Jan; Trnková, L.; Němec, M.

    2003-01-01

    Roč. 60, 1-2 (2003), s. 29-36 ISSN 1567-5394 R&D Projects: GA AV ČR IAA4004110; GA ČR GA203/02/0422 Institutional research plan: CEZ:AV0Z5004920; CEZ:MSM 143100005 Keywords : electrochemical determination of metallothionein and heavy metals * yeast * Yarrowia lipolytica Subject RIV: BO - Biophysics Impact factor: 1.482, year: 2003

  18. Histological changes, apoptosis and metallothionein levels in Triturus carnifex (Amphibia, Urodela) exposed to environmental cadmium concentrations.

    Science.gov (United States)

    Capaldo, Anna; Gay, Flaminia; Scudiero, Rosaria; Trinchella, Francesca; Caputo, Ivana; Lepretti, Marilena; Marabotti, Anna; Esposito, Carla; Laforgia, Vincenza

    2016-04-01

    The aim of this study was to verify if the freshwater safety values established from the European Community (1998) and the Italian Ministry of Health (2001) for cadmium (44.5nM/L in drinking water and 178nM/L in sewage waters) were safe for amphibians, since at these same concentrations cadmium induced endocrine disruption in the newt Triturus carnifex. Adult male specimens of T. carnifex were exposed daily to cadmium (44.5nM/L and 178nM/L as CdCl2, nominal concentrations), respectively, during 3- and 9-months; at the same time, control newts were exposed to tap water only. The accumulation of cadmium in the skin, liver and kidney, the levels of metallothioneins in the skin and the liver, the expression of metallothionein mRNA in the liver, as well as the presence of histological alterations and of apoptosis in the target organs were evaluated. The 9-months exposure induced cadmium accumulation in all the tissues examined; moreover, histological changes were observed in all the tissues examined, irrespective of the dose or the time of exposure. Apoptosis was only detected in the kidney, whereas metallothioneins and metallothionein mRNA did not increase. This study demonstrates that the existing chronic water quality criterion established for cadmium induces in the newt T. carnifex cadmium accumulation and histological alterations in the target organs examined. Together with our previous results, showing that, at these same concentrations, cadmium induced endocrine disruption, the present results suggest that the existing chronic water quality criterion for cadmium appears to be not protective of amphibians. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Recombinational micro-evolution of functionally different metallothionein promoter alleles from Orchesella cincta

    Directory of Open Access Journals (Sweden)

    van Straalen Nico M

    2007-06-01

    Full Text Available Abstract Background Metallothionein (mt transcription is elevated in heavy metal tolerant field populations of Orchesella cincta (Collembola. This suggests that natural selection acts on transcriptional regulation of mt in springtails at sites where cadmium (Cd levels in soil reach toxic values This study investigates the nature and the evolutionary origin of polymorphisms in the metallothionein promoter (pmt and their functional significance for mt expression. Results We sequenced approximately 1600 bp upstream the mt coding region by genome walking. Nine pmt alleles were discovered in NW-European populations. They differ in the number of some indels, consensus transcription factor binding sites and core promoter elements. Extensive recombination events between some of the alleles can be inferred from the alignment. A deviation from neutral expectations was detected in a cadmium tolerant population, pointing towards balancing selection on some promoter stretches. Luciferase constructs were made from the most abundant alleles, and responses to Cd, paraquat (oxidative stress inducer and moulting hormone were studied in cell lines. By using paraquat we were able to dissect the effect of oxidative stress from the Cd specific effect, and extensive differences in mt induction levels between these two stressors were observed. Conclusion The pmt alleles evolved by a number of recombination events, and exhibited differential inducibilities by Cd, paraquat and molting hormone. In a tolerant population from a metal contaminated site, promoter allele frequencies differed significantly from a reference site and nucleotide polymorphisms in some promoter stretches deviated from neutral expectations, revealing a signature of balancing selection. Our results suggest that the structural differences in the Orchesella cincta metallothionein promoter alleles contribute to the metallothionein -over-expresser phenotype in cadmium tolerant populations.

  20. Freezing of body fluids induces metallothionein gene expression in earthworms (Dendrobaena octaedra).

    Science.gov (United States)

    Fisker, Karina Vincents; Holmstrup, Martin; Sørensen, Jesper Givskov

    2016-01-01

    The molecular mechanisms activated by environmental contaminants and natural stressors such as freezing need to be investigated in order to better understand the mechanisms of interaction and potential effects that combined stressors may have on organisms. Using the freeze-tolerant earthworm Dendrobaena octaedra as model species, we exposed worms to freezing and exposure to sublethal copper in a factorial design and investigated the transcription of candidate genes for metal and cold stress. We hypothesised that both freezing and copper would induce transcription of genes coding for heat shock proteins (hsp10 and hsp70), metallothioneins (mt1 and mt2), and glutathione-S-transferase (gst), and that the combined effects of these two stressors would be additive. The gene transcripts hsp10, hsp70, and gst were significantly upregulated by freezing, but only hsp10 was upregulated by copper. We found that copper at the time of sampling had no effect on transcription of two metallothionein genes whereas transcription was strongly upregulated by freezing. Moreover, there was a significant interaction causing more than additive transcription rates of mt1 in the copper/freezing treatment suggesting that freeze-induced cellular dehydration increases the concentration of free copper ions in the cytosol. This metallothionein response to freezing is likely adaptive and possibly provides protection against freeze-induced elevated metal concentrations in the cytosol and excess ROS levels due to hypoxia during freezing. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Podocyte-specific overexpression of metallothionein mitigates diabetic complications in the glomerular filtration barrier and glomerular histoarchitecture: a transmission electron microscopy stereometric analysis.

    Science.gov (United States)

    Carlson, Edward C; Chhoun, Jennifer M; Laturnus, Donna I; Bikash, K C; Berg, Brittany; Zheng, Shirong; Epstein, Paul N

    2013-02-01

    We previously demonstrated that cellular and extracellular components of the blood-urine barrier in renal glomeruli are susceptible to damage in OVE transgenic mice, a valuable model of human diabetic nephropathy that expresses profound albuminuria. To test our hypothesis that glomerular filtration barrier damage in OVE mice may be the result of oxidative insult to podocytes, 150-day-old bi-transgenic OVENmt diabetic mice that overexpress the antioxidant metallothionein specifically in podocytes were examined by enzyme-linked immunosorbent assay for albuminuria mitigation and by unbiased transmission electron microscopy (TEM) stereometry for protection from chronic structural diabetic complications. Although blood glucose and HbA(1c) levels were indistinguishable in OVE and OVENmt animals, albuminuria was significantly reduced (average >7-fold) in OVENmt mice through 8 months of age. Interestingly, the Nmt transgene provided significant glomerular protection against diabetic nephropathic complications outside of the podocyte. Glomerular filtration barrier damage was reduced in OVENmt mice, including significantly increased area occupied by endothelial luminal fenestrations (~13%), significantly reduced glomerular basement membrane (GBM) thickening (~17%) and significantly less podocyte effacement (~18%). In addition, OVENmt mice exhibited significantly reduced glomerular volume (~50%), fewer glomerular endothelial cells (~33%), fewer mesangial cells (~57%) and fewer total glomerular cells (~40%). These results provide evidence of oxidative damage to podocytes induces primary diabetic nephropathic features including severe and sustained albuminuria, specific glomerular filtration barrier damage and alterations in glomerular endothelial and mesangial cell number. Importantly, these diabetic complications are significantly mitigated by podocyte targeted metallothionein overexpression. Copyright © 2012 John Wiley & Sons, Ltd.

  2. Self-Identity After Bereavement : Reduced Self-Clarity and Loss-Centrality in Emotional Problems After the Death of a Loved One

    NARCIS (Netherlands)

    Boelen, Paul A

    2017-01-01

    There is evidence that both the centrality of a loss-event as well as reduced self-concept clarity are involved in emotional problems after the death of a loved one. One issue that is still unexplored is the relative importance of these two concepts in predicting bereavement outcome. The current

  3. Towards better understanding of the response of Sphagnum peatland to increased temperature and reduced precipitation in Central Europe

    Science.gov (United States)

    Juszczak, Radoslaw; Basińska, Anna; Chojnicki, Bogdan; Gąbka, Maciej; Hoffmann, Mathias; Józefczyk, Damian; Lamentowicz, Mariusz; Leśny, Jacek; Łuców, Dominika; Moni, Christophe; Reczuga, Monika; Samson, Mateusz; Silvennoinen, Hanna; Stróżecki, Marcin; Urbaniak, Marek; Zielińska, Małgorzata; Olejnik, Janusz

    2017-04-01

    With respect to climate change peatlands are highly vulnerable ecosystems. Especially a potential drying in future might result in a major carbon source and release to the atmosphere. We carried out a field climate manipulation experiment at Rzecin peatland in western Poland to assess how increased temperature and reduced precipitation may impact carbon balance, vegetation, microbes and water chemistry of the Sphagnum peatland. Here, we present results of measurements conducted in two contrasting years (417 mm and 678 mm of precipitation in very dry 2015 and wet 2016, respectively). The experimental design consists of four treatments, each one replicated three times (control, CO; simulated warming, W; prolonged drought, D and warming & drought, W+D). Increased temperatures (T) during the year were achieved by infrared heaters (400W × 4 per site, approx. 60 Wṡm-2 addition of LW radiation). Precipitation was reduced using an automatic curtain, covering the site during nighttime hours of the growth seasons. The manipulation experiment was successful during both years, increasing the air (30 cm height) and soil temperature (5 cm depth, sites W and D) by up to 0.2 oC and 1.0 oC, respectively. Precipitation was reduced to 37 % during both years. At W+D site the peat temperature was nearly two times higher than on W site indicating the impact of drought on T increase. To study the C exchange we developed an automatic mobile platform for measuring CO2/CH4/H2O fluxes (LGR) as well as 13CO2 and 13CH4 fluxes (PICARRO CRDS G2201-i). Measurements were performed, using dynamic ecosystem chambers (for NEE and Reco) and combined with simultaneous measurements of surface spectral properties. Flux calculation and gap filling was done according to Hoffmann et al. 2015. Methane emissions were significantly higher on manipulated plots than on CO (25 gCṡm-2yr-1) during both years, but only in the very dry 2015, CH4 fluxes were the highest on W+D site (33 gC gCṡm-2yr-1). Besides

  4. Histological changes, apoptosis and metallothionein levels in Triturus carnifex (Amphibia, Urodela) exposed to environmental cadmium concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Capaldo, Anna, E-mail: anna.capaldo@unina.it [Department of Biology, University of Naples Federico II, Naples (Italy); Gay, Flaminia [Department of Chemistry and Biology, University of Salerno, Salerno (Italy); Scudiero, Rosaria; Trinchella, Francesca [Department of Biology, University of Naples Federico II, Naples (Italy); Caputo, Ivana; Lepretti, Marilena; Marabotti, Anna; Esposito, Carla [Department of Chemistry and Biology, University of Salerno, Salerno (Italy); Laforgia, Vincenza [Department of Biology, University of Naples Federico II, Naples (Italy)

    2016-04-15

    Highlights: • Specimens of the newt Triturus carnifex were exposed to environmental Cd doses. • Newts exposed to Cd during 9 months accumulated Cd in their tissues. • Cd induced histological alterations in the skin, liver and kidneys. • Cd induced apoptosis only in the kidneys. • Cd did not increase metallothionein levels in the skin and the liver, nor MTs mRNA. - Abstract: The aim of this study was to verify if the freshwater safety values established from the European Community (1998) and the Italian Ministry of Health (2001) for cadmium (44.5 nM/L in drinking water and 178 nM/L in sewage waters) were safe for amphibians, since at these same concentrations cadmium induced endocrine disruption in the newt Triturus carnifex. Adult male specimens of T. carnifex were exposed daily to cadmium (44.5 nM/L and 178 nM/L as CdCl{sub 2}, nominal concentrations), respectively, during 3- and 9-months; at the same time, control newts were exposed to tap water only. The accumulation of cadmium in the skin, liver and kidney, the levels of metallothioneins in the skin and the liver, the expression of metallothionein mRNA in the liver, as well as the presence of histological alterations and of apoptosis in the target organs were evaluated. The 9-months exposure induced cadmium accumulation in all the tissues examined; moreover, histological changes were observed in all the tissues examined, irrespective of the dose or the time of exposure. Apoptosis was only detected in the kidney, whereas metallothioneins and metallothionein mRNA did not increase. This study demonstrates that the existing chronic water quality criterion established for cadmium induces in the newt T. carnifex cadmium accumulation and histological alterations in the target organs examined. Together with our previous results, showing that, at these same concentrations, cadmium induced endocrine disruption, the present results suggest that the existing chronic water quality criterion for cadmium appears to

  5. Metallothioneins I and II: neuroprotective significance during CNS pathology

    DEFF Research Database (Denmark)

    Penkowa, Milena; Stankovic, Roger; Chung, Roger

    2006-01-01

    expression across animal phyla suggests that MTs may play an important physiological role, MT-I, II knock out (KO) mice survive to adulthood. In both central and peripheral nervous tissues, MT-I, II have neuroprotective roles, which are also induced by exogenous MT-I and/or MT-II treatment. Hence, MT-I, II...

  6. In cirrhotic patients reduced muscle strength is unrelated to muscle capacity for ATP turnover suggesting a central limitation

    DEFF Research Database (Denmark)

    Gam, Christiane Marie Bourgin; Nielsen, H B; Secher, Niels H.

    2011-01-01

      We investigated whether in patients with liver cirrhosis reduced muscle strength is related to dysfunction of muscle mitochondria.......  We investigated whether in patients with liver cirrhosis reduced muscle strength is related to dysfunction of muscle mitochondria....

  7. Trace metals and over-expression of metallothioneins in bladder tumoral lesions: a case-control study

    Directory of Open Access Journals (Sweden)

    Cymbron Teresa

    2009-07-01

    Full Text Available Abstract Background Previous studies have provided some evidence of a possible association between cancer and metallothioneins. Whether this relates to an exposure to carcinogenic metals remains unclear. Methods In order to examine the association between the expression of metallothioneins and bladder tumors, and to compare the levels of arsenic, cadmium, chromium, lead and nickel in animals with bladder tumors and animals without bladder tumors, 37 cases of bovine bladder tumors and 17 controls were collected. The detection and quantification of metallothioneins in bladder tissue of both cases and controls was performed by immunohistochemistry. And the quantification of metals in tissue and hair was assessed by inductively coupled plasma – mass spectrometry. Results Increased expression of metallothioneins was associated with bladder tumors when compared with non-tumoral bladder tissue (OR = 9.3, 95% CI: 1.0 – 480. The concentrations of cadmium, chromium, lead and nickel in hair of cases were significantly higher than those of controls. However, as for the concentration of metals in bladder tissue, the differences were not significant. Conclusion Though the sample size was small, the present study shows an association between bladder tumors and metallothioneins. Moreover, it shows that concentrations of metals such as cadmium, chromium, lead and nickel in hair may be used as a biomarker of exposure.

  8. Cell death in the injured brain: roles of metallothioneins

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Larsen, Agnete; Stoltenberg, Meredin

    2009-01-01

    oxygen species (ROS). ROS promote oxidative stress, which leads to neurodegeneration and ultimately results in programmed cell death (secondary injury). Since this delayed, secondary tissue loss occurs days to months following the primary injury it provides a therapeutic window where potential......In traumatic brain injury (TBI), the primary, irreversible damage associated with the moment of impact consists of cells dying from necrosis. This contributes to fuelling a chronic central nervous system (CNS) inflammation with increased formation of proinflammatory cytokines, enzymes and reactive...

  9. Hsp27, Hsp70, and metallothionein in MDCK and LLC-PK1 renal epithelial cells: effects of prolonged exposure to cadmium

    International Nuclear Information System (INIS)

    Bonham, Rita T.; Fine, Michael R.; Pollock, Fiona M.; Shelden, Eric A.

    2003-01-01

    Cadmium is a widely distributed industrial and environmental toxin. The principal target organ of chronic sublethal cadmium exposure is the kidney. In renal epithelial cells, acute high-dose cadmium exposure induces differential expression of proteins, including heat shock proteins. However, few studies have examined heat shock protein expression in cells after prolonged exposure to cadmium at sublethal concentrations. Here, we assayed total cell protein, neutral red uptake, cell death, and levels of metallothionein and heat shock proteins Hsp27 and inducible Hsp70 in cultures of MDCK and LLC-PK1 renal epithelial cells treated with cadmium for 3 days. Treatment with cadmium at concentrations equal to or greater than 10 μM (LLC-PK1) or 25 μM (MDCK) reduced measures of cell vitality and induced cell death. However, a concentration-dependent increase in Hsp27 was detected in both cell types treated with as little as 5 μM cadmium. Accumulation of Hsp70 was correlated only with cadmium treatment at concentrations also causing cell death. Metallothionein was maximally detected in cells treated with cadmium at concentrations that did not reduce cell vitality, and further increases were not detected at greater concentrations. These results reveal that heat shock proteins accumulate in renal epithelial cells during prolonged cadmium exposure, that cadmium induces differential expression of heat shock protein in epithelial cells, and that protein expression patterns in epithelial cells are specific to the cadmium concentration and degree of cellular injury. A potential role for Hsp27 in the cellular response to sublethal cadmium-induced injury is also implicated by our results

  10. Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T

    1995-01-01

    rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP...... revealed that histochemically reactive zinc had disappeared from the lesion site. Extracellular albumin and metallothionein-positive astrocytes were absent approximately 2 weeks after the lesion, whereas reactive astrocytosis was still observed. These results show that a lesion of the neonatal rat brain......Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed...

  11. The role of metallothionein in oncogenesis and cancer prognosis

    DEFF Research Database (Denmark)

    Pedersen, Mie Ø; Larsen, Agnete; Stoltenberg, Meredin

    2009-01-01

    in various human cancers; such as breast, kidney, lung, nasopharynx, ovary, prostate, salivary gland, testes, urinary bladder, cervical, endometrial, skin carcinoma, melanoma, acute lymphoblastic leukemia (ALL), and pancreatic cancers, where MT-I+II expression is sometimes correlated to higher tumor grade....../stage, chemotherapy/radiation resistance, and poor prognosis. However, MT-I+II are downregulated in other types of tumors (e.g. hepatocellular, gastric, colorectal, central nervous system (CNS), and thyroid cancers) where MT-I+II is either inversely correlated or unrelated to mortality. Large discrepancies exist...

  12. The Building Blocks of Metallothioneins: Heterometallic Zn(2+) and Cd(2+) clusters from first-principles calculations

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta; Rykær, Martin

    2010-01-01

    Electronic structures of Zn2+ and Cd2+ thiolate clusters found in metallothioneins (MT) have been obtained using density functional theory. We have found that the inherent asymmetry of cluster architectures gives rise to seven distinct metal sites. Whereas the non-strained bond lengths of such te......Electronic structures of Zn2+ and Cd2+ thiolate clusters found in metallothioneins (MT) have been obtained using density functional theory. We have found that the inherent asymmetry of cluster architectures gives rise to seven distinct metal sites. Whereas the non-strained bond lengths...

  13. A cadmium metallothionein gene of ridgetail white prawn Exopalaemon carinicauda (Holthuis, 1950) and its expression

    Science.gov (United States)

    Zhang, Jiquan; Wang, Jing; Xiang, Jianhai

    2013-11-01

    Metallothioneins (MTs) are a group of low molecular weight cysteine-rich proteins capable of binding heavy metal ions. A cadmium metallothionein ( EcMT — Cd) cDNA with a 189 bp open reading frame (ORF) that encoded a 62 amino acid protein was obtained from Exopalaemon carinicauda. Seventeen cysteines were in the deduced amino acid sequence, and the cysteine (Cys)-rich characteristic was revealed in different metallothioneins in other species. In addition, the deduced amino acid sequence did not contain any aromatic amino acid residues, such as tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe). EcMT—Cd mRNA was expressed in all tested tissues (the ovary, muscle, stomach, and hepatopancreas), and its expression profiles in the hepatopancreas were very different when shrimps were exposed to seawater containing either 50 μmol/L CuSO4 or 2.5 μmol/L CdCl 2. The expression of EcMT-Cd was significantly up-regulated in shrimp exposed to CuSO4 for 12 h and down-regulated in shrimps exposed to CdCl2 for 12 h. After 24 h exposure to both metals, its expression was down-regulated. By contrast, at 48 h the EcMT-Cd was up-regulated in test shrimps exposed to CdCl2. The transcript of EcMT-Cd was very low or even absent before the zoea stage, and the expression of EcMT-Cd was detected from mysis larvae-I, then its expression began to rise. In conclusion, a cadmium MT exists in E. carinicauda that is expressed in different tissues and during different developmental stages, and responds to the challenge with heavy metal ions, which provides a clue to understanding the function of cadmium MT.

  14. Cucumber Metallothionein-Like 2 (CsMTL2 Exhibits Metal-Binding Properties

    Directory of Open Access Journals (Sweden)

    Yu Pan

    2016-11-01

    Full Text Available We identified a novel member of the metallothionein (MT family, Cucumis sativus metallothionein-like 2 (CsMTL2, by screening a young cucumber fruit complementary DNA (cDNA library. The CsMTL2 encodes a putative 77-amino acid Class II MT protein that contains two cysteine (Cys-rich domains separated by a Cys-free spacer region. We found that CsMTL2 expression was regulated by metal stress and was specifically induced by Cd2+ treatment. We investigated the metal-binding characteristics of CsMTL2 and its possible role in the homeostasis and/or detoxification of metals by heterologous overexpression in Escherichia coli cells. Furthermore, we produced a deletion mutant form of the protein, CsMTL2m, that contained the two Cys-rich clusters but lacked the spacer region, in E. coli. We compared the metal-binding properties of CsMTL2 with those of CsMTL2m, the β domain of human metallothionein-like protein 1 (HsMTXb, and phytochelatin-like (PCL heterologously expressed in E. coli using metal-binding assays. We found that E. coli cells expressing CsMTL2 accumulated the highest levels of Zn2+ and Cd2+ of the four transformed cell types, with levels being significantly higher than those of control cells containing empty vector. E. coli cells expressing CsMTL2 had a higher tolerance for cadmium than for zinc ions. These findings show that CsMTL2 improves metal tolerance when heterologously expressed in E. coli. Future studies should examine whether CsMTL2 improves metal tolerance in planta.

  15. Screening of Cd tolerant genotypes and isolation of metallothionein genes in alfalfa (Medicago sativa L.)

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xiaojuan, E-mail: xiaojuanwang@lzu.edu.cn [School of Pastoral Agriculture Science and Technology, Lanzhou University, P.O. Box 61, Lanzhou 730020 (China); Song, Yu [School of Pastoral Agriculture Science and Technology, Lanzhou University, P.O. Box 61, Lanzhou 730020 (China); Environment Management College of China, Qinhuangdao 066004 (China); Ma Yanhua [Hebei Normal University of Science and Technology, Qinhuangdao 066004 (China); Zhuo Renying [Key Lab of Tree Genomics, Research Institute of Subtropical of Forest, Chinese Academy of Forest, Fuyang 311400 (China); Jin Liang [School of Pastoral Agriculture Science and Technology, Lanzhou University, P.O. Box 61, Lanzhou 730020 (China)

    2011-12-15

    In order to evaluate Cd tolerance in wide-ranging sources of alfalfa (Medicago sativa) and to identify Cd tolerant genotypes which may potentially be useful for restoring Cd-contaminated environments, thirty-six accessions of alfalfa were screened under hydroponic culture. Our results showed that the relative root growth rate varied from 0.48 to 1.0, which indicated that different alfalfa accessions had various responses to Cd stress. The candidate fragments derived from differentially expressed metallothionein (MT) genes were cloned from leaves of two Cd tolerant genotypes, YE and LZ. DNA sequence and the deduced protein sequence showed that MsMT2a and MsMT2b had high similarity to those in leguminous plants. DDRT-PCR analysis showed that MsMT2a expressed in both YE and LZ plants under control and Cd stress treatment, but MsMT2b only expressed under Cd stress treatment. This suggested that MsMT2a was universally expressed in leaves of alfalfa but expression of MsMT2b was Cadmium (Cd) inducible. - Highlights: > Evaluate Cd tolerance in wide sources of alfalfa accessions. > Identify Cd-hyperaccumulators potentially useful for restoring Cd-contaminated environments. > Cloned differentially expressed metallothionein (MT) genes. > Characteristics and deduced protein sequence of MsMT2a and MsMT2b were analyzed. > MsMT2a might be a universally gene of alfalfa but MsMT2b might be an inductive gene. - Two Cd tolerant alfalfa genotypes were screened and their metallothionein genes were cloned which showed that MsMT2a was universally expressed but MsMT2b was Cd inducible expression.

  16. Screening of Cd tolerant genotypes and isolation of metallothionein genes in alfalfa (Medicago sativa L.)

    International Nuclear Information System (INIS)

    Wang Xiaojuan; Song, Yu; Ma Yanhua; Zhuo Renying; Jin Liang

    2011-01-01

    In order to evaluate Cd tolerance in wide-ranging sources of alfalfa (Medicago sativa) and to identify Cd tolerant genotypes which may potentially be useful for restoring Cd-contaminated environments, thirty-six accessions of alfalfa were screened under hydroponic culture. Our results showed that the relative root growth rate varied from 0.48 to 1.0, which indicated that different alfalfa accessions had various responses to Cd stress. The candidate fragments derived from differentially expressed metallothionein (MT) genes were cloned from leaves of two Cd tolerant genotypes, YE and LZ. DNA sequence and the deduced protein sequence showed that MsMT2a and MsMT2b had high similarity to those in leguminous plants. DDRT-PCR analysis showed that MsMT2a expressed in both YE and LZ plants under control and Cd stress treatment, but MsMT2b only expressed under Cd stress treatment. This suggested that MsMT2a was universally expressed in leaves of alfalfa but expression of MsMT2b was Cadmium (Cd) inducible. - Highlights: → Evaluate Cd tolerance in wide sources of alfalfa accessions. → Identify Cd-hyperaccumulators potentially useful for restoring Cd-contaminated environments. → Cloned differentially expressed metallothionein (MT) genes. → Characteristics and deduced protein sequence of MsMT2a and MsMT2b were analyzed. → MsMT2a might be a universally gene of alfalfa but MsMT2b might be an inductive gene. - Two Cd tolerant alfalfa genotypes were screened and their metallothionein genes were cloned which showed that MsMT2a was universally expressed but MsMT2b was Cd inducible expression.

  17. Alterations in radioresistance of eucaryotic cells after the transfer of genomic wildtype DNA and metallothionein genes

    International Nuclear Information System (INIS)

    Lohrer, H.

    1987-01-01

    The presented paper describes experiments concerning the alteration of radiosensitivity of eucaryotic cells after gene transfer. Ionizing radiation (γ- or X-ray) induces DNA single- or double strand breaks, which are religated by an unknown repair system. Repair deficient cells are highly sensitive to ionizing radiation. In the experiments described, cells from a patient with the heritable disease Ataxia telangiectasia were used as well as two X-ray sensitive CHO mutant cell lines. After gene transfer of an intact human DNA repair gene or a metallothionein gene the cells should regain radioresistance. (orig.) [de

  18. Full quantum-mechanical structure of the human protein Metallothionein-2

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2012-01-01

    Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented...... structures are accurate to ~0.03Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein...

  19. Neuronal apoptosis, metallothionein expression and proinflammatory responses during cerebral malaria in mice

    DEFF Research Database (Denmark)

    Wiese, Lothar; Kurtzhals, Jørgen A L; Penkowa, Milena

    2006-01-01

    BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy in humans due to the infection with Plasmodium falciparum. Neuro-cognitive impairment following CM occurs in about 10% of the treated survivors, while the precise pathophysiological mechanism remains unknown. Metallothionein I + II (MT......-I + II) are increased during CNS pathology and disorders. As previously shown, MT-I + II are neuroprotective through anti-inflammatory, antioxidant and antiapoptotic functions. We have analyzed neuronal apoptosis and MT-I + II expression in brains of mice with experimental CM. METHODS: C57BL/6j mice...

  20. Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2003-01-01

    Metallothioneins I+II (MT-I+II) are antioxidant, neuroprotective factors. We previously showed that MT-I+II deficiency during experimental autoimmune encephalomyelitis (EAE) leads to increased disease incidence and clinical symptoms. Moreover, the inflammatory response of macrophages and T cells......, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...

  1. Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan; Moos, Torben

    1997-01-01

    The cerebral distribution of metallothioneins I and II (MT-I + II) was studied in adult rats subjected to i.p. injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey matter regions of the brainstem heralded numerous OX-42-positive macrophages and microglia, indicating that 6-AN primarily...... caused damage to this part of the brain. In the grey matter regions infiltrated with OX-42-positive cells, astrocytes identified by anti-GFAP and MT-I + II antibodies were almost absent. By contrast, in the peripheral zone of the lesioned regions numerous reactive GFAP- and MT-I + II-positive astrocytes...

  2. Retracted: Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    2018-02-01

    Following on from the Expression of Concern (10.1002/glia.22466) previously published by GLIA, the following Original Article has been retracted by the journal Editors and Publisher: Metallothionein I+II expression and their role in experimental autoimmune encephalomyelitis By Milena Penkowa and Juan Hidalgo GLIA (2000), 32(3), 247-263 DOI: 10.1002/1098-1136(200012)32:33.0.CO;2-T Discrepancies in the type and number of animals used in experiments performed by Milena Penkowa and reported in Table 1, identified during the course of investigations into Ms Penkowa's research, render the data and conclusions drawn from them unreliable. © 2017 Wiley Periodicals, Inc.

  3. Increased astrocytic expression of metallothioneins I + II in brainstem of adult rats treated with 6-aminonicotinamide

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan; Moos, Torben

    1997-01-01

    The cerebral distribution of metallothioneins I and II (MT-I + II) was studied in adult rats subjected to i.p. injection with the gliotoxin 6-aminonicotinamide (6-AN). Grey matter regions of the brainstem heralded numerous OX-42-positive macrophages and microglia, indicating that 6-AN primarily...... were observed. The blood-brain barrier (BBB) to serum albumin was compromised in the entire brainstem. The astrocytic expression of MT-I + II could reflect the brains needs to scavenge metal ions released from either damaged cells or plasma proteins entering the brain due to the injured BBB, as well...

  4. Expression response of duplicated metallothionein 3 gene to copper stress in Silene vulgaris ecotypes

    Czech Academy of Sciences Publication Activity Database

    Nevrtalová, Eva; Baloun, Jiří; Hudzieczek, Vojtěch; Čegan, Radim; Vyskot, Boris; Doležel, Jaroslav; Šafář, Jan; Milde, D.; Hobza, Roman

    2014-01-01

    Roč. 251, č. 6 (2014), s. 1427-1439 ISSN 0033-183X R&D Projects: GA ČR(CZ) GAP501/12/2220; GA ČR(CZ) GBP501/12/G090; GA ČR(CZ) GP13-34962P; GA ČR(CZ) GA522/09/0083 Institutional support: RVO:68081707 Keywords : Copper * Gene duplication * Metallothionein Subject RIV: BO - Biophysics; EF - Botanics (UEB-Q) Impact factor: 2.651, year: 2014

  5. Light-Emitting Diode Phototherapy Reduces Nocifensive Behavior Induced by Thermal and Chemical Noxious Stimuli in Mice: Evidence for the Involvement of Capsaicin-Sensitive Central Afferent Fibers.

    Science.gov (United States)

    Pigatto, Glauce Regina; Coelho, Igor Santos; Aquino, Rosane Schenkel; Bauermann, Liliane Freitas; Santos, Adair Roberto Soares

    2017-07-01

    Low-intensity phototherapy using light fonts, like light-emitting diode (LED), in the red to infrared spectrum is a promising alternative for the treatment of pain. However, the underlying mechanisms by which LED phototherapy reduces acute pain are not yet well understood. This study investigated the analgesic effect of multisource LED phototherapy on the acute nocifensive behavior of mice induced by thermal and chemical noxious stimuli. The involvement of central afferent C fibers sensitive to capsaicin in this effect was also investigated. Mice exposed to multisource LED (output power 234, 390, or 780 mW and power density 10.4, 17.3, and 34.6 mW/cm 2 , respectively, from 10 to 30 min of stimulation with a wavelength of 890 nm) showed rapid and significant reductions in formalin- and acetic acid-induced nocifensive behavior. This effect gradually reduced but remained significant for up to 7 h after LED treatment in the last model used. Moreover, LED (390 mW, 17.3 mW/cm 2 /20 min) irradiation also reduced nocifensive behavior in mice due to chemical [endogenous (i.e., glutamate, prostaglandins, and bradykinin) or exogenous (i.e., formalin, acetic acid, TRPs and ASIC agonist, and protein kinase A and C activators)] and thermal (hot plate test) stimuli. Finally, ablating central afferent C fibers abolished LED analgesia. These experimental results indicate that LED phototherapy reduces the acute painful behavior of animals caused by chemical and thermal stimuli and that LED analgesia depends on the integrity of central afferent C fibers sensitive to capsaicin. These findings provide new information regarding the underlying mechanism by which LED phototherapy reduces acute pain. Thus, LED phototherapy may be an important tool for the management of acute pain.

  6. Patrilineal populations show more male transmission of reproductive success than cognatic populations in Central Asia, which reduces their genetic diversity.

    Science.gov (United States)

    Heyer, Evelyne; Brandenburg, Jean-Tristan; Leonardi, Michela; Toupance, Bruno; Balaresque, Patricia; Hegay, Tanya; Aldashev, Almaz; Austerlitz, Frederic

    2015-08-01

    The extent to which social organization of human societies impacts the patterns of genetic diversity remains an open question. Here, we investigate the transmission of reproductive success in patrilineal and cognatic populations from Central Asia using a coalescent approach. We performed a study on the mitochondrial DNA (mtDNA) and Y chromosome polymorphism of patrilineal and cognatic populations from Central Asia. We reconstructed the gene genealogies in each population for both kind of markers and inferred the imbalance level of these genealogies, a parameter directly related to the level of transmission of reproductive success. This imbalance level appeared much stronger for the Y chromosome in patrilineal populations than in cognatic populations, while no difference was found for mtDNA. Furthermore, we showed that this imbalance level correlates negatively with Y-chromosomal, mtDNA, and autosomal genetic diversity. This shows that patrilineality might be one of the factors explaining the male transmission of reproductive success, which, in turn, lead to a reduction of genetic diversity. Thus, notwithstanding the fact that our population genetic approach clearly shows that there is a strong male-biased transmission of reproductive success in patrilineal societies, it also highlights the fact that a social process such as cultural transmission of reproductive success could play an important role in shaping human genetic diversity, although we cannot formally exclude that this transmission has also a genetic component. © 2015 Wiley Periodicals, Inc.

  7. Effect of dietary zinc deficiency on the accumulation of cadmium and metallothionein in selected tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Waalkes, M.P.

    1986-01-01

    The effect of continuous dietary zinc deficiency on the metabolism of the toxic heavy metal cadmium has not been widely studied. This investigation was designed to assess the effects of subadequate dietary zinc intake on the accumulation of dietary cadmium and on metallothionein (MT) and zinc concentrations in target organs of cadmium toxicity. Adult male Wistar rats (180-200 g) were allowed, ad libitum, diets either adequate (60 ppm) or deficient (7 ppm) in zinc for a total of 9 wk. The zinc-deficient diet resulted in an approximately 40% reduction in plasma zinc (assessed at 3, 6, and 9 wk) in the absence of overt signs of zinc deficiency (i.e., reduced weight gain, alopecia, etc.). Separate groups of rats were also maintained on zinc-defined diets for a total of 9 wk, but cadmium was added to the diet (0, 12.5, 25, 50, 100, and 200 ppm) a the end of wk 3 and maintained at that level throughout the remaining 6 wk of the study, when the rats were killed. The feeding of the zinc-deficient diet markedly enhanced the accumulation of cadmium in the liver, kidney, and testes. Hepatic, renal, and testicular zinc concentrations were not affected by suboptimal zinc intake alone. However, marked reductions in renal and testicular zinc concentrations were caused by zinc deficiency in concert with cadmium exposure. MT levels, when related to tissue cadmium concentrations, were elevated to a significantly lesser extent in the kidneys of zinc-deficient animals. These results indicate that marginal zinc deficiency markedly increases cadmium accumulation in various organs and reduces zinc content and MT induction in some organs.

  8. The Metallothionein Gene, TaMT3, from Tamarix androssowii Confers Cd2+ Tolerance in Tobacco

    Directory of Open Access Journals (Sweden)

    Boru Zhou

    2014-06-01

    Full Text Available Cadmium (Cd is a nonessential microelement and low concentration Cd2+ has strong toxicity to plant growth. Plant metallothioneins, a class of low molecular, cystein(Cys-rich and heavy-metal binding proteins, play an important role in both metal chaperoning and scavenging of reactive oxygen species (ROS with their large number of cysteine residues and therefore, protect plants from oxidative damage. In this study, a metallothionein gene, TaMT3, isolated from Tamarix androssowii was transformed into tobacco (Nicotiana tobacum through Agrobacterium-mediated leaf disc method, and correctly expressed under the control of 35S promoter. Under Cd2+ stress, the transgenic tobacco showed significant increases of superoxide dismutase (SOD activity and chlorophyll concentration, but decreases of peroxidase (POD activity and malondialdehyde (MDA accumulation when compared to the non-transgenic tobacco. Vigorous growth of transgenic tobacco was observed at the early development stages, resulting in plant height and fresh weight were significantly larger than those of the non-transgenic tobacco under Cd2+ stress. These results demonstrated that the expression of the exogenous TaMT3 gene increased the ability of ROS cleaning-up, indicating a stronger tolerance to Cd2+ stress.

  9. The metallothionein gene, TaMT3, from Tamarix androssowii confers Cd2+ tolerance in tobacco.

    Science.gov (United States)

    Zhou, Boru; Yao, Wenjing; Wang, Shengji; Wang, Xinwang; Jiang, Tingbo

    2014-06-10

    Cadmium (Cd) is a nonessential microelement and low concentration Cd2+ has strong toxicity to plant growth. Plant metallothioneins, a class of low molecular, cystein(Cys)-rich and heavy-metal binding proteins, play an important role in both metal chaperoning and scavenging of reactive oxygen species (ROS) with their large number of cysteine residues and therefore, protect plants from oxidative damage. In this study, a metallothionein gene, TaMT3, isolated from Tamarix androssowii was transformed into tobacco (Nicotiana tobacum) through Agrobacterium-mediated leaf disc method, and correctly expressed under the control of 35S promoter. Under Cd2+ stress, the transgenic tobacco showed significant increases of superoxide dismutase (SOD) activity and chlorophyll concentration, but decreases of peroxidase (POD) activity and malondialdehyde (MDA) accumulation when compared to the non-transgenic tobacco. Vigorous growth of transgenic tobacco was observed at the early development stages, resulting in plant height and fresh weight were significantly larger than those of the non-transgenic tobacco under Cd2+ stress. These results demonstrated that the expression of the exogenous TaMT3 gene increased the ability of ROS cleaning-up, indicating a stronger tolerance to Cd2+ stress.

  10. Function of Metallothionein-3 in Neuronal Cells: Do Metal Ions Alter Expression Levels of MT3?

    Science.gov (United States)

    Bousleiman, Jamie; Pinsky, Alexa; Ki, Sohee; Su, Angela; Morozova, Irina; Kalachikov, Sergey; Wiqas, Amen; Silver, Rae; Sever, Mary; Austin, Rachel Narehood

    2017-01-01

    A study of factors proposed to affect metallothionein-3 (MT3) function was carried out to elucidate the opaque role MT3 plays in human metalloneurochemistry. Gene expression of Mt2 and Mt3 was examined in tissues extracted from the dentate gyrus of mouse brains and in human neuronal cell cultures. The whole-genome gene expression analysis identified significant variations in the mRNA levels of genes associated with zinc homeostasis, including Mt2 and Mt3. Mt3 was found to be the most differentially expressed gene in the identified groups, pointing to the existence of a factor, not yet identified, that differentially controls Mt3 expression. To examine the expression of the human metallothioneins in neurons, mRNA levels of MT3 and MT2 were compared in BE(2)C and SH-SY5Y cell cultures treated with lead, zinc, cobalt, and lithium. MT2 was highly upregulated by Zn2+ in both cell cultures, while MT3 was not affected, and no other metal had an effect on either MT2 or MT3. PMID:28587098

  11. Variation in metallothionein gene expression is associated with adaptation to copper in the earthworm Dendrobaena octaedra.

    Science.gov (United States)

    Fisker, Karina Vincents; Holmstrup, Martin; Sørensen, Jesper Givskov

    2013-03-01

    Evolution of resistance to heavy metals has been reported for several populations of soil living organisms occurring at metal contaminated sites. Such genetically based and heritable resistance contribute to the persistence of populations in contaminated areas. Here we report on molecular responses to experimental copper in populations of the earthworm, Dendrobaena octaedra, originating from copper contaminated soil near Gusum (Sweden) where heavy metal pollution has been present for several decades. We studied gene expression of six genes potentially involved in resistance to copper toxicity using F2-generations of D. octaedra populations, originating from reference sites and contaminated (High, Medium and Low) sites around Gusum. The main result was different expression patterns of genes encoding for two different isoforms (mt1 and mt2) of metallothionein proteins during experimental exposure to copper contaminated soil. Expression of mt1 showed a fast and significant upregulation in the High population and a slower, albeit significant, upregulation in Medium and Low populations. However, in the three reference populations no upregulation were seen. In comparison, a fast upregulation was also seen for the High population in the isoform mt2, whereas, gene expression of all other populations, including reference populations, showed slower upregulation in response to experimental copper. The results indicate that copper resistance in D. octaedra from contaminated areas is related to an increased expression of metallothioneins. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. A copper-induced metallothionein gene from Exopalaemon carinicauda and its response to heavy metal ions.

    Science.gov (United States)

    Zhang, Jiquan; Wang, Jing; Gui, Tianshu; Sun, Zheng; Xiang, Jianhai

    2014-09-01

    A full-length copper-induced metallothionein (EcMT-Cu) cDNA was obtained from Exopalaemon carinicauda (Holthuis) and it contained a 198 bp open reading frame that encoded a peptide with 65 amino acid residues. Twenty-one cysteines were found in deduced amino acid sequence and the cysteine (Cys)-rich characteristic was also reported in different types of metallothioneins from other species. EcMT-Cu mRNA expression profile showed that it is the hepatopancreas specific gene. The expression of EcMT-Cu was extremely different when shrimp were exposed to seawater containing 50 μM CuSO4 or 2.5 μM CdCl2. The expression of EcMT-Cu in shrimp was significantly up-regulated at 12 and 24 h after exposure to CuSO4, however, its expression was not induced compared to that of pretreatment (p>0.05) when shrimp were exposed to CdCl2. The transcript of EcMT-Cu was found to be extremely low at gastrula and nauplius stage and expression of EcMT-Cu could be detected from egg protozoa stage. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Effects of exogenous metallothionein against thallium-induced oxidative stress in rat liver.

    Science.gov (United States)

    Kiliç, Gözde Aydoğan; Kutlu, Mehtap

    2010-03-01

    Metallothionein (MT) is a low-molecular weight sulfur-rich protein that plays role in metal homeostasis/detoxification and radical scavenging. The following study investigated the ability of exogenous MT to protect against oxidative damage induced by thallium (TI) in rat liver. Male Wistar rats were divided into four groups; a control and three experimental groups. The control group received physiological saline. Group 1 animals were injected with thallium acetate intraperitoneally (i.p.) at a single dose of LD(50) (32 mg/kg). In group 2 and group 3, metallothionein I was administrated once at two different doses (1 or 2.5mg/kg i.p., respectively) 1h before TI intoxication. Levels of endogenous antioxidants, oxidative stress markers were measured and histopathological examinations were performed 4 days after TI administration. TI accumulation in liver decreased related to the dose of MT. Mostly all of the alterations in the levels antioxidants restored to normal levels in MT administrated animals. H(2)O(2) levels and lipid peroxidation decreased, integrity of hepatocytes and membranous structures inside the cells were preserved. The toxic effects of TI were modulated in MT administrated animals particularly at the dose of 2.5mg/kg. These findings suggest an active role of exogenous MT against TI-induced oxidative stress in rat liver. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  14. A Simple Metallothionein-Based Biosensor for Enhanced Detection of Arsenic and Mercury

    Directory of Open Access Journals (Sweden)

    Gordon W. Irvine

    2017-03-01

    Full Text Available Metallothioneins (MTs are a family of cysteine-rich proteins whose biological roles include the regulation of essential metal ions and protection against the harmful effects of toxic metals. Due to its high affinity for many toxic, soft metals, recombinant human MT isoform 1a was incorporated into an electrochemical-based biosensor for the detection of As3+ and Hg2+. A simple design was chosen to maximize its potential in environmental monitoring and MT was physically adsorbed onto paper discs placed on screen-printed carbon electrodes (SPCEs. This system was tested with concentrations of arsenic and mercury typical of contaminated water sources ranging from 5 to 1000 ppb. The analytical performance of the MT-adsorbed paper discs on SPCEs demonstrated a greater than three-fold signal enhancement and a lower detection limit compared to blank SPCEs, 13 ppb for As3+ and 45 ppb for Hg2+. While not being as low as some of the recommended drinking water limits, the sensitivity of the simple MT-biosensor would be potentially useful in monitoring of areas of concern with a known contamination problem. This paper describes the ability of the metal binding protein metallothionein to enhance the effectiveness of a simple, low-cost electrochemical sensor.

  15. Comparison of Metallothionein Detection by Using Brdicka Reaction and Enzyme-Linked Immunosorbent Assay Employing Chicken Yolk Antibodies

    Czech Academy of Sciences Publication Activity Database

    Křížková, S.; Bláhová, P.; Nakielna, J.; Fabrik, I.; Adam, V.; Eckschlager, T.; Beklová, M.; Svobodová, Z.; Horák, Vratislav; Krížek, R.

    2009-01-01

    Roč. 21, č. 23 (2009), s. 2575-2583 ISSN 1040-0397 Institutional research plan: CEZ:AV0Z50450515 Keywords : Metallothionein * Differential pulse voltammetry * ELISA Subject RIV: CG - Electrochemistry Impact factor: 2.630, year: 2009

  16. Altered inflammatory response and increased neurodegeneration in metallothionein I+II deficient mice during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Martínez-Cáceres, E M

    2001-01-01

    Metallothionein-I+II (MT-I+II) are antioxidant, neuroprotective proteins, and in this report we have examined their roles during experimental autoimmune encephalomyelitis (EAE) by comparing MT-I+II-knock-out (MTKO) and wild-type mice. We herewith show that EAE susceptibility is higher in MTKO mice...

  17. Effect of four weeks high intensity interval training versus aerobic exercise on metallothionein levels of myocardial tissue in rats

    Directory of Open Access Journals (Sweden)

    M. Shabani

    2016-08-01

    Full Text Available Background: Oxidative species produced during exercise can cause damages to some tissues such as kidney, liver and skeletal muscle. It seems that metallothionein plays a protective role against these actions. Objective: To assess the effect of four weeks of high intensity interval training versus aerobic exercise on metallothionein levels of myocardial tissue in healthy male rats. Methods: This experimental study was done on 36 male Wistar rats (2 months of age with an average weight of 180±20 in 2015.The rats were randomly divided into three groups: control (n=12, high intensity interval training (n=12, and aerobic training (n=12 groups. The experimental groups exercised according to the training program 5 days a week for 4 weeks. During this period, the control group did not have any training programs. One-way ANOVA was used to analyze the data. Findings: The results indicate no significant difference among the mean metallothionein in control, aerobic exercise and high intensity interval training groups. However, the amount of myocardial metallothionein increased as a result of high intensity interval training and decreased during aerobic exercise. Conclusion: It seems that the duration and intensity of exercise need to be adjusted in order to obtain better results.

  18. A PU.1 suppressive target gene, metallothionein 1G, inhibits retinoic acid-induced NB4 cell differentiation.

    Directory of Open Access Journals (Sweden)

    Naomi Hirako

    Full Text Available We recently revealed that myeloid master regulator SPI1/PU.1 directly represses metallothionein (MT 1G through its epigenetic activity of PU.1, but the functions of MT1G in myeloid differentiation remain unknown. To clarify this, we established MT1G-overexpressing acute promyelocytic leukemia NB4 (NB4MTOE cells, and investigated whether MT1G functionally contributes to all-trans retinoic acid (ATRA-induced NB4 cell differentiation. Real-time PCR analyses demonstrated that the inductions of CD11b and CD11c and reductions in myeloperoxidase and c-myc by ATRA were significantly attenuated in NB4MTOE cells. Morphological examination revealed that the percentages of differentiated cells induced by ATRA were reduced in NB4MTOE cells. Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we observed a decrease in G1 accumulation, as well as decreases in p21WAF1/CIP1 and cyclin D1 inductions, by ATRA in NB4MTOE cells. Nitroblue tetrazolium (NBT reduction assays revealed that the proportions of NBT-positive cells were decreased in NB4MTOE cells in the presence of ATRA. Microarray analyses showed that the changes in expression of several myeloid differentiation-related genes (GATA2, azurocidin 1, pyrroline-5-carboxylate reductase 1, matrix metallopeptidase -8, S100 calcium-binding protein A12, neutrophil cytosolic factor 2 and oncostatin M induced by ATRA were disturbed in NB4MTOE cells. Collectively, overexpression of MT1G inhibits the proper differentiation of myeloid cells.

  19. Central nervous system exposure of next generation quinoline methanols is reduced relative to mefloquine after intravenous dosing in mice

    Science.gov (United States)

    2011-01-01

    Background The clinical use of mefloquine (MQ) has declined due to dose-related neurological events. Next generation quinoline methanols (NGQMs) that do not accumulate in the central nervous system (CNS) to the same extent may have utility. In this study, CNS levels of NGQMs relative to MQ were measured and an early lead chemotype was identified for further optimization. Experimental design The plasma and brain levels of MQ and twenty five, 4-position modified NGQMs were determined using LCMS/MS at 5 min, 1, 6 and 24 h after IV administration (5 mg/kg) to male FVB mice. Fraction unbound in brain tissue homogenate was assessed in vitro using equilibrium dialysis and this was then used to calculate brain-unbound concentration from the measured brain total concentration. A five-fold reduction CNS levels relative to mefloquine was considered acceptable. Additional pharmacological properties such as permeability and potency were determined. Results The maximum brain (whole/free) concentrations of MQ were 1807/4.9 ng/g. Maximum whole brain concentrations of NGQMs were 23 - 21546 ng/g. Maximum free brain concentrations were 0.5 to 267 ng/g. Seven (28%) and two (8%) compounds exhibited acceptable whole and free brain concentrations, respectively. Optimization of maximum free brain levels, IC90s (as a measure or potency) and residual plasma concentrations at 24 h (as a surrogate for half-life) in the same molecule may be feasible since they were not correlated. Diamine quinoline methanols were the most promising lead compounds. Conclusion Reduction of CNS levels of NGQMs relative to mefloquine may be feasible. Optimization of this property together with potency and long half-life may be feasible amongst diamine quinoline methanols. PMID:21645370

  20. Microbiological and 16S rRNA analysis of sulphite-reducing clostridia from river sediments in central Italy

    Directory of Open Access Journals (Sweden)

    Marcheggiani Stefania

    2008-10-01

    Full Text Available Abstract Background Microbiological indicators are commonly used in the assessment of public health risks associated with fecal contamination of freshwater ecosystems. Sediments are a reservoir of microorganisms, and can thus provide information on past pollution events, not obtainable through the testing of surface water. Moreover, pathogens present in sediment may represent future threats to human health. Clostridium perfringens, a typical colonizer of sediments, has been suggested as an alternative indicator of fecal pollution. In order to be suitable for such purpose, the microorganism should be widely distributed in contaminated environments. The objective of this study was thus to determine the composition of the anaerobic community in sediment samples of the lower Tiber basin, in central Italy, through a combined approach involving granulometric analysis of sediment samples, as well as a microbiological and molecular (16S rRNA analysis of strains. Results Granulometry showed a similar, clayey sediment composition, in most sampling sites. The microbiological method, employing, an adaptation of the standard method, proved to be effective in isolating anaerobic bacteria from the environmental matrix for the purpose of genetic analysis. Eighty-three strains of bacteria were isolated and the partial 16S rRNA gene sequenced. While biochemical analysis detected only C. perfringens strains, phylogenetic analysis indicated the presence of three clusters: C. perfringens, C. bifermentans and B. cereus, comprising eight taxa. C. perfringens, the commonest in almost all sediment sampling sites, was present in all sites, and in both seasons (seasonal sampling was carried out only along the Tiber and Aniene rivers. None of the described genetic profiles showed complete similarity with GenBank sequences. Conclusion The study underlines the value of C. perfringens as an alternative microbial indicator of fecal contamination in river sediments. This is

  1. Microbiological and 16S rRNA analysis of sulphite-reducing clostridia from river sediments in central Italy.

    Science.gov (United States)

    Marcheggiani, Stefania; Iaconelli, Marcello; D'angelo, Annamaria; Pierdominici, Elio; La Rosa, Giuseppina; Muscillo, Michele; Equestre, Michele; Mancini, Laura

    2008-10-08

    Microbiological indicators are commonly used in the assessment of public health risks associated with fecal contamination of freshwater ecosystems. Sediments are a reservoir of microorganisms, and can thus provide information on past pollution events, not obtainable through the testing of surface water. Moreover, pathogens present in sediment may represent future threats to human health. Clostridium perfringens, a typical colonizer of sediments, has been suggested as an alternative indicator of fecal pollution. In order to be suitable for such purpose, the microorganism should be widely distributed in contaminated environments. The objective of this study was thus to determine the composition of the anaerobic community in sediment samples of the lower Tiber basin, in central Italy, through a combined approach involving granulometric analysis of sediment samples, as well as a microbiological and molecular (16S rRNA) analysis of strains. Granulometry showed a similar, clayey sediment composition, in most sampling sites. The microbiological method, employing, an adaptation of the standard method, proved to be effective in isolating anaerobic bacteria from the environmental matrix for the purpose of genetic analysis. Eighty-three strains of bacteria were isolated and the partial 16S rRNA gene sequenced. While biochemical analysis detected only C. perfringens strains, phylogenetic analysis indicated the presence of three clusters: C. perfringens, C. bifermentans and B. cereus, comprising eight taxa. C. perfringens, the commonest in almost all sediment sampling sites, was present in all sites, and in both seasons (seasonal sampling was carried out only along the Tiber and Aniene rivers). None of the described genetic profiles showed complete similarity with GenBank sequences. The study underlines the value of C. perfringens as an alternative microbial indicator of fecal contamination in river sediments. This is supported by the bacterium's presence in all sampling sites

  2. Non-enzymatic modifications in metallothioneins connected to lipid membrane damages: structural and biomimetic studies under reductive radical stress.

    Science.gov (United States)

    Torreggiani, Armida; Chatgilialoglu, Chryssostomos; Ferreri, Carla; Melchiorre, Michele; Atrian, Silvia; Capdevila, Merce'

    2013-10-30

    Metallothioneins (MTs) are small cysteine-rich proteins with the ability to coordinate heavy metal atoms through metal-thiolate bonds, which are widely distributed among the animal and plant kingdoms. Multifunctional roles for MTs have been proposed, including their ability to scavenger various radicals and reactive oxygen species. In the present article we summarize available information of four MT polypeptides from different organisms, forming metal complexes with Zn(II), Cd(II) or Cu (I) ions. Non-enzymatic modifications of MTs under ionizing radiations and their consequences on the lipidic membrane compartment were studied by Raman spectroscopy and a biomimetic model, respectively. The latter is based on liposome technology and allows to measure the trans unsaturated fatty acid content as a result of reductive radical stress on MTs. The effect of radical stress on the cell metabolism and functions is a very active field of research connecting various disciplines in life sciences. In this contest tandem radical damage has been the subject of recent investigations that pointed out its harmfulness in the general scenario of establishing the consequences of radical stress. By using biomimetic models of tandem damage we have for the first time tested the capability of metallothioneins (MTs), small metalloproteins rich of Cys residues, to damage another cell compartment like lipid membranes when they are undergone to reductive radical stress. The connection of MT reactivity with membrane lipid transformation can give a contribution to the puzzling context of radical stress occurring to biomolecules and the role as biological signaling. To this purpose, MT polypeptides from different organisms, exhibiting different sequence peculiarities, have been analyzed here. The spectroscopic analysis of these systems has allowed to identify modifications affecting metal-thiolate clusters, cystines, and Met residues, acting as efficient interceptors of reducing radical species

  3. Glucagon-Like Peptide 1 and Its Analogs Act in the Dorsal Raphe and Modulate Central Serotonin to Reduce Appetite and Body Weight.

    Science.gov (United States)

    Anderberg, Rozita H; Richard, Jennifer E; Eerola, Kim; López-Ferreras, Lorena; Banke, Elin; Hansson, Caroline; Nissbrandt, Hans; Berqquist, Filip; Gribble, Fiona M; Reimann, Frank; Wernstedt Asterholm, Ingrid; Lamy, Christophe M; Skibicka, Karolina P

    2017-04-01

    Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation. Serotonin turnover and expression of 5-hydroxytryptamine (5-HT) 2A (5-HT 2A ) and 5-HT 2C serotonin receptors in the hypothalamus were altered by GLP-1R activation. We demonstrate that the 5-HT 2A , but surprisingly not the 5-HT 2C , receptor is critical for weight loss, anorexia, and fat mass reduction induced by central GLP-1R activation. Importantly, central 5-HT 2A receptors are also required for peripherally injected liraglutide to reduce feeding and weight. Dorsal raphe (DR) harbors cell bodies of serotonin-producing neurons that supply serotonin to the hypothalamic nuclei. We show that GLP-1R stimulation in DR is sufficient to induce hypophagia and increase the electrical activity of the DR serotonin neurons. Finally, our results disassociate brain metabolic and emotionality pathways impacted by GLP-1R activation. This study identifies serotonin as a new critical neural substrate for GLP-1 impact on energy homeostasis and expands the current map of brain areas impacted by GLP-1R activation. © 2017 by the American Diabetes Association.

  4. Regular, high, and moderate intake of vegetables rich in antioxidants may reduce cataract risk in Central African type 2 diabetics

    Directory of Open Access Journals (Sweden)

    Mvitu M

    2012-06-01

    .Conclusion: Red beans intake and adequate quantity of intake of vegetables rich in antioxidants were found to be associated with reduced risk of cataract in these Congolese with type 2 diabetes mellitus. Education on nutrition and health promotion programs are needed to encourage people to eat vegetables and fruit.Keywords: red beans, cataract extraction, socioeconomic status, public health implications

  5. Pruning high-value Douglas-fir can reduce dwarf mistletoe severity and increase longevity in central Oregon

    Science.gov (United States)

    Maffei, Helen M; Filip, Gregory M; Gruelke, Nancy E; Oblinger, Brent W; Margolis, Ellis; Chadwick, Kristen L

    2016-01-01

    little effect on resources available for tree growth and maintenance. In the severely pruned trees, tree-ring width was reduced for several years post-pruning, but then compensated with larger ring width in later years. Both NDVI and LCR increment were significantly higher for the pruned trees than the control trees, while the development of severe infections and/or dead tops was significantly (5X and 3X) higher for the controls. If possible, multiple indicators of tree vitality should be evaluated. Pruning can be worthwhile even if all the mistletoe is not removed, because mistletoe intensification is delayed. The impact of removing the brooms seems to be minimal, and post-pruning crowns had greater NDVI values.

  6. Transcription patterns of genes encoding four metallothionein homologs in Daphnia pulex exposed to copper and cadmium are time- and homolog-dependent

    Energy Technology Data Exchange (ETDEWEB)

    Asselman, Jana, E-mail: jana.asselman@ugent.be [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, Ghent (Belgium); Shaw, Joseph R.; Glaholt, Stephen P. [The School of Public and Environmental Affairs, Indiana University, Bloomington, IN (United States); Colbourne, John K. [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); De Schamphelaere, Karel A.C. [Laboratory of Environmental Toxicology and Aquatic Ecology, Ghent University, Ghent (Belgium)

    2013-10-15

    Highlights: •Transcription patterns of 4 metallothionein isoforms in Daphnia pulex. •Under cadmium and copper stress these patterns are time-dependent. •Under cadmium and copper stress these patterns are homolog-dependent. •The results stress the complex regulation of metallothioneins. -- Abstract: Metallothioneins are proteins that play an essential role in metal homeostasis and detoxification in nearly all organisms studied to date. Yet discrepancies between outcomes of chronic and acute exposure experiments hamper the understanding of the regulatory mechanisms of their isoforms following metal exposure. Here, we investigated transcriptional differences among four identified homologs (mt1–mt4) in Daphnia pulex exposed across time to copper and cadmium relative to a control. Transcriptional upregulation of mt1 and mt3 was detected on day four following exposure to cadmium, whereas that of mt2 and mt4 was detected on day two and day eight following exposure to copper. These results confirm temporal and metal-specific differences in the transcriptional induction of genes encoding metallothionein homologs upon metal exposure which should be considered in ecotoxicological monitoring programs of metal-contaminated water bodies. Indeed, the mRNA expression patterns observed here illustrate the complex regulatory system associated with metallothioneins, as these patterns are not only dependent on the metal, but also on exposure time and the homolog studied. Further phylogenetic analysis and analysis of regulatory elements in upstream promoter regions revealed a high degree of similarity between metallothionein genes of Daphnia pulex and Daphnia magna, a species belonging to the same genus. These findings, combined with a limited amount of available expression data for D. magna metallothionein genes, tentatively suggest a potential generalization of the metallothionein response system between these Daphnia species.

  7. Efficacy of reduced-fluence photodynamic therapy for central serous chorioretinopathy associated with combined serous retinal detachment and fovea-involving pigment epithelial detachment.

    Science.gov (United States)

    Arf, Serra; Hocaoglu, Mumin; Sayman Muslubas, Isil; Karacorlu, Murat

    2017-06-01

    The purpose of the study was to evaluate the effect of reduced-fluence photodynamic therapy (RFPDT) for chronic central serous chorioretinopathy (CSC) associated with serous retinal detachment (SRD) and fovea-involving pigment epithelial detachment (PED). Ten eyes of ten patients with chronic CSC associated with combined SRD and PED involving the fovea were included. RFPDT was applied to the hyperfluorescent area identified at the mid-to-late phase of indocyanine green angiography, which indicated the area of leakage. We evaluated the changes in best-corrected visual acuity (BCVA) and optical coherence tomography at month 1 and final follow-up visit. The mean age of the participants was 47.4 ± 7 years. The mean follow-up duration was 6.3 ± 4 months. At month 3, the SRD had resolved completely in all ten eyes (100 %), and PED had resolved in seven eyes (70 %). The initial mean BCVA improved from 20/50 at baseline to 20/32 at the last visit (P > 0.05). The mean central retinal thickness was reduced from 534 ± 279 µm at baseline to 194 ± 46 µm at the last examination (P < 0.001). The mean subfoveal choroidal thickness decreased from 461 ± 57 at baseline to 369 ± 75 at the final visit (P < 0.001). Reduced-fluence PDT appears as an effective treatment for chronic CSC cases associated with SRD and fovea-involving PED.

  8. Autoradiographical studies on the localization of metallothionein in proximal tubular cells of the rat kidney

    International Nuclear Information System (INIS)

    Murakami, M.; Tsukuba Univ., Sakura, Ibaraki; Tohyama, C.; Sano, K.; Kawamura, R.; Kubota, K.

    1983-01-01

    The renal distribution of 125 I-labelled metallothionein ( 125 I-MT), administered as a tracer dose to female Wistar rats, has been investigated by light and electron microscopical autoradiography. 125 I-MT was absorbed rapidly and 80% of the administered dose was observed in the kidney within 60 min after dosing. At 30 min, a high density of silver grains due to 125 I, was observed by light microscopy in the convoluted proximal tubules. Electron microscopical autoradiography showed that silver grains were located in large apical vacuoles and cytoplasmic bodies (heterolysosomes) of the endocytotic system in the apical or middle regions of the cells lining convoluted proximal tubules. The results suggest that endocytotic systems are associated with 125 I-MT absorption by epithelial cells lining the renal convoluted proximal tubules. The apparent inconsistency on the distribution pattern of silver grains due to 109 Cd-labelled MT and 125 I-labelled MT in these is also discussed. (orig.)

  9. Adaptative evolution of metallothionein 3 in the Cd/Zn hyperaccumulator Thlaspi caerulescens

    Energy Technology Data Exchange (ETDEWEB)

    Roosens, N.H.; Bernard, C.; Verbruggen, N. [Lab. de Physiologie et Genetique Moleculaire des Plantes, Univ. Libre de Bruxelles, Brussels (Belgium); Leplae, R. [Service de Conformation des Macromolecules Biologiques et Bioinformatique, Univ. Libre de Bruxelles, Brussels (Belgium)

    2005-04-01

    A functional screening in yeast allowed to identify various cDNAs from the Cd/Zn hyper-accumulator Thlaspi caerulescens. TcMT3 displayed high identity with its closest homologue in Arabidopsis thaliana but variation in its Cys residues. Functional analysis in yeast supported a higher binding capacity for Cu, but not for Cd or Zn, of TcMT3 compared to AtMT3. Expression analysis in plants indicated that metallothionein 3 (MT3) like all the other T. caerulescens genes from the screen studied is overexpressed in all studied populations of T. caerulescens compared to A. thaliana. TcMT3 was induced by Cu, but not by Cd. Moreover significant variation in expression within T. caerulescens populations that have contrasting tolerance and accumulation capacities indicated a possible local adaptation of MT3. (orig.)

  10. Metallothioneins, Unconventional Proteins from Unconventional Animals: A Long Journey from Nematodes to Mammals

    Directory of Open Access Journals (Sweden)

    Gloria Isani

    2014-04-01

    Full Text Available Metallothioneins (MTs are ubiquitous low molecular weight cysteine-rich proteins characterized by high affinity for d10 electron configuration metals, including essential (Zn and Cu and non-essential (Cd and Hg trace elements. The biological role of these ancient and well-conserved multifunctional proteins has been debated since MTs were first discovered in 1957. Their main hypothesized functions are: (1 homeostasis of Zn and Cu; (2 detoxification of Cd, and Hg; and (3 free radical scavenging. This review will focus on MTs in unconventional animals, those not traditionally studied in veterinary medicine but of increasing interest in this field of research. Living in different environments, these animals represent an incredible source of physiological and biochemical adaptations still partly unexplored. The study of metal-MT interactions is of great interest for clinicians and researchers working in veterinary medicine, food quality and endangered species conservation.

  11. Effect of gamma irradiation, culture conditions and media composition on metallothionein production by Bacillus pantothenticus

    International Nuclear Information System (INIS)

    Tawfik, Z.S.; Swailam, H.M.; EL-Sonbaty, S.M.; Sayed, M.A.

    2010-01-01

    Metallothioneins (MTs) are cystine rich proteins found in all living organisms and play important roles as a radical scavenger and in metal homeostasis. Their optimum culture conditions and media composition of B. pantothenticuszn and B.pantothenticuscu were 1.5 g/L maltose and 1.5 g/l lactose as media carbon sources respectively, 48 hrs incubation period, 35 degree C, ph 8, 200 r.p.m. agitation speed, 26 g/L ammonium dihydrogen orthophosphate as nitrogen source, 0.5 g/L cysteine, 6% of 2.5x107 c.f.u./ml. inoculum size and exposure to a level dose of 4 kGy of gamma radiation. All the previous parameters increased the production of MT by B. pantothenticuszn and B.pantothenticuscu strains 12 and 10 times, respectively compared to the parent strains

  12. Metallothionein responses in the Asiatic clam (Corbicula fluminea) after exposure to trivalent arsenic.

    Science.gov (United States)

    Diniz, Mário S; Santos, Hugo M; Costa, Pedro M; Peres, Isabel; Costa, Maria H; Capelo, José L

    2007-01-01

    The main objective of this work was to evaluate arsenic effects on metallothionein (MT) induction by exposing a freshwater Asiatic clam (Corbicula fluminea) to different concentrations of this metalloid. The presence of MT-like proteins was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared with a standard rabbit MT. In addition, the polarographic response showed good correspondence between standard MT and MT-like curves from C. fluminea, allowing MT quantification. The results show that clams exposed to different concentrations of arsenic are able to induce significant levels of MTs. Although variability was found in MT induction, significant differences in MT levels were found after 28 days of exposure in all treatments in comparison with the controls, suggesting that exposure to arsenic induced MT-like proteins in C. fluminea.

  13. A Determination of Metallothionein in Larvae of Freshwater Midges (Chironomus riparius Using Brdicka Reaction

    Directory of Open Access Journals (Sweden)

    Rene Kizek

    2008-07-01

    Full Text Available Among wide spectrum of biomolecules induced by various stress factors low molecular mass protein called metallothionein (MT is suitable for assessment of the heavy metal environmental pollution. The aim of this work was to determine the metallothionein and total thiols content in larvae of freshwater midges (Chironomus riparius sampled from laboratory exposure to cadmium(II ions and from field studies using differential pulse voltammetry Brdicka reaction. Unique electrochemical instrument, stationary electrochemical analyser Autolab coupled with autosampler, was utilized for the analysis of the samples. The detection limit for MT was evaluated as 5 nM. The larvae exposed to two doses (50 ng/g or 50 μg/g of cadmium(II ions for fifteen days under laboratory controlled conditions were at the end of the exposure killed, homogenized and analysed. MT content in control samples was 1.2 μM, in larvae exposed to 50 ng Cd/g it was 2.0 μM and in larvae exposed to 50 μg Cd/g 2.9 μM. Moreover at field study chironomid larvae as well as sediment samples have been collected from eight field sites with different levels of pollution by heavy. The metals content (chromium, nickel, copper, zinc, arsenic, molybdenum, cadmium, tin and lead in the sediment and or MT content in the chironomid larvae were determined by inductively coupled plasma mass spectrometry or Brdicka reaction, respectively.

  14. Estimating the Impact of Reducing Under-Nutrition on the Tuberculosis Epidemic in the Central Eastern States of India: A Dynamic Modeling Study.

    Directory of Open Access Journals (Sweden)

    Olivia Oxlade

    Full Text Available Tuberculosis (TB and under-nutrition are widespread in many low and middle-income countries. Momentum to prioritize under-nutrition has been growing at an international level, as demonstrated by the "Scaling Up Nutrition" movement. Low body mass index is an important risk factor for developing TB disease. The objective of this study was to project future trends in TB related outcomes under different scenarios for reducing under-nutrition in the adult population in the Central Eastern states of India.A compartmental TB transmission model stratified by body mass index was parameterized using national and regional data from India. We compared TB related mortality and incidence under several scenarios that represented a range of policies and programs designed to reduce the prevalence of under-nutrition, based on the experience and observed trends in similar countries.The modeled nutrition intervention scenarios brought about reductions in TB incidence and TB related mortality in the Central Eastern Indian states ranging from 43% to 71% and 40% to 68% respectively, relative to the scenario of no nutritional intervention. Modest reductions in under-nutrition averted 4.8 (95% UR 0.5, 17.1 million TB cases and 1.6 (95% UR 0.5, 5.2 million TB related deaths over a period of 20 years of intervention, relative to the scenario of no nutritional intervention. Complete elimination of under-nutrition in the Central Eastern states averted 9.4 (95% UR 1.5, 30.6 million TB cases and 3.2 (95% UR 0.7-, 10.1 million TB related deaths, relative to the scenario of no nutritional intervention.Our study suggests that intervening on under-nutrition could have a substantial impact on TB incidence and mortality in areas with high prevalence of under-nutrition, even if only small gains in under-nutrition can be achieved. Focusing on under-nutrition may be an effective way to reduce both rates of TB and other diseases associated with under-nutrition.

  15. Barley metallothioneins

    DEFF Research Database (Denmark)

    Hegelund, Josefine Nymark; Schiller, Michaela; Kichey, Thomas

    2012-01-01

    and cadmium (Cd) in MT4, which was not the case for MT3. When complementary DNAs from barley MTs were expressed in Cu- or Cd-sensitive yeast mutants, MT3 provided a much stronger complementation than did MT4. We conclude that MT3 may play a housekeeping role in metal homeostasis, while MT4 may function in Zn...... storage in developing and mature grains. The localization of MT4 and its discrimination against Cd make it an ideal candidate for future biofortification strategies directed toward increasing food and feed Zn concentrations....

  16. An In Vivo Rabbit Model for the Evaluation of Antimicrobial Peripherally Inserted Central Catheter to Reduce Microbial Migration and Colonization as Compared to an Uncoated PICC

    Directory of Open Access Journals (Sweden)

    Nicholas D. Allan

    2012-01-01

    Full Text Available Infection is the leading complication associated with intravascular devices, and these infections develop when a catheter becomes colonized by microorganisms. To combat this issue, medical device manufacturers seek to provide healthcare facilities with antimicrobial medical devices to prevent or reduce the colonization. In order to adequately evaluate these devices, an in vivo model is required to accurately assess the performance of the antimicrobial devices in a clinical setting. The model presented herein was designed to provide a simulation of the subcutaneous tunnel environment to evaluate the ability of an antimicrobial peripherally inserted central catheter (PICC, coated with chlorhexidine based technology, to reduce microbial migration and colonization compared to an uncoated PICC. Three samples of control, uncoated PICCs and three samples of coated PICCs were surgically tunneled into the backs of female New Zealand White rabbits. The insertion sites were then challenged with Staphylococcus aureus at the time of implantation. Animals were evaluated out to thirty days and sacrificed. Complete en bloc dissection and evaluation of the catheter and surrounding tissue demonstrated that the chlorhexidine coated catheter was able to significantly reduce microbial colonization and prevent microbial migration as compared to the standard, un-treated catheter.

  17. Comparative Efficacy of Antimicrobial Central Venous Catheters in Reducing Catheter-Related Bloodstream Infections in Adults: Abridged Cochrane Systematic Review and Network Meta-Analysis.

    Science.gov (United States)

    Chong, Huey Yi; Lai, Nai Ming; Apisarnthanarak, Anucha; Chaiyakunapruk, Nathorn

    2017-05-15

    The efficacy of antimicrobial central venous catheters (CVCs) remains questionable. In this network meta-analysis, we aimed to assess the comparative efficacy of antimicrobial CVC impregnations in reducing catheter-related infections in adults. We searched 4 electronic databases (Medline, the Cochrane Central Register of Controlled Trials, Embase, CINAHL) and internet sources for randomized controlled trials, ongoing clinical trials, and unpublished studies up to August 2016. Studies that assessed CVCs with antimicrobial impregnation with nonimpregnated catheters or catheters with another impregnation were included. Primary outcomes were clinically diagnosed sepsis, catheter-related bloodstream infection (CRBSI), and all-cause mortality. We performed a network meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI). Sixty studies with 17255 catheters were included. The effects of 14 impregnations were investigated. Both CRBSI and catheter colonization were the most commonly evaluated outcomes. Silver-impregnated CVCs significantly reduced clinically diagnosed sepsis compared with silver-impregnated cuffs (RR, 0.54 [95% CI, .29-.99]). When compared to no impregnation, significant CRBSI reduction was associated with minocycline-rifampicin (RR, 0.29 [95% CI, .16-.52]) and silver (RR, 0.57 [95% CI, .38-.86]) impregnations. No impregnations significantly reduced all-cause mortality. For catheter colonization, significant decreases were shown by miconazole-rifampicin (RR, 0.14 [95% CI, .05-.36]), 5-fluorouracil (RR, 0.34 [95% CI, .14-.82]), and chlorhexidine-silver sulfadiazine (RR, 0.60 [95% CI, .50-.72]) impregnations compared with no impregnation. None of the studies evaluated antibiotic/antiseptic resistance as the outcome. Current evidence suggests that the minocycline-rifampicin-impregnated CVC appears to be the most effective in preventing CRBSI. However, its overall benefits in reducing clinical sepsis and mortality remain uncertain

  18. Protective effects of protein transduction domain-metallothionein fusion proteins against hypoxia- and oxidative stress-induced apoptosis in an ischemia/reperfusion rat model.

    Science.gov (United States)

    Lim, Kwang Suk; Cha, Min-Ji; Kim, Jang Kyoung; Park, Eun Jeong; Chae, Ji-Won; Rhim, Taiyoun; Hwang, Ki-Chul; Kim, Yong-Hee

    2013-08-10

    Ischemic heart diseases caused by insufficient oxygen supply to the cardiac muscle require pharmaceutical agents for the prevention of the progress and recurrence. Metallothionein (MT) has a potential as a protein therapeutic for the treatment of this disease due to its anti-oxidative effects under stressful conditions. In spite of its therapeutic potential, efficient delivery systems need to be developed to overcome limitations such as low transduction efficiency, instability and short half-life in the body. To enhance intra-cellular transduction efficiency, Tat sequence as a protein transduction domain (PTD) was fused with MT in a recombinant method. Anti-apoptotic and anti-oxidative effects of Tat-MT fusion protein were evaluated under hyperglycemia and hypoxia stress conditions in cultured H9c2 cells. Recovery of cardiac functions by anti-apoptotic and anti-fibrotic effects of Tat-MT was confirmed in an ischemia/reperfusion (I/R) rat myocardial infarction model. Tat-MT fusion protein effectively protected H9c2 cells under stressful conditions by reducing intracellular ROS production and inhibiting caspase-3 activation. Tat-MT fusion protein inhibited apoptosis, reduced fibrosis area and enhanced cardiac functions in I/R. Tat-MT fusion protein could be a promising therapeutic for the treatment of ischemic heart diseases. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Histamine activates p38 MAP kinase and alters local lamellipodia dynamics, reducing endothelial barrier integrity and eliciting central movement of actin fibers

    Science.gov (United States)

    Adderley, Shaquria P.; Lawrence, Curtis; Madonia, Eyong; Olubadewo, Joseph O.

    2015-01-01

    The role of the actin cytoskeleton in endothelial barrier function has been debated for nearly four decades. Our previous investigation revealed spontaneous local lamellipodia in confluent endothelial monolayers that appear to increase overlap at intercellular junctions. We tested the hypothesis that the barrier-disrupting agent histamine would reduce local lamellipodia protrusions and investigated the potential involvement of p38 mitogen-activated protein (MAP) kinase activation and actin stress fiber formation. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) expressing green fluorescent protein-actin were studied using time-lapse fluorescence microscopy. The protrusion and withdrawal characteristics of local lamellipodia were assessed before and after addition of histamine. Changes in barrier function were determined using electrical cell-substrate impedance sensing. Histamine initially decreased barrier function, lamellipodia protrusion frequency, and lamellipodia protrusion distance. A longer time for lamellipodia withdrawal and reduced withdrawal distance and velocity accompanied barrier recovery. After barrier recovery, a significant number of cortical fibers migrated centrally, eventually resembling actin stress fibers. The p38 MAP kinase inhibitor SB203580 attenuated the histamine-induced decreases in barrier function and lamellipodia protrusion frequency. SB203580 also inhibited the histamine-induced decreases in withdrawal distance and velocity, and the subsequent actin fiber migration. These data suggest that histamine can reduce local lamellipodia protrusion activity through activation of p38 MAP kinase. The findings also suggest that local lamellipodia have a role in maintaining endothelial barrier integrity. Furthermore, we provide evidence that actin stress fiber formation may be a reaction to, rather than a cause of, reduced endothelial barrier integrity. PMID:25948734

  20. Investigation of the Antioxidant Properties of Metallothionein in Transgenic Tobacco Plants using Voltammetry at a Carbon Paste Electrode

    Czech Academy of Sciences Publication Activity Database

    Shetivska, V.; Adam, V.; Prášek, J.; Macek, Tomáš; Macková, M.; Havel, L.; Dioplan, V.; Zehnálek, J.; Hubálek, J.; Kižek, R.

    2011-01-01

    Roč. 6, č. 7 (2011), s. 2869-2883 ISSN 1452-3981 Grant - others:GA ČR(CZ) GA522/07/0692; GA ČR(CZ) GA102/08/1546 Institutional research plan: CEZ:AV0Z40550506 Keywords : square wave voltammetry * carbon paste electrode * DNA * metallothionein Subject RIV: CG - Electrochemistry Impact factor: 3.729, year: 2011

  1. Papillomavirus infection of roe deer in the Czech Republic and fibropapilloma-associated levels of metallothionein, zinc, and oxidative stress

    OpenAIRE

    Král, Jiří; Banďouchová, Hana; Brichta, Jiří; Kovacova, Veronika; Ondráček, Karel; Osičková, Jitka; Hrubá, Hana; Hutařová, Zdeňka; Komínková, Markéta; Cernei, Natalia Vladimirovna; Konečná, Marie; Tmejová, Kateřina; Zítka, Ondřej; Adam, Vojtěch; Kízek, René

    2015-01-01

    The present study aimed at the aetiological diagnosis of skin tumours of roe deer (Capreolus capreolus) in the Czech Republic. A total of 33 roe deer specimens showing skin masses were sampled for histopathology, virus detection and identification using polymerase chain reaction (PCR) and deoxyribonucleic acid sequence (DNA) analysis, and to investigate fibropapilloma-associated levels of metallothionein, zinc and oxidative stress in 2012 and 2013. Ticks (Ixodes ricinus) and deer keds (Lipopt...

  2. Utilizing od adsorptive transfer stripping technique Brdicka reaction for determination of metallothioneins level in melanoma cells, blood serum and tissues

    Czech Academy of Sciences Publication Activity Database

    Křížková, S.; Fabrik, I.; Adam, V.; Kukačka, J.; Průša, R.; Chavis, G. J.; Trnková, L.; Strnádel, Ján; Horák, Vratislav; Kizek, R.

    2008-01-01

    Roč. 8, - (2008), s. 3106-3122 ISSN 1424-8220 R&D Projects: GA AV ČR IAA600450601; GA ČR(CZ) GA524/04/0102 Grant - others:GA AV ČR(CZ) IAA401990701 Institutional research plan: CEZ:AV0Z50450515 Keywords : metallothionein * protein * tumour marker Subject RIV: FD - Oncology ; Hematology Impact factor: 1.870, year: 2008

  3. Expression of the copper metallothionein CUPI from Saccharomyces cerevisiae in the cyanobacterium Synechococcus R2-PIM8(smtA).

    Science.gov (United States)

    McCormick, P M; Cannon, G C; Heinhorst, S

    1999-03-01

    The coding sequence for Saccharomyces cerevisiae copper metallothionein (CUPI), the protein responsible for enhanced sequestration of Cu2+ in yeast, was placed under the control of an inducible synthetic Escherichia coli promoter in the cyanobacterial vector pTrcIK. Strain R2-PIM8(smtA) of Synechococcus sp. PCC 7942 was transformed with the resulting construct pMcK2, and the yeast CUPI gene was integrated into its genome via homologous recombination. The pMcK2 plasmid directed the synthesis of a protein product of the expected size in an in vitro E. coli transcription/translation system. In the transgenic cyanobacteria, the integrated CUPI gene was transcribed and produced a protein product with the expected metallothionein characteristics, as determined by 109Cd2+ binding assays. At this level of expression, the yeast metallothionein, although functional, did not increase the tolerance range of the transgenic Synechococcus to Cu2+ or Cd2+ beyond that of the untransformed R2-PIM8(smtA).

  4. Zn, Cu, Cd and Hg binding to metallothioneins in harbour porpoises Phocoena phocoena from the southern North Sea

    Directory of Open Access Journals (Sweden)

    Jauniaux Thierry

    2006-02-01

    Full Text Available Abstract Background Harbour porpoises Phocoena phocoena from the southern North Sea are known to display high levels of Zn and Hg in their tissues linked to their nutritional status (emaciation. The question arises regarding a potential role of metallothioneins (MTs with regard to these high metal levels. In the present study, metallothionein detection and associated Zn, Cd, Cu and Hg concentrations were investigated in the liver and kidney of 14 harbour porpoises collected along the Belgian coast. Results Metallothioneins seemed to play a key role in essential metal homeostasis, as they were shown to bind 50% of the total hepatic Zn and 36% of the total hepatic Cu concentrations. Renal MTs also participated in Cd detoxification, as they were shown to bind 56% of the total renal Cd. Hg was mainly found in the insoluble fraction of both liver and kidney. Concomitant increases in total Zn concentration and Zn bound to MTs were observed in the liver, whereas Zn concentration bound to high molecular weight proteins remained constant. Cu, Zn and Cd were accumulated preferentially in the MT fraction and their content in this fraction increased with the amount in the hepatocytosol. Conclusion MTs have a key role in Zn and Cu homeostasis in harbour porpoises. We demonstrated that increasing hepatic Zn concentration led to an increase in Zn linked to MTs, suggesting that these small proteins take over the Zn overload linked to the poor body condition of debilitated harbour porpoises.

  5. Differential expression of metallothionein type-2 homologues in leaves and roots of Black pepper (Piper nigrum L

    Directory of Open Access Journals (Sweden)

    Susan M. Alex

    2008-01-01

    Full Text Available Black pepper (Piper nigrum L., member of the family Piperaceae is indigenous to India and is one of the most widely used spices in the world. In this paper we report the results of our attempts to identify a set of genes differentially expressed in the leaves of Piper nigrum, which could facilitate targeted engineering of this valuable crop. A PCR-based Suppression Subtractive Hybridization (SSH technique was used to generate a leaf-specific subtracted cDNA library of Piper nigrum. A tester population of leaf cDNA was subtracted with a root derived driver cDNA. The efficiency of subtraction was confirmed by PCR analysis using the housekeeping gene actin. On sequence analysis, almost 30% of the clones showed homology to metallothionein type-2 gene. The predominance of metallothionein transcripts in the leaf was further confirmed using Real-Time PCR analyses and Northern blot. The possible role of metallothionein type-2 homologues in the leaf is discussed along with the feasibility of using SSH technique for identification of more number of tissue-specific genes from Piper nigrum.

  6. Evaluation of fluralaner and afoxolaner treatments to control flea populations, reduce pruritus and minimize dermatologic lesions in naturally infested dogs in private residences in west central Florida USA.

    Science.gov (United States)

    Dryden, Michael W; Canfield, Michael S; Kalosy, Kimberly; Smith, Amber; Crevoiserat, Lisa; McGrady, Jennifer C; Foley, Kaitlin M; Green, Kathryn; Tebaldi, Chantelle; Smith, Vicki; Bennett, Tashina; Heaney, Kathleen; Math, Lisa; Royal, Christine; Sun, Fangshi

    2016-06-28

    A study was conducted to evaluate and compare the effectiveness of two different oral flea and tick products to control flea infestations, reduce pruritus and minimize dermatologic lesions over a 12 week period on naturally infested dogs in west central FL USA. Thirty-four dogs with natural flea infestations living in 17 homes were treated once with a fluralaner chew on study day 0. Another 27 dogs living in 17 different homes were treated orally with an afoxolaner chewable on day 0, once between days 28-30 and once again between days 54-60. All products were administered according to label directions by study investigators. Flea populations on pets were assessed using visual area counts and premise flea infestations were assessed using intermittent-light flea traps on days 0, 7, 14, 21, and once between days 28-30, 40-45, 54-60 and 82-86. Dermatologic assessments were conducted on day 0 and once monthly. Pruritus assessments were conducted by owners throughout the study. No concurrent treatments for existing skin disease (antibiotics, anti-inflammatories, anti-fungals) were allowed. Following the first administration of fluralaner or afoxolaner, flea populations on pets were reduced by 99.0 % and 99.3 %, respectively within 7 days. Flea populations on the fluralaner treated dogs were 0 (100 % efficacy) on days 54-60 and 82-86 after the administration of a single dose on day 0. Administration of 3 monthly doses of afoxolaner reduced flea populations by 100 % on days 82-86. Flea numbers in indoor-premises were markedly reduced in both treatment groups by days 82-86, with 100 % and 98.9 % reductions in flea trap counts in the fluralaner and afoxolaner treatment groups, respectively. Marked improvement was observed in FAD lesion scoring, Atopic Dermatitis lesions scoring (CADESI-4) and pruritus scores with both formulations. In a clinical field investigation conducted during the summer of 2015 in subtropical Florida, a single administration of an oral

  7. Evaluation of sarolaner and spinosad oral treatments to eliminate fleas, reduce dermatologic lesions and minimize pruritus in naturally infested dogs in west Central Florida, USA.

    Science.gov (United States)

    Dryden, Michael W; Canfield, Michael S; Niedfeldt, Emily; Kinnon, Amanda; Kalosy, Kimberly; Smith, Amber; Foley, Kaitlin M; Smith, Vicki; Bress, Todd S; Smith, Nicole; Endrizzi, Mike; Login, Joyce

    2017-08-17

    An in-home investigation of naturally flea infested dogs was conducted in West Central Florida, USA to evaluate and compare the effectiveness of two different oral flea adulticides to control flea infestations, minimize dermatologic lesions and reduce pruritus over an 8-week period. Twenty-nine dogs living in 19 homes and another 26 dogs residing in 16 different homes were orally administered either a sarolaner or spinosad chewable, respectively on day 0 and once between days 28-30. Products were administered by study personnel according to label directions. Flea populations on dogs were estimated using visual area counts and flea infestations in the indoor premises were assessed using intermittent-light flea traps on days 0, 7, 14, 21 and once between days 28-30, 40-45, and 56-60. Assessments of dermatologic lesions were conducted monthly during the study and severity of pruritus was evaluated throughout the study on the same schedule as flea counts were conducted. Concurrent treatments for existing skin disease were not allowed. The administration of sarolaner or spinosad reduced flea populations on dogs by 99.0% and 97.3%, respectively within 7 days. Flea infestations on the sarolaner- and spinosad-treated dogs were reduced by > 99% at every counting period from day 14 post-treatment through the end of the 8-week study. At the end of the study 96.4 and 92.0% of the dogs treated with sarolaner and spinosad, respectively were flea-free. Flea populations in the indoor premises were also markedly reduced the end of the study, with 100 and 99.8% reductions in flea trap counts in the sarolaner and spinosad treatment groups, respectively. FAD lesion scores, atopic dermatitis lesions scores (CADESI-4) and pruritus severity scores were also markedly improved with both formulations. An in-home clinical field study conducted during the summer of 2016 in subtropical Florida demonstrated that two-monthly administrations of either sarolaner or spinosad chewables almost

  8. Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    Nourani MR

    2011-05-01

    Full Text Available Mohammad Reza Nourani1, Majid Ebrahimi1, Mehryar Habibi Roudkenar3, Ensieh Vahedi1, Mostafa Ghanei1, Abbas Ali Imani Fooladi21Chemical Injury Research Center; 2Microbial Product Research Center, Baqiyatallah University of Medical Sciences; 3Research Center, Iranian Blood Transfusion Organization, Tehran, IranBackground: Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran–Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that this disorder is strongly associated with oxidative stress due to excessive production of harmful reactive substances and decreased levels of endogenous antioxidants. Metallothioneins (MTs are a group of low molecular weight sulfhydryl-rich intracellular proteins, and several isoforms have been identified in humans. MT-1A is an inducible and important MT isoform, which is transcriptionally activated by a variety of stress stimuli, such as free radicals.Methods: MT-1 mRNA expression and protein levels in endobronchial biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control cases were evaluated by semiquantitative reverse transcriptase polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry.Results: mRNA- MT-1A expression levels in sulfur mustard-exposed patients were upregulated compared with normal samples. Protein expression was also markedly higher in controls than in sulfur mustard-exposed patients.Conclusion: Upregulation of MT-1A mRNA in patients who have been exposed to sulfur mustard seems to be due to oxidative stress, which is induced in an attempt to ameliorate this

  9. Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Xia; Zhou, Shanshan [The First Hospital of Jilin University, Changchun, 130021 (China); KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202 (United States); Zheng, Yang, E-mail: zhengyang@jlu.edu.cn [The First Hospital of Jilin University, Changchun, 130021 (China); Tan, Yi [KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202 (United States); Chinese–American Research Institute for Diabetic Complications, Wenzhou Medical College School of Pharmacy, Wenzhou, 325035 (China); Kong, Maiying [Department of Bioinformatics and Biostatistics, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40202 (United States); Wang, Bo [KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202 (United States); Department of Pathology, Inner Mongolia Forestry General Hospital, Yakeshi, 022150 (China); Feng, Wenke [Department of Medicine, School of Medicine, University of Louisville, Louisville, 40202 (United States); Epstein, Paul N. [KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202 (United States); Cai, Jun, E-mail: j0cai002@louisville.edu [KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202 (United States); Cai, Lu [KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202 (United States); Chinese–American Research Institute for Diabetic Complications, Wenzhou Medical College School of Pharmacy, Wenzhou, 325035 (China); Department of Medicine, School of Medicine, University of Louisville, Louisville, 40202 (United States)

    2014-05-15

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (IH) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in OSA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult OSA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O{sub 2}/8% O{sub 2} F{sub I}O{sub 2} (30 episodes per hour) with 20 s at the nadir F{sub I}O{sub 2} for 12 h a day during daylight. IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic IH induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes. - Highlights: • The effect of intermittent hypoxia (IH) on cardiac metallothionein (MT) • Cardiac MT expression was up-regulated in response to 3-day IH. • Exposure to 4- or 8-week IH downregulated cardiac MT expression. • Overexpression of cardiac MT protects from IH-induced cardiac damage. • Global deletion of MT gene made the heart more sensitive to IH damage.

  10. Field transplantation of the freshwater bivalve Corbicula fluminea along a polymetallic contamination gradient (River Lot, France): 2. Metallothionein response to metal exposure

    Energy Technology Data Exchange (ETDEWEB)

    Baudrimont, M.; Andres, S.; Metivaud, J.; Lapaquellerie, Y.; Ribeyre, F.; Maillet, N.; Latouche, C.; Boudou, A.

    1999-11-01

    Specimens of the Asiatic clam Corbicula fluminea were transplanted from a clean lacustrine site to four stations along a polymetallic pollution gradient in the river Lot, France, downstream from an old Zn ore treatment facility (see Part 1). From April to September 1996, the authors studied Cd and Zn bioaccumulation and the metallothionein-like metal-binding protein (MT) concentrations by subsampling the ages at t = 0, 21, 49, 85, 120, and 150 d. Marked differences were observed among the four stations. At the most polluted station Riou-Mort, MT concentrations did not increase despite very rapid metal accumulation; all mollusks died between days 49 and 85, suggesting that the metal detoxification mechanisms were overwhelmed at this station. At the next station downstream, the final levels of bioaccumulated metal after 150 d were as high as those at the Riou-Mort station, but in this case the MT concentrations also increased progressively with positive correlations between MT and metal concentrations; no mortality was observed, but a significant growth inhibition was revealed in comparison to the reference site, with a lack of correlation between MT and reduced growth. Subcellular metal partitioning, as determined by size-exclusion chromatography, revealed that most of the Cd was sequestered by MT. In contrast, most of the Zn was bound to low molecular weight proteins, the MT fraction representing only 12% of cytosolic zn. These data show the marked role of MT toward Cd bioaccumulation and toxic effects on this freshwater bivalve species.

  11. Alterations of tissue metallothionein and vitellogenin concentrations in tropical cup oysters (Saccostrea sp.) following short-term (96 h) exposure to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Moncaleano-Niño, Angela M.; Barrios-Latorre, Sergio A.; Poloche-Hernández, Javier F. [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Becquet, Vanessa; Huet, Valérie [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Villamil, Luisa [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Thomas-Guyon, Hélène [Littoral Environnement et Sociétés (LIENSs) – UMR 7266, CNRS-Université de La Rochelle, Bâtiment ILE 2, rue Olympe de Gouges, 17 000 La Rochelle (France); Ahrens, Michael J., E-mail: michael.ahrens@utadeo.edu.co [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia); Luna-Acosta, Andrea [Department of Biological Sciences, Universidad de Bogota Jorge Tadeo Lozano, Carrera 4 No. 22-61, Bogota (Colombia)

    2017-04-15

    Highlights: • The cup oyster Saccostrea sp. is present in Santa Marta, Colombian Caribbean. • 96 h exposure of oysters to Cd increased metallothionein concentrations in digestive glands up to 2-fold. • 96 h exposure of oysters to Cd decreased vitellogenin concentrations in gonads up to 6-fold. • Metallothionein and vitellogenin tissue concentrations correlated with whole tissue Cd concentrations. • Significant changes in metallothionein and vitellogenin levels were only evident at Cd concentrations above 100 μg/L. - Abstract: Metallothioneins and vitellogenins are low molecular weight proteins that have been used widely in environmental monitoring as biomarkers of exposure and damage to metals and estrogenic compounds, respectively. In the present study, the responses of metallothionein and vitellogenin tissue concentrations were measured following acute (96 h) aqueous exposures to cadmium in Saccostrea sp., a tropical cup oyster native to the Western Pacific Ocean that has recently established itself in the Caribbean Sea. Adult oysters (1.5–5.0 cm shell length) collected from the municipal marina of Santa Marta, Colombia (Caribbean Sea) and acclimated for 5 days in the laboratory, were exposed to Cd at five concentrations (0, 1, 10, 100 and 1000 μg/L) and their tissues (gills, digestive gland and adductor muscle) were analyzed in pools of 5 individuals (3 replicates per concentration). Metallothioneins in digestive glands of oysters exposed to Cd concentrations ≥ 100 μg/L showed a significant increase, from 8.0 to 14.8 μg MT/mg total protein, whereas metallothionein concentrations in gills increased to lesser extent, and no differences were observed in adductor muscle. Metallothionein concentrations in digestive gland and gills correlated directly with whole soft tissue Cd concentrations (ranging from 2 to 297 μg/g dw Cd). Vitellogenin in homogenates of oyster gonad tissue, after 96 h of exposure to 1000 μg/L Cd, were significantly lower (0

  12. Task failure during exercise to exhaustion in normoxia and hypoxia is due to reduced muscle activation caused by central mechanisms while muscle metaboreflex does not limit performance

    Directory of Open Access Journals (Sweden)

    Rafael eTorres-Peralta

    2016-01-01

    Full Text Available To determine whether task failure during incremental exercise to exhaustion (IE is principally due to reduced neural drive and increased metaboreflex activation eleven men (22±2 years performed a 10s control isokinetic sprint (IS; 80 rpm after a short warm-up. This was immediately followed by an IE in normoxia (Nx, PIO2:143 mmHg and hypoxia (Hyp, PIO2:73 mmHg in random order, separated by a 120 min resting period. At exhaustion, the circulation of both legs was occluded instantaneously (300 mmHg during 10 or 60s to impede recovery and increase metaboreflex activation. This was immediately followed by an IS with open circulation. Electromyographic recordings were obtained from the vastus medialis and lateralis. Muscle biopsies and blood gases were obtained in separate experiments. During the last 10s of the IE, pulmonary ventilation, VO2, power output and muscle activation were lower in hypoxia than in normoxia, while pedaling rate was similar. Compared to the control sprint, performance (IS-Wpeak was reduced to a greater extent after the IE-Nx (11% lower P<0.05 than IE-Hyp. The root mean square (EMGRMS was reduced by 38 and 27% during IS performed after IE-Nx and IE-Hyp, respectively (Nx vs. Hyp: P<0.05. Post-ischemia IS-EMGRMS values were higher than during the last 10s of IE. Sprint exercise mean (IS-MPF and median (IS-MdPF power frequencies, and burst duration, were more reduced after IE-Nx than IE-Hyp (P<0.05. Despite increased muscle lactate accumulation, acidification, and metaboreflex activation from 10 to 60s of ischemia, IS-Wmean (+23% and burst duration (+10% increased, while IS-EMGRMS decreased (-24%, P<0.05, with IS-MPF and IS-MdPF remaining unchanged. In conclusion, close to task failure, muscle activation is lower in hypoxia than in normoxia. Task failure is predominantly caused by central mechanisms, which recover to great extent within one minute even when the legs remain ischemic. There is dissociation between the recovery of

  13. Identification of ATF-7 and the insulin signaling pathway in the regulation of metallothionein in C. elegans suggests roles in aging and reactive oxygen species

    Science.gov (United States)

    McElwee, Matthew K.; Freedman, Jonathan H.

    2017-01-01

    It has been proposed that aging results from the lifelong accumulation of intracellular damage via reactions with reactive oxygen species (ROS). Metallothioneins are conserved cysteine-rich proteins that function as efficient ROS scavengers and may affect longevity. To better understand mechanisms controlling metallothionein expression, the regulatory factors and pathways that controlled cadmium-inducible transcription of the C. elegans metallothionein gene, mtl-1, were identified. The transcription factor ATF-7 was identified in both ethylmethanesulfonate mutagenesis and candidate gene screens. PMK-1 and members of the insulin signaling pathway, PDK-1 and AKT-1/2, were also identified as mtl-1 regulators. Genetic and previous results support a model for the regulation of cadmium-inducible mtl-1 transcription based on the derepression of the constitutively active transcription factor ELT-2. In addition, knockdown of the mammalian homologs of PDK1 and ATF7 in HEK293 cells resulted in changes in metallothionein expression, suggesting that this pathway was evolutionarily conserved. The insulin signaling pathway is known to influence the aging process; however, various factors responsible for affecting the aging phenotype are unknown. Identification of portions of the insulin signaling pathway as regulators of metallothionein expression supports the hypothesis that longevity is affected by the expression of this efficient ROS scavenger. PMID:28632756

  14. Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease.

    Science.gov (United States)

    Spencer, Brian; Potkar, Rewati; Metcalf, Jeff; Thrin, Ivy; Adame, Anthony; Rockenstein, Edward; Masliah, Eliezer

    2016-01-22

    Neuropeptide Y (NPY) is one of the most abundant protein transmitters in the central nervous system with roles in a variety of biological functions including: food intake, cardiovascular regulation, cognition, seizure activity, circadian rhythms, and neurogenesis. Reduced NPY and NPY receptor expression is associated with numerous neurodegenerative disorders including Alzheimer disease (AD). To determine whether replacement of NPY could ameliorate some of the neurodegenerative and behavioral pathology associated with AD, we generated a lentiviral vector expressing NPY fused to a brain transport peptide (apoB) for widespread CNS delivery in an APP-transgenic (tg) mouse model of AD. The recombinant NPY-apoB effectively reversed neurodegenerative pathology and behavioral deficits although it had no effect on accumulation of Aβ. The subgranular zone of the hippocampus showed a significant increase in proliferation of neural precursor cells without further differentiation into neurons. The neuroprotective and neurogenic effects of NPY-apoB appeared to involve signaling via ERK and Akt through the NPY R1 and NPY R2 receptors. Thus, widespread CNS-targeted delivery of NPY appears to be effective at reversing the neuronal and glial pathology associated with Aβ accumulation while also increasing NPC proliferation. Overall, increased delivery of NPY to the CNS for AD might be an effective therapy especially if combined with an anti-Aβ therapeutic. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. A silver-alginate-coated dressing to reduce peripherally inserted central catheter (PICC) infections in NICU patients: a pilot randomized controlled trial.

    Science.gov (United States)

    Hill, M L; Baldwin, L; Slaughter, J C; Walsh, W F; Weitkamp, J-H

    2010-07-01

    Our aim was to evaluate the safety of a silver-alginate-containing dressing to reduce peripherally inserted central catheter (PICC) infections in neonatal intensive care unit (NICU) patients. Patients were randomized 3:1 to receive a patch containing silver, alginate and maltodextrin or standard of care. Patches were placed under the regular transparent retention dressing at the PICC exit site at insertion and were replaced with every dressing change at least every 2 weeks until PICC discontinuation. All study infants were monitored for adverse skin reactions. A total of 100 infants were followed up for 1922 person-days, including 75 subjects with 89 PICCs who received the patch. The median birth weight (1330 g) and median gestational age (30 weeks) was lower in the patch group when compared with the controls (P=0.001 and 0.005, respectively). Study patients received the patch with their PICC at a median age of 5 days; the patch stayed in place for a median of 13 days. We noted no adverse skin reactions and found no evidence that the patch alters the microbiology of PICC-associated infections. This pilot trial suggests that silver-alginate-coated dressings are skin safe and their inclusion in future trials aimed at reduction of PICC-associated bloodstream infections in the NICU should be considered.

  16. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    Science.gov (United States)

    Roel, María; Rubiolo, Juan A.; Ternon, Eva; Thomas, Olivier P.; Vieytes, Mercedes R.; Botana, Luis M.

    2015-01-01

    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. PMID:26225985

  17. Seasonal and spatial comparison of metallothioneins in frog Rana ridibunda from feral populations.

    Science.gov (United States)

    Falfushynska, Halina I; Romanchuk, Liliya D; Stolyar, Oksana B

    2008-11-01

    The aim of this study was to elucidate the seasonal and spatial regularity of the properties of metallothioneins (MTs) from the liver and kidney of the frog Rana ridibunda in rural (R) and urban (U) sites in Western Ukraine. This allowed examination of their possibility use in biomonitoring of environmental quality. The positive correlation for Zn and negative correlation for Cu were reflected between their content in the liver and MTs. The content of MTs was higher in summer compared to other seasons and also at the U site compare to the R site. MTs had been comprised of two chromatographic forms (MT-1 and MT-2/MT-2a), with lesser and variable MT-2/2a in frogs from the U site, particularly in the kidney. MTs accumulated about 75% of Cd in the liver. In summary, the ability MTs to elevate content as a stress response, together with the sensitivity of MT-2, may be explored to understand the health status of the frog in each season, reflecting the higher overall anthropogenic impact at the U site.

  18. Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?

    Science.gov (United States)

    Heger, Zbynek; Rodrigo, Miguel Angel Merlos; Krizkova, Sona; Ruttkay-Nedecky, Branislav; Zalewska, Marta; Del Pozo, Elena Maria Planells; Pelfrene, Aurelie; Pourrut, Bertrand; Stiborova, Marie; Eckschlager, Tomas; Emri, Gabriella; Kizek, Rene; Adam, Vojtech

    2016-01-01

    Cardiotoxicity is a serious complication of anticancer therapy by anthracycline antibiotics. Except for intercalation into DNA/RNA structure, inhibition of DNA-topoisomerase and histone eviction from chromatin, the main mechanism of their action is iron-mediated formation of various forms of free radicals, which leads to irreversible damage to cancer cells. The most serious adverse effect of anthracyclines is, thus, cardiomyopathy leading to congestive heart failure, which is caused by the same mechanisms. Here, we briefly summarize the basic types of free radicals formed by anthracyclines and the main processes how to scavenge them. From these, the main attention is paid to metallothioneins. These low-molecular cysteine-rich proteins are introduced and their functions and properties are reviewed. Further, their role in detoxification of metals and drugs is discussed. Based on these beneficial roles, their use as a new therapeutic agent against oxidative stress and for cardioprotection is critically evaluated with respect to their ability to increase chemoresistance against some types of commonly used cytostatics.

  19. Metallothionein is induced and trace element balance changed in target organs of a common viral infection

    International Nuclear Information System (INIS)

    Ilbaeck, Nils-Gunnar; Glynn, Anders W.; Wikberg, Lotta; Netzel, Elvy; Lindh, Ulf

    2004-01-01

    In experimental studies on the common human coxsackievirus B type 3 (CB3) infection, administered cadmium (Cd) is known to accumulate in the liver and kidneys. CB3 adapted to Balb/c mice was used to study whether infection affects the Cd-binding protein, metallothionein (MT) and if this alters the normal physiological trace element balance in the liver, kidney, spleen and brain. On day 3 of infection, degradation of liver proteins (44%, P<0.01) occurred, whereas in the spleen, protein increased (63%, P<0.05). The infection increased MT five-fold (P<0.01) in liver and kidneys, and in spleen by 34% (P<0.05). A redistribution of Cd and copper (Cu) from the liver to the kidney was associated with this increase in MT, resulting in an increased (P<0.01) kidney/liver ratio for both elements. The infection increased the zinc (Zn) concentration more in the kidney than in the liver, but the kidney/liver ratio was not significantly affected. Results show that MT is increased in several organs during the early phase of infection and is associated with redistribution of both essential and non-essential trace elements. This may be a normal response in common infections that could adversely influence the pathogenesis when the host is concomitantly exposed to potentially toxic trace elements, even at levels in the physiological range

  20. Metallothioneins and trace elements dyshomeostasis induced by exposure to gasoline vapor in mice.

    Science.gov (United States)

    Grebić, Damir; Tota, Marin; Jakovac, Hrvoje; Broznić, Dalibor; Marinić, Jelena; Canadi, Gordana; Milin, Cedomila; Radosević-Stasić, Biserka

    2014-03-01

    To investigate the effects of air pollution related with the gasoline/petrochemical industry the expression of metallothionein I (MT-I) mRNA and tissue metals were analyzed in organs of mice, exposed to gasoline (G) vapor in laboratory conditions. Control groups consisted of intact mice and of those exposed in the metabolic chamber to fresh air. The data obtained by RT-PCR and inductively coupled plasma spectrometry have shown that exposure to G vapor leads to upregulation of MT-I mRNA in organs that receive a strong respiratory and olfactory input or participate in gasoline degradation and elimination (lungs, brain, kidney and liver). Besides, in the brain and in the lungs, kidney and liver a decreased tissue content of Zn²⁺ or Cu²⁺ and Mg²⁺ was found (p<0.001). Some of these changes were obtained also in mice closed in the metabolic chamber, pointing to the involvement of stress-induced mechanisms in the transcriptional regulation of MTs.

  1. The influence of biological and environmental factors on metallothionein concentration in the blood.

    Science.gov (United States)

    Kowalska, Katarzyna; Bizoń, Anna; Zalewska, Marta; Milnerowicz, Halina

    2015-01-01

    The concentration of metallothionein (MT), a low-molecular-weight protein, is regulated by many factors, primarily metals (zinc, cadmium, copper), cytokines, glucocorticoides and free radicals. These factors are determined by such aspects of human biology as gender, pregnancy and age, as well as by environmental factors including the use of oral contraceptives and cigarette smoking, all which may affect MT levels in the body. The aim of this study was to investigate the influence of these biological and environmental factors on MT concentrations in erythrocyte lysate and in plasma. MT concentrations were determined by a two-step direct enzyme-linked immunosorbent assay. Evaluation of exposure to cigarette smoking was performed by checking cotinine levels in the plasma of subjects. The studies showed higher MT concentrations in both the erythrocyte lysate and plasma of women when compared to men. Furthermore, pregnancy causes an increase of MT concentration in plasma, while oral contraceptives cause an elevated concentration of MT in erythrocyte lysate. Age impacts plasma MT concentrations in men, whereas it does not affect concentrations of MT in erythrocyte lysate. Copyright © 2014 Elsevier GmbH. All rights reserved.

  2. Localization and Spectroscopic Analysis of the Cu(I Binding Site in Wheat Metallothionein Ec-1

    Directory of Open Access Journals (Sweden)

    Katsiaryna Tarasava

    2016-03-01

    Full Text Available The early cysteine-labeled metallothionein (MT from Triticum aestivum (common wheat, denoted Ec-1, features two structurally well-defined domains, γ and βE, coordinating two and four Zn(II ions, respectively. While the protein is currently assumed to function mainly in zinc homeostasis, a low amount of copper ions was also recently detected in a native Ec-1 sample. To evaluate the observed copper binding in more detail, the recombinant Zn6Ec-1 form was exposed to different amounts of Cu(I ions and the resulting species characterized with spectroscopic methods. Data reveal that the first Cu(I equivalent coordinates exclusively to the N-terminal γ-domain of the protein and replaces one Zn(II ion. To analyze the ability of the γ-domain for coordination of monovalent metal ions in more detail, the γ-Ec-1 peptide fragment was incubated with increasing amounts of Cu(I and the process monitored with UV–VIS, circular dichroism, and luminescence spectroscopy. Closely similar spectra are observed regardless if the apo- or the metal ion-loaded and, hence, pre-folded forms, were used for the titration experiments with Cu(I. The results indicate that low amounts of Cu(I ions displace the two metal ions subsequently and stoichiometrically, despite the different coordination geometry requirements of Cu(I and Zn(II.

  3. Characterization of a Type 1 Metallothionein Gene from the Stresses-Tolerant Plant Ziziphus jujuba

    Directory of Open Access Journals (Sweden)

    Mingxia Yang

    2015-07-01

    Full Text Available Plant metallothioneins (MTs are a family of low molecular weight, cysteine-rich, and metal-binding proteins, which play an important role in the detoxification of heavy metal ions, osmotic stresses, and hormone treatment. Sequence analysis revealed that the open-reading frame (ORF of ZjMT was 225 bp, which encodes a protein composed of 75 amino acid residues with a calculated molecular mass of 7.376 kDa and a predicated isoelectric point (pI of 4.83. ZjMT belongs to the type I MT, which consists of two highly conserved cysteine-rich terminal domains linked by a cysteine free region. Our studies showed that ZjMT was primarily localized in the cytoplasm and the nucleus of cells and ZjMT expression was up-regulated by NaCl, CdCl2 and polyethylene glycol (PEG treatments. Constitutive expression of ZjMT in wild type Arabidopsis plants enhanced their tolerance to NaCl stress during the germination stage. Compared with the wild type, transgenic plants accumulate more Cd2+ in root, but less in leaf, suggesting that ZjMT may have a function in Cd2+ retension in roots and, therefore, decrease the toxicity of Cd2+.

  4. Bioadsorption of cadmium ion by cell surface-engineered yeasts displaying metallothionein and hexa-His

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, K.; Ueda, M. [Lab. of Applied Biological Chemistry, Kyoto Univ., Yoshida, Kyoto (Japan)

    2004-07-01

    The Cd{sup 2+}-chelating abilities of yeast metallothionein (YMT) and hexa-His displayed on the yeast-cell surface were compared. Display of YMT and hexa-His by {alpha}-agglutinin-based cell-surface engineering was confirmed by immunofluorescent labeling. Surface-engineered yeast cells with YMT and hexa-His fused in tandem showed superior cell-surface adsorption and recovery of Cd{sup 2+} under EDTA treatment on the cell surface than hexa-His-displaying cells. YMT was demonstrated to be more effective than hexa-His for the adsorption of Cd{sup 2+}. Yeast cells displaying YMT and/or hexa-His exhibited a higher potential for the adsorption of Cd{sup 2+} than Escherichia coli cells displaying these molecules. In order to investigate the effect of the displayed YMT and hexa-His on sensitivity to toxic Cd{sup 2+}, growth in Cd{sup 2+}-containing liquid medium was monitored. Unlike hexa-His-displaying cells, cells displaying YMT and hexa-His fused in tandem induced resistance to Cd{sup 2+} through active and enhanced adsorption of toxic Cd{sup 2+}. These results indicate that YMT-displaying yeast cells are a unique bioadsorbent with a functional chelating ability superior to that of E. coli. (orig.)

  5. Cloning metallothionein gene in Zacco platypus and its potential as an exposure biomarker against cadmium.

    Science.gov (United States)

    Lee, Sangwoo; Kim, Cheolmin; Kim, Jungkon; Kim, Woo-Keun; Shin, Hyun Suk; Lim, Eun-Suk; Lee, Jin Wuk; Kim, Sunmi; Kim, Ki-Tae; Lee, Sung-Kyu; Choi, Cheol Young; Choi, Kyungho

    2015-07-01

    Zacco platypus, pale chub, is an indigenous freshwater fish of East Asia including Korea and has many useful characteristics as indicator species for water pollution. While utility of Z. platypus as an experimental species has been recognized, genetic-level information is very limited and warrants extensive research. Metallothionein (MT) is widely used and well-known biomarker for heavy metal exposure in many experimental species. In the present study, we cloned MT in Z. platypus and evaluated its utility as a biomarker for metal exposure. For this purpose, we sequenced complete complementary DNA (cDNA) of MT in Z. platypus and carried out phylogenetic analysis with its sequences. The transcription-level responses of MT gene following the exposure to CdCl2 were also assessed to validate the utility of this gene as an exposure biomarker. Analysis of cDNA sequence of MT gene demonstrated high conformity with those of other fish. MT messenger RNA (mRNA) expression and enzymatic MT content significantly increased following CdCl2 exposure in a concentration-dependent manner. The level of CdCl2 that resulted in significant MT changes in Z. platypus was within the range that was reported from other fish. The MT gene of Z. platypus sequenced in the present study can be used as a useful biomarker for heavy metal exposure in the aquatic environment of Korea and other countries where this freshwater fish species represents the ecosystem.

  6. Differential hepatic metal and metallothionein levels in three Feral fish species along a metal pollution gradient.

    Science.gov (United States)

    Bervoets, Lieven; Knapen, Dries; De Jonge, Maarten; Van Campenhout, Karen; Blust, Ronny

    2013-01-01

    The accumulation of cadmium, copper and zinc and the induction of metallothioneins (MT) in liver of three freshwater fish species was studied. Gudgeon (Gobio gobio), roach (Rutilus rutilus) and perch (Perca fluviatilis) were captured at 6 sampling sites along a cadmium and zinc gradient and one reference site in a tributary of the Scheldt River in Flanders (Belgium). At each site up to 10 individuals per species were collected and analyzed on their general condition factor (K), hepatosomatic index (HSI) and gonadosomatic index (GSI). From each individual fish the liver was dissected and analyzed on Cd, Cu and Zn and MT-content. Although not all species were present at each site, hepatic Cd and Zn levels generally followed the pollution gradient and highest levels were measured in perch, followed by roach and gudgeon. Nevertheless also an effect of site was observed on this order. MT-levels appeared to be the highest in gudgeon although differences with the other species were not very pronounced and depended on the site. Significant relationships were found between hepatic zinc accumulation and MT levels. For each species the ratio MT(theoretical)/ MT(measured) was calculated, which gives an indication of the relative capacity to induce MTs and thus immobilize the metals. Perch had the lowest capacity in inducing MTs (highest ratio). Relationships between hepatic metal levels and fish condition indices were absent or very weak.

  7. Metallothionein bioconjugates as delivery vehicles for bismuth-212 alpha particle therapy

    International Nuclear Information System (INIS)

    Macklis, R.M.; Morris, C.; Humm, J.; Hines, J.; Atcher, R.

    1991-01-01

    Metallothioneins (MTHs) are small cysteine-rich polypeptides that binds cationic metals at physiologic pH ranges through noncovalent -SH ligand interactions. Some leucine-rich renal MTHs have a particular avidity for bismuth. The authors have examined the ability of MTHs to selectively incorporate Bi-212, a short-lived high-energy alpha particle emitter currently under exploration as a potential therapeutic radiolabel for use in molecularly targeted cancer therapy. They find that under physiologic conditions, MTH will selectively incorporate Bi-212 after incubation with an equilibrium mixture of its upstream and downstream parents. The MTH moieties may be linked to tumor-binding macromolecules such as antibodies via thiolation reactions using SPDP, and the resultant Bismuth-avid molecules may be used either as primary delivery vehicles for the Bi-212 or as part of a 2-step release-and-catch isotope localization system in which the MTH-antibody conjugate is pre-localized at the tumor site and the radiometal is then administered and chelated in situ. They present the chemistry, dosimetry and potential clinical applications of this system

  8. Metallothioneins and trace metals in the dogwhelk Nucella lapillus (L.) collected from Icelandic coasts

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Kenneth M.Y. [Sandgeroi Marine Centre, Garovegi 1, 245 Sandgeroi (Iceland)]. E-mail: kmyleung@hkucc.hku.hk; Dewhurst, Rachel E. [School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX (United Kingdom); Halldorsson, Halldor [Sandgeroi Marine Centre, Garovegi 1, 245 Sandgeroi (Iceland); Institute of Biology, University of Iceland, Sturlugata 7, 101 Reykjavik (Iceland); Svavarsson, Joerundur [Sandgeroi Marine Centre, Garovegi 1, 245 Sandgeroi (Iceland); Institute of Biology, University of Iceland, Sturlugata 7, 101 Reykjavik (Iceland)

    2005-07-01

    Different sizes of the dogwhelk Nucella lapillus were collected from eight locations along the southwest and north coasts of Iceland. Concentrations of total metallothioneins (MTs) and heavy metals (Cd, Cu, Cr, Mn, Ni, and Zn) were analysed using the silver saturation method and inductively coupled plasma-atomic emission spectrometry. The level of tributyltin (TBT) contamination was also assessed using imposex indices, the vas deferens stage index (VDSI) and relative penis size index (RPSI). Gufunes N. lapillus presented the highest values of VDSI (4.0) and RPSI (11.1), followed by Grenivik individuals (VDSI = 3.0; RPSI = 0.9), while the Strandakirkja population showed the lowest VDSI (0.3) and zero RPSI. At a standardised size (0.25 g dry soft-body weight), Grenivik N. lapillus exhibited significantly higher concentrations of all metals whereas overall metal concentrations were significantly lower in individuals from Strandakirkja and Garoskagi compared to other study sites. Partial correlation analyses with size correction indicated that MT concentrations were better correlated with Cd and Cu concentrations than with other metals. At the standard size, the pattern of MT concentrations in N. lapillus from different sites was, however, very different from those of metal profiles. Such discrepancies between the patterns of MT and metals in N. lapillus might be explained by the fact that MT induction could be influenced by various factors such as temperature, dietary metal intake, growth rate and co-existence of other MT-inducing chemicals.

  9. Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival.

    Science.gov (United States)

    Theocharis, Stamatios; Klijanienko, Jerzy; Giaginis, Constantinos; Rodriguez, Jose; Jouffroy, Thomas; Girod, Angelique; Point, Daniel; Tsourouflis, Gerasimos; Sastre-Garau, Xavier

    2011-09-01

    Metallothionein (MT) has been implicated in several aspects of cancer pathobiology, such as differentiation, proliferation, apoptosis and invasion. The aim of the present study was to evaluate the clinical significance of MT expression in mobile tongue squamous cell carcinoma (SCC). MT protein expression was assessed immunohistochemically on 49 mobile tongue SCC specimens, and was analysed in relation to clinicopathological characteristics, and overall and disease-free patient survival. All of the examined mobile tongue SCC cases showed MT positivity in tumour cells; however, neither MT overexpression nor staining intensity was significantly associated with clinicopathological parameters. MT cellular distribution was significantly associated with histopathological grade of differentiation and depth of invasion (P = 0.0188 and P = 0.0484, respectively). MT staining intensity was identified as a significant predictor of overall patient survival at both univariate (P = 0.0377) and multivariate (P = 0.0472) levels. Twenty-seven (55.10%) of the examined SCC cases showed MT positivity in squamous tongue epithelium adjacent to the tumour, the MT positivity being correlated with depth of invasion (P = 0.0281), vascular invasion (P = 0.0194), and the existence of lymph node metastases (P = 0.0194). MT may be implicated in the development and progression of mobile tongue SCC and could be considered as a useful clinical marker for patient management and prognosis. © 2011 Blackwell Publishing Limited.

  10. Expression of metallothionein type 2 and 3 genes in Prosopis glandulosa leaves treated with copper.

    Science.gov (United States)

    Michel-Lopez, C; Zapata-Pérez, O; González-Mendoza, D; Grimaldo-Juarez, O; Ceceña-Duran, C; Tzintzun-Camacho, O

    2017-03-16

    For a better understanding of the strategies that are used by Prosopis glandulosa in heavy metal tolerance, the present study evaluated the gene expression of three metallothioneins (MTs; PgMt2-1, PgMt2, and PgMt3) in plants exposed to sub-lethal concentrations of copper. The PgMt2-1, PgMt2, and PgMt3 sequences were homologous to the MT type 2 (isoform 1), Mt2, and Mt3 sequences of other plant species found in GenBank. A reverse transcriptase-polymerase chain reaction showed that treatment with 100 mM Cu 2+ induced a significant increase in PgMt2 and PgMt3 expression during the first 4 h of exposure compared to that of PgMt2-1. However, after 8 h of exposure, the expression levels of PgMt2 and PgMt3 were significantly lower than those of PgMt2-1. PgMt transcript levels only increased significantly during the first hour after exposure to copper, suggesting that PgMts could play a key role in the plant's detoxification mechanism. However, additional studies are required to confirm MTs as a mechanism of heavy metal tolerance and accumulation in this species.

  11. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Directory of Open Access Journals (Sweden)

    Alicja M Kmiecik

    Full Text Available It has been recently found that metallothionein-3 (MT3 enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001. Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC, nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  12. Metallothionein-3 Increases Triple-Negative Breast Cancer Cell Invasiveness via Induction of Metalloproteinase Expression.

    Science.gov (United States)

    Kmiecik, Alicja M; Pula, Bartosz; Suchanski, Jaroslaw; Olbromski, Mateusz; Gomulkiewicz, Agnieszka; Owczarek, Tomasz; Kruczak, Anna; Ambicka, Aleksandra; Rys, Janusz; Ugorski, Maciej; Podhorska-Okolow, Marzena; Dziegiel, Piotr

    2015-01-01

    It has been recently found that metallothionein-3 (MT3) enhances the invasiveness and tumorigenesis of prostate cancer cells. This finding is in contrast to those of earlier studies, which indicated that overexpression of MT3 in breast cancer and prostate cancer cell lines inhibits their growth in vitro. Therefore, to clarify the role of MT3 in breast cancer progression, we analyzed the effect of MT3-overexpression on proliferation, invasiveness, migration, and tumorigenesis of breast cancer MDA-MB-231/BO2 cells. It was found that MDA-MB-231/BO2 cells overexpressing MT3 were characterized by increased invasiveness in vitro, compared to the control cells. Interestingly, this increased invasiveness correlated with a highly increased concentration of MMP3 in the culture supernatants (p<0.0001). Our data suggest that MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. These experimental results, obtained using triple-negative MDA-MB-231/BO2 cells, were further supported by clinical data. It was found that, in triple-negative breast cancer (TNBC), nuclear MT3 immunoreactivity in cancer cells tended to be associated with patients' shorter disease-specific survival, suggesting that nuclear MT3 expression may be a potential marker of poor prognosis of triple-negative TNBC cases.

  13. Screening of Cd tolerant genotypes and isolation of metallothionein genes in alfalfa (Medicago sativa L.).

    Science.gov (United States)

    Wang, Xiaojuan; Song, Yu; Ma, Yanhua; Zhuo, Renying; Jin, Liang

    2011-12-01

    In order to evaluate Cd tolerance in wide-ranging sources of alfalfa (Medicago sativa) and to identify Cd tolerant genotypes which may potentially be useful for restoring Cd-contaminated environments, thirty-six accessions of alfalfa were screened under hydroponic culture. Our results showed that the relative root growth rate varied from 0.48 to 1.0, which indicated that different alfalfa accessions had various responses to Cd stress. The candidate fragments derived from differentially expressed metallothionein (MT) genes were cloned from leaves of two Cd tolerant genotypes, YE and LZ. DNA sequence and the deduced protein sequence showed that MsMT2a and MsMT2b had high similarity to those in leguminous plants. DDRT-PCR analysis showed that MsMT2a expressed in both YE and LZ plants under control and Cd stress treatment, but MsMT2b only expressed under Cd stress treatment. This suggested that MsMT2a was universally expressed in leaves of alfalfa but expression of MsMT2b was Cadmium (Cd) inducible. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. The Balance between Life and Death of Cells: Roles of Metallothioneins

    Directory of Open Access Journals (Sweden)

    Allan Evald Nielsen

    2006-01-01

    Full Text Available Metallothionein (MT is a highly conserved, low-molecular-weight, cysteine-rich protein that occurs in 4 isoforms (MT-I to MT-IV, of which MT-I+II are the major and best characterized proteins. This review will focus on mammalian MT-I+II and their functional impact upon cellular survival and death, as seen in two rather contrasting pathological conditions: Neurodegeneration and neoplasms. MT-I+II have analogous functions including: 1 Antioxidant scavenging of reactive oxygen species (ROS; 2 Cytoprotection against degeneration and apoptosis; 3 Stimulation of cell growth and repair including angiogenesis/revascularization, activation of stem/progenitor cells, and neuroregeneration. Thereby, MT-I+II mediate neuroprotection, CNS restoration and clinical recovery during neurodegenerative disorders. Due to the promotion of cell survival, increased MT-I+II levels have been associated with poor tumor prognosis, although the data are less clear and direct causative roles of MT-I+II in oncogenesis remain to be identifi ed. The MT-I+II molecular mechanisms of actions are not fully elucidated. However, their role in metal ion homeostasis might be fundamental in controlling Zn-dependent transcription factors, protein synthesis, cellular energy levels/metabolism and cell redox state. Here, the neuroprotective and regenerative functions of MT-I+II are reviewed, and the presumed link to oncogenesis is critically perused.

  15. Detection of Metallothionein in Javanese Medaka (Oryzias javanicus, Using a scFv-Immobilized Protein Chip

    Directory of Open Access Journals (Sweden)

    Euiyeon Lee

    2018-04-01

    Full Text Available Environmental pollution by various industrial chemicals and biological agents poses serious risks to human health. Especially, marine contamination by potentially toxic elements (PTEs has become a global concern in recent years. Many efforts have been undertaken to monitor the PTE contamination of the aquatic environment. However, there are few approaches available to assess the PTE exposure of aquatic organisms. In this research, we developed a strategy to evaluate the heavy metal exposure of marine organisms, by measuring the expression levels of metallothionein protein derived from Oryzias javanicus (OjaMT. OjaMT is a biomarker of heavy metal exposure because the expression level increases upon heavy metal exposure. The developed assay is based on a real-time, label-free surface plasmon resonance (SPR measurement. Anti-OjaMT antibody and anti-OjaMT single-chain fragment of variable region (scFv were used as detection probes. Two types of SPR sensor chips were fabricated, by immobilizing antibody or Cys3-tagged scFv (scFv-Cys3 in a controlled orientation and were tested for in situ label-free OjaMT detection. Compared to the antibody-presenting sensor chips, the scFv-presenting sensor chips showed improved performance, displaying enhanced sensitivity and enabling semi-quantitative detection. The portable SPR system combined with scFv-immobilized sensor chips is expected to provide an excellent point-of-care testing system that can monitor target biomarkers in real time.

  16. Immunoelectron microscopic studies on metallothionein induction in Nile cichlid due to heavy metal stress

    International Nuclear Information System (INIS)

    Chatterjee, S.; Singh, L.; Das, T.K.; Mukhopadhyay, S.K.

    2010-01-01

    Heavy metals are important environmental pollutants and many of them are toxic even in low concentrations. The uncontrolled input of such elements in milieu is undesirable because once accumulated, are hard to remove. The release of toxic metals in biologically available forms by human activity may damage or alter both natural and man-made ecosystems. The cellular adaptation to toxicity of metals is one of the important factors for organisms living in the stressful conditions. The major type of cellular effect at the cytoplasmic level involves binding of metals through specific metal binding proteins. One of these metalloproteins is metallothionein (MT), MT is a low-molecular-weight (6-7 kDa) cysteine rich protein ubiquitous in the animal kingdom and can bind with essential (Cu + and Zn 2+ ) and nonessential (Cd 2+ , Hg 2+ and Ag + ) metals with a high thermodynamic and low kinetic stability. Again, the induction of MT by other heavy metals such as Cr, Mn and Pb was also reported by several workers

  17. Distribution of metallothionein I + II and vesicular zinc in the developing central nervous system: correlative study in the rat

    DEFF Research Database (Denmark)

    Penkowa, M; Nielsen, H; Hidalgo, J

    1999-01-01

    and ventricles in the brainstem. By contrast, astrocytes were widespread throughout the developing brain. In embryonic and neonatal brain, MT I + IIir astrocytes were almost selectively observed in the septum and fascia dentate hilus (hi) of the hippocampus. With increasing postnatal age, they also occurred...

  18. An Effect of Cadmium and Lead Ions on Escherichia coli with the Cloned Gene for Metallothionein (MT-3) Revealed by Electrochemistry

    International Nuclear Information System (INIS)

    Adam, Vojtech; Chudobova, Dagmar; Tmejova, Katerina; Cihalova, Kristyna; Krizkova, Sona; Guran, Roman; Kominkova, Marketa; Zurek, Michal; Kremplova, Monika; Jimenez, Ana Maria Jimenez; Konecna, Marie

    2014-01-01

    This study was focused on the application of electrochemical methods for studying of bacterial strains Escherichia coli and Escherichia coli expressing human metallothionein gene (MT-3) before and after the application of cadmium and/or lead ions in four concentrations (25, 50, 75 and 150 μM). Bacterial strains Escherichia coli and Escherichia coli expressing human metallothionein gene (MT-3) were used like model organisms for studying of metals influence to metallothionein expression. Metallothionein was isolated using fast protein liquid chromatography and quantified by electrochemical methods. The occurrence of metallothionein in E.coli was confirmed by gel electrophoresis by the presence of the bands at 15 (MT dimer) and 22 kDa (MT trimer). The changes in electrochemical records due to the interactions of metallothioneins (MT-3 and MT-2A) with cadmium and lead ions showed decline of Cat2 signal of MT with the increasing interaction time because of metal ions binding to cysteines. Electrochemical determination also revealed that Cd(II) remains in E. coli cells in the higher amount than Pb (II). Opposite situation was found at E. coli–MT-3 strain. The antimicrobial effect of cadmium ions was determined by IC 50 and was statistically calculated as 39.2 and 95.5 μM for E. coli without cloned MT-3 and E. coli carrying MT-3 gene, respectively. High provided concentration IC 50 in strains after lead ions application (352.5 μM for E. coli without cloning and 207.0 μM for E. coli carrying cloned MT-3 gene) indicates lower toxicity of lead ions on bacterial strains compared to the cadmium ions

  19. Manufacturing combustible briquettes from forestry and timber industries` wastes in order to reduce the overexploitation of fuelwood in Central American forests

    Energy Technology Data Exchange (ETDEWEB)

    Ortiz, L.; Gonzalez, E. [Renewable Energies Institute, Soria (Spain)

    1993-12-31

    A serious degradation of Central American forest is currently taking place because of uncontrolled fuelwood overexploitation. As an example, in Guatemala over 40% of forest destruction is caused by this reason. In the meanwhile, waste biomass from the sawmills representing 30 to 50% of total wood volume processed, due to low technological level of the facilities, and having an energetic potential equivalent to their thermal and electric needs is destroyed through uncontrolled burning, thus causing important environmental and landscape impact, since the byproducts are incinerated outdoors on the spot the constant smoke together with the noise level produced by the diesel power generators makes working conditions painful for the large labor force usually operating these sawmills because of low wages in these countries. To help solve this increasing problem, it would be possible to use the waste biomass for the production of electric power, through cogeneration, for sawmill selfuse or selling to the public electric lines, or even manufacturing of fuel briquettes which would have a potential market in countries such as Republica Dominicana, Honduras Guatemala, etc. as a substitute for charcoal and fuelwood, thus permitting a considerable reduction of the environmental degradation and predation suffered by forest areas in these countries. For these reasons, we consider it of interest to study briquetting techniques and their intrinsic problems in depth. For such purpose, we have carried out a series of real scale briquetting experiences with different types of lignocelulosic wastes and mixtures of them under different conditions, aiming to optimize procedure methodology and reduce production expenses, thus making offer increase easier. Manufacturing procedure and analytics developed to carry out the experiences are described in the present document. Main results obtained are summarized, and mathematical, energetic, analytical and economic aspects are discussed as well.

  20. Current irrigation practices in the central United States reduce drought and extreme heat impacts for maize and soybean, but not for wheat.

    Science.gov (United States)

    Zhang, Tianyi; Lin, Xiaomao; Sassenrath, Gretchen F

    2015-03-01

    In this study, we assessed the adaptive effects of irrigation on climatic risks for three crops (maize, soybean, and wheat) at the regional scale from 1981 to 2012 in the Central US. Based on yields of 183 counties for maize, 121 for soybean and 101 for wheat, statistical models were developed for irrigated, rainfed and county-level yields. Results show that irrigation has a statistically significant effect on abating detrimental climate impacts, specifically drought and extreme heat, in maize and soybean but not in wheat. On average, irrigation reduces the negative influences of extreme heat by around 7.2% for maize and 5.0% for soybean yields for each additional 10 degree-days above the optimal temperature for each crop. This is approximately two-thirds of the negative effects of extreme heat under rainfed management. The remaining third of the yield reduction is caused by heat damage that cannot be alleviated by irrigation. No significant differences were detected between county yields and irrigated yields for maize and soybean, suggesting that the existing irrigation practices were reasonably efficient. Efforts to mitigate future climate risks for these two crops should focus on improving the heat sensitivity contributing to the yield losses from heat damage. In contrast, the existing irrigation does not improve the resilience of wheat to climate risks. Both increased temperature and drought were critical to wheat production, which was potentially caused by relatively poor irrigation supplies for wheat. Further enhancement of wheat yield may be possible through improved irrigation management. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Effect of metallothionein 2A gene polymorphism on allele-specific gene expression and metal content in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Krześlak, Anna; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland); Chwatko, Grażyna [Department of Environmental Chemistry, University of Łódź, Pomorska 163, 90-236 Łódź (Poland); Jóźwiak, Paweł; Szymczyk, Agnieszka [Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland); Wilkosz, Jacek; Różański, Waldemar [2nd Department of Urology, Medical University of Łódź, Pabianicka 62, 93-513 Łódź (Poland); Bryś, Magdalena, E-mail: zreg@biol.uni.lodz.pl [Department of Cytobiochemistry, University of Łódź, Pomorska 141/143, 90-236 Łódź (Poland)

    2013-05-01

    Metallothioneins (MTs) are highly conserved, small molecular weight, cysteine rich proteins. The major physiological functions of metallothioneins include homeostasis of essential metals Zn and Cu and protection against cytotoxicity of heavy metals. The aim of this study was to determine whether there is an association between the − 5 A/G single nucleotide polymorphism (SNP; rs28366003) in core promoter region and expression of metallothionein 2A (MT2A) gene and metal concentration in prostate cancer tissues. MT2A polymorphism was determined by the polymerase chain reaction–restriction fragment length polymorphism technique (PCR–RFLP) using 412 prostate cancer tissue samples. MT2A gene expression analysis was performed by real-time RT-PCR method. A significant association between rs28366003 genotype and MT2A expression level was found. The average mRNA level was found to be lower among minor allele carriers (the risk allele) than average expression among homozygotes for the major allele. Metal levels were analyzed by flamed atomic absorption spectrometer system. Highly statistically significant associations were detected between the SNP and Cd, Zn, Cu and Pb levels. The results of Spearman's rank correlation showed that the expressions of MT2A and Cu, Pb and Ni concentrations were negatively correlated. On the basis of the results obtained in this study, we suggest that SNP polymorphism may affect the MT2A gene expression in prostate and this is associated with some metal accumulation. - Highlights: • MT2A gene expression and metal content in prostate cancer tissues • Association between SNP (rs28366003) and expression of MT2A • Significant associations between the SNP and Cd, Zn, Cu and Pb levels • Negative correlation between MT2A gene expression and Cu, Pb and Ni levels.

  2. Prion protein and its interactions with metal ions (Cu2+, Zn2+, and Cd2+) and metallothionein 3

    OpenAIRE

    Ruttkay - Nedecky, Branislav; Sedlackova, Eliska; Chudobova, Dagmar; Cihalova, Kristyna; Jimenez Jimenez, Ana Maria; Krizkova, Sona; Richtera, Lukas; Adam, Vojtech; Kizek, Rene

    2015-01-01

    The effects of heavy metals (Zn2+, Cu2+, and/or Cd2+) on Escherichia coli expressing either prion (hPrPC ) or metallothionein 3 (MT-3) brain proteins capable of binding these metals were investigated. The expression of hPrPC or MT-3 in E.coli was confirmed using western-blot and dot-blot methods. After analyzing growth curves, we found that bacteria expressing prion protein better tolerated the presence of Zn2+ in comparison with wild-type bacteria and bacteria expressing MT-3. The addition o...

  3. Metallothionein-Like Proteins and Energy Reserve Levels after Ni and Pb Exposure in the Pacific White Prawn Penaeus vannamei

    Directory of Open Access Journals (Sweden)

    Gabriel Nunez-Nogueira

    2010-01-01

    Full Text Available This study analyzed the changes in metallothionein-like proteins (MTLPs and Energy Reserves (ERs in hepatopancreas and abdominal muscle of the white prawn Penaeus vannamei. Realistic metal concentration exposure for 10 days to Ni and Pb in solution revealed that juvenile prawns partially induce MTLP in hepatopancreas after Pb exposure. Ni was distributed equally between soluble and insoluble fractions, while Pb was present only in the insoluble fraction, suggesting different detoxification strategy. No changes in lipids and glycogen concentration were detected under these experimental conditions in both tissues analyzed. MTLP could not be considered as a suitable indicator for lead exposure in hepatopancreas.

  4. Optimization of capillary electrophoresis?inductively coupled plasma mass spectrometry for species analysis of metallothionein-like proteins extracted from liver tissues of Elbe-bream and Roe deer

    Science.gov (United States)

    Pröfrock, Daniel; Prange, Andreas; Schaumlöffel, Dirk; Ruck, Wolfgang

    2003-08-01

    Species analysis of metallothionein-like proteins (MLP) in liver tissues from Elbe-Bream ( Abramis brama L.) and Roe Deer ( Capreolus capreolus L.) using capillary electrophoresis (CE) combined with inductively coupled plasma mass spectrometry detection is described. In order to allow systematic development of the method, commercially available metallothionein (MT) preparations of rabbit liver were used. Optimum separation efficiency was obtained by investigating the influence of parameters such as voltage, capillary temperature, buffer concentration, buffer pH and the use of different buffer systems. Instrumental parameters such as CE capillary position, interface adjustment and contamination problems are also discussed. Separation was performed using uncoated fused silica capillaries with 75 μm i.d. and 70 cm length. The optimum conditions were found to be: Separation voltage 30 kV, positive polarity, capillary temperature 288.15 K and a buffer concentration of 100 mmol l -1 Tricine-NH 3 adjusted to pH 7.2. Sample preparation was performed so as to minimize oxidation and heavy metal contamination of the samples. The high molecular mass protein matrix was reduced by acetonitrile precipitation. For commercial MT preparations the relative standard deviations (R.S.D) in the retention times were 0.9% for MT-1 and 1.9% for MT-2; the R.S.D.'s in the peak areas were less than 6% for MT-1 and 16% for MT-2, respectively. Under optimized conditions the MLPs in the real samples could be separated efficiently in less than 10 min. By comparison with the migration times of commercially available MT preparations, two of the observed peaks could be assigned to MT-1 and MT-2.

  5. Optimization of capillary electrophoresis-inductively coupled plasma mass spectrometry for species analysis of metallothionein-like proteins extracted from liver tissues of Elbe-bream and Roe deer

    Energy Technology Data Exchange (ETDEWEB)

    Proefrock, Daniel; Prange, Andreas E-mail: andreas.prange@gkss.de; Schaumloeffel, Dirk; Ruck, Wolfgang

    2003-08-15

    Species analysis of metallothionein-like proteins (MLP) in liver tissues from Elbe-Bream (Abramis brama L.) and Roe Deer (Capreolus capreolus L.) using capillary electrophoresis (CE) combined with inductively coupled plasma mass spectrometry detection is described. In order to allow systematic development of the method, commercially available metallothionein (MT) preparations of rabbit liver were used. Optimum separation efficiency was obtained by investigating the influence of parameters such as voltage, capillary temperature, buffer concentration, buffer pH and the use of different buffer systems. Instrumental parameters such as CE capillary position, interface adjustment and contamination problems are also discussed. Separation was performed using uncoated fused silica capillaries with 75 {mu}m i.d. and 70 cm length. The optimum conditions were found to be: Separation voltage 30 kV, positive polarity, capillary temperature 288.15 K and a buffer concentration of 100 mmol l{sup -1} Tricine-NH{sub 3} adjusted to pH 7.2. Sample preparation was performed so as to minimize oxidation and heavy metal contamination of the samples. The high molecular mass protein matrix was reduced by acetonitrile precipitation. For commercial MT preparations the relative standard deviations (R.S.D) in the retention times were 0.9% for MT-1 and 1.9% for MT-2; the R.S.D.'s in the peak areas were less than 6% for MT-1 and 16% for MT-2, respectively. Under optimized conditions the MLPs in the real samples could be separated efficiently in less than 10 min. By comparison with the migration times of commercially available MT preparations, two of the observed peaks could be assigned to MT-1 and MT-2.

  6. Optimization of capillary electrophoresis-inductively coupled plasma mass spectrometry for species analysis of metallothionein-like proteins extracted from liver tissues of Elbe-bream and Roe deer

    International Nuclear Information System (INIS)

    Proefrock, Daniel; Prange, Andreas; Schaumloeffel, Dirk; Ruck, Wolfgang

    2003-01-01

    Species analysis of metallothionein-like proteins (MLP) in liver tissues from Elbe-Bream (Abramis brama L.) and Roe Deer (Capreolus capreolus L.) using capillary electrophoresis (CE) combined with inductively coupled plasma mass spectrometry detection is described. In order to allow systematic development of the method, commercially available metallothionein (MT) preparations of rabbit liver were used. Optimum separation efficiency was obtained by investigating the influence of parameters such as voltage, capillary temperature, buffer concentration, buffer pH and the use of different buffer systems. Instrumental parameters such as CE capillary position, interface adjustment and contamination problems are also discussed. Separation was performed using uncoated fused silica capillaries with 75 μm i.d. and 70 cm length. The optimum conditions were found to be: Separation voltage 30 kV, positive polarity, capillary temperature 288.15 K and a buffer concentration of 100 mmol l -1 Tricine-NH 3 adjusted to pH 7.2. Sample preparation was performed so as to minimize oxidation and heavy metal contamination of the samples. The high molecular mass protein matrix was reduced by acetonitrile precipitation. For commercial MT preparations the relative standard deviations (R.S.D) in the retention times were 0.9% for MT-1 and 1.9% for MT-2; the R.S.D.'s in the peak areas were less than 6% for MT-1 and 16% for MT-2, respectively. Under optimized conditions the MLPs in the real samples could be separated efficiently in less than 10 min. By comparison with the migration times of commercially available MT preparations, two of the observed peaks could be assigned to MT-1 and MT-2

  7. Expression analysis of metallothioneins and mineral contents in tomato (Lycopersicon esculentum) under heavy metal stress.

    Science.gov (United States)

    Kısa, Dursun; Öztürk, Lokman; Doker, Serhat; Gökçe, İsa

    2017-04-01

    Heavy metals are considered to be the most important pollutants in the contamination of soils; they adversely affect plant growth and development and cause some physiological and molecular changes. The contamination of agricultural soils by heavy metals has changed the mineral element content of vegetables. Plant metallothioneins (MTs) are thought to have the functional role in heavy metal homeostasis, and they are used as the biomarkers for evaluating environmental pollution. We aimed to evaluate the expression of MT isoforms (MT1, 2, 3 and 4) and some mineral element composition of tomato roots, leaves and fruits exposed to copper and lead. Heavy metal applications increased MT1 and MT2 gene expressions compared to the control in the tissues of tomato. The highest level of MT1 and MT2 transcripts was found in roots and leaves, respectively. The expression of MT3 is induced in roots, leaves and fruits except for Pb treatment in roots. MT4 expression increased in fruits; however, other tissues did not show a clear change. Our results indicated that Cu content was higher than Pb in all tissues of tomato. The lower doses of Cu (10 ppm) increased the content of Mg, Fe, Ca and Mn in roots. Pb generally increased the level of minerals in leaves and fruits, but it decreased Mg, Mn and Fe contents in roots. Both heavy metals not only moved to aerial parts but also caused alterations to mineral element levels. These results show that MT transcripts are regulated by Cu and Pb, and expression pattern changes to MT isoforms and tissue types. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  8. Reactivity of metallothioneins of frog Rana ridibunda treated by copper and zinc ions.

    Science.gov (United States)

    Falfushynska, H I; Romanchuk, L D; Stoliar, O B

    2010-01-01

    The metal-buffering and stress proteins metallothioneins (MTs) of frog are characterised by unusually high content of copper as for vertebrate animals and instability that was shown in our previous studies. They easily lost copper and especially zinc under unfavourable conditions. The aim of this study was to examine the reactivity of SH groups in the MTs from the liver of frog Rana ridibunda after the effect of Cu2+ (0.01 mg/l) and Zn2+ (0.1 mg/l) ions on the organism during 14 days. The alpha- and beta-domains of MTs with molecular weights of about 4 kDa were separated by the size-exclusion chromatography on Sephadex G-50. Unlike higher vertebrates, frogs demonstrated higher reactivity of alpha-domain than beta-domain with the Ellman's reagent (DTNB). The signs of partial oxidations in beta-domain included the creation of by-products with molecular weight about 12 kDa, low reactivity of SH-groups, and typical of -S-S-bonds peculiarities of UV-spectra. The effect of both metal ions on frog provoked the elevation of SH-groups reactivity in a-domain with the appearance of by-product with molecular weight of 16 kDa and its reduction in beta-domain. The incubation of MTs of control animals with 0.5 and 5.0 mM of H2O2 did not affect its chromatographic characteristics. In the frogs loaded by Cu2+ and Zn2+ the effect of 5.0 mM H2O2 on MTs provoked the release of 4 kDa product. So the alpha-domain is responsible for the increased release of metals from injured MTs in frogs, whereas extremely high oxidizability of beta-domain makes its participation in the exchange of metals elusive and provokes the aggregation of MTs.

  9. Characterization of three distinct metallothionein genes of the Ag-hyperaccumulating ectomycorrhizal fungus Amanita strobiliformis.

    Science.gov (United States)

    Hložková, Kateřina; Matěnová, Michaela; Žáčková, Petra; Strnad, Hynek; Hršelová, Hana; Hroudová, Miluše; Kotrba, Pavel

    2016-03-01

    Mechanisms evolved in eukaryotes to handle heavy metals involve cytosolic, metal-binding metallothioneins (MTs). We have previously documented that the sequestration of silver (Ag) in the Ag-hyperaccumulating Amanita strobiliformis is dominated by 34-amino-acid (AA) AsMT1a, 1b, and 1c isoforms. Here we show that in addition to AsMT1a, 1b, and 1c isogenes, the fungus has two other MT genes: AsMT2 encoding a 34-AA AsMT2 similar to MTs known from other species, but unrelated to AsMT1s; AsMT3 coding for a 62-AA AsMT3 that shares substantial identity with as-yet-uncharacterized conserved peptides predicted in agaricomycetes. Transcription of AsMT1s and AsMT3 in the A. strobiliformis mycelium was specifically inducible by treatments with Ag or copper (Cu) and zinc (Zn) or cadmium (Cd), respectively; AsMT2 showed a moderate upregulation in the presence of Cd. Expression of AsMTs in the metal-sensitive Saccharomyces cerevisiae revealed that all AsMTs confer increased Cd tolerance (AsMT3 proved the most effective) and that, unlike AsMT1 and AsMT2, AsMT3 can protect the yeasts against Zn toxicity. The highest level of Cu tolerance was observed with yeasts expressing AsMT1a. Our data indicate that A. strobiliformis can specifically employ different MT genes for functions in the cellular handling of Ag and Cu (AsMT1s) and Zn (AsMT3). Copyright © 2015 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  10. Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanoma.

    Science.gov (United States)

    Weinlich, G; Topar, G; Eisendle, K; Fritsch, P O; Zelger, B

    2007-05-01

    Metallothioneins (MT) are ubiquitous, intracellular small proteins with high affinity for heavy metal ions. Immunohistochemical MT overexpression in paraffin-embedded tissues of patients with primary melanoma is associated with poor prognosis. While sentinel lymph node (SLN) biopsy is an established surgical technique for high-risk melanoma patients with predictive value for progression, the benefit of this procedure for the individual patient's overall survival remains unclear. We examined the role of MT overexpression in comparison with SLN biopsy in melanoma patients as a prognostic marker for progression and survival. One hundred and fifty-eight (158) patients underwent SLN biopsy due to high-risk melanoma. Primary melanoma specimens were investigated by using a monoclonal antibody against MT on routinely fixed, paraffin-embedded tissues. The patients were followed up (median 37 months); the data of disease free survival and overall survival were calculated with a broad panel of statistical analyses. Twenty-eight (18%) out of 158 recruited melanoma patients developed metastases, 17 (11%) patients died due to widespread disease. Kaplan-Meier curves gave significant disadvantages for the MT-positive as well as the SLN-positive group for progression and survival. In the Fisher's exact test and Pearson's chi(2)-test MT overexpression was highly significant for progression, whereas SLN biopsy failed significance. In univariate as well as multivariate Cox regression analysis MT overexpression proved an excellent marker for progression (P=0.007 and P=0.009), although the P-values for survival were not significant. In contrast, while in the univariate analysis SLN biopsy did not show significant results for progression it did for survival, and in the multivariate analysis reached a P-value < 0.05 for both measured endpoints. Results corroborate the validity of MT overexpression in primary melanoma as a useful prognostic marker in melanoma patients. Accuracy is

  11. Characterization of a cDNA encoding metallothionein 3 from cotton (Gossypium hirsutum L.).

    Science.gov (United States)

    Jordan, Robin H; Turley, Rickie B; Defauw, Sherri L; Steele, Mark

    2005-04-01

    A cDNA encoding metallothionein (MT) was isolated from a library constructed with poly A(+) RNA purified from 48 h etiolated cotton (Gossypium hirsutum L.) cotyledons. This cDNA encodes a deduced protein with 63 residues and a molecular weight of 6.3 kDa. The protein has 10 cysteines of which 4 are within the CXXCXCXXXXXC amino-terminus motif and six are within the CXCXXXCXCXXCXC carboxyl-terminus motif characteristic of the type III MT (MT3). The cotton MT3 protein sequence is 76.2, 69.8, 66.7, 60.3 and 33.5% identical to MT3 from Carica papaya, Rubus idaeus, Ribes nigrum, Citrus unshiu, and Gossypium hirsutum type I MT, respectively. A fusion protein was constructed by producing PCR primers for the 5' and 3' ends of the cotton MT3 cDNA and ligating the PCR product inframe at the 3' end of a bacterial glutathione S-transferase (GST) gene in the pGEX3 vector. The 5' PCR primer incorporated a segment of the cotton MT3 noncoding region, resulting in an addition of 9 residues to the MT3 (after Factor Xa digestion site) which increased the size of the expressed protein to 72 residues and 7.6 kDa. Expression of the 7.6 kDa protein in bacteria was confirmed by SDS-PAGE. Induction and accumulation of the GST-MT3 protein began inhibiting bacterial growth after 1 h. Addition of Cu (1 muM to 1 mM), 1 mM cysteine, or 1 mM cystine to the media did not rescue growth. Additionally, this protein was evaluated for its ability to bind Cd, Cu, Ni and Zn in the bacterial expression system. We found that cotton MT3 preferentially binds Cu.

  12. Transcriptional responses of metallothionein gene to different stress factors in Pacific abalone (Haliotis discus hannai).

    Science.gov (United States)

    Lee, Sang Yoon; Nam, Yoon Kwon

    2016-11-01

    A novel metallothionein (MT) gene from the Pacific abalone H. discus hannai was characterized and its mRNA expression patterns (tissue distribution, developmental expression and differential expression in responsive to various in vivo stimulatory treatments) were examined. Abalone MT shares conserved structural features with previously known gastropod orthologs at both genomic (i.e., tripartite organization) and amino acid (conserved Cys motifs) levels. The 5'-flanking regulatory region of abalone MT gene displayed various transcription factor binding motifs particularly including ones related with metal regulation and stress/immune responses. Tissue distribution and basal expression patterns of MT mRNAs indicated a potential association between ovarian MT expression and sexual maturation. Developmental expression pattern suggested the maternal contribution of MT mRNAs to embryonic and early larval developments. Abalone MT mRNAs could be significantly induced by various heavy metals in different tissues (gill, hepatopancreas, muscle and hemocyte) in a tissue- and/or metal-dependent fashion. In addition, the abalone MT gene was highly modulated in responsive to other non-metal, stimulatory treatments such as immune challenge (LPS, polyI:C and bacterial injections), hypoxia (decrease from normoxia 8 ppm-2 ppm), thermal elevation (increase from 20 °C to 30 °C), and xenobiotic exposure (250 ppb of 17α-ethynylestradiol and 0.25 ppb of 2,3,7,8-tetrachlorodibenzodioxin) where differential expression patterns were toward either up- or down-regulation depending on types of stimulations and tissues examined. Taken together, our results highlight that MT is a multifunctional effector playing in wide criteria of cellular pathways especially associated with development and stress responses in this abalone species. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Sulfur mustard induces expression of metallothionein-1A in human airway epithelial cells.

    Science.gov (United States)

    Nourani, Mohammad Reza; Ebrahimi, Majid; Roudkenar, Mehryar Habibi; Vahedi, Ensieh; Ghanei, Mostafa; Imani Fooladi, Abbas Ali

    2011-01-01

    Sulfur mustard can cause several long-term complications in the organs of individuals exposed to this toxic gas, and among these, pulmonary sequelae are the most important. More than 25 years after the Iran-Iraq war, thousands of Iranians are suffering from the chronic respiratory complications of sulfur mustard. Currently, based on several clinical findings, bronchiolitis obliterans is confirmed as the major diagnosis in these patients. Numerous studies have revealed that this disorder is strongly associated with oxidative stress due to excessive production of harmful reactive substances and decreased levels of endogenous antioxidants. Metallothioneins (MTs) are a group of low molecular weight sulfhydryl-rich intra-cellular proteins, and several isoforms have been identified in humans. MT-1A is an inducible and important MT isoform, which is transcriptionally activated by a variety of stress stimuli, such as free radicals. MT-1 mRNA expression and protein levels in endobronchial biopsy samples from 24 sulfur mustard-exposed patients and 15 unexposed control cases were evaluated by semi-quantitative reverse transcriptase polymerase chain reaction, real-time reverse transcriptase polymerase chain reaction, and immunohistochemistry. mRNA- MT-1A expression levels in sulfur mustard-exposed patients were upregulated compared with normal samples. Protein expression was also markedly higher in controls than in sulfur mustard-exposed patients. Upregulation of MT-1A mRNA in patients who have been exposed to sulfur mustard seems to be due to oxidative stress, which is induced in an attempt to ameliorate this harmful situation by reestablishment of homeostasis, but depletion of its protein might be due to secondary consequences of sulfur mustard toxicity, which are as yet not understood.

  14. Cadmium Accumulation and Metallothionein Response in the Freshwater Bivalve Corbicula fluminea Under Hydrodynamic Conditions.

    Science.gov (United States)

    Geng, Nan; Wang, Chao; Wang, Peifang; Qi, Ning; Ren, Lingxiao

    2015-06-01

    Freshwater bivalves such as Corbicula fluminea (Müller) are useful biomonitors for cadmium pollution because they absorb heavy metals and accumulate them in their tissues. We exposed C. fluminea in the laboratory to natural and cadmium (Cd)-spiked sediments below flowing water in order to evaluate the organisms' Cd accumulation and metallothionein (MT) response under hydrodynamic conditions. The accumulation of Cd and the induction of MT in C. fluminea were determined at 0, 1, 3, 6, 10, 16, and 23 days. Hydrodynamic conditions, represented by a water flow rate of 14 or 3.2 cm/s, increased Cd accumulation in the visceral mass, gill, foot, and mantle of C. fluminea in the first 3 or 6 days in the natural sediment. Cd concentrations in the C. fluminea tissues kept increasing over time in the three treatments, and significant differences were observed in Cd accumulation after 6 (visceral mass), 10 (foot) and 16 (gill and mantle) days among the three groups. The MT concentrations were barely affected by hydrodynamic conditions and were significantly linearly related to the Cd concentration in the visceral mass in the natural sediment and binomially related to it in the Cd-spiked sediment. Hydrodynamic conditions enhanced the accumulation of Cd in the soft tissues of C. fluminea, especially in the Cd-spiked sediment, but stronger hydrodynamic forces did not increase Cd accumulation. MT may be considered an indicator for Cd accumulation in C. fluminea under hydrodynamic conditions, but only when the Cd concentrations in the tissue remain below the toxic threshold values.

  15. Metallothionein-I/II null mice are sensitive to chronic oral cadmium-induced nephrotoxicity.

    Science.gov (United States)

    Liu, Y; Liu, J; Habeebu, S M; Waalkes, M P; Klaassen, C D

    2000-09-01

    Chronic exposure to cadmium (Cd) via food and drinking water is a major human health concern. We have previously shown that metallothionein (MT), a metal-binding protein, plays an important role in protecting against Cd toxicity produced by repeated sc injections. However, it is unclear whether MT protects against Cd-induced nephrotoxicity following chronic oral exposure, a route with obvious human relevance. To clarify this issue, MT-I/II knockout (MT-null) and background-matched wild-type (WT) mice were allowed free access to drinking water containing CdCl(2) (30, 100, and 300 ppm Cd), or feed containing CdCl(2) (100 ppm Cd) for 6 months, and the resultant nephrotoxicity was examined. Chronic oral Cd exposure produced a dose-dependent accumulation of Cd in liver and kidney of WT mice, reaching levels up to 50 microg Cd/g tissue. Immunohistological localization of renal MT indicated that chronic oral Cd exposure in WT mice greatly increased MT in the proximal tubules and the medulla, with cellular localization in both the cytoplasm and nuclei. As expected, no MT was detected in kidneys of MT-null mice. After 6 months of Cd exposure, tissue Cd concentrations in MT-null mice were only about one-fifth of that in WT mice. Even though the renal Cd concentrations were much lower in the MT-null mice, they were more sensitive than WT mice to Cd-induced renal injury, as evidenced by more severe nephropathic lesions, increased urinary excretion of gamma-glutamyl-transferase and glucose, and elevated blood urea nitrogen. Six months of Cd exposure to MT-null animals resulted in greater increases in renal caspase-3 activity, an indicator of apoptosis, than to WT mice. In conclusion, this study demonstrates that lack of MT renders MT-null mice vulnerable to Cd-induced nephrotoxicity after chronic oral exposure, the primary route of human Cd exposure.

  16. Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

    International Nuclear Information System (INIS)

    Grider, A. Jr.

    1986-01-01

    The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the 109 Cd-saturation/hemolysate method, and by the 65 Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the 65 Zn-MT binding assay (3-fold) and by the 109 Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of 65 Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age

  17. Diurnal-and sex-related difference of metallothionein expression in mice

    Directory of Open Access Journals (Sweden)

    Zhang Dan

    2012-07-01

    Full Text Available Abstract Background Metallothionein (MT is a small, cysteine-rich, metal-binding protein that plays an important role in protecting against toxicity of heavy metal and chemicals. This study was aimed to define diurnal and sex variation of MT in mice. Methods Adult mice were maintained in light- and temperature-controlled facilities for 2 weeks with light on at 8:00 and light off at 20:00. The blood, liver, and kidneys were collected every 4 h during the 24 h period. Total RNA was isolated, purified, and subjected to real-time RT-PCR analysis and MT protein was determined by western blot and the Cd/hemoglobin assay. Results The diurnal variations in mRNA levels of MT-1 and MT-2in liver were dramatic, up to a 40-foldpeak/trough ratio. MT mRNA levels in kidneys and blood also showed diurnal variation, up to 5-fold peak/trough ratio. The diurnal variation of MT mRNAs resembled the clock gene albumin site D-binding protein (Dbp, and was anti-phase to the clock gene Brain and Muscle ARNT-like Protein 1 (Bmal1 in liver and kidneys. The peaks of MT mRNA levels were higher in females than in males. Hepatic MT protein followed a similar pattern, with about a 3-fold difference. Conclusion MT mRNA levels and protein showed diurnal- and sex-variation in liver, kidney, and blood of mice, which could impact the body defense against toxic stimuli.

  18. Identification of two metallothioneins as novel inhalative coffee allergens cof a 2 and cof a 3.

    Science.gov (United States)

    Peters, Ulrike; Frenzel, Karsten; Brettschneider, Reinhold; Oldenburg, Marcus; Bittner, Cordula

    2015-01-01

    Dust of green coffee beans is known to be a relevant cause for occupational allergic disorders in coffee industry workers. Recently, we described the first coffee allergen (Cof a 1) establishing an allergenic potential of green coffee dust. Our aim was to identify allergenic components of green coffee in order to enhance inhalative coffee allergy diagnosis. A Coffea arabica pJuFo cDNA phage display library was created and screened for IgE binding with sera from allergic coffee workers. Two further coffee allergens were identified by sequence analysis, expressed in E. coli, and evaluated by Western blots. The prevalence of sensitization to recombinant Cof a 1, Cof a 2, and Cof a 3 and to commercially available extract was investigated by ELISA (enzyme-linked immunosorbent assay) respectively CAP (capacity test) screening in 18 sera of symptomatic coffee workers. In addition to the previously described chitinase Cof a 1, two Coffea arabica cysteine-rich metallothioneins of 9 and 7 kDa were identified and included in the IUIS Allergen Nomenclature as Cof a 2 and Cof a 3. Serum IgE antibodies to at least one of the recombinant allergens were found in 8 out of 18 symptomatic coffee workers (44%). Only 2 of the analysed sera (11%) had reacted previously to the commercial allergy test. In addition to the previously described Cof a 1 we have identified two further coffee proteins to be type I coffee allergens (Cof a 2 and Cof a 3) which may have a relevant potential for the specific diagnosis and/or therapy of coffee allergy.

  19. Identification of two metallothioneins as novel inhalative coffee allergens cof a 2 and cof a 3.

    Directory of Open Access Journals (Sweden)

    Ulrike Peters

    Full Text Available Dust of green coffee beans is known to be a relevant cause for occupational allergic disorders in coffee industry workers. Recently, we described the first coffee allergen (Cof a 1 establishing an allergenic potential of green coffee dust.Our aim was to identify allergenic components of green coffee in order to enhance inhalative coffee allergy diagnosis.A Coffea arabica pJuFo cDNA phage display library was created and screened for IgE binding with sera from allergic coffee workers. Two further coffee allergens were identified by sequence analysis, expressed in E. coli, and evaluated by Western blots. The prevalence of sensitization to recombinant Cof a 1, Cof a 2, and Cof a 3 and to commercially available extract was investigated by ELISA (enzyme-linked immunosorbent assay respectively CAP (capacity test screening in 18 sera of symptomatic coffee workers.In addition to the previously described chitinase Cof a 1, two Coffea arabica cysteine-rich metallothioneins of 9 and 7 kDa were identified and included in the IUIS Allergen Nomenclature as Cof a 2 and Cof a 3. Serum IgE antibodies to at least one of the recombinant allergens were found in 8 out of 18 symptomatic coffee workers (44%. Only 2 of the analysed sera (11% had reacted previously to the commercial allergy test.In addition to the previously described Cof a 1 we have identified two further coffee proteins to be type I coffee allergens (Cof a 2 and Cof a 3 which may have a relevant potential for the specific diagnosis and/or therapy of coffee allergy.

  20. Metallothionein (MT) response after chronic palladium exposure in the zebra mussel, Dreissena polymorpha

    International Nuclear Information System (INIS)

    Frank, Sabrina N.; Singer, Christoph; Sures, Bernd

    2008-01-01

    The effects of different exposure concentrations of palladium (Pd) on relative metallothionein (MT) response and bioaccumulation were investigated in zebra mussels (Dreissena polymorpha). The mussels were exposed to 0.05, 5, 50, and 500 μg/L Pd 2+ for 10 weeks under controlled temperature and fasting conditions. Relative MT contents were assessed by a modified Ag-saturation method, which allows to discriminate between MT bound to Pd (Pd-MT) and MT bound to unidentified metals (Ag-MT). Determination of metal contents resulted from atomic absorption spectrometry following a microwave digestion. For unexposed mussels and mussels exposed to 0.05 μg/L Pd no metal accumulation could be detected. All other exposure concentrations resulted in detectable Pd accumulation in mussels with final tissue concentrations of 96 μg/g (500 μg/L), 45 μg/g (50 μg/L), and 9 μg/g (5 μg/L). Compared with initial levels Pd-MT concentrations at the end of the exposure period were 600 (500 μg/L), 160 (50 μg/L), and 27 (5 μg/L) times higher. These results show that an increase in MTs in D. polymorpha already occurs at relatively low aqueous Pd concentrations indicating that there is the need for detoxification of Pd in the mussel. Furthermore, correlations between Ag-MT and Pd accumulation indicate that higher exposure concentrations are associated with adverse effects on the mussels. Thus, harmful effects of chronic Pd exposure of organisms even in lowest concentrations cannot be excluded in the environment

  1. Protection against UVA-induced photooxidative damage in mammalian cell lines expressing increased levels of metallothionein

    International Nuclear Information System (INIS)

    Dudek, E.J.; Roth, R.M.

    1990-01-01

    Metallothionein (MT) is an endogenous low molecular weight protein that is inducible in a variety of eukaryotic cells and has the ability to selectivity bind heavy metal ions such as zinc and the cadmium. Although the exact physiological role of MT is still not understood, there is strong evidence that MT is involved in providing cellular resistance against the damaging effects of heavy metals and in the regulation of intracellular zinc and copper. Recently, it has been demonstrated that MT can scavenge radiation-induced reactive oxygen intermediates in vitro, specifically hydroxyl and superoxide radicals, and because of these observations it has been suggested that MT may provide protection against radiation-induced oxidative stress in vivo. Cell lines expressing increased levels of MT have demonstrated resistance to ionizing radiation, to ultraviolet radiation, and also to various DNA damaging agents including melphalan and cis-diaminedichloroplatinum. It is therefore important to gain some insight into the relationship between cellular MT content and cellular resistance to radiation and other DNA damaging agents. In this study we investigated the role of MT in providing protection against monochromatic 365-nm UVA radiation, which is known to generate intracellular reactive oxygen species that are involved in both DNA damage and cell killing. For this purpose, we used zinc acetate, a potent inducer of MT, to elevate MT levels in V79 Chinese hamster fibroblasts prior to UVA exposure and determined cell survival for uninduced and induced cultures. In order to eliminate any zinc effects other than MT induction, we also isolated and characterized cadmium chloride-resistant clones of V79 cells that have increased steady-state levels of both MT mRNA and protein, and we examined their survival characteristics against 365-nm radiation in the absence of zinc acetate. 14 refs., 3 figs

  2. Induction of a putative metallothionein gene in the blood cockle, Anadara granosa, exposed to cadmium.

    Science.gov (United States)

    Chan, M K; Othman, R; Zubir, D; Salmijah, S

    2002-02-01

    The relationship between a putative metallothionein gene (MT) and exposure to cadmium (Cd) in blood cockles (Anadara granosa) is reported. In a 96-h dose-response experiment, mortality of cockles was found to proportionately increase in the range of 0.2-5.0 mg/l Cd with a calculated LC(50) of 2.94 mg/l. Exposure to 0.25 mg/l Cd for 16 days caused significant increases (P<0.05) in Cd concentrations in whole tissues, gills and hepatopancreas, and the accumulation of Cd in these tissues increased with the duration of exposure. Two cDNA libraries constructed using the hepatopancreas from control and Cd-treated cockles gave titres of 5.62 x 10(5) and 1.94 x 10(5) pfu/microg vector, respectively. A putative MT gene, AnaMT, of 510 nucleotides in length, was isolated from the treated cDNA library using a heterologous probe MT20 from the blue mussel, Mytilus edulis. Northern analyses using AnaMT as a probe indicated low expression of the MT mRNA in control animals. In cockles treated with 0.25 mg/l Cd for 4 days, MT mRNA level increased to approximately 168%, but declined to 108% at day 8. After 12 and 16 days of Cd treatment, expression of the MT gene was 138% and 187%, respectively, compared to the controls. These observations suggest that induction of the MT gene by a sublethal dose of Cd is rapid, occurring within 4 days of treatment.

  3. Gene response profiles for Daphnia pulex exposed to the environmental stressor cadmium reveals novel crustacean metallothioneins

    Directory of Open Access Journals (Sweden)

    Davey Jennifer C

    2007-12-01

    Full Text Available Abstract Background Genomic research tools such as microarrays are proving to be important resources to study the complex regulation of genes that respond to environmental perturbations. A first generation cDNA microarray was developed for the environmental indicator species Daphnia pulex, to identify genes whose regulation is modulated following exposure to the metal stressor cadmium. Our experiments revealed interesting changes in gene transcription that suggest their biological roles and their potentially toxicological features in responding to this important environmental contaminant. Results Our microarray identified genes reported in the literature to be regulated in response to cadmium exposure, suggested functional attributes for genes that share no sequence similarity to proteins in the public databases, and pointed to genes that are likely members of expanded gene families in the Daphnia genome. Genes identified on the microarray also were associated with cadmium induced phenotypes and population-level outcomes that we experimentally determined. A subset of genes regulated in response to cadmium exposure was independently validated using quantitative-realtime (Q-RT-PCR. These microarray studies led to the discovery of three genes coding for the metal detoxication protein metallothionein (MT. The gene structures and predicted translated sequences of D. pulex MTs clearly place them in this gene family. Yet, they share little homology with previously characterized MTs. Conclusion The genomic information obtained from this study represents an important first step in characterizing microarray patterns that may be diagnostic to specific environmental contaminants and give insights into their toxicological mechanisms, while also providing a practical tool for evolutionary, ecological, and toxicological functional gene discovery studies. Advances in Daphnia genomics will enable the further development of this species as a model organism for

  4. Effects of metallothionein on zinc metabolism in lethal-milk mutant mice

    Energy Technology Data Exchange (ETDEWEB)

    Grider, A. Jr.

    1986-01-01

    The lethal-milk mice (C57BL/6J-Im) exhibit various pleiotropic effects, including a congenital otolith defect, production of zinc-deficient milk, and clinical signs of a systemic Zn deficiency by one year of age. The clinical signs include alopecia, dermatitis, and skin lesions. The systemic zinc deficiency may be due to increased levels of metallothionein (MT) in the intestine and/or liver of Im mice. The untreated Im mice contain twice as much intestinal MT as do C57BL/6J-(+/sup im//+ /sup Im/) (B6) controls. This was determined by a sulfhydryl assay, by the /sup 109/Cd-saturation/hemolysate method, and by the /sup 65/Zn-binding assay. Various concentrations of Cd or Zn were added to the drinking water three days before assaying for MT. Compared to B6 mice, the Im mice exhibited more MT in their liver by the /sup 65/Zn-MT binding assay (3-fold) and by the /sup 109/Cd-saturation/hemolysate method (18-fold). The effects of the two zinc treatments did not differ significantly between Im and B6 mice. The retention and excretion of /sup 65/Zn (administered intraperitoneally) were determined over a 14-day period, but the results did not different between the Im and B6 mice. The increased concentrations of MT within the Im mice was not significantly different for the intestine and liver. Based on these data and other studies, the Im mice may exhibit alterations in zinc homeostasis due to some deregulation of MT metabolism, including the inner ear of the fetus, the lactating mammary gland, and the intestine and liver of adults by one year of age.

  5. The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?

    Science.gov (United States)

    Tekin, Deniz; Kayaaltı, Zeliha; Söylemezoğlu, Tülin

    2012-08-01

    Numerous studies indicate that certain genetic polymorphisms modify lead toxicokinetics. Metallothioneins are protective against the toxicity of many metals, including lead. The aim of this study was to determine whether the maternal metallothionein 2A (MT2A) -5 A/G single-nucleotide polymorphism is related to the lead levels in maternal blood, placental tissue and cord blood in 91 pregnant women and their newborns. Venous blood from the mother was collected to investigate lead levels and MT2A polymorphism. Cord blood and placenta were collected for lead levels. Analyses were made using an Atomic Absorption Graphite Furnace Spectrophotometer. Standard PCR-RFLP technique was used to determine MT2A polymorphism. Blood lead levels of heterozygote genotype (AG) mothers were statistically higher than those of homozygote genotype (AA) (P lead levels were significantly associated with cord blood lead levels for pregnant women with AA genotype (P lead level for newborns with mothers of AG genotype was slightly higher than others, though the difference was not significant. No significant difference existed in placenta lead levels between the groups. This study suggests that pregnant women with AG genotype for MT2A polymorphism might have high blood lead levels and their newborns may be at risk of low-level cord blood lead variation.

  6. Effect of reduced glutathione, surface active agents, and ionic strength on the detection of metallothioneins by using of Brdicka reaction

    Czech Academy of Sciences Publication Activity Database

    Křížková, S.; Fabrik, I.; Adam, V.; Kukačka, J.; Průša, R.; Trnková, L.; Strnádel, Ján; Horák, Vratislav; Kizek, R.

    2009-01-01

    Roč. 21, 3-5 (2009), s. 640-644 ISSN 1040-0397. [International Conference on Electroanalysis /12./. Prague, 16.06.2008-19.06.2008] Grant - others:GA AV ČR(CZ) IAA401990701 Institutional research plan: CEZ:AV0Z50450515 Keywords : differential pulse voltammetry * adsorptive transfer stripping technique * proteins Subject RIV: CG - Electrochemistry Impact factor: 2.630, year: 2009

  7. Can Energy Structure Optimization, Industrial Structure Changes, Technological Improvements, and Central and Local Governance Effectively Reduce Atmospheric Pollution in the Beijing–Tianjin–Hebei Area in China?

    Directory of Open Access Journals (Sweden)

    Xinxuan Cheng

    2018-02-01

    Full Text Available Economic growth in the Beijing–Tianjin–Hebei region has been achieved by consuming large amounts of fossil fuels. This produces a large number of pollutants, which damage the physical and mental health of residents, and prevent sustainable economic development. The most urgent task at present is improving the quality of the environment. This paper takes carbon emission as a pollution index, and adopts an extended stochastic impacts by regression on population, affluence, and technology (STIRPAT model in order to study the impact of the optimization of industry structure (in particular the reduction of the proportion of energy-intensive secondary industry, the optimization of the energy structure, and technological improvements on the atmospheric environmental quality. We obtain some important and enlightening discoveries. First of all, the rapid economic growth that has been based on magnanimous fossil fuel consumption is still the main reason for the deterioration of the atmospheric environment. This means that the main driving force of economic growth still comes from high pollution industries, despite a strategy for the transformation of the pattern of economic growth having been proposed for many years. Second, the optimization of the industrial structure has not played a significant role in promoting the reduction of carbon emissions. Through further research, we believe that this may be due to the low-quality development of the third industry. In other words, the traditional service industry related to high energy consumption accounts for a large proportion in regional total output, while the high-end service industry related to small pollution accounts for a relatively small proportion. Third, reducing the consumption of coal and improving the technological level can effectively curb the deterioration of the environmental quality. In addition, we find that transboundary pollution is an important factor affecting the environment in

  8. High cadmium-binding ability of a novel Colocasia esculenta metallothionein increases cadmium tolerance in Escherichia coli and tobacco.

    Science.gov (United States)

    Kim, Yeon-Ok; Patel, Darshan H; Lee, Dae-Seok; Song, Younho; Bae, Hyeun-Jong

    2011-01-01

    Experimental evidence in vivo as to the functional roles and binding properties to cadmium (Cd) of type-2 plants metallothionein (MT) has been limited thus far. We investigated the biological role of metallothionein from Colocasia esculenta (CeMT2b) in Escherichia coli and tobacco, and developed a new model for the relationship between Cd tolerance and Cd-binding ability. Heterologous expression of CeMT2b in Escherichia coli greatly enhanced Cd tolerance and accumulated Cd content as compared to control cells. The molecular weight of CeMT2b increased with Cd, and CeMT2b bound up to 5.96±1 molar ratio (Cd/protein). Under Cd stress, transgenic tobacco plants displayed much better seedling growth and high Cd accumulation than the wild type. The presence of an extra CXC motif in CeMT2b contributed to the enhanced Cd-tolerance. The present study provides the first insight into the ability of type-2 plant MT to bind physiological Cd.

  9. Heavy metals in the fishery products of low Lazio and the use of metallothionein as a biomarker of contamination.

    Science.gov (United States)

    Papetti, P; Rossi, G

    2009-12-01

    This study aims to investigate the use of metallothionein as a biomarker and its environmental impact on aquatic systems. According to the species' characteristics, the interactions of toxic elements with living organisms in marine water can lead to biomagnifications in the trophic chain or bioconcentration of what is in the water. In many aquatic organisms, the presence of metallothionein proteins was studied. The chemical analysis of these bioindicators establishes, therefore, a sensitive method for the measurement of bioavailability which, over the years, allows for the quantification of the current pollution agents in the environment. Two study areas were selected along the Latium coasts. They are differentiated by their economic activities and their kind and level of environmental impact (mainly on marine pollution). These areas were selected in order to differentiate the maximum degree of both economic development and environmental quality. In particular, the presence of pollutants in the sea due to land activities was evaluated to compare the quality of the fishing products obtained from locations subject to various environmental impacts. The heavy metal concentrations were evaluated in water samples taken from different 30 sections of the fishes in order to understand the metabolism and origin of these contaminants. The primary metals studied were: mercury (Hg), zinc (Zn), nickel (Ni), lead (Pb), cadmium (Cd), and copper (Cu). All data produced were analyzed via multivariate analyses in order to provide a final and reliable indicator.

  10. Overexpression of metallothionein in CHO cells and its effect on cell killing by ionizing radiation and alkylating agents

    International Nuclear Information System (INIS)

    Lohrer, H.; Robson, T.

    1989-01-01

    Metallothionein protein protects cells from the toxic effects of heavy metal ions. To establish its protective function against ionizing radiation and alkylating agents, a model system was created by transfecting two CHO cell lines (wild-type, K1-2 and X-ray sensitive, xrs-2 subclone Bc11) with the human metallothionein II-A (hMTII-A) gene integrated in a bovine papilloma derived autonomously replicating vector. The isolated transfectants are cadmium-resistant (Cd 1 ), due to the overexpression of the hMTII-A gene. Their steady-state level of hMTII-A mRNA can be increased up to 40-fold after Cd treatment and 20-fold after induction with ionizing radiation. The transfected cell lines proved to be as sensitive as the recipient cell lines to ionizing radiation and bleomycin but the transfectants were significantly more resistant to N-methyl-nitro-nitrosoguanidine (MNNG) and mitomycin C (MMC). These results lead to the conclusion that the MT protein does provide a defence mechanism to protect cells from monofunctional alkylating and cross-linking agents but not from free radicals. (author)

  11. Survey of ABC transporter and metallothionein genes expressions in tall fescue inoculated with Funneliformis intraradices under Nickel toxicity

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    Massomeh Rafiei-Demneh

    2016-09-01

    Full Text Available In plants, there are complex network of transport, chelation, and sequestration processes that functions in maintaining concentrations of essential metal ions in different cellular compartments, thus minimizing the damage caused by entry of non-essential metal ions into the cytosol. In the presence of toxic ones, arbuscular mycorrhizal (AM fungi are able to alleviate metal toxicity in the plant. In this study the effect of an arbuscular mycorrhizal fungi Funneliformis intraradices on growth, Nickel tolerance, and ABC transporter and metallothionein expression in leaves and roots of tall fescue (Festuca arundinacea plants cultivated in Ni polluted soil were evaluated. The fungi infected (M+ and uninfected (M- fescue plants were cultivated in soil under different Ni concentrations (0, 30, 90 and 180 ppm for 3 months. Results demonstrated the positive effect of fungi colonization on the increase in growth and reduction in Ni uptake (90 and 180 ppm and Ni translocation from roots to shoot of tall fescue under Ni stress. The results also demonstrated that the level of ABC transporterand metallothionein transcripts accumulation in roots was considerably higher for both M- and M+ plants compared to the control. Also, M+ plants showed less ABC and MET expression compared to the M- plants. These results demonstrated the importance of mycorrhizal colonization of F. intraradices in reduction of Ni transport from root to shoot of tall fescue which alleviates Ni-induced stress.

  12. Coordinated responses of phytochelatin synthase and metallothionein genes in black mangrove, Avicennia germinans, exposed to cadmium and copper

    International Nuclear Information System (INIS)

    Gonzalez-Mendoza, Daniel; Moreno, Adriana Quiroz; Zapata-Perez, Omar

    2007-01-01

    To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd 2+ and Cu 2+ concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid increase in AvPCS expression may contribute to Cd 2+ and Cu 2+ detoxification. Moreover, we found that A. germinans has the capacity to over-express both genes (AvMt2 and AvPCS), which may constitute a coordinated detoxification response mechanism targeting non-essential metals. Nonetheless, our results confirm that AvPCS was the most active gene involved in the regulation of essential metals (e.g., Cu 2+ ) in A. germinans leaves

  13. Metallothionein induction, antioxidative responses, glycogen and growth changes in Tubifex tubifex (Oligochaete) exposed to the fungicide, fenhexamid

    International Nuclear Information System (INIS)

    Mosleh, Yahia Y.; Paris-Palacios, Severine; Couderchet, Michel; Biagianti-Risbourg, Sylvie; Vernet, Guy

    2005-01-01

    Laboratory studies were conducted to determine the effects of different concentrations of fenhexamid (0.1, 1, and 10 mg L -1 ) on growth, oxidative stress, protein, glycogen, and metallothionein (MT) contents in Tubifex tubifex after an exposure of 2, 4, and 7 days. In addition, residues of the fungicide were followed in water and in the worms. In water, fenhexamid concentration decreased slowly (maximum - 2±0.03% after 2 days for 1 mg L -1 ). In the worms, it increased after 4 days and decreased thereafter, confirming that the worms were exposed to the fungicide and not to a degradation product. LC 50 values were between 95.22±5.36 and 32.11±1.8 mg L -1 depending on exposure time. Exposure to fenhexamid had a negative effect on T. tubifex growth (maximum effect -12.2±0.8% after 7 days with 10 mg L -1 ) demonstrating the toxic effect of the pesticide. This growth rate decrease was accompanied by a reduction in protein and glycogen contents. The activity of catalase (CAT), and glutathione reductase (GR) increased in response to the fungicide demonstrating an oxidative stress in the worms. In contrast glutathion-S-transferase activity (GST) decreased. Exposure to fenhexamid also induced synthesis of MT (maximum +78±8% after 2 days for 10 mg L -1 ). The specificity of MT concentration increase in response to metals is discussed. - Exposure to the fungicide fenhexamid increased metallothionein levels in Tubifex tubifex

  14. Early-phase immunodetection of metallothionein and heat shock proteins in extruded earthworm coelomocytes after dermal exposure to metal ions

    Energy Technology Data Exchange (ETDEWEB)

    Homa, Joanna [Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, R. Ingardena 6, PL 30-060 Cracow (Poland); Olchawa, Ewa [Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, R. Ingardena 6, PL 30-060 Cracow (Poland); Stuerzenbaum, Stephen R. [Cardiff School of Biosciences, Cardiff University, PO Box 915, Cardiff Wales CF10 3TL (United Kingdom); John Morgan, A. [Cardiff School of Biosciences, Cardiff University, PO Box 915, Cardiff Wales CF10 3TL (United Kingdom); Plytycz, Barbara [Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, R. Ingardena 6, PL 30-060 Cracow (Poland)]. E-mail: plyt@zuk.iz.uj.edu.pl

    2005-05-01

    This paper provides direct evidence that earthworm immune cells, coelomocytes, are exposed to bio-reactive quantities of metals within 3 days after dermal exposure, and that they respond by upregulating metallothionein (MT) and heat shock protein (HSP70, HSP72) expression. Indirect support for the hypothesis that coelomocytes are capable of trafficking metals was also obtained. Coelomocytes were expelled from adult individuals of Eisenia fetida after 3-day exposure either to metal ions (Zn, Cu, Pb, Cd) or to distilled water (controls) via filter papers. The number of coelomocytes was significantly decreased after Cu, Pb, or Cd treatment. Cytospin preparations of coelomocytes were subjected to immunoperoxidase staining with monoclonal antibodies against human heat shock proteins (HSP70 or HSP72), or rabbit polyclonal antibodies raised against metallothionein 2 (w-MT2) of Lumbricus rubellus. Applied antibodies detected the respective proteins of E. fetida and revealed that the expression of HSP70, HSP72 and w-MT2 proteins was either induced or significantly enhanced in coelomocytes from metal-exposed animals. In conclusion, stress protein expression in earthworm coelomocytes may be used as sensitive biomarkers of metal contaminations. Further experimentation is needed for quantitative analysis of kinetics of metal-induced stress protein expression in earthworm coelomocytes. - Metals upregulate stress response proteins in earthworm coelomocytes.

  15. Early-phase immunodetection of metallothionein and heat shock proteins in extruded earthworm coelomocytes after dermal exposure to metal ions

    International Nuclear Information System (INIS)

    Homa, Joanna; Olchawa, Ewa; Stuerzenbaum, Stephen R.; John Morgan, A.; Plytycz, Barbara

    2005-01-01

    This paper provides direct evidence that earthworm immune cells, coelomocytes, are exposed to bio-reactive quantities of metals within 3 days after dermal exposure, and that they respond by upregulating metallothionein (MT) and heat shock protein (HSP70, HSP72) expression. Indirect support for the hypothesis that coelomocytes are capable of trafficking metals was also obtained. Coelomocytes were expelled from adult individuals of Eisenia fetida after 3-day exposure either to metal ions (Zn, Cu, Pb, Cd) or to distilled water (controls) via filter papers. The number of coelomocytes was significantly decreased after Cu, Pb, or Cd treatment. Cytospin preparations of coelomocytes were subjected to immunoperoxidase staining with monoclonal antibodies against human heat shock proteins (HSP70 or HSP72), or rabbit polyclonal antibodies raised against metallothionein 2 (w-MT2) of Lumbricus rubellus. Applied antibodies detected the respective proteins of E. fetida and revealed that the expression of HSP70, HSP72 and w-MT2 proteins was either induced or significantly enhanced in coelomocytes from metal-exposed animals. In conclusion, stress protein expression in earthworm coelomocytes may be used as sensitive biomarkers of metal contaminations. Further experimentation is needed for quantitative analysis of kinetics of metal-induced stress protein expression in earthworm coelomocytes. - Metals upregulate stress response proteins in earthworm coelomocytes

  16. Coordinated responses of phytochelatin synthase and metallothionein genes in black mangrove, Avicennia germinans, exposed to cadmium and copper.

    Science.gov (United States)

    Gonzalez-Mendoza, Daniel; Moreno, Adriana Quiroz; Zapata-Perez, Omar

    2007-08-01

    To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd2+ and Cu2+ concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4h. Results strongly suggest that the rapid increase in AvPCS expression may contribute to Cd2+ and Cu2+ detoxification. Moreover, we found that A. germinans has the capacity to over-express both genes (AvMt2 and AvPCS), which may constitute a coordinated detoxification response mechanism targeting non-essential metals. Nonetheless, our results confirm that AvPCS was the most active gene involved in the regulation of essential metals (e.g., Cu2+) in A. germinans leaves.

  17. Coordinated responses of phytochelatin synthase and metallothionein genes in black mangrove, Avicennia germinans, exposed to cadmium and copper

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Mendoza, Daniel [Departamento de Recursos del Mar, Cinvestav-Unidad Merida, Merida, Yucatan (Mexico); Moreno, Adriana Quiroz [Unidad de biotecnologia, CICY, Merida, Yucatan (Mexico); Zapata-Perez, Omar [Departamento de Recursos del Mar, Cinvestav-Unidad Merida, Merida, Yucatan (Mexico)]. E-mail: ozapata@mda.cinvestav.mx

    2007-08-01

    To evaluate the role of phytochelatins and metallothioneins in heavy metal tolerance of black mangrove Avicennia germinans, 3-month-old seedlings were exposed to cadmium or copper for 30 h, under hydroponic conditions. Degenerate Mt2 and PCS primers were synthesized based on amino acid and nucleotide alignment sequences reported for Mt2 and PCS in other plant species found in GenBank. Total RNA was isolated from A. germinans leaves and two partial fragments of metallothionein and phytochelatin synthase genes were isolated. Gene expression was evaluated with reverse transcripatase-polymerase chain reaction (RT-PCR) amplification technique. Temporal analysis showed that low Cd{sup 2+} and Cu{sup 2+} concentrations caused a slight (but not significant) increase in AvMt2 expression after a 16 h exposure time, while AvPCS expression showed a significant increase under the same conditions but only after 4 h. Results strongly suggest that the rapid increase in AvPCS expression may contribute to Cd{sup 2+} and Cu{sup 2+} detoxification. Moreover, we found that A. germinans has the capacity to over-express both genes (AvMt2 and AvPCS), which may constitute a coordinated detoxification response mechanism targeting non-essential metals. Nonetheless, our results confirm that AvPCS was the most active gene involved in the regulation of essential metals (e.g., Cu{sup 2+}) in A. germinans leaves.

  18. Evaluation of metallothionein formation as a proxy for zinc absorption in an in vitro digestion/caco-2 cell culture model

    Science.gov (United States)

    Caco-2 cell metallothionein (MT) formation was studied to determine if MT could be used as a proxy for zinc (Zn) absorption in a cell culture model. MT intracellular concentration was determined by using a cadmium/hemoglobin affinity assay. Cellular Zn uptake was determined in acid digests (5% HNO3)...

  19. Influence of Cadmium(II Ions and Brewery Sludge on Metallothionein Level in Earthworms (Eisenia fetida – Bio- transforming of Toxic Wastes

    Directory of Open Access Journals (Sweden)

    Rene Kizek

    2008-02-01

    Full Text Available Metallothioneins belong to a group of intracellular, high molecular andcysteine-rich proteins whose content in an organism increase with increasing concentrationof a heavy metal. The aim of this work was to apply the electrochemical analysis for theanalysis of metallothioneins in earthworms exposed to cadmium ions and brewery sludge.Here we utilized adsorptive transfer technique coupled with differential pulse voltammetryBrdicka reaction to determine metallothionein in different biological samples. By meansthis very sensitive technique it was possible to analyze metallothionein in concentrationsbelow 1 μmol.l-1 with the standard deviation of 4-5%. We found out that the average MTlevel in the non-treated earthworms oscillated between 19 and 48 μmol.l-1. When weanalysed samples of earthworms treated by cadmium, we observed that the MT contentincreased with the exposition length and increase dose of cadmium ions. Finally, weattempted to study and compare the toxicity of the raw sludge and its leach by using ofearthworms. The raw brewery sludge caused the death of the earthworms quickly.Earthworms held in the presence of leach from brewery sludge increased their weight of147 % of their original weight because they ingested the nutrients from the sludge. Themetallothionein level changes markedly with increasing time of exposition and applieddose of toxic compound. It clearly follows from the obtained results that the MT synthesisis insufficient in the first hours of the exposition and increases after more than 24 h.

  20. Metallothionein isoform 2A expression is inducible and protects against ROS-mediated cell death in rotenone-treated HeLa cells.

    NARCIS (Netherlands)

    Reinecke, F.; Levanets, O.; Olivier, Y.; Louw, R.; Semete, B.; Grobler, A.; Hidalgo, J.; Smeitink, J.A.M.; Olckers, A.; Westhuizen, F.H. van der

    2006-01-01

    The role of MT (metallothionein) gene expression was investigated in rotenone-treated HeLa cells to induce a deficiency of NADH:ubiquinone oxidoreductase (complex I). Complex I deficiency leads to a diversity of cellular consequences, including production of ROS (reactive oxygen species) and

  1. Evaluation and standardization of different purification procedures for fish bile and liver metallothionein quantification by spectrophotometry and SDS-PAGE analyses.

    Science.gov (United States)

    Tenório-Daussat, Carolina Lyrio; Resende, Marcia Carolina Martinho; Ziolli, Roberta L; Hauser-Davis, Rachel Ann; Schaumloffel, Dirk; Saint'Pierre, Tatiana D

    2014-03-01

    Fish bile metallothioneins (MT) have been recently reported as biomarkers for environmental metal contamination; however, no studies regarding standardizations for their purification are available. Therefore, different procedures (varying centrifugation times and heat-treatment temperatures) and reducing agents (DTT, β-mercaptoethanol and TCEP) were applied to purify MT isolated from fish (Oreochromis niloticus) bile and liver. Liver was also analyzed, since these two organs are intrinsically connected and show the same trend regarding MT expression. Spectrophotometrical analyses were used to quantify the resulting MT samples, and SDS-PAGE gels were used to qualitatively assess the different procedure results. Each procedure was then statistically evaluated and a multivariate statistical analysis was then applied. A response surface methodology was also applied for bile samples, in order to further evaluate the responses for this matrix. Heat treatment effectively removes most undesired proteins from the samples, however results indicate that temperatures above 70 °C are not efficient since they also remove MTs from both bile and liver samples. Our results also indicate that the centrifugation times described in the literature can be decreased in order to analyze more samples in the same timeframe, of importance in environmental monitoring contexts where samples are usually numerous. In an environmental context, biliary MT was lower than liver MT, as expected, since liver accumulates MT with slower detoxification rates than bile, which is released from the gallbladder during feeding, and then diluted by water. Therefore, bile MT seems to be more adequate in environmental monitoring scopes regarding recent exposure to xenobiotics that may affect the proteomic and metalloproteomic expression of this biological matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Global warming likely reduces crop yield and water availability of the dryland cropping systems in the U.S. central Great Plains

    Science.gov (United States)

    We investigated impacts of GCM-projected climate change on dryland crop rotations of wheat-fallow and wheat-corn-fallow in the Central Great Plains (Akron in Colorado, USA) using the CERES 4.0 crop modules in RZWQM2. The climate change scenarios for CO2, temperature, and precipitation were produced ...

  3. Maize-grain legume intercropping is an attractive option for ecological intensification that reduces climatic risk for smallholder farmers in central Mozambique

    NARCIS (Netherlands)

    Rusinamhodzi, L.; Corbeels, M.; Nyamangara, J.; Giller, K.E.

    2012-01-01

    Many farmers in central Mozambique intercrop maize with grain legumes as a means to improve food security and income. The objective of this study was to understand the farming system, and to evaluate the suitability of maize–legume intercropping to alleviate the biophysical and socio-economic

  4. Concentration of metallothionein in mice livers after a small dose of irradiation

    International Nuclear Information System (INIS)

    Saitou, Mikio; Yanai, Takanori; Hasegawa, Hidenao; Otsu, Hiroshi; Sato, Fumiaki; Akata, Naofumi; Kanaiwa-Kudo, Shouko; Matsumoto, Tsuneya; Noda, Yuko

    1998-01-01

    This study was made to determine whether metallothionein (MT) is induced by a small dose (0.5 Gy) irradiation. One hundred B6C3F1/Nrs mice of each sex, 8-10 weeks old, were used in the sham study (unirradiated controls) and experimental (irradiated) groups. Eighty mice of each sex were given acute whole body irradiation with 197 Csγ-rays under SPF conditions; two doses of 0.5 and 5.0 Gy at 30 cm distance from the source at the rate of 0.563 Gy/min. Twenty mice of each sex were used in the sham study. Every ten male and female mouse was killed by cervical dislocation on days 1, 7, 14 and 21 after irradiation. The same numbers of male and female control mice were killed on days 0 and 21. Livers were removed immediately after death, and concentration of MT was examined. In both the males and females, the MT concentration of the 5 Gy-group peaked on the first day after irradiation, and there was no difference in comparison with the control values between the 7th and 21st days. In contrast, on no day did the MT concentration for the 0.5 Gy-group showed a significant difference from the control group. The time dependency patterns of the female and male mice also showed no significant differences for 5 Gy- and 0.5 Gy-groups, but the mean values of the MT concentration was lower in the males than in the females on the 1st day. Results of the direct quantitation of MT by the enzyme-linked immunoabsorbent assay (ELISA) also showed peak MT accumulation on the 1st day for both male and female mice. These were also shown by the atomic absorption spectrometry (AAS) and the inductively coupled plasma mass spectrometry (ICP-MS) analyses. But peak heights for the males and females showed a tendency inverse to that of the AAS and ICP-MS analyses. This discrepancy is attributable to the technical problem encountered in the experiment. On the basis of our findings, MT does not seem to be related to acquired radioresistance in mice. (K.H.)

  5. Expression and function analysis of metallothionein in the testis of Portunus trituberculatus exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Dong-Fang [School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211 (China); The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058 (China); Zhu, Jun-Quan; Jin, Shan [School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211 (China); Hu, Yan-Jun [Department of Reproductive Endocrinology, Women' s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006 (China); Tan, Fu-Qing [The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003 (China); Yang, Wan-Xi, E-mail: wxyang@spermlab.org [The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang 310058 (China)

    2013-09-15

    Highlights: •We identified P. trituberculatus MT-1 and MT-2 complete cDNA sequence. •We analyzed the protein alignment comparisons and phylogenetic trees of MT-1 and MT-2. •RT-PCR analysis the tissue expression of MT-1 and MT-2 mRNA. •The spatial and temporal distribution pattern of MT-1 and MT-2 mRNA during spermiogenesis. •Testis MT-1 and MT-2 mRNA expression are dramatically affected after the cadmium exposure. -- Abstract: Metallothioneins (MTs) possess a unique molecular structure that provides metal-binding and redox capabilities. These capabilities include the maintenance of metal equilibria that protect against heavy metals (especially cadmium) and oxidative damage. Past studies have focused on the function of MTs in vertebrates. However, the functions of MTs during spermiogenesis in invertebrates remain unclear. In order to investigate the function of MTs during spermiogenesis in Portunus trituberculatus, we used RT-PCR and RACE to identify two MT complete cDNA sequences in the total RNA from the P. trituberculatus testis. The 450 bp MT-1 cDNA consists of a 77 bp 5′ untranslated region, a 196 bp 3′ untranslated region, and a 177 bp open reading frame that encodes 58 amino acids including 19 cysteines. The 581 bp MT-2 cDNA consists of 73 bp 5′ untranslated region, a 328 bp 3′ untranslated region, and a 180 bp open reading frame that encodes 59 amino acids including 18 cysteines. MT-1 and MT-2 of P. trituberculatus more closely resemble invertebrate (especially crab) MT homologues than vertebrate MT homologues as indicated by protein alignment comparisons and phylogenetic tree analysis. MT-1 and MT-2 were detected in the heart, testis, muscle, hepatopancreas, and gill of P. trituberculatus by tissue expression analysis. In addition, MT-1 and MT-2 are present during the entire process of spermiogenesis in P. trituberculatus as indicated by H and E staining and in situ hybridization. MT-1 and MT-2 expression levels significantly increase

  6. Differential expression and characterization of three metallothionein-like genes in Cavendish banana (Musa acuminata).

    Science.gov (United States)

    Liu, Pei; Goh, Chong-Jin; Loh, Chiang-Shiong; Pua, Eng-Chong

    2002-02-01

    Metallothioneins (MTs) are cysteine-rich polypeptides that are involved in metal detoxification and homeostasis in both prokaryotes and eukaryotes. In this study, we report the isolation and characterization of three members (MT2A, MT2B and MT3) of the MT-like gene family from ripening banana fruit and their differential expression in various banana organs and during fruit development and ripening. All members of the MT-like gene encode small cysteine-rich polypeptides of 65-79 amino acid residues. MT2A shared a high sequence similarity (54-77%) with several type-2 MTs in plants, while MT3 was highly homologous (51-61%) with type-3 MTs. The three members expressed differentially in various organs but transcripts were generally more abundant in reproductive than vegetative organs. During fruit development, the MT2A transcript was barely detectable in ovary but increased to a high level in young fruit at 20 days after shooting (DAS) and declined gradually thereafter as fruit developed. In contrast, both MT2B and MT3 expressed poorly in young fruits (20-60 DAS) and transcripts were detected only in fruits at later stages of development. As ripening progressed, expression of MT2A decreased but that of MT3 increased. Expression of MT members during ripening appeared to be differentially regulated by ethylene, whose levels were low in FG and TY fruit but surged climacteristically in MG and declined sharply as ripening advanced further. Exogenous application of ethylene at 5 ppm or higher concentrations down-regulated MT2A expression and the inhibitory effect of ethylene could be partially suppressed by the presence of norbornadiene, an inhibitor of ethylene action. Ethylene had no effect on transcript accumulation of MT2B and MT3. However, MT3 expression was greatly enhanced in response to metals such as CdSO4, CuSO4 and ZnSO4. These results suggest that increased MT3 expression may be associated with excess metal ions present in ripening fruit tissues. This study also

  7. Location-specific epigenetic regulation of the metallothionein 3 gene in esophageal adenocarcinomas.

    Directory of Open Access Journals (Sweden)

    Dunfa Peng

    Full Text Available Metallothionein 3 (MT3 maintains intracellular metal homeostasis and protects against reactive oxygen species (ROS-induced DNA damage. In this study, we investigated the epigenetic alterations and gene expression of the MT3 gene in esophageal adenocarcinomas (EACs.Using quantitative bisulfite pyrosequencing, we detected unique DNA methylation profiles in the MT3 promoter region. The CpG nucleotides from -372 to -306 from the transcription start site (TSS were highly methylated in tumor (n = 64 and normal samples (n = 51, whereas CpG nucleotides closest to the TSS (-4 and +3 remained unmethylated in all normal and most tumor samples. Conversely, CpG nucleotides in two regions (from -139 to -49 and +296 to +344 were significantly hypermethylated in EACs as compared to normal samples [FDR3.0]. The DNA methylation levels from -127 to -8 CpG sites showed the strongest correlation with MT3 gene expression (r = -0.4, P<0.0001. Moreover, the DNA hypermethylation from -127 to -8 CpG sites significantly correlated with advanced tumor stages and lymph node metastasis (P = 0.005 and P = 0.0313, respectively. The ChIP analysis demonstrated a more repressive histone modification (H3K9me2 and less active histone modifications (H3K4me2, H3K9ace in OE33 cells than in FLO-1 cells; concordant with the presence of higher DNA methylation levels and silencing of MT3 expression in OE33 as compared to FLO-1 cells. Treatment of OE33 cells with 5-Aza-deoxycitidine restored MT3 expression with demethylation of its promoter region and reversal of the histone modifications towards active histone marks.In summary, EACs are characterized by frequent epigenetic silencing of MT3. The choice of specific regions in the CpG island is a critical step in determining the functional role and prognostic value of DNA methylation in cancer cells.

  8. Structure and function of the human metallothionein gene family: Final technical report

    International Nuclear Information System (INIS)

    Karin, M.

    1986-01-01

    The full nucleotide sequence of two additional human metallothionein (hMT) genes has been determined. These genes, hMT-I/sub B/ and hMT-I/sub F/, are located within the MT-I gene cluster we have described originally. The hMT-I/sub F/ gene is the first hMT-I gene whose amino acid sequence is in complete agreement with the published sequence of the human MT-I proteins. Therefore it is likely to be an active gene encoding a functional protein. However, since we have just completed the sequence analysis, we have not characterized this gene further yet. The hMT-I/sub B/ gene is closely linked to the hMT-I/sub A/ gene, and two pseudogenes, hMT-I/sub C/ and hMT-I/sub D/ separate the two. From its nucleotide sequence hMT-I/sub B/ seems to be an active gene, encoding a functional protein even though it differs in four positions from the published sequence of human MT-I proteins. This gene is expressed in a human hepatoma cell line, HepG2, and its expression is stimulated by Cd ++ . Using gene fusions to the viral thymidine-kinase gene we find that hMT-I/sub B/, like the hMT-I/sub A/ and hMT-II/sub A/ genes, contains a heavy metal responsive promoterregulatory element within its 5' flanking region. We analyzed the level of hMT-I/sub B/ mRNA in a variety of human cell lines by the S1 nuclease technique, and compared it to the expression of the hMT-II/sub A/ gene. While the hMT-II/sub A/ gene was expressed in all of the cell lines analyzed, the hMT-I/sub B/ gene was expressed in liver and kidney derived cell lines cells. This suggest that the expression of the hMT-I/sub B/ gene is controlled in a tissue specific manner. 13 refs

  9. Intracellular sequestration of zinc, cadmium and silver in Hebeloma mesophaeum and characterization of its metallothionein genes.

    Science.gov (United States)

    Sácký, Jan; Leonhardt, Tereza; Borovička, Jan; Gryndler, Milan; Briksí, Aleš; Kotrba, Pavel

    2014-06-01

    Sequestration of intracellular heavy metals in eukaryotes involves compartmentalization and binding with cytosolic, cysteine-rich metallothionein (MT) peptides. We examined the roles of these processes in handling of zinc (Zn), cadmium (Cd) and silver (Ag) in sporocarps and a metal-exposed extraradical mycelium of Hebeloma mesophaeum, the Zn-accumulating ectomycorrhizal (EM) species frequently associated with metal disturbed sites. Size exclusion chromatography revealed that the majority of Zn and Cd in the sporocarps and mycelium was contained in a low molecular mass fraction attributable to compartmentalized metal. The staining of hyphal cells with the Zn-specific Zinquin and Cd-specific Leadmium fluorescent tracers labeled Zn and Cd in small, punctuated vesicles and vacuoles, respectively. By contrast, the sporocarp and mycelium Ag was associated with cysteine-rich, 5-kDa peptides. The peptides of the same size were also identified in minor Zn and Cd complexes from the metal-exposed mycelium. We have further isolated and characterized HmMT1, HmMT2 and HmMT3 genes coding for different 5-kDa MTs of H. mesophaeum collected at a lead smelter site. Heterologous complementation assays in metal-sensitive yeast mutants indicated that HmMTs encode functional, metal-specific peptides: only HmMT1 was able to complement sensitivity to Zn; HmMT1 conferred higher tolerance to Cd and Cu than HmMT2 or HmMT3; and both HmMT2 and HmMT3, but not HmMT1, conferred increased tolerance to Ag. The presence of HmMT1 and HmMT3, but not HmMT2, was also confirmed in a H. mesophaeum isolate from an unpolluted site. Gene expression analysis in the extraradical mycelium of this isolate revealed that the transcription of HmMT1 was preferentially induced in the presence of Zn and Cd, while Ag was a stronger inducer of HmMT3. Altogether, these results improve our understanding of the handling of intracellular Zn, Cd and Ag in Hebeloma and represent the first evidence suggesting involvement of MTs

  10. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    OpenAIRE

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.; Novembre, Francis J.

    2009-01-01

    The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our S...

  11. Impact and appreciation of two methods aiming at reducing hazardous drug environmental contamination: The centralization of the priming of IV tubing in the pharmacy and use of a closed-system transfer device.

    Science.gov (United States)

    Guillemette, Annie; Langlois, Hélène; Voisine, Maxime; Merger, Delphine; Therrien, Roxane; Mercier, Genevieve; Lebel, Denis; Bussières, Jean-François

    2014-12-01

    The main objective was to evaluate the impact of two methods aiming at reducing hazardous drug environmental contamination: the centralization of the priming of IV tubing in the pharmacy and the use of a closed-system transfer device. The secondary objective was to evaluate the satisfaction of pharmacy technicians using a survey. Sites in the hematology-oncology satellite pharmacy and care unit were analyzed for the presence of cyclophosphamide, ifosfamide and methotrexate before and after the centralization of the priming of IV tubing in the pharmacy and before and after using a closed-system transfer device. The limits of detection for cyclophosphamide, ifosfamide and methotrexate were, respectively, of 0.0015 ng/cm(2), 0.0012 ng/cm(2) and 0.0060 ng/cm(2). The pharmacy technician satisfaction was evaluated using a questionnaire. A total of 225 samples was quantified. After the centralization of priming in the pharmacy, no significant difference was found in the proportion of positive samples for cyclophosphamide, ifosfamide and methotrexate. Traces of cyclophosphamide found on the floor in patient care areas was significantly reduced (median[min-max] 0.08[0.06-0.09]ng/cm(2) vs. 0.03[0.02-0.05], p handling difficulties). The centralization of the priming of IV tubing in the pharmacy reduced floor contamination in patient care areas without increasing surface contamination in the pharmacy. Closed-system transfer devices reduced contamination in pharmacy, but handling issues were raised by pharmacy technicians. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Trace-elements, methylmercury and metallothionein levels in Magellanic penguin (Spheniscus magellanicus) found stranded on the Southern Brazilian coast.

    Science.gov (United States)

    Kehrig, Helena A; Hauser-Davis, Rachel A; Seixas, Tércia G; Fillmann, Gilberto

    2015-07-15

    Magellanic penguins have been reported as good biomonitors for several types of pollutants, including trace-elements. In this context, selenium (Se), total mercury, methylmercury, inorganic mercury (Hg(inorg)), cadmium (Cd) and lead (Pb), as well as metallothionein (MT) levels, were evaluated in the feathers, liver and kidney of juvenile Magellanic penguins found stranded along the coast of Southern Brazil. The highest concentrations of all trace-elements and methylmercury were found in internal organs. Concentrations of Cd and Se in feathers were extremely low in comparison with their concentrations in soft tissues. The results showed that both Se and MT are involved in the detoxification of trace-elements (Cd, Pb and Hg(inorg)) since statistically significant relationships were found in liver. Conversely, hepatic Se was shown to be the only detoxifying agent for methylmercury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Metallothionein-mediated antioxidant defense system and its response to exercise training are impaired in human type 2 diabetes

    DEFF Research Database (Denmark)

    Scheede-Bergdahl, Celena; Penkowa, Milena; Hidalgo, Juan

    2005-01-01

    the MT-I+II-mediated antioxidant capacity and its response to exercise training in the skeletal muscle of patients with type 2 diabetes, biopsies and blood samples were taken from 13 matched subjects (type 2 diabetes n = 8, control subjects n = 5) both before and after 8 weeks of exercise training......-I+II in muscle and plasma, as well as the deficient MT-I+II response to exercise, indicate that this antioxidant defense is impaired. This study presents a novel candidate in the pathogenesis of complications related to oxidative stress in type 2 diabetes.......Oxidative stress is implicated in diabetes complications, during which endogenous antioxidant defenses have important pathophysiological consequences. To date, the significance of endogenous antioxidants such as metallothioneins I and II (MT-I+II) in type 2 diabetes remains unclear. To examine...

  14. Metallothionein coding sequence identification and seasonal mRNA expression of detoxification genes in the bivalve Corbicula fluminea.

    Science.gov (United States)

    Bigot, Aurélie; Doyen, Périne; Vasseur, Paule; Rodius, François

    2009-02-01

    The aim of this study was to identify a metallothionein (MT) coding sequence from the freshwater bivalve Corbicula fluminea and to measure the seasonal transcriptional pattern of MT in parallel with several detoxification genes: superoxide dismutase (SOD), catalase (CAT), glutathione S-transferases (GST) and glutathione peroxidases (GPx), in the digestive gland and the gills of this bivalve during a 1-year period. We identified a C. fluminea MT complete cDNA sequence using RT-PCR and RACE-PCR. The amino acid sequence deduced from the coding sequence encodes for a protein of 73 amino acids containing 21 cysteine residues. This protein exhibits high identities and similarities with the MT sequences of numerous bivalves. MT, SOD, CAT, pi-GST and Se-GPx expression patterns did not exhibit major seasonal variations. A slight increase of MT was observed in July. Therefore, the mRNA expression of these five genes could be used as biomarkers for monitoring studies.

  15. Thermodynamics of Pb(ii) and Zn(ii) binding to MT-3, a neurologically important metallothionein.

    Science.gov (United States)

    Carpenter, M C; Shami Shah, A; DeSilva, S; Gleaton, A; Su, A; Goundie, B; Croteau, M L; Stevenson, M J; Wilcox, D E; Austin, R N

    2016-06-01

    Isothermal titration calorimetry (ITC) was used to quantify the thermodynamics of Pb(2+) and Zn(2+) binding to metallothionein-3 (MT-3). Pb(2+) binds to zinc-replete Zn7MT-3 displacing each zinc ion with a similar change in free energy (ΔG) and enthalpy (ΔH). EDTA chelation measurements of Zn7MT-3 and Pb7MT-3 reveal that both metal ions are extracted in a tri-phasic process, indicating that they bind to the protein in three populations with different binding thermodynamics. Metal binding is entropically favoured, with an enthalpic penalty that reflects the enthalpic cost of cysteine deprotonation accompanying thiolate ligation of the metal ions. These data indicate that Pb(2+) binding to both apo MT-3 and Zn7MT-3 is thermodynamically favourable, and implicate MT-3 in neuronal lead biochemistry.

  16. Somatostatin is targeted to the regulated secretory pathway of gonadotrophs in transgenic mice expressing a metallothionein-somatostatin gene.

    Science.gov (United States)

    Low, M J; Stork, P J; Hammer, R E; Brinster, R L; Warhol, M J; Mandel, G; Goodman, R H

    1986-12-05

    The pituitaries of transgenic mice that express a metallothionein-somatostatin fusion gene contain high concentrations of somatostatin-14 exclusively in the gonadotrophic cells. The purpose of this study was to determine whether somatostatin expressed from the foreign fusion gene enters the normal secretory pathway within these cells. Immuno-gold labeling of serial thin sections localized somatostatin to the secretory granules of gonadotropin-producing cells. The gonadotroph-specific hypophysiotropic factor, luteinizing hormone-releasing hormone caused a dose-dependent secretion of somatostatin when applied to primary pituitary cultures from these mice. Growth hormone-releasing hormone, thyrotropin-releasing hormone, corticotropin releasing factor, and dopamine did not affect somatostatin secretion. These experiments demonstrate that a neurosecretory peptide encoded by a foreign gene can enter the regulated secretory pathway of pituitary cells from transgenic mice.

  17. The role of metallothioneins, selenium and transfer to offspring in mercury detoxification in Franciscana dolphins (Pontoporia blainvillei).

    Science.gov (United States)

    Romero, M B; Polizzi, P; Chiodi, L; Das, K; Gerpe, M

    2016-08-15

    The concentrations of mercury (Hg), selenium (Se) and metallothioneins (MT) were evaluated in fetuses, calves, juveniles and adults of the endangered coastal Franciscana dolphin (Pontoporia blainvillei) from Argentina. Mercury concentrations varied among analyzed tissues (liver, kidney, muscle and brain), with liver showing the higher concentrations in all specimens. An age-dependent accumulation was found in liver, kidney and brain. No significant relationship between Hg and MT concentrations was found for all tissues analyzed. Hepatic Hg molar concentrations were positively correlated with those of Se, indicating a great affinity between these two elements. Furthermore, dark granules of HgSe were observed in Kupffer cells in the liver by electron microscopy, suggesting the role of this macrophage in the detoxification of Hg. A transfer of Hg through placenta was proved. The presence of Hg in brain in all age classes did not show concentrations associated with neurotoxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Effect of cadmium on glutathione S-transferase and metallothionein gene expression in coho salmon liver, gill and olfactory tissues

    International Nuclear Information System (INIS)

    Espinoza, Herbert M.; Williams, Chase R.; Gallagher, Evan P.

    2012-01-01

    Highlights: ► Developed qPCR assays to distinguish closely related GST isoforms in salmon. ► Examined the effect of cadmium on GST and metallothionein genes in 3 tissues. ► Modulation of GST varied among isoforms, tissues, and included a loss of expression. ► Metallothionein outperformed, but generally complemented, GSTs as biomarkers. ► Salmon olfactory genes were among the most responsive to cadmium. - Abstract: The glutathione S-transferases (GSTs) are a multifunctional family of phase II enzymes that detoxify a variety of environmental chemicals, reactive intermediates, and secondary products of oxidative damage. GST mRNA expression and catalytic activity have been used as biomarkers of exposure to environmental chemicals. However, factors such as species differences in induction, partial analyses of multiple GST isoforms, and lack of understanding of fish GST gene regulation, have confounded the use of GSTs as markers of pollutant exposure. In the present study, we examined the effect of exposure to cadmium (Cd), a prototypical environmental contaminant and inducer of mammalian GST, on GST mRNA expression in coho salmon (Oncorhynchus kisutch) liver, gill, and olfactory tissues. GST expression data were compared to those for metallothionein (MT), a prototypical biomarker of metal exposure. Data mining of genomic databases led to the development of quantitative real-time PCR (qPCR) assays for salmon GST isoforms encompassing 9 subfamilies, including alpha, mu, pi, theta, omega, kappa, rho, zeta and microsomal GST. In vivo acute (8–48 h) exposures to low (3.7 ppb) and high (347 ppb) levels of Cd relevant to environmental scenarios elicited a variety of transient, albeit minor changes (<2.5-fold) in tissue GST profiles, including some reductions in GST mRNA expression. In general, olfactory GSTs were the earliest to respond to cadmium, whereas, more pronounced effects in olfactory and gill GST expression were observed at 48 h relative to earlier time

  19. Role of pCeMT, a putative metallothionein from Colocasia esculenta, in response to metal stress.

    Science.gov (United States)

    Kim, Yeon-Ok; Jung, Sera; Kim, Kyounghyoun; Bae, Hyeun-Jong

    2013-03-01

    Metallothioneins (MTs) play a major role in metal homeostasis and/or detoxification in plants. In this study, a novel gene, pCeMT, was isolated from Colocasia esculenta and characterized. Our results indicate that Escherichia coli cells expressing pCeMT exhibited enhanced Cd, Cu, and Zn tolerance and accumulation compared with control cells. Furthermore, pCeMT-overexpressing tobacco seedlings displayed better growth under Cd, Cu, and Zn stresses and accumulated more Cd and Zn compared with the wild type. Interestingly, transgenic tobacco displayed markedly decreased hydrogen peroxide (H(2)O(2)) and lipid peroxidation levels under Cd, Cu, and Zn treatments. These results suggest that pCeMT could play an important role in the protection of plant cells from oxidative stress by reactive oxygen species (ROS) scavenging and in the detoxification of free metals by metal binding, leading to improved plant metal tolerance. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

    International Nuclear Information System (INIS)

    Adams, Scott V.; Barrick, Brian; Christopher, Emily P.; Shafer, Martin M.; Makar, Karen W.; Song, Xiaoling; Lampe, Johanna W.; Vilchis, Hugo; Ulery, April; Newcomb, Polly A.

    2015-01-01

    Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.

  1. Dominance of metallothionein in metal ion buffering in yeast capable of synthesis of (gamma EC)nG isopeptides.

    Science.gov (United States)

    Yu, W; Santhanagopalan, V; Sewell, A K; Jensen, L T; Winge, D R

    1994-08-19

    The relationship of yeast metallothionein (MT) and (gamma EC)nG isopeptides (phytochelatins) in metal ion buffering was assessed. The effect of constitutive expression of yeast metallothionein (MT) genes on accumulation of metal-(gamma EC)nG isopeptide (phytochelatin) complexes was analyzed in Candida glabrata and Schizosaccharomyces pombe cultures incubated in the presence of cadmium salts. Constitutive expression of the Saccharomyces cerevisiae MT (CUP1) gene inhibited the accumulation of metal-phytochelatin complexes in both C. glabrata and S. pombe. Intracellular Cd(II) sequestration occurred by formation of CdMT complexes. Phytochelatin (gamma EC)nG complexes appear to function in metal buffering in cells when MT genes are not present or expressed. A third condition in which metal-(gamma EC)nG complexes are observed is when constitutively expressed MT does not accumulate. We observed that C. glabrata lacking the AMT1 gene necessary for copper induction of the MT genes expressed MTII constitutively, but this expression does not lead to CdMTII accumulation. Only Cd-(gamma EC)nG complexes accumulate. Likewise, metal exposed cultures of S. cerevisiae (cup1) transformed with C. glabrata MTII under the constitutive ADH1 promoter resulted in constitutive expression of MTII and accumulation of CuMTII complexes but no CdMTII complexes. The inability of constitutively expressed C. glabrata MTII to buffer Cd(II) ions may arise in part from an inherent kinetic lability of CdMTII complexes. Incubation of ZnMTII with a metallochromic chelator, 4-(2-pyridylazo)resorcinol resulted in greater Zn(II) loss than Zn(II) complexes with CUP1 MT and C. glabrata MTI. C. glabrata MTII appears to be the first MT described which forms an unstable Cd(II) complex.

  2. Expression and characterization analysis of type 2 metallothionein from grey mangrove species (Avicennia marina) in response to metal stress

    Energy Technology Data Exchange (ETDEWEB)

    Huang Guoyong, E-mail: huang_gyh@sina.com [Key Laboratory of Tropical Marine Environmental Dynamics, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301 (China); State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640 (China); Wang Youshao [Key Laboratory of Tropical Marine Environmental Dynamics, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301 (China)

    2010-08-01

    Metallothioneins (MTs) are a family of low-molecular-weight cysteine-rich proteins and are thought to play possible roles in metal metabolism or detoxification. To evaluate the roles of metallothioneins in metal homeostasis or tolerance in Avicennia marina, a real-time quantitative PCR protocol was developed to directly evaluate the expression of AmMT2 mRNA, when A. marina seedlings were exposed to different concentrations of zinc (Zn), copper (Cu) or lead (Pb) for 3 and 7 d. Real-time quantitative PCR results indicated that the regulation of AmMT2 mRNA expression by Zn, Cu and Pb was strongly dependent on concentration and time of exposure. A significant increase in the transcripts of AmMT2 gene was also found in response to Zn, Cu and Pb, at least under some experimental conditions. When AmMT2 was overexpressed in Escherichia coli BL21 as a carboxy-terminal extension of glutathione-S-transferase (GST), the transgenic bacteria showed an increased tolerance to Zn, Cu, Pb and Cd exposure as compared to control strains. Moreover, GST-AmMT2 was purified from E. coli cells grown in the presence of 400 {mu}M Zn, Cu, Pb or Cd. The purified GST-AmMT2 fusion protein could bind higher levels of all four metals than GST alone. Taken together, these data support the hypothesis that AmMT2 may be involved in processes of metal homeostasis or tolerance in A. marina.

  3. Papillomavirus infection of roe deer in the Czech Republic and fibropapilloma-associated levels of metallothionein, zinc, and oxidative stress

    Directory of Open Access Journals (Sweden)

    Jiří Král

    2015-01-01

    Full Text Available The present study aimed at the aetiological diagnosis of skin tumours of roe deer (Capreolus capreolus in the Czech Republic. A total of 33 roe deer specimens showing skin masses were sampled for histopathology, virus detection and identification using polymerase chain reaction (PCR and deoxyribonucleic acid sequence (DNA analysis, and to investigate fibropapilloma-associated levels of metallothionein, zinc and oxidative stress in 2012 and 2013. Ticks (Ixodes ricinus and deer keds (Lipoptena cervi were also collected and pooled from sampled game specimens. Ticks found on dogs in hunting grounds under study were pooled into another sample. Skin tumours, ranging from 2 to 10 per inspected specimen and 2 to 5 cm in size, were classified as fibropapillomas by histopathology. All 33 viral-infection-suspected skin samples from roe deer in South Moravia and South Bohemia were PCR positive. The nucleotide sequences of PCR products were 100% homologous to the Western roe deer papillomavirus 1 isolate CcPV-1. Ticks and deer keds from positive roe deer and ticks from dogs were PCR and DNA sequence positive for the roe deer papillomavirus. Viral DNA was also demonstrated in one blood sample from a roe deer female. Differences in metallothionein, zinc, taurine and electrochemical index among samples from lesions and normal skin of affected roe deer and negative controls from papillomavirus-non-infected animals were non-significant. While we have demonstrated circulation of specific roe deer papillomavirus in the Czech Republic that results in multiple fibropapillomatous skin tumours, many ecological and epidemiological issues of this wildlife disease still remain unanswered.

  4. Protective/detoxicative function of metallothionein in the rat brain and blood induced by controlled cadmium doses

    Directory of Open Access Journals (Sweden)

    H. N. Shiyntum

    2015-09-01

    Full Text Available Cadmiumclassified as a major carcinogen is considered a poisonous and unwanted heavy metal to a lot of tissues in many organisms. Of many publications already available, the general consensus is that the cadmium attenuating element is metallothionein (MT through its interchangeable mechanism with Zn triggered by the presence of Cd, providing binding sites for Cd ions. MT was first discovered in the kidney cortex of the horse; it represents a low molecular weight protein, rich in cysteine residues which effectively bind with metals. Its functions consist in detoxification of heavy metals like mercury, arsenic, cadmium, homeostasis of essential metals including copper and zinc, anti-oxidation against reactive oxygen species, protection against DNA damage, oxidative stress, cell survival, angiogenesis, apoptosis, and increase of proliferation. In this work, we sought to highlight the protective function of MT in the brain and serum of rats by means of detoxification under induced effects of controlled Cd doses. We have done this by exposing Wistar rats to Cd at different doses in drinking water at different time intervals. In two independent experiments, 58 rats were subjected to 0.1 or 1.0 µg Cd2+/kg of body weight for 15 or 36 days under different conditions. The obtained data indicates the different functioning systems for the brain and the blood for MT metabolism under Cd effect. Our results indicate significant loss of metallothionein level in the brain and important increases in the amount of MT in serum proving that even minimal ingestion of toxic Cd is enough to trigger the release of MT protein in blood.

  5. Expression and characterization analysis of type 2 metallothionein from grey mangrove species (Avicennia marina) in response to metal stress.

    Science.gov (United States)

    Huang, Guo-Yong; Wang, You-Shao

    2010-08-01

    Metallothioneins (MTs) are a family of low-molecular-weight cysteine-rich proteins and are thought to play possible roles in metal metabolism or detoxification. To evaluate the roles of metallothioneins in metal homeostasis or tolerance in Avicennia marina, a real-time quantitative PCR protocol was developed to directly evaluate the expression of AmMT2 mRNA, when A. marina seedlings were exposed to different concentrations of zinc (Zn), copper (Cu) or lead (Pb) for 3 and 7d. Real-time quantitative PCR results indicated that the regulation of AmMT2 mRNA expression by Zn, Cu and Pb was strongly dependent on concentration and time of exposure. A significant increase in the transcripts of AmMT2 gene was also found in response to Zn, Cu and Pb, at least under some experimental conditions. When AmMT2 was overexpressed in Escherichia coli BL21 as a carboxy-terminal extension of glutathione-S-transferase (GST), the transgenic bacteria showed an increased tolerance to Zn, Cu, Pb and Cd exposure as compared to control strains. Moreover, GST-AmMT2 was purified from E. coli cells grown in the presence of 400 microM Zn, Cu, Pb or Cd. The purified GST-AmMT2 fusion protein could bind higher levels of all four metals than GST alone. Taken together, these data support the hypothesis that AmMT2 may be involved in processes of metal homeostasis or tolerance in A. marina. Copyright 2010 Elsevier B.V. All rights reserved.

  6. Prophylactic penicillin by the full moon: a novel approach in Central Australia that may help to reduce the risk of rheumatic heart disease.

    Science.gov (United States)

    Kearns, T M; Schultz, R; McDonald, V; Andrews, R M

    2010-01-01

    Uptake of penicillin prophylaxis to prevent recurrent rheumatic fever and its sequela rheumatic heart disease (RHD) is not optimal in the Northern Territory of Australia. The Full Moon Strategy (the Strategy) was introduced in the Central Australian region in June 2006 to improve the uptake of prophylactic penicillin: clients and healthcare workers were encouraged to use the full moon as a cue for the timing of the 4 weekly prophylactic penicillin injection. To determine the impact and effectiveness of the Strategy on knowledge and uptake of benzathine penicillin prophylaxis for clients at risk of RHD, and for primary healthcare workers in Central Australia. Clients at risk of RHD in four remote Aboriginal communities and the town camps of Alice Springs were identified from the RHD database. Consenting clients or their carers were interviewed about their knowledge of the Strategy and the health promotional tools used. Their healthcare records were then reviewed for prophylaxis uptake 2 years prior to and 2 years following the introduction of the Strategy. Primary healthcare workers in the four remote communities who were available at the time of the study visit were interviewed about their knowledge and use of the Strategy and the health promotional tools. Fifty RHD clients and 19 healthcare workers were interviewed. Most were aware of the flipchart but less than half knew of the calendar poster, hand-held card or radio advertisement. Prophylaxis uptake increased significantly from 47% in the 2 years prior to the introduction of the Strategy, to 57% 2 years after the Strategy was introduced. Introduction of the Strategy coincided with an improvement in uptake of prophylaxis but not around the time of the full moon. Uptake of benzathine penicillin remains inadequate and further innovative measures are needed to control rheumatic fever and its sequela in Aboriginal and Torres Strait Islander people.

  7. Chlorhexidine gluconate or polyhexamethylene biguanide disc dressing to reduce the incidence of central-line-associated bloodstream infection: a feasibility randomized controlled trial (the CLABSI trial).

    Science.gov (United States)

    Webster, J; Larsen, E; Marsh, N; Choudhury, A; Harris, P; Rickard, C M

    2017-07-01

    A number of antimicrobial-impregnated discs to prevent central-line-associated bloodstream infection (CLABSI) are marketed but it is unclear which disc is most effective. To investigate the feasibility and safety of comparing two antimicrobial-impregnated discs to prevent CLABSI. A single-centre, parallel group, randomized controlled trial was conducted in a 929-bed tertiary referral hospital. Hospital inpatients requiring a peripherally inserted central catheter were randomized to chlorhexidine gluconate (CHG) or polyhexamethylene biguanide (PHMB) disc dressing group. Dressings were replaced every seven days, or earlier, if clinically required. Participants were followed until device removal or hospital discharge. Feasibility outcomes included: proportion of potentially eligible participants who were enrolled; proportion of protocol violations; and proportion of patients lost to follow-up. Clinical outcomes were: CLABSI incidence, diagnosed by a blinded infection control practitioner; all-cause bloodstream infection (BSI); and product-related adverse events. Of 143 patients screened, 101 (71%) were eligible. Five (3.5%) declined participation. There was one post-randomization exclusion. Two (2%) protocol violations occurred in the CHG group. No patients were lost to follow-up. Three (3%) BSIs occurred; two (2%) were confirmed CLABSIs (one in each group) and one a mucosal barrier injury-related BSI. A total of 1217 device-days were studied, resulting in 1.64 CLABSIs per 1000 catheter-days. One (1%) disc-related adverse event occurred in the CHG group. Disc dressings containing PHMB are safe to use for infection prevention at catheter insertion sites. An adequately powered trial to compare PHMB and CHG discs is feasible. Copyright © 2017 The Healthcare Infection Society. All rights reserved.

  8. Closing the Translation Gap: Toolkit-based Implementation of Universal Decolonization in Adult Intensive Care Units Reduces Central Line-associated Bloodstream Infections in 95 Community Hospitals.

    Science.gov (United States)

    Septimus, Edward; Hickok, Jason; Moody, Julia; Kleinman, Ken; Avery, Taliser R; Huang, Susan S; Platt, Richard; Perlin, Jonathan

    2016-07-15

    Challenges exist in implementing evidence-based strategies, reaching high compliance, and achieving desired outcomes. The rapid adoption of a publicly available toolkit featuring routine universal decolonization of intensive care unit (ICU) patients may affect catheter-related bloodstream infections. Implementation of universal decolonization-treatment of all ICU patients with chlorhexidine bathing and nasal mupirocin-used a prerelease version of a publicly available toolkit. Implementation in 136 adult ICUs in 95 acute care hospitals across the United States was supported by planning and deployment tactics coordinated by a central infection prevention team using toolkit resources, along with coaching calls and engagement of key stakeholders. Operational and process measures derived from a common electronic health record system provided real-time feedback about performance. Healthcare-associated central line-associated bloodstream infections (CLABSIs), using National Healthcare Safety Network surveillance definitions and comparing the preimplementation period of January 2011 through December 2012 to the postimplementation period of July 2013 through February 2014, were assessed via a Poisson generalized linear mixed model regression for CLABSI events. Implementation of universal decolonization was completed within 6 months. The estimated rate of CLABSI decreased by 23.5% (95% confidence interval, 9.8%-35.1%; P = .001). There was no evidence of a trend over time in either the pre- or postimplementation period. Adjusting for seasonality and number of beds did not materially affect these results. Dissemination of universal decolonization of ICU patients was accomplished quickly in a large community health system and was associated with declines in CLABSI consistent with published clinical trial findings. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  9. Desulfonatronovibrio halophilus sp. nov., a novel moderately halophilic sulfate-reducing bacterium from hypersaline chloride-sulfate lakes in Central Asia

    NARCIS (Netherlands)

    Sorokin, D.Y.; Tourova, T.P.; Abbas, B.; Suhacheva, M.V.; Muyzer, G.

    2012-01-01

    Four strains of lithotrophic sulfate-reducing bacteria (SRB) have been enriched and isolated from anoxic sediments of hypersaline chloride-sulfate lakes in the Kulunda Steppe (Altai, Russia) at 2 M NaCl and pH 7.5. According to the 16S rRNA gene sequence analysis, the isolates were closely related

  10. Effect of metallothionein core promoter region polymorphism on cadmium, zinc and copper levels in autopsy kidney tissues from a Turkish population

    International Nuclear Information System (INIS)

    Kayaalti, Zeliha; Mergen, Goerkem; Soeylemezoglu, Tuelin

    2010-01-01

    Metallothioneins (MTs) are metal-binding, low molecular weight proteins and are involved in pathophysiological processes like metabolism of essential metals, metal ion homeostasis and detoxification of heavy metals. Metallothionein expression is induced by various heavy metals especially cadmium, mercury and zinc; MTs suppress toxicity of heavy metals by binding themselves to these metals. The aim of this study was to investigate the association between the - 5 A/G metallothionein 2A (MT2A) single nucleotide polymorphism (SNP) and Cd, Zn and Cu levels in the renal cortex from autopsy cases. MT2A core promoter region - 5 A/G SNP was analyzed by PCR-RFLP method using 114 autopsy kidney tissues and the genotype frequencies of this polymorphism were found as 87.7% homozygote typical (AA), 11.4% heterozygote (AG) and 0.9% homozygote atypical (GG). In order to assess the Cd, Zn and Cu levels in the same autopsy kidney tissues, a dual atomic absorption spectrophotometer system was used and the average levels of Cd, Zn and Cu were measured as 95.54 ± 65.58 μg/g, 181.20 ± 87.72 μg/g and 17.14 ± 16.28 μg/g, respectively. As a result, no statistical association was found between the - 5 A/G SNP in the MT2A gene and the Zn and Cu levels in the renal cortex (p > 0.05), but considerably high accumulation of Cd was monitored for individuals having AG (151.24 ± 60.21 μg/g) and GG genotypes (153.09 μg/g) compared with individuals having AA genotype (87.72 ± 62.98 μg/g) (p < 0.05). These results show that the core promoter region polymorphism of metallothionein 2A increases the accumulation of Cd in human renal cortex.

  11. Particle image velocimetry-validated, computational fluid dynamics-based design to reduce shear stress and residence time in central venous hemodialysis catheters.

    Science.gov (United States)

    Mareels, Guy; Kaminsky, Radoslav; Eloot, Sunny; Verdonck, Pascal R

    2007-01-01

    As crucial factors in blood clot formation, shear stress distribution and low flow zones are assessed in different central venous catheter tip designs by using a combined numeric and experimental approach. Computational Fluid Dynamics was validated with Particle Image Velocimetry by comparing simulated and measured velocities and shear strains in three designs of the blood withdrawing arterial lumen: cylindrical and with tip (1) cut straight, (2) cut at an angle, or (3) cut straight with a sleeve entrance. After validation, four additional designs were studied: (4) with two side holes and tip cut straight or (5) at an angle, (6) concentric lumens, and (7) Ash Split-based. In these seven designs, shear stress (SS), blood residence time (RT), and Platelet Lysis Index, which combines the influence of shear stress magnitude and exposure time, were simulated. Concentric catheter was discarded due to highly elevated SS. Ash Split-based design had elevated RT values in the distal tip zone as major inflow occurs through the most proximal side holes, but this is compensated by low average SS. A straight-cut tip and possibly two side holes are preferred when aiming at minimal SS and RT. These data may lead to more patent catheters.

  12. Behavioral and hygienic characteristics of primary schoolchildren which can be modified to reduce the prevalence of geohelminth infections: a study in central Java, Indonesia.

    Science.gov (United States)

    Albright, Julia W; Hidayati, Nur Rokhmah; Basaric-Keys, Jasna

    2005-05-01

    Five schools in central Java that enroll more than 500 students in grades one through six were chosen for a study of the prevalence of parasitic geohelminths and selected protozoan infections. The schools are located in regions that differ in geological features, density of vegetation and cultural and economic attributes. The prevalence of soil-transmitted helminths among children in the five schools ranged from 8.7% to 76.1%, and protozoan infections from 2.8% to 32.1%. The principal objective of the study was to identify physical, hygienic and behavioral characteristics of the children that increase the likelihood of becoming infected. Although most of the characteristics studied are considered to be contributing factors, few previous attempts have been made to rank them in order of importance in causing infection. The results of this study suggest that a systematic and sustained effort to teach children to (a) avoid certain types of behavior that favor infection, and (b) practice good personal hygiene, are the best approaches to significant and enduring reduction of the scourge of intestinal parasitism.

  13. How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial [ISRCTN75884221

    Directory of Open Access Journals (Sweden)

    Blanchard Colline

    2006-05-01

    Full Text Available Abstract Background Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop®, Smith-Nephew provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW infants during insertion of a PICC. Methods Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP. A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. Results Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58. Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117. Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group. No serious harms were observed. Conclusion Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants.

  14. Response of the common cutworm Spodoptera litura to zinc stress: Zn accumulation, metallothionein and cell ultrastructure of the midgut

    Energy Technology Data Exchange (ETDEWEB)

    Shu, Yinghua [Key Laboratory of Agro-Environments in Tropics, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642 (China); Key Laboratory of Agroecology and Rural Environment of Guangdong Regular Higher Education Institutions, South China Agricultural University, Guangzhou 510642 (China); Institute of Tropical and Subtropical Ecology, South China Agricultural University, Guangzhou 510642 (China); State Key Laboratory of Biological Control and Institute of Entomology, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Guren [State Key Laboratory of Biological Control and Institute of Entomology, Sun Yat-sen University, Guangzhou 510275 (China); Wang, Jianwu, E-mail: wangjw@scau.edu.cn [Key Laboratory of Agro-Environments in Tropics, Ministry of Agriculture, South China Agricultural University, Guangzhou 510642 (China); Key Laboratory of Agroecology and Rural Environment of Guangdong Regular Higher Education Institutions, South China Agricultural University, Guangzhou 510642 (China); Institute of Tropical and Subtropical Ecology, South China Agricultural University, Guangzhou 510642 (China)

    2012-11-01

    By exposing the common cutworm Spodoptera litura Fabricius larvae to a range of Zinc (Zn) stress, we investigated the effects of dietary Zn on Zn accumulation, metallothionein (MT), and on the ultrastructure of the midgut. The techniques we used were inductively coupled plasma-atomic emission spectrometer (ICP-AES), real-time PCR combined with cadmium-hemoglobin total saturation, and transmission electron microscopy (TEM), respectively. There was a significant dose-response relationship between the Zn accumulations in the midgut of the larvae and the Zn concentrations in the diet. Furthermore, both MT content and MT gene expression in the midgut were significantly induced in the 50-500 mg Zn/kg treatments, and were significantly positively correlated with the Zn accumulations in the midgut. When S. litura larvae were fed with the diet treated with 500 mg Zn/kg, Zn accumulation and MT content in the midgut was 4450.85 mg Zn/kg and 372.77 mg/kg, respectively, thereafter there was a little increase; the level of MT gene expression was maximal, thereafter there was a sharp decrease. TEM showed that numerous electron-dense granules (EDGs) and vacuoles appeared in the cytoplasm of the midgut cells, their number and size being closely correlated with the Zn accumulations in the midgut. Moreover, the nuclei were strongly influenced by Zn stress, evidenced by chromatin condensation and irregular nuclear membranes. Therefore, after being exposed to Zn in the threshold (500 mg Zn/kg) range, S. litura larvae could accumulate Zn in the midgut, which led to the induction of MT and changes in cell ultrastructure (mainly the presence of EDGs). The induction of MT and precipitation of Zn in EDGs may be the effective detoxification mechanisms by which the herbivorous insect S. litura defends itself against heavy metals. -- Graphical abstract: When the herbivorous insect Spodoptera litura Fabricius larvae were fed on the artificial diet with different concentrations of Zn, amounts of

  15. The Effort to Reduce a Muscle Fatigue Through Gymnastics Relaxation and Ergonomic Approach for Computer Users in Central Building State University of Medan

    Science.gov (United States)

    Gultom, Syamsul; Darma Sitepu, Indra; Hasibuan, Nurman

    2018-03-01

    Fatigue due to long and continuous computer usage can lead to problems of dominant fatigue associated with decreased performance and work motivation. Specific targets in the first phase have been achieved in this research such as: (1) Identified complaints on workers using computers, using the Bourdon Wiersma test kit. (2) Finding the right relaxation & work posture draft for a solution to reduce muscle fatigue in computer-based workers. The type of research used in this study is research and development method which aims to produce the products or refine existing products. The final product is a prototype of back-holder, monitoring filter and arranging a relaxation exercise as well as the manual book how to do this while in front of the computer to lower the fatigue level for computer users in Unimed’s Administration Center. In the first phase, observations and interviews have been conducted and identified the level of fatigue on the employees of computer users at Uniemd’s Administration Center using Bourdon Wiersma test and has obtained the following results: (1) The average velocity time of respondents in BAUK, BAAK and BAPSI after working with the value of interpretation of the speed obtained value of 8.4, WS 13 was in a good enough category, (2) The average of accuracy of respondents in BAUK, in BAAK and in BAPSI after working with interpretation value accuracy obtained Value of 5.5, WS 8 was in doubt-category. This result shows that computer users experienced a significant tiredness at the Unimed Administration Center, (3) the consistency of the average of the result in measuring tiredness level on computer users in Unimed’s Administration Center after working with values in consistency of interpretation obtained Value of 5.5 with WS 8 was put in a doubt-category, which means computer user in The Unimed Administration Center suffered an extreme fatigue. In phase II, based on the results of the first phase in this research, the researcher offers

  16. Reducing the global threat of radiological terrorism in Central Asia and Caucus regions. The global threat reduction initiative approach to radioactive source security

    International Nuclear Information System (INIS)

    Smith, E.

    2010-01-01

    The security of radioactive sources is of worldwide concern, due to their wide use in civilian commerce and the potentially devastating effects of their misuse. In cooperation with host countries and international partners, the Global Threat Reduction Initiative has utilized a proven process for providing technical and financial assistance to protect radioactive sources in diverse uses and unique circumstances at hundreds of sites worldwide. The mission of the Department of Energy, National Nuclear Security Administration's program includes reducing the risk posed by vulnerable radiological materials that could be used in a Radioactive Dispersal Device). The program's objectives are to identify, consolidate, secure, and/or dispose of high-activity radiological materials to prevent their theft and malicious use. The Global Threat Reduction Initiative Program's scope is global, with projects in over 100 countries at more than 755 radiological sites, including industrial, medical and commercial facilities. In addition to working bilaterally, the Program works closely with the International Atomic Energy Agency (IAEA) and other partner countries. (author)

  17. Reducing Greenhouse Gas Emissions in Grassland Ecosystems of the Central Lithuania: Multi-Criteria Evaluation on a Basis of the ARAS Method

    Directory of Open Access Journals (Sweden)

    Ligita Balezentiene

    2012-01-01

    Full Text Available N2O, CH4, and CO2 are potential greenhouse gas (GHG contributing to climate change; therefore, solutions have to be sought to reduce their emission from agriculture. This work evaluates GHG emission from grasslands submitted to different mineral fertilizers during vegetation period (June–September in two experimental sites, namely, seminatural grassland (8 treatments of mineral fertilizers and cultural pasture (intensively managed in the Training Farm of the Lithuanian University of Agriculture. Chamber method was applied for evaluation of GHG emissions on the field scale. As a result, soil chemical composition, compactness, temperature, and gravimetric moisture as well as biomass yield of fresh and dry biomass and botanical composition, were assessed during the research. Furthermore, a simulation of multi-criteria assessment of sustainable fertilizers management was carried out on a basis of ARAS method. The multicriteria analysis of different fertilizing regimes was based on a system of environmental and productivity indices. Consequently, agroecosystems of cultural pasture (N180P120K150 and seminatural grassland fertilizing rates N180P120K150 and N60P40K50 were evaluated as the most sustainable alternatives leading to reduction of emissions between biosphere-atmosphere and human-induced biogenic pollution in grassland ecosystems, thus contributing to improvement of countryside environment.

  18. Metallothionein-III protects against 6-hydroxydopamine-induced oxidative stress by increasing expression of heme oxygenase-1 in a PI3K and ERK/Nrf2-dependent manner

    International Nuclear Information System (INIS)

    Hwang, Yong Pil; Kim, Hyung Gyun; Han, Eun Hee; Jeong, Hye Gwang

    2008-01-01

    The zinc-binding protein metallothionein-III (MT-III) is associated with resistance to neuronal injury. However, the underlying mechanism for its effects is unclear. In this study, we demonstrate that MT-III prevents the accumulation of reactive oxygen species (ROS) in dopaminergic SH-SY5Y cells challenged with the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA) by a mechanism that involves phosphatidylinositol 3-kinase (PI3K) and ERK kinase/NF-E2-related factor 2 (Nrf2) dependent induction of the stress response protein heme oxygenase-1 (HO-1). Pretreatment of SH-SY5Y cells with MT-III significantly reduced 6-OHDA-induced generation of ROS, caspase-3 activation, and subsequent cell death. Also, MT-III up-regulates HO-1 expression and this expression confers neuroprotection against oxidative injury induced by 6-OHDA. Moreover, MT-III induces Nrf2 nuclear translocation, which is upstream of MT-III-induced HO-1 expression, and PI3K and ERK1/2 activation, a pathway that is involved in induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. Taken together, these results suggest that the PI3K and ERK/Nrf2 signaling pathway controls the intracellular levels of ROS by regulating the expression of the antioxidant enzyme HO-1

  19. Prevention of hospital infections by intervention and training (PROHIBIT): results of a pan-European cluster-randomized multicentre study to reduce central venous catheter-related bloodstream infections.

    Science.gov (United States)

    van der Kooi, Tjallie; Sax, Hugo; Pittet, Didier; van Dissel, Jaap; van Benthem, Birgit; Walder, Bernhard; Cartier, Vanessa; Clack, Lauren; de Greeff, Sabine; Wolkewitz, Martin; Hieke, Stefanie; Boshuizen, Hendriek; van de Kassteele, Jan; Van den Abeele, Annemie; Boo, Teck Wee; Diab-Elschahawi, Magda; Dumpis, Uga; Ghita, Camelia; FitzGerald, Susan; Lejko, Tatjana; Leleu, Kris; Martinez, Mercedes Palomar; Paniara, Olga; Patyi, Márta; Schab, Paweł; Raglio, Annibale; Szilágyi, Emese; Ziętkiewicz, Mirosław; Wu, Albert W; Grundmann, Hajo; Zingg, Walter

    2018-01-01

    To test the effectiveness of a central venous catheter (CVC) insertion strategy and a hand hygiene (HH) improvement strategy to prevent central venous catheter-related bloodstream infections (CRBSI) in European intensive care units (ICUs), measuring both process and outcome indicators. Adult ICUs from 14 hospitals in 11 European countries participated in this stepped-wedge cluster randomised controlled multicentre intervention study. After a 6 month baseline, three hospitals were randomised to one of three interventions every quarter: (1) CVC insertion strategy (CVCi); (2) HH promotion strategy (HHi); and (3) both interventions combined (COMBi). Primary outcome was prospective CRBSI incidence density. Secondary outcomes were a CVC insertion score and HH compliance. Overall 25,348 patients with 35,831 CVCs were included. CRBSI incidence density decreased from 2.4/1000 CVC-days at baseline to 0.9/1000 (p < 0.0001). When adjusted for patient and CVC characteristics all three interventions significantly reduced CRBSI incidence density. When additionally adjusted for the baseline decreasing trend, the HHi and COMBi arms were still effective. CVC insertion scores and HH compliance increased significantly with all three interventions. This study demonstrates that multimodal prevention strategies aiming at improving CVC insertion practice and HH reduce CRBSI in diverse European ICUs. Compliance explained CRBSI reduction and future quality improvement studies should encourage measuring process indicators.

  20. Treatment with metallothionein prevents demyelination and axonal damage and increases oligodendrocyte precursors and tissue repair during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Penkowa, Milena; Hidalgo, Juan

    2003-01-01

    and neuroprotective proteins that are expressed during EAE and MS. We have shown recently that exogenous administration of Zn-MT-II to Lewis rats with EAE significantly reduced clinical symptoms and the inflammatory response, oxidative stress, and apoptosis of the infiltrated central nervous system areas. We show...... for the first time that Zn-MT-II treatment during EAE significantly prevents demyelination and axonal damage and transection, and stimulates oligodendroglial regeneration from precursor cells, as well as the expression of the growth factors basic fibroblast growth factor (bFGF), transforming growth factor (TGF...

  1. Long-term consumption of dried bonito dashi (a traditional Japanese fish stock) reduces anxiety and modifies central amino acid levels in rats.

    Science.gov (United States)

    Funatsu, Shoichiro; Kondoh, Takashi; Kawase, Takahiro; Ikeda, Hiromi; Nagasawa, Mao; Denbow, D Michael; Furuse, Mitsuhiro

    2015-08-01

    Dried bonito dashi, a traditional Japanese fish stock, enhances palatability of various dishes because of its specific flavor. Daily intake of dashi has also been shown to improve mood status such as tension-anxiety in humans. This study aimed at investigating beneficial effects of dashi ingestion on anxiety/depression-like behaviors and changes in amino acid levels in the brain and plasma in rats. Male Wistar rats were given either dried bonito dashi or water for long-term (29 days; Experiment 1) or single oral administration (Experiment 2). Anxiety and depression-like behaviors were tested using the open field and forced swimming tests, respectively. Concentrations of amino acids were measured in the hippocampus, hypothalamus, cerebellum, and jugular vein. During the long-term (29 days) consumption, rats given 2% dashi frequently entered the center zone and spent more time compared with the water controls in the open field test. However, the dashi was ineffective on depression-like behavior. In the hippocampus, concentrations of hydroxyproline, anserine, and valine were increased by dashi while those of asparagine and phenylalanine were decreased. In the hypothalamus, the methionine concentration was decreased. In a single oral administration experiment, the dashi (1%, 2% or 10%) showed no effects on behaviors. Significance was observed only in the concentrations of α-aminoadipic acid, cystathionine, and ornithine in the hippocampus. Dried bonito dashi is a functional food having anxiolytic-like effects. Daily ingestion of the dashi, even at lower concentrations found in the cuisine, reduces anxiety and alters amino acid levels in the brain.

  2. Does antimicrobial lock solution reduce catheter-related infections in hemodialysis patients with central venous catheters? A Bayesian network meta-analysis.

    Science.gov (United States)

    Zhang, Jun; Wang, Bo; Li, Rongke; Ge, Long; Chen, Kee-Hsin; Tian, Jinhui

    2017-04-01

    The purpose of our study is to carry out a Bayesian network meta-analysis comparing the efficacy of different antimicrobial lock solutions (ALS) for prevention of catheter-related infections (CRI) in patients with hemodialysis (HD) and ranking these ALS for practical consideration. We searched six electronic databases, earlier relevant meta-analysis and reference lists of included studies for randomized controlled trials (RCTs) that compared ALS for preventing episodes of CRI in patients with HD either head-to-head or against control interventions using non-ALS. Two authors independently assessed the methodological quality of included studies using the Cochrane risk of bias tool and extracted relevant information according to a predesigned extraction form. Data were analysed using the WinBUGS (V.1.4.3) and the Stata (V.13.0). Finally, 18 studies involving 2395 patients and evaluating 9 ALS strategies were included. Network meta-analysis showed that gentamicin plus citrate (OR 0.07, 95% CrI 0.00-0.48) and gentamicin plus heparin (OR 0.04, 95% CrI 0.00-0.23) were statistically superior to heparin alone in terms of reducing CRBSI. For exit site infection and all-cause mortality, no significant difference in the intervention effect (p > 0.05) was detected for all included ALS when compared to heparin. Moreover, all ALS were similar in efficacy (p > 0.05) from each other for CRBSI, exit site infection and all-cause mortality. Our findings indicated that gentamicin plus heparin may be selected for the prophylaxis of CRI in patients undergoing HD with CVCs. Whether this strategy will lead to antimicrobial resistance remains unclear in view of the relatively short duration of included studies. More attentions should be made regarding head-to-head comparisons of the most commonly used ALS in this field.

  3. Evaluating the Long-Term Health and Economic Impacts of Central Residential Air Filtration for Reducing Premature Mortality Associated with Indoor Fine Particulate Matter (PM2.5 of Outdoor Origin

    Directory of Open Access Journals (Sweden)

    Dan Zhao

    2015-07-01

    Full Text Available Much of human exposure to fine particulate matter (PM2.5 of outdoor origin occurs in residences. High-efficiency particle air filtration in central heating, ventilating, and air-conditioning (HVAC systems is increasingly being used to reduce concentrations of particulate matter inside homes. However, questions remain about the effectiveness of filtration for reducing exposures to PM2.5 of outdoor origin and adverse health outcomes. Here we integrate epidemiology functions and mass balance modeling to estimate the long-term health and economic impacts of HVAC filtration for reducing premature mortality associated with indoor PM2.5 of outdoor origin in residences. We evaluate 11 classifications of filters (MERV 5 through HEPA using six case studies of single-family home vintages and ventilation system combinations located in 22 U.S. cities. We estimate that widespread use of higher efficiency filters would reduce premature mortality by 0.002–2.5% and increase life expectancy by 0.02–1.6 months, yielding annual monetary benefits ranging from $1 to $1348 per person in the homes and locations modeled herein. Large differences in the magnitude of health and economic impacts are driven largely by differences in rated filter efficiency and building and ventilation system characteristics that govern particle infiltration and persistence, with smaller influences attributable to geographic location.

  4. Oncoplastic central quadrantectomies

    Science.gov (United States)

    Pasta, Vittorio; D’Orazi, Valerio; Merola, Raffaele; Frusone, Federico; Amabile, Maria Ida; Buè, Rosanna; Monti, Marco

    2016-01-01

    Tumors localized in the central quadrant (centrally located breast tumors) have always represented a challenge for the surgeon because of the critical aesthetical matters related to the nipple-areola complex (NAC). Many years of experience with breast cancer patients treated by using various oncoplastic techniques, has allowed us to develop the modified hemibatwing for the treatment of central breast tumors, where the NAC is involved. Modified hemibatwing—along with the removal of the NAC—is a useful oncoplastic technique and it represents an ideal option for the treatment of central tumors because it assures oncological safety, a reduced surgical timetable and greater aesthetical results. PMID:27563564

  5. Is the digestive gland of Mytilus galloprovincialis a tissue of choice for estimating cadmium exposure by means of metallothioneins?

    International Nuclear Information System (INIS)

    Raspor, Biserka; Dragun, Zrinka; Erk, Marijana; Ivankovic, Dusica; Pavicic, Jasenka

    2004-01-01

    A study performed over 12 months with caged mussels Mytilus galloprovincialis in the coastal marine zone, which is under urban pressure, reveals a temporal variation of digestive gland mass, which causes 'biological dilution' of cytosolic metallothionein (MT) and trace metal (Cd, Cu, Zn, Fe, Mn) concentrations. The dilution effect was corrected by expressing the cytosolic MT and metal concentrations as the tissue content. Consequently, the changes of the average digestive gland mass coincide with the changes of MT and trace metal contents. From February to June, MT contents are nearly twice and trace metal contents nearly three times higher than those of the other months. The period of increased average digestive gland mass, of MT and trace metal contents probably overlaps with the sexual maturation of mussels (gametogenesis) and enhanced food availability. Since natural factors contribute more to the MT content than the sublethal levels of Cd, the digestive gland of M. galloprovincialis is not considered as a tissue of choice for estimating Cd exposure by means of MTs

  6. Fluorescence-tagged metallothionein with CdTe quantum dots analyzed by the chip-CE technique

    Energy Technology Data Exchange (ETDEWEB)

    Guszpit, Ewelina, E-mail: ewelina.guszpit@gmail.com [Wroclaw Medical University, Department of Biomedical and Environmental Analysis, Faculty of Pharmacy (Poland); Krizkova, Sona [Mendel University in Brno, Department of Chemistry and Biochemistry, Faculty of Agronomy (Czech Republic); Kepinska, Marta [Wroclaw Medical University, Department of Biomedical and Environmental Analysis, Faculty of Pharmacy (Poland); Rodrigo, Miguel Angel Merlos [Mendel University in Brno, Department of Chemistry and Biochemistry, Faculty of Agronomy (Czech Republic); Milnerowicz, Halina [Wroclaw Medical University, Department of Biomedical and Environmental Analysis, Faculty of Pharmacy (Poland); Kopel, Pavel; Kizek, Rene [Mendel University in Brno, Department of Chemistry and Biochemistry, Faculty of Agronomy (Czech Republic)

    2015-11-15

    Quantum dots (QDs) are fluorescence nanoparticles (NPs) with unique optic properties which allow their use as probes in chemical, biological, immunological, and molecular imaging. QDs linked with target ligands such as peptides or small molecules can be used as tumor biomarkers. These particles are a promising tool for selective, fast, and sensitive tagging and imaging in medicine. In this study, an attempt was made to use QDs as a marker for human metallothionein (MT) isoforms 1 and 2. Four kinds of CdTe QDs of different sizes bioconjugated with MT were analyzed using the chip-CE technique. Based on the results, it can be concluded that MT is willing to interact with QDs, and the chip-CE technique enables the observation of their complexes. It was also observed that changes ranging roughly 6–7 kDa, a value corresponding to the MT monomer, depend on the hydrodynamic diameters of QDs; also, the MT sample without cadmium interacted stronger with QDs than MT saturated with cadmium. Results show that MT is willing to interact with smaller QDs (blue CdTe) rather than larger ones QDs (red CdTe). To our knowledge, chip-CE has not previously been applied in the study of CdTe QDs interaction with MT.Graphical Abstract.

  7. Prion protein and its interactions with metal ions (Cu2+, Zn2+, and Cd2+ and metallothionein 3

    Directory of Open Access Journals (Sweden)

    Branislav Ruttkay-Nedecky

    2015-09-01

    Full Text Available The effects of heavy metals (Zn2+, Cu2+, and/or Cd2+ on Escherichia coli expressing either prion (hPrPC or metallothionein 3 (MT-3 brain proteins capable of binding these metals were investigated. The expression of hPrPC or MT-3 in E.coli was confirmed using western-blot and dot-blot methods. After analyzing growth curves, we found that bacteria expressing prion protein better tolerated the presence of Zn2+ in comparison with wild-type bacteria and bacteria expressing MT-3. The addition of Cd2+ and Cu2+ was well tolerated by bacteria expressing MT-3, whereas the bacteria expressing prion protein displayed slower growth when compared to the wild-type. We subsequently determined total content of the MT in bacteria using differential pulsed voltammetry (DPV, and depending on the treatment of the individual metals. MT expression in MT3 transformed cells as well as in control E.coli cells increased at the lowest metal concentration (25 µM, followed by a decrease at higher metal concentrations (50, 75, and 150 µM. The highest increase by Cd2+ were observed.  MT expression pattern in hPrPC transformed cells was different. After application of Cu2+ an increase in MT expression continued also at higher metal concentrations; and after application of Cd2+ and Zn2+ no decrease in MT expression at higher metal concentrations was observed.

  8. Expression and function analysis of metallothionein in the testis of stone crab Charybdis japonica exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Mao Huan [Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Tan Fuqing [The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou (China); Wang Dahui [Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Zhu Junquan [Faculty of Life Science and Bioengineering, Ningbo University, Zhejiang 315211 (China); Zhou Hong [Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China); Yang Wanxi, E-mail: wxyang@spermlab.org [Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058 (China)

    2012-11-15

    Metallothionein (MT) participates in metallic homeostasis and detoxification in living animals. Previous studies have focused mainly on the functions of MT in vertebrates, but the functions of MT during spermiogenesis in invertebrates remain unclear. In order to investigate the functions of MT during spermiogenesis in the Japanese stone crab (Charybdis japonica), we identified the C. japonica MT complete cDNA sequence from the total RNA of the testis using RT-PCR and RACE. The 587 bp MT cDNA contains: an 80 bp 5 Prime untranslated region, a 333 bp 3 Prime untranslated region, and a 174 bp open reading frame. MT has 57 amino acids including 19 cysteines. The protein alignment between MT sequences of C. japonica and other crabs shows a high similarity and a strong identity in cysteine residues vital for the metal-binding affinity of MT. After the cadmium (Cd) exposure, the testis displays both abnormal morphology and MT mRNA expression both of which indicate a sensitive response of testis MT to Cd. Therefore, we suggest that MT is an excellent biomarker candidate for evaluating Cd pollution.

  9. Metallothionein Induction in the Coelomic Fluid of the Earthworm Lumbricus terrestris following Heavy Metal Exposure: A Short Report

    Directory of Open Access Journals (Sweden)

    A. Calisi

    2014-01-01

    Full Text Available Earthworms are useful bioindicator organisms for soil biomonitoring. Recently the use of pollution biomarkers in earthworms has been increasingly investigated for soil monitoring and assessment. Earthworm coelomic fluid is particularly interesting from a toxicological perspective, because it is responsible for pollutant disposition and tissue distribution to the whole organism. The aim of the present work was to study the effect of heavy metal exposure on metallothionein (Mt induction in the coelomic fluid of Lumbricus terrestris in view of future use as sensitive biomarker suitable for application to metal polluted soil monitoring and assessment. L. terrestris coelomic fluid showed a detectable Mt concentration of about 4.0±0.6 μg/mL (mean ± SEM, n=10 in basal physiological condition. When the animals were exposed to CuSO4 or CdCl2 or to a mixture of the two metals in OECD soils for 72 h, the Mt specific concentration significantly (P<0.001 increased. The Mt response in the coelomic fluid perfectly reflected the commonly used Mt response in the whole organism when the two responses were compared on the same specimens. These findings indicate the suitability of Mt determination in L. terrestris coelomic fluid as a sensitive biomarker for application to metal polluted soil monitoring and assessment.

  10. Relation between metallothionein, RNA/DNA and heavy metals in juveniles of colossoma macropomun (Cuvier, 1818 in natural conditions

    Directory of Open Access Journals (Sweden)

    Lemus M.

    2013-04-01

    Full Text Available Metal content, Metallotionein and physiological condition (RNA/DNA ratio were analyzed in Cachama, Colossoma macropomum from the Orinoco River. Juvenile samples were dissected and one gram of white muscle gills, kidney and liver was taken. Cu, Cd, Pb, Ni and Fe were analyzed by atomic absorption spectrophotometer using TORT and LUTSI as reference material. Metallothioneins were determined with Ellman´s reagent and RNA/DNA ratio was analyzed by fluorometric method. Results showed that Cd, Cu, Ni, Fe, and Pb levels were significantly higher in liver than muscle. There was no difference statistically between Mts concentrations in liver, kidney and gills; muscle showed the lowest Mts concentrations. Multivariate analysis ACP determined relationship between Mts-L and Cu and Mts-G and Cd. The Mts in muscle was related with Pb and Cd. There was no association between physiological condition and metals concentrations, however, the RNA/ DNA showed relationship with Mts-M and Mts-L

  11. Metallothionein-1+2 deficiency increases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin 6

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Hernández, Joaquín

    2002-01-01

    Transgenic expression of IL-6 under the control of the GFAP gene promoter (GFAP-IL6 mice) in the CNS causes significant damage and alters the expression of many genes, including the metallothionein (MT) family, especially in the cerebellum. The crossing of GFAP-IL6 mice with MT-1+2 knock out (MTKO......) mice provided evidence that the increased MT-1+2 expression normally observed in the GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, the GFAP-IL6xMTKO mice showed a decreased body weight gain and an impaired performance in the rota-rod test, as well as a higher upregulation...... of cytokines such as IL-6, IL-1alpha,beta, and TNFalpha and recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. Clear symptoms of increased oxidative stress and apoptotic cell death caused by MT-1+2 deficiency were observed in the GFAP-IL6xMTKO mice...

  12. Metallothionein-I overexpression decreases brain pathology in transgenic mice with astrocyte-targeted expression of interleukin-6

    DEFF Research Database (Denmark)

    Molinero, Amalia; Penkowa, Milena; Hernández, Joaquín

    2003-01-01

    Transgenic expression of interleukin-6 (IL-6) in the CNS under the control of the glial fibrillary acidic protein (GFAP) gene promoter (GFAP-IL6 mice) causes significant damage and alters the expression of many genes, including a dramatic upregulation of metallothionein-I (MT-I). The findings...... in this report support the idea that the upregulation of MT-I observed in GFAP-IL6 mice is an important mechanism for coping with brain damage. Thus, GFAP-IL6 mice that were crossed with TgMTI transgenic mice (GFAP-IL6xTgMTI) and overexpressed MT-I in the brain showed a decreased upregulation of cytokines...... such as IL-6 and a diminished recruitment and activation of macrophages and T cells throughout the CNS but mainly in the cerebellum. The GFAP-IL6 mice showed clear evidence of increased oxidative stress, which was significantly decreased by MT-I overexpression. Interestingly, MT-I overexpression increased...

  13. Pressurized liquid extraction-assisted mussel cytosol preparation for the determination of metals bound to metallothionein-like proteins

    International Nuclear Information System (INIS)

    Santiago-Rivas, Sandra; Moreda-Pineiro, Antonio; Bermejo-Barrera, Pilar; Moreda-Pineiro, Jorge; Alonso-Rodriguez, Elia; Muniategui-Lorenzo, Soledad; Lopez-Mahia, Purificacion; Prada-Rodriguez, Dario

    2007-01-01

    The possibilities of pressurized liquid extraction (PLE) have been novelty tested to assist the cytosol preparation from wet mussel soft tissue before the determination of metals bound to metallothionein-like proteins (MLPs). Results obtained after PLE were compared with those obtained after a classical blending procedure for mussel cytosolic preparation. Isoforms MLP-1 (retention time of 4.1 min) and MLP-2 (retention time of 7.4 min) were separated by anion exchange high-performance liquid chromatography (HPLC) and the concentrations of Ba, Cu, Mn, Sr and Zn bound to MLP isoforms were directly measured by inductively coupled plasma-atomic emission spectrometry (ICP-OES) as a multi-element detector. The optimized PLE-assisted mussel cytosol preparation has consisted of one extraction cycle at room temperature and 1500 psi for 2 min. Since separation between the solid mussel residue and the extract (cytosol) is performed by the PLE system, the cytosol preparation method is faster than conventional cytosol preparation methods by cutting/blending using Ultraturrax or Stomacher devices

  14. Metallothionein-II Inhibits Lipid Peroxidation and Improves Functional Recovery after Transient Brain Ischemia and Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Araceli Diaz-Ruiz

    2014-01-01

    Full Text Available After transient cerebral ischemia and reperfusion (I/R, damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats. Male Wistar rats were transiently occluded at the middle cerebral artery for 2 h, followed by reperfusion. Rats received either MT (10 μg per rat i.p. or vehicle after ischemia. Lipid peroxidation (LP was measured 22 h after reperfusion in frontal cortex and hippocampus; also, neurological deficit was evaluated after ischemia, using the Longa scoring scale. Infarction area was analyzed 72 hours after ischemia. Results showed increased LP in frontal cortex (30.7% and hippocampus (26.4%, as compared to control group; this effect was fully reversed by MT treatment. Likewise, we also observed a diminished neurological deficit assessed by the Longa scale in those animals treated with MT compared to control group values. The MT-treated group showed a significant (P<0.05 reduction of 39.9% in the infarction area, only at the level of hippocampus, as compared to control group. Results suggest that MT-II may be a novel neuroprotective treatment to prevent ischemia injury.

  15. CYP1A and metallothionein expression in the hepatopancreas of Merluccius merluccius and Mullus barbatus from the Adriatic Sea

    Directory of Open Access Journals (Sweden)

    MIRJANA MIHAILOVIĆ

    2010-08-01

    Full Text Available The enzyme CYP1A is an established biomarker of fish exposure to polycyclic aromatic hydrocarbons (PAHs and polychlorinated biphenyls (PCBs. The metallothioneins (MT, a family of Cys-rich proteins, bind a wide range of metals and participate in their metabolism. The aim of the study was to examine the correlation between CYP1A and MT expression in commercially important fish species Mullus barbatus and Merluccius merluccius and contaminants (PAHs, PCBs, toxic metals in seawater and sediment from three localities with different level of contamination in the Adriatic Sea in winter, i.e., Platamuni, Valdanos and the port of Bar. The relative concentration of CYP1A was the highest in both fish species from Bar. Increased concentrations of PCBs in the seawater were observed only in Bar. A species-specific higher increase in the protein concentration of CYP1A was observed in Mullus barbatus compared to Merluccius merluccius. The levels of MT were the highest in Merluccius merluccius from Bar and in Mullus barbatus from Valdanos. The induction of MT correlated with the elevated concentrations of Cu and Pb determined by chemical analysis of the seawater from Bar and Valdanos, respectively. According to the chemical analysis of the seawater and the biological response of the fish, the Platamuni locality exhibited the lowest level of contamination.

  16. Residue Modification and Mass Spectrometry for the Investigation of Structural and Metalation Properties of Metallothionein and Cysteine-Rich Proteins.

    Science.gov (United States)

    Irvine, Gordon W; Stillman, Martin J

    2017-04-26

    Structural information regarding metallothioneins (MTs) has been hard to come by due to its highly dynamic nature in the absence of metal-thiolate cluster formation and crystallization difficulties. Thus, typical spectroscopic methods for structural determination are limited in their usefulness when applied to MTs. Mass spectrometric methods have revolutionized our understanding of protein dynamics, structure, and folding. Recently, advances have been made in residue modification mass spectrometry in order to probe the hard-to-characterize structure of apo- and partially metalated MTs. By using different cysteine specific alkylation reagents, time dependent electrospray ionization mass spectrometry (ESI-MS), and step-wise "snapshot" ESI-MS, we are beginning to understand the dynamics of the conformers of apo-MT and related species. In this review we highlight recent papers that use these and similar techniques for structure elucidation and attempt to explain in a concise manner the data interpretations of these complex methods. We expect increasing resolution in our picture of the structural conformations of metal-free MTs as these techniques are more widely adopted and combined with other promising tools for structural elucidation.

  17. Vermicomposting of Tea Factory Coal Ash: metal accumulation and metallothionein response in Eisenia fetida (Savigny) and Lampito mauritii (Kinberg).

    Science.gov (United States)

    Goswami, L; Sarkar, S; Mukherjee, S; Das, S; Barman, S; Raul, P; Bhattacharyya, P; Mandal, N C; Bhattacharya, S; Bhattacharya, S S

    2014-08-01

    Earthworms can accumulate heavy metals in their intestines to a great extent. Impact of feed materials and duration of metal exposure on natural activity of earthworms are rather unclear; this investigation therefore addresses the impact of metal rich Tea Factory Coal Ash (TFCA) on reproduction, composting and metal accumulation ability of Eisenia fetida and Lampito mauritii. Earthworm count and cocoon production increased significantly during vermicomposting. pH of the vermicomposted mixtures shifted toward neutrality, total organic C decreased substantially and total N enhanced significantly compared to composting. High heavy metal (Mn, Zn, Cu, As) accumulation was recorded in the intestine of both the earthworm species. Moreover, gradual increase in the metal-inducible metallothionein concentration indicated the causal mechanism of metal accumulation in these species. TFCA+cow dung (CD) (1:1) were most favorable feed mixture for E. fetida and TFCA+CD (1:2) were good for L. mauritii in regard to metal accumulation and compost quality. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Metallothionein mRNA induction is correlated with the decrease of DNA strand breaks in cadmium exposed zebra mussels.

    Science.gov (United States)

    Vincent-Hubert, Françoise; Châtel, Amélie; Gourlay-Francé, Catherine

    2014-05-15

    We have previously shown that cadmium (Cd) and benzo[a]pyrene (BaP) induced early DNA damages in zebra mussels, and that the level of DNA strand breaks (SB) returned to a basal level after 3 days of exposure to Cd. The aim of the present study was to go further in the mechanisms of Cd and BaP detoxification. For that purpose, expression of genes encoding for metallothionein (MT), aryl hydrocarbon receptor (AHR), P-gp, catalase, glutathione S-transferase and heat shock protein 70 (HSP70) proteins have been measured using RT-qPCR. Data reported here show that Cd is a strong inducer of MT and HSP70 genes, and that BaP is a strong inducer of P-gp and AHR genes. Exposure to Cd and BaP resulted in moderate changes in antioxidant enzymes mRNA. Since the increase of MT mRNA occurred when the DNA SB level returned to its basal level, we can suggest that MT is implicated in cadmium detoxification. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Assessment of potential biomarkers, metallothionein and vitellogenin mRNA expressions in various chemically exposed benthic Chironomus riparius larvae

    Science.gov (United States)

    Park, Kiyun; Kwak, Inn-Sil

    2012-12-01

    The objective of this study was conducted to identify the possibility of using Chironomus metallothionein (MT) and vitellogenin (VTG) as biomarkers of stress caused by endocrinedisrupting chemicals (EDCs), heavy metals, herbicides and veterinary antibiotics. We characterized the MT and VTG cDNA in Chironomus riparius and evaluated their mRNA expression profiles following exposure to different environmental pollutants. The gene expression analysis showed that the MT mRNA levels increased significantly after long-term exposure to cadmium (Cd), copper (Cu), Lead (Pb), di(2-ethylhexyl) phthalate (DEHP), and 2,4-dichlorophenoxyacetic acid (2,4-D). Moreover, the VTG mRNA expression increased significantly in C. riparius larvae exposed to BPA, NP, DEHP, Cd, 2,4-D and fenbendazole. Evaluation of the long-term effects of environmental pollutants revealed up regulation of Chironomus MT mRNA in response to DEHP exposure among EDCs, and the level of the VTG mRNA was increased significantly following treatment with Cd and herbicide 2,4-D at all concentrations in a dose-dependent manner. These results indicate that VTG could be used as a potential biomarker of herbicide and Cd as well as EDCs, while MT was a potential biomarker of heavy metals such as Cd, Cu, and Pb in aquatic environments.

  20. Immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, bcl-2, c-kit, telomerase, and metallothionein as a diagnostic aid in benign, borderline, and malignant serous and mucinous ovarian tumors

    Directory of Open Access Journals (Sweden)

    Ozer Hatice

    2012-09-01

    Full Text Available Abstract Background In many tumors including ovarian cancer, cell proliferation and apoptosis are important in pathogenesis and there are many alterations in most of the genes related to the cell cycle. This study was designed to evaluate immunohistochemistry with apoptotic-antiapoptotic proteins (p53, p21, bax, and bcl-2, c-kit, telomerase, and metallothionein as a diagnostic aid in typing of benign, borderline, and malignant serous and mucinous ovarian tumors. Methods Total of 68 ovarian tumors, 25 benign [13 (19.1% serous and12 (17.6% mucinous], 16 borderline [9 (13.2% serous and 7(10.3% mucinous], and 27 malignant ovarian tumors [24 (35.3% serous and 3 (4.4% mucinous tumors] were included in the study. Immunohistochemical expression of p53, p21, bax, bcl–2, telomerase, c-kit, and metallothionein were evaluated. Results When all 68 cases were evaluated as benign, borderline, and malignant ovarian tumors without considering histopathological subtypes, the p53, p21, bax and metallothionein showed significantly higher staining scores in the borderline and malignant ones (p  Conclusions In conclusion, p53, p21, bax, c-kit, and metallothionein may be helpful for the typing of ovarian tumors as benign, borderline and malignant or serous and mucinous. p53, p21, bax, c-kit, and metallothionein may have different roles in the pathogenesis of ovarian tumor types. p53 and metallothionein may be helpful in the typing of borderline and malignant ovarian tumors. The immunohistochemical staining with bcl-2 and telomerase may not provide meaningful contribution for the typing of ovarian tumors. Virtual slide The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2013030833768498

  1. The unique C- and N-terminal sequences of Metallothionein isoform 3 mediate growth inhibition and Vectorial active transport in MCF-7 cells.

    Science.gov (United States)

    Voels, Brent; Wang, Liping; Sens, Donald A; Garrett, Scott H; Zhang, Ke; Somji, Seema

    2017-05-25

    The 3rd isoform of the metallothionein (MT3) gene family has been shown to be overexpressed in most ductal breast cancers. A previous study has shown that the stable transfection of MCF-7 cells with the MT3 gene inhibits cell growth. The goal of the present study was to determine the role of the unique C-terminal and N-terminal sequences of MT3 on phenotypic properties and gene expression profiles of MCF-7 cells. MCF-7 cells were transfected with various metallothionein gene constructs which contain the insertion or the removal of the unique MT3 C- and N-terminal domains. Global gene expression analysis was performed on the MCF-7 cells containing the various constructs and the expression of the unique C- and N- terminal domains of MT3 was correlated to phenotypic properties of the cells. The results of the present study demonstrate that the C-terminal sequence of MT3, in the absence of the N-terminal sequence, induces dome formation in MCF-7 cells, which in cell cultures is the phenotypic manifestation of a cell's ability to perform vectorial active transport. Global gene expression analysis demonstrated that the increased expression of the GAGE gene family correlated with dome formation. Expression of the C-terminal domain induced GAGE gene expression, whereas the N-terminal domain inhibited GAGE gene expression and that the effect of the N-terminal domain inhibition was dominant over the C-terminal domain of MT3. Transfection with the metallothionein 1E gene increased the expression of GAGE genes. In addition, both the C- and the N-terminal sequences of the MT3 gene had growth inhibitory properties, which correlated to an increased expression of the interferon alpha-inducible protein 6. Our study shows that the C-terminal domain of MT3 confers dome formation in MCF-7 cells and the presence of this domain induces expression of the GAGE family of genes. The differential effects of MT3 and metallothionein 1E on the expression of GAGE genes suggests unique roles of

  2. Cd, Cu, Zn, Se, and metallothioneins in two amphibians, Necturus maculosus (Amphibia, Caudata) and Bufo bufo (Amphibia, Anura).

    Science.gov (United States)

    Dobrovoljc, Katarina; Falnoga, Ingrid; Žnidarič, Magda Tušek; Mazej, Darja; Ščančar, Janez; Bulog, Boris

    2012-12-01

    The accumulation of cadmium, its affinity for metallothioneins (MTs), and its relation to copper, zinc, and selenium were investigated in the experimental mudpuppy Necturus maculosus and the common toad Bufo bufo captured in nature. Specimens of N. maculosus were exposed to waterborne Cd (85 μg/L) for up to 40 days. Exposure resulted in tissue-dependent accumulation of Cd in the order kidney, gills > intestine, liver, brain > pancreas, skin, spleen, and gonads. During the 40-day exposure, concentrations increased close to 1 μg/g in kidneys and gills (0.64-0.95 and 0.52-0.76; n = 4), whereas the levels stayed below 0.5 in liver (0.14-0.29; n = 4) and other organs. Cd exposure was accompanied by an increase of Zn and Cu in kidneys and Zn in skin, while a decrease of Cu was observed in muscles and skin. Cytosol metallothioneins (MTs) were detected as Cu,Zn-thioneins in liver and Zn,Cu-thioneins in gills and kidney, with the presence of Se in all cases. After exposure, Cd binding to MTs was clearly observed in cytosol of gills as Zn,Cu,Cd-thionein and in pellet extract of kidneys as Zn,Cu,Cd-thioneins. The results indicate low Cd storage in liver with almost undetectable Cd in liver MT fractions. In field trapped Bufo bufo (spring and autumn animals), Cd levels were followed in four organs and found to be in the order kidney > liver (0.56-5.0 μg/g >0.03-0.72 μg/g; n = 11, spring and autumn animals), with no detectable Cd in muscle and skin. At the tissue level, high positive correlations between Cd, Cu, and Se were found in liver (all r > 0.80; α = 0.05, n = 5), and between Cd and Se in kidney (r = 0.76; n = 5) of autumn animals, possibly connected with the storage of excess elements in biologically inert forms. In the liver of spring animals, having higher tissue level of Cd than autumn ones, part of the Cd was identified as Cu,Zn,Cd-thioneins with traces of Se. As both species are special in having liver Cu levels higher than

  3. Formation of oxidative and non-oxidative dimers in metallothioneins: Implications for charge-state analysis for structural determination.

    Science.gov (United States)

    Irvine, Gordon W; Heinlein, Lina; Renaud, Justin B; Sumarah, Mark W; Stillman, Martin J

    2017-12-30

    Metallothioneins (MTs) are a class of dynamic proteins that have been investigated extensively using mass spectrometric methods due to their amenability to ionization. Here we detect the formation of oxidative and non-oxidative MT dimers using high-resolution mass spectrometry (HRMS) which has previously been overlooked with lower-resolution techniques. Recombinant human MT1a and its isolated domain fragments were analyzed by high-resolution Thermo Q-Exactive and Bruker time-of-flight (TOF) mass spectrometers. Covalent Cys modification was performed using N-ethylmalemide to probe the effect of Cys oxidation on dimer formation. Dimerization was detected in the analysis of select charge states of Zn 7 MT and apo-βMT. Specifically, high resolution (140 k) revealed the +6 dimer peaks overlapping with the +3 charge state, but not with the other charge states (+4, +5, +6). The proteins with covalently modified Cys did not show dimer formation in any of their charge states. Apo-α and apo-βαMT also did not form dimers under the conditions tested. Dimerization of MT was detected for zinc metalated and certain apo-MT forms with HRMS, which was not seen with lower-resolution techniques. These dimers appear overlapped only with certain charge states, confounding their analysis for structural characterization of MTs. The Zn-MT dimers appeared to be non-oxidative; however, the formation of dimers in the apo-protein is likely dependent on Cys oxidation. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Determination of metallothioneins by fluorescence and resonance light scattering strategies based on ciprofloxacin–Cu(II) system

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Lu [College of Public Health, University of South China, Hengyang 421001 (China); Wang, Yong-Sheng, E-mail: yongsheng.w@tom.com [College of Public Health, University of South China, Hengyang 421001 (China); Xue, Jin-Hua; Yang, Hui-Xian; Li, Qiu; Zhou, Bin; Wang, Jia-Cheng; Yin, Ji-Cheng; Wang, Yong-Song [College of Public Health, University of South China, Hengyang 421001 (China); Xiao, Xi-Lin [College of Chemistry and Chemical Engineering, University of South China, Hengyang 421001 (China)

    2013-06-15

    Based on ciprofloxacin (CIP)–Cu(II) system, the novel methods for the detection of metallothioneins (MTs) have been developed by fluorescence (FL) and resonance light scattering (RLS) strategies. The FL strategy avoids the label and derivatization steps in common methods, while the RLS strategy can be applied for determining bio-macromolecules and small molecules without native fluorescence. The response signals linearly correlated with the concentration of MTs over the ranges of 1.03×10{sup −8}–1.23×10{sup −6} mol L{sup −1} for FL, and of 2.56×10{sup −7}–1.54×10{sup −6} mol L{sup −1} for RLS. The limits of detection (LOD) are 3.1×10{sup −9} mol L{sup −1} for FL and 7.68×10{sup −8} mol L{sup −1} for RLS. This study represents the comparison of these two methods using the same CIP–Cu{sup 2+}–MTs system. They not only allow practical application for MTs detection but also serve as a potential choice for the operators according to their concrete needs. In addition, the mechanisms for FL and RLS enhancement of the system were also discussed. -- Highlights: ► Determination of MTs was developed based on CIP–Cu(II) system by FL and RLS strategies. ► FL strategy provides lower limit of detection and wider linear range, and avoids the label and derivatization steps. ► RLS strategy can be applied for determining bio-macromolecules and small molecules. ► The mechanism of interaction of MTs with CIP–Cu(II) chelate was discussed.

  5. Metallothionein polymorphisms in a Northern Spanish population with neovascular and dry forms of age-related macular degeneration.

    Science.gov (United States)

    García, Montserrat; Álvarez, Lydia; Fernández, Ángela; González-Iglesias, Héctor; Escribano, Julio; Fernández-Vega, Beatriz; Villota, Eva; Fernández-Vega Cueto, Luis; Fernández-Vega, Álvaro; Coca-Prados, Miguel

    2017-01-01

    To elucidate the potential role of single nucleotide polymorphisms (SNPs) in the metallothionein (MT) genes in Northern Spanish patients with age-related macular degeneration (AMD). A total of 130 unrelated Northern Spanish natives diagnosed with AMD (46 dry, 35 neovascular, and 49 mixed) and 96 healthy controls, matched by age and ethnicity, were enrolled in a case-control study. DNA was isolated from peripheral blood and genotyped for 14 SNPs located at 5 MT genes (MT1A: rs11076161, rs 11640851, rs8052394, and rs7196890; MT1B: rs8052334, rs964372, and rs7191779; MT1M: rs2270836 and rs9936741; MT2A: rs28366003, rs1610216, rs10636, and rs1580833; MT3: rs45570941) using TaqMan probes. The association study was performed using the HaploView 4.0 software. The allelic and genotypic frequencies analysis revealed that rs28366003 at MT2A gene is significantly associated with dry AMD. The frequency of genotype AG was significantly higher in dry AMD than in control cases (p = 2.65 × 10 -4 ; AG vs. AA) conferring more than ninefold increased risk to dry AMD (OR = 9.39, 95% CI: 2.11-41.72), whereas the genotype AA confers disease protection (OR = 0.82, 95% CI: 0.71-0.95). No statistically significant differences were observed between AMD subjects and controls in the rest of the 14 SNPs analyzed. The present study is the first to investigate the potential association of SNPs at MT genes with susceptibility to AMD. We found a significant association of SNP rs28366003 at MT2A gene with susceptibility to the dry form of AMD in a Northern Spanish population.

  6. Assessment of complex water pollution with heavy metals and Pyrethroid pesticides on transcript levels of metallothionein and immune related genes.

    Science.gov (United States)

    Ghazy, Haneen A; Abdel-Razek, Mohamed A S; El Nahas, Abeer F; Mahmoud, Shawky

    2017-09-01

    Alteration of immunological function of an aquatic organism can be used as an indicator for evaluating the direct effect of exposure to pollutants. The aim of this work is to assess the impact of complex water pollution with special reference to Pyrethroid pesticides and heavy metals on mRNA transcript levels of Metallothionine and some immune related genes of Nile tilapia (Oreochromas Niloticus). Residues of six heavy metals and six Pyrethroid were assessed in water as well as fish tissues at three different sites of Lake Burullus, located at Northern Egypt. Variations of water physicochemical properties associated with different levels of heavy metals at the three different sections were recorded. Tissue residues of Fe, Mn and Zn, Cu, Ni exceed water levels in contrast to elevated water level of Pb. All assessed Pyrethroids are detected in fish tissue samples with higher concentration (3-42 folds) than that found in water samples especially Cypermethrin. Significant down-regulation of expression levels of metallothionein (MT) at the three sections of the lake was observed. The expression of immune related genes (IgM) and inflammatory cytokines (TNF, IL.8 and IL.1) were affected. IgM and TNF were significantly down-regulated at eastern and western section of the lake; meanwhile the expression of IL8 is down regulated at the three sections of the lack. IL1 was significantly up-regulated at eastern and middle sections. We conclude that, variable gene expression of MT and immune-related genes at the three sections of the lack impose different response to complex water pollution in relation to variable aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Induction of two major isoforms of metallothionein in crucian carp (Carassius cuvieri) by air-pumping stress, dexamethasone, and metals

    Energy Technology Data Exchange (ETDEWEB)

    Muto, N.; Ren, H.-W.; Hwang, G.-S.; Tominaga, S.; Itoh, N.; Tanaka, K. [Laboratory of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871 (Japan)

    1999-01-01

    The induction of metallothionein (MT) by physical and chemical stress was assessed using the fresh-water fish, crucian carp (Carassius cuvieri Temminck et Schlegel). The fish exposed to violent air-pumping stress for 6 days revealed time-dependent induction of MT-like metal-binding proteins in both their livers and kidneys. Their hepatic contents after exposure to stress were elevated to twice the basal level with 24 h, resulting in more than a 3-fold increase at 144 h, whereas their renal contents gradually increased after 24 h and reached the same level as that in the liver around 96 h. Two major inducible proteins were purified from livers of fish exposed to stress and were shown to be MT based upon their chromatographic behavior, UV absorption spectra and their molecular weights. Consequently, they were termed ccMT-1 and ccMT-2, according to their elution sequence upon anion-exchange chromatography. Both proteins mainly bound zinc in their endogenous forms and showed different immunogenicity to rat and rabbit MTs. Dexamethasone, a potent inducer for MT synthesis in mammals, induced the production of both isoforms in crucian carp, whereas cadmium and zinc ions prominently induced the synthesis of ccMT-2. These results indicate that crucian carp have the ability to produce MTs in response to various kinds of environmental stress and that violent air-pumping stress in crucian carp may induce MT synthesis, in part, via the release of endogenous factor(s), such as glucocorticoids. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  8. Bioaccumulation and metallothionein response in the Asiatic clam (Corbicula fluminea) after experimental exposure to cadmium and inorganic mercury

    Energy Technology Data Exchange (ETDEWEB)

    Baudrimont, M.; Metivaud, J.; Maury-Brachet, R.; Ribeyre, F.; Boudou, A. [Univ. Bordeaux I/CNRS, Talence (France). Lab. d`Ecotoxicologie

    1997-10-01

    The involvement of metallothioneins (MTs) in cadmium (Cd) and inorganic mercury (Hg[II]) bioaccumulation by the freshwater bivalve Corbicula fluminea was experimentally investigated after 0, 15, 30 and 45 d of exposure from the water column source. Three levels of contamination were studied for each metal: 0, 5, and 35 {micro}g Cd/L and 0, 1.45, and 5 {micro}g Hg/L, with two replicates per condition. Forty eight experimental units (EUs) were conducted simultaneously. The mollusks were fed twice a week by additions of phytoplanktonic algae. Quantification of MTs was done by Hg-saturation assay, using cold Hg(II). A partial purification of these proteins was conducted by gel-filtration chromatography, followed by Cd determinations in the different eluted fractions. Results at the whole organism (soft tissues) and organ or tissue group (gills, mantle, foot, visceral mass) levels show high metal concentrations, with a fourfold greater accumulation of inorganic Hg than Cd after 30 d exposure at the same concentration of 5 {micro}g/L. Gills and visceral mass were the principal storage compartments. A significant increase in MT concentrations was revealed in these two organs after exposure to Cd: ratios between the MT concentrations in contaminated and control mollusks were 2.4 and 2.8, respectively, for 5 and 35 {micro}g Cd/L. Cd burdens in the cytosol and in {le}18-kDa protein fractions, similar to purified mammal MTs, correspond to 30 and 14% of the total Cd accumulated in the whole organisms. No significant increase in MT biosynthesis was observed after exposure to inorganic Hg, despite the high metal concentrations in the organs.

  9. Induction of hepatic and renal metallothionein synthesis by ferric nitrilotriacetate in mice: the role of MT as an antioxidant

    International Nuclear Information System (INIS)

    Min, Kyong-Son; Morishita, Fumio; Tetsuchikawahara, Noriko; Onosaka, Satomi

    2005-01-01

    Metallothionein (MT) demonstrates strong antioxidant properties, yet the physiological relevance of its antioxidant action is not clear. Injection of mice with ferric nitrilotriacetate (Fe-NTA) caused a dose-dependent increase in hepatic and renal MT. Fe-NTA caused a greater increase in hepatic and renal MT concentration (2.5- and 4-fold) compared with FeCl 3 at the same dose of ferric ion. MT mRNA levels were markedly elevated in both of tissues. Thiobarbituric acid (TBA) values in both tissues reached a maximum after 2-4 h. The MT concentrations were significantly increased after 2-4 h in liver and after 8-16 h in kidneys. Plasma concentrations of cytokines such as IL-6 and TNFα were elevated by 4 h; IL-6 levels were 24 times higher after Fe-NTA than that after injection of FeCl 3 . Pretreatment of mice with ZnSO 4 attenuated nephrotoxicity induced by Fe-NTA after 2 h, but was not effective 4 h after injection. After a Fe-NTA injection, a loss of Cd-binding properties of preinduced MT was observed only in kidneys of Zn-pretreated mice but not in liver. Treatment with BSO, glutathione (GSH) depletor, intensified a loss of its Cd-binding properties after a Fe-NTA injection. These results indicate that induction of MT synthesis may result from reactive oxygen species (ROS) generated by Fe-NTA, and MT may act in vivo as a complementary antioxidant

  10. Isolation and characterization of a self-sufficient one-domain protein. (Cd)-metallothionein from Eisenia foetida.

    Science.gov (United States)

    Gruber, C; Stürzenbaum, S; Gehrig, P; Sack, R; Hunziker, P; Berger, B; Dallinger, R

    2000-01-01

    Earthworms have been shown to accumulate trace elements in general, and particularly high amounts of metal ions such as cadmium, copper and zinc. The earthworm's response to metal contamination has been linked to the induction and expression of metallothionein (MT) proteins, a detoxification strategy analogous to that found in other biological systems. The present study focuses on an inducible Cd-MT isolated from the compost-dwelling brandling worm Eisenia foetida (Savigny). A full characterization of the protein (including protein induction, MT cDNA, amino-acid sequence and metal stoichiometry) revealed a new dimension of knowledge to the molecular genetic information available to date. Whereas the elucidated cDNA codes for a putative protein which possesses 80 amino-acid residues, the characterized protein bears only 41 amino acids. The isolated product has evidently attained its size and shape by cleavage near the N-terminal site and at the linker region between the two putative metal-binding domains of the translated product, yielding a small MT moiety which contains 12 Cys residues (including one triple Cys-motif) binding four cadmium ions. It can be shown that the isolated MT molecule represents a self-sufficient one-domain MT which is stable in vitro. The isolation of the single-domain MT peptide raises the question about the method of formation and significance in vivo of such small MT moieties from tissues of E. foetida and possibly other terrestrial invertebrates. In this respect, two hypotheses are discussed: firstly, the possibility of formation of small MT peptides due to enzymatic cleavage of the intact protein during the process of preparation and isolation; and secondly, the possibility of deliberate post-translational processing of the translated gene product to yield functional one-domain MT moieties.

  11. The response of metallothionein and malondialdehyde after exclusive and combined Cd/Zn exposure in the crab Sinopotamon henanense.

    Directory of Open Access Journals (Sweden)

    Yingjun Li

    Full Text Available The purpose of this paper is to show the interactions of Cd and Zn in the freshwater crab Sinopotamon henanense through metallothionein (MT and malondialdehyde (MDA level measurements. Laboratory acclimated S.henanense were exposed to Cd (50 µg/L, 100 µg/L, 500 µg/L , and Zn (100 µg/L, 1000 µg/L alone and in combined treatments (100 µg/L Zn+50 µg/L Cd, 100 µg/L Zn+100 µg/L Cd, 100 µg/L Zn+500 µg/L Cd, 1000 µg/L Zn+50 µg/L Cd, 1000 µg/L Zn+100 µg/L Cd, 1000 µg/L Zn+500 µg/L Cd for 7, 14, 21, 28, 35 days. The results demonstrated that the MDA contents increased with exposure time and dose and showed time- and dose-dependence in both gills and hepatopancreas of S.henanense after single Cd exposure, while the changes of MDA levels were not significant with single Zn exposure. The MDA levels decreased when the crabs were exposed to metal mixtures compared to Cd exposure alone, indicating that Zn mediated the cellular toxicity of Cd. MT contents increased after single Cd exposure and also showed a time- and dose-dependence, in a tissue-specific way. Zn showed a limited ability of MT induction both in gills and hepatopancreas of S.henanense. The MT contents represented not a simple addition of single metal exposures but were enhanced at a higher concentration of Zn combined with different Cd concentrations compared to single metal exposure. Whether MT can be used as a biomarker for complex field conditions need to be considered cautiously since different induction patterns of MT were found among single Zn, Cd and combined groups. It is suggested that several biomarkers together as a suite should be used in the monitoring of heavy metal pollution in the aquatic environment.

  12. A plasmid containing the human metallothionein II gene can function as an antibody-assisted electrophoretic biosensor for heavy metals.

    Science.gov (United States)

    Wooten, Dennis C; Starr, Clarise R; Lyon, Wanda J

    2016-01-01

    Different forms of heavy metals affect biochemical systems in characteristic ways that cannot be detected with typical metal analysis methods like atomic absorption spectrometry. Further, using living systems to analyze interaction of heavy metals with biochemical systems can be laborious and unreliable. To generate a reliable easy-to-use biologically-based biosensor system, the entire human metallothionein-II (MT-II) gene was incorporated into a plasmid (pUC57-MT) easily replicated in Escherichia coli. In this system, a commercial polyclonal antibody raised against human metal-responsive transcription factor-1 protein (MTF-1 protein) could modify the electrophoretic migration patterns (i.e. cause specific decreases in agarose gel electrophoretic mobility) of the plasmid in the presence or absence of heavy metals other than zinc (Zn). In the study here, heavy metals, MTF-1 protein, and polyclonal anti-MTF-1 antibody were used to assess pUC57-MT plasmid antibody-assisted electrophoretic mobility. Anti-MTF-1 antibody bound both MTF-1 protein and pUC57-MT plasmid in a non-competitive fashion such that it could be used to differentiate specific heavy metal binding. The results showed that antibody-inhibited plasmid migration was heavy metal level-dependent. Zinc caused a unique mobility shift pattern opposite to that of other metals tested, i.e. Zn blocked the antibody ability to inhibit plasmid migration, despite a greatly increased affinity for DNA by the antibody when Zn was present. The Zn effect was reversed/modified by adding MTF-1 protein. Additionally, antibody inhibition of plasmid mobility was resistant to heat pre-treatment and trypsinization, indicating absence of residual DNA extraction-resistant bacterial DNA binding proteins. DNA binding by anti-DNA antibodies may be commonly enhanced by xenobiotic heavy metals and elevated levels of Zn, thus making them potentially effective tools for assessment of heavy metal bioavailability in aqueous solutions and

  13. Effect of Pre-Gamma Irradiation Induction of Metallothionein on potentially Radiation-Induced Toxic Heavy Metals Ions In Rats

    International Nuclear Information System (INIS)

    El-Shamy, El.

    2004-01-01

    Metallothionein, which is a cystein-rich metal binding protein, can act as free radical scavenger and involved in resistance to heavy metal toxicity. The induction of synthesis has been shown to protect organs from the toxic effect of radiation. This study aimed to stud the effects of pre-irradiation induction of by heavy metal (Zinc sulfate) on potentially gamma radiation-induced toxic heavy metals ions in rate liver and kidney tissues. Forty eight albino rats were included in this study. They were divided into eight groups each of six animals. Two control groups injected with saline. Two Zinc sulfate-treated groups injected with zinc sulfate, two Irradiated groups exposed to a single dose level (7 Gy) of whole body gamma irradiation and two combined zinc sulfate and irradiation groups injected with zinc sulfate and exposed to whole body gamma irradiation (at dose 7 Gy). Animals of all groups were sacrificed 24 and 48 hours after last either zinc sulfate dose or irradiation. Samples of liver and kidney's tissues were subjected to the following investigations: Estimation of tissue heavy Metals (Zinc, Iron and Copper), and tissue (MT). After irradiation, liver and kidney MT were increased approximately 10-fold and 2-fold respectively after irradiation. Accumulation of zinc and iron in both liver and kidney tissues were detected, while accumulation of copper only in the liver tissues. The pre-irradiation treatment with zinc sulfate (Zn SO4) resulted in highly significant decrease in zinc, iron, and copper levels in both liver and kidney tissues in comparison with irradiation groups. Conclusion, it can be supposed that pre-irradiation injection of ZnSO 4 exerted protective effect against the potentially radiation-induced toxic heavy metals ions through MT induction

  14. Inducibility of metallothionein biosynthesis in the whole soft tissue of zebra mussels Dreissena polymorpha exposed to cadmium, copper, and pentachlorophenol.

    Science.gov (United States)

    Ivanković, Dusica; Pavicić, Jasenka; Beatović, Vanja; Klobucar, Roberta Sauerborn; Klobucar, Göran Igor Vinko

    2010-04-01

    Freshwater mussels Dreissena polymorpha (Pallas, 1771) were exposed to the elevated concentrations of Cd (10, 50, 100, and 500 microg/L), Cu (10, 30, 50, and 80 microg/L), and an organochlorinated pesticide, pentachlorophenol (PCP) (1, 10, and 100 microg/L). Induced synthesis of biomarker metallothionein (MT) and changes in concentrations of cytosolic Cd, Cu, and Zn in the whole soft tissue of mussels were monitored after a 7-day laboratory exposure to the contaminants. A clear dose-dependent elevation in the MT concentration was observed after exposure to Cd at doses of 10-100 microg/L, and this increase of MT content was accompanied with a linear increase of cytosolic Cd. Cd concentration of 500 microg/L caused no additional increase of MT and Cd in mussel cytosol, suggesting possible toxic effects due to exceeding cellular inducible/defense capacity. Cu exposure resulted with variable changes in MT concentrations, with no clear linear relationship between MT and Cu concentrations in water, although a progressive dose-dependent accumulation of Cu in the soluble fraction of mussel tissues was recorded. A decrease of cytosolic Zn was evident at higher exposure concentrations of both metals used. PCP in concentrations applied was unable to induce MT synthesis, but the higher concentrations of PCP influenced the cytosolic metal concentrations. In conclusion, the results obtained confirm the specificity of MT induction in D. polymorpha as an biological response on metal stimulation, especially by cadmium, being more closely correlated to MT than copper within the ecologically relevant concentration range. The strong induction potential of cadmium as well as an absence of MT induction following exposure to PCP as an organic chemical contaminant are supporting evidences for usage of zebra mussel MT as a specific biomarker of Cd exposure in biomonitoring programs.

  15. Simple method for identification of metallothionein isoforms in cultured human prostate cells by MALDI-TOF/TOF mass spectrometry.

    Science.gov (United States)

    Wang, Rongying; Sens, Donald A; Albrecht, Amy; Garrett, Scott; Somji, Seema; Sens, Mary Ann; Lu, Xiaoning

    2007-06-15

    The present paper describes a rapid method for identification and characterization of human metallothionein (MT) isoforms in complex cell cultures using high-resolution matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF). In the proposed method, the sample preparation of MTs from cultured cells is both simple and fast. It is accomplished by trypsin cleavage of cell proteins into small peptide species, the majority of which are subsequently removed by gel filtration using beads with an exclusion limit of 4000 Da. In contrast to most cell proteins, MTs remain intact (undigested) upon being treated with trypsin, being excluded by the gel beads and thus recovered by low-speed centrifugation. To identify the protein constitutes of the MT preparation, the MT sample is divided into two parts, one for intact protein accurate mass measurement, the other for tryptic digestion followed by MS and MS/MS analyses. In the latter case, the MT proteins are denatured by the addition of EDTA which strips heavy metals from MTs and renders them susceptible to tryptic digestion. The obtained accurate mass with the unique peptide sequences of each MT isoform allows for unambiguous identification of MT isoforms in the prepared mixture. The method has been applied to RWPE-1 cells derived from normal human prostate epithelium. Four MT isoforms, 1E, 1G, 1X, and 2A, have been confidently identified, being primarily acetylated at N-termini. These results are in agreement with the expression of MT mRNAs in RWPE-1 cells determined by real-time reverse-transcription polymerase chain reaction (RT-PCR).

  16. Cooked oatmeal consumption is associated with better diet quality, better nutrient intakes, and reduced risk for central adiposity and obesity in children 2–18 years: NHANES 2001–2010

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    Carol E. O'Neil

    2015-05-01

    Full Text Available Background: None of the studies of whole grains that have looked either at diet or weight/adiposity measures have focused exclusively on oatmeal. Objective: The objective of this study was to assess the association between oatmeal consumption and nutrient intake, diet quality, and weight/adiposity of children aged 2–18. Design: A nationally representative sample of children aged 2–18 (N=14,690 participating in National Health and Nutrition Examination Survey 2001–2010 was used. Intake was determined from a single 24-h dietary recall. Diet quality was measured using the Healthy Eating Index-2010 (HEI-2010. Covariate-adjusted regression analyses, using appropriate sample weights, were used to determine differences between oatmeal consumers and non-consumers for demographics, nutrient intakes, diet quality, and weight/adiposity measures (p<0.01. Logistic regression was performed to calculate odds ratios for weight measures and obesity (p<0.05. Results: Compared to non-consumers, oatmeal consumers were more likely to be younger and less likely to be smokers. Consumers had higher intakes of dietary fiber, vitamin A, thiamin, riboflavin, calcium, phosphorus, magnesium, iron, copper, and potassium, and significantly lower intakes of total, monounsaturated and saturated fatty acids, cholesterol, and sodium. Oatmeal consumers had higher dietary quality scores attributable to higher intakes of whole grains and lower intakes of refined grains and empty calories. Children consuming oatmeal were at lower risk for having central adiposity and being obese. Conclusions: Consumption of oatmeal by children was associated with better nutrient intake, diet quality, and reduced risk for central adiposity and obesity and should be encouraged as part of an overall healthful diet.

  17. Organic Matter Reduces Copper Toxicity for the Earthworm Eisenia fetida in Soils from Mining Areas in Central Chile Materia Orgánica Reduce la Toxicidad del Cobre para la Lombriz Eiseniafetida en Suelos de Áreas Mineras en Chile Central

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    Gonzalo Ávila

    2009-06-01

    Full Text Available The Aconcagua River basin (Central Chile is one of the most important agricultural areas in the country. However, several copper (Cu mining operations are located in the basin. The objective of the study was to determine Cu toxicity for the earthworm Eisenia fetida (Savigny 1826 in the agricultural soils of the basin. We determined the production of cocoons and juveniles of earthworms in the studied soils. The soils differed in the concentrations of organic matter (OM, range 2-6%, pH (range 7.3-8.3, texture (from loamy sand to clay loam, and total Cu concentrations (range 230-960 mg kg-1. Concentrations of Cu and OM in the soils were the variables that determined the earthworms’ biological response. In contrast, pH and texture did not affect this response. Cocoon and juvenile production decreased considerably in soils with elevated Cu concentrations (>500 mg kg-1, regardless of OM concentrations. Cocoon production decreased in the soils with Cu concentrations below 500 mg kg-1 when OM concentrations were below 3.5%. In contrast, cocoon production did not vary when OM concentrations were above 3.5%. The same effect of OM was observed on juvenile production. In this case, the threshold for OM concentration was 2.5%. It was concluded that it is important to consider OM concentrations in order to predict the biological response of earthworms in these soils.La cuenca del Río Aconcagua (Chile Central es una de las más importantes áreas agrícolas en el país. Por otro lado, varias industrias de la minería de cobre (Cu se encuentran ubicadas en esta cuenca. El objetivo del estudio fue determinar la toxicidad de Cu para la lombriz Eiseniafetida (Savigny 1826 en los suelos agrícolas de la cuenca. Se determinó la producción de capullos y juveniles de la lombriz en suelos estudiados. Los suelos se diferenciaron por las concentraciones de materia orgánica (MO, rango 2-6%, pH (rango 7,3-8,3, textura (entre arenoso franca y franco arcillosa y

  18. TISSUE INHIBITOR OF METALLOPROTEINASE 1, MATRIX METALLOPROTEINASE 9, ALPHA-1 ANTITRYPSIN, METALLOTHIONEIN AND UROKINASE TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN SKIN BIOPSIES FROM PATIENTS AFFECTED BY AUTOIMMUNE BLISTERING DISEASES

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    Ana Maria Abreu Velez

    2013-07-01

    Full Text Available Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for alpha-1-antitrypsin, human matrix metalloproteinase 9 (MMP9, human tissue inhibitor of metalloproteinases 1 (TIMP-1, metallothionein and urokinase type plasminogen activator receptor (uPAR. We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP, 20 with pemphigus vulgaris (PV, 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH. Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.

  19. Effect of temperature and season on reproduction, neutral red retention and metallothionein responses of earthworms exposed to metals in field soils

    Energy Technology Data Exchange (ETDEWEB)

    Svendsen, Claus [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: csv@ceh.ac.uk; Hankard, Peter K. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: pkh@ceh.ac.uk; Lister, Lindsay J. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: llist@ceh.ac.uk; Fishwick, Samantha K. [Environment Agency, Block 1 Government Buildings, Burghill Road, Westbury-on-Trym, Bristol BS10 6BF (United Kingdom)]. E-mail: samantha.fishwick@environment-agency.gov.uk; Jonker, Martijs J. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: mjonker@science.uva.nl; Spurgeon, David J. [Centre for Ecology and Hydrology, Monks Wood, Abbots Ripton, Huntingdon, Cambridgeshire PE28 2LS (United Kingdom)]. E-mail: dasp@ceh.ac.uk

    2007-05-15

    This study investigated the short-term survival, reproduction and physiological (lysosomal membrane stability, metallothionein transcript copy number, body tissue metal concentrations) responses of Lumbricus rubellus exposed to metal contaminated field soils under different laboratory temperatures (10, 15 and 20 {sup o}C) and physiological responses of earthworms collected from the field in three different seasons (spring, autumn, winter). In the laboratory, metal contaminated soils had significant effects on reproduction (p < 0.001), metallothionein-2 (MT-2) expression (p = 0.033) and earthworm As (p = 0.003), Cd (p = 0.001), Pb (p < 0.001) and Zn (p < 0.001) concentration, but not lysosomal membrane stability and tissue Hg and Cu. No effect of temperature was found for any parameter. Principal component analysis of extractable and tissue metal concentrations indicated PC1 as a measure of metal stress. Both cocoon production (r = - 0.75) and MT-2 induction (r = 0.41) were correlated with PC1. A correlation was also found between cocoon production and MT-2 expression (r = - 0.41). Neutral red retention and MT-2 measurements in worms collected from the field sites in three seasons confirmed the absence of a temperature effect on these responses. - Laboratory and field studies demonstrate metal effects on earthworm life-cycle and biochemical responses are not influenced by temperature regime.

  20. Heterologous expression of a rice metallothionein isoform (OsMTI-1b in Saccharomyces cerevisiae enhances cadmium, hydrogen peroxide and ethanol tolerance

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    Zahra Ansarypour

    Full Text Available Abstract Metallothioneins are a superfamily of low-molecular-weight, cysteine (Cys-rich proteins that are believed to play important roles in protection against metal toxicity and oxidative stress. The main purpose of this study was to investigate the effect of heterologous expression of a rice metallothionein isoform (OsMTI-1b on the tolerance of Saccharomyces cerevisiae to Cd2+, H2O2 and ethanol stress. The gene encoding OsMTI-1b was cloned into p426GPD as a yeast expression vector. The new construct was transformed to competent cells of S. cerevisiae. After verification of heterologous expression of OsMTI-1b, the new strain and control were grown under stress conditions. In comparison to control strain, the transformed S. cerevisiae cells expressing OsMTI-1b showed more tolerance to Cd2+ and accumulated more Cd2+ ions when they were grown in the medium containing CdCl2. In addition, the heterologous expression of GST-OsMTI-1b conferred H2O2 and ethanol tolerance to S. cerevisiae cells. The results indicate that heterologous expression of plant MT isoforms can enhance the tolerance of S. cerevisiae to multiple stresses.

  1. Extremely low-frequency electromagnetic field induces neural differentiation of hBM-MSCs through regulation of (Zn)-metallothionein-3.

    Science.gov (United States)

    Aikins, Anastasia Rosebud; Hong, Sung-Won; Kim, Hyun-Jung; Yoon, Cheol-Ho; Chung, Joo-Hee; Kim, MiJung; Kim, Chan-Wha

    2017-07-01

    Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as β-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. The Dual Nature of Metallothioneins in the Metabolism of Heavy Metals and Reactive Oxygen Species in Aquatic Organisms: Implications of Use as a Biomarker of Heavy-Metal Effects in Field Investigations

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    F. Gagné

    2008-01-01

    Full Text Available The purpose of this study was to examine the function of metallothioneins (MT in respect to the mobilization of heavy metals and superoxide anion (O 2 – scavenging in aquatic organisms. Using an O 2 – generating system, liberation of free zinc from native and zinc MT (Zn-MT was measured in vitro. Addition of the O 2 – generating system and H 2 O 2 readily increased the di- and trimeric forms of MT as determined by gel electrophoresis analysis. To determine whether the proportion of oxidized MT could change in contaminated environments, metal-contaminated Mya arenaria clams were collected from a harbour in the St. Lawrence Estuary. The levels of labile zinc, superoxide dismutase (O 2 – scavenging enzyme, lipid peroxidation (LPO and the oxidized/metallic form of MT were determined in the digestive gland. The results revealed that the induction of total MT levels was the result of increased oxidized MT at the expense of the reduced or metallic form of MT. Both superoxide dismutase (SOD and labile zinc (Zn levels were induced and they were significantly correlated with the oxidized form of MT, but not the metallic form, in feral clam populations. We concluded that the level of total MT was related to Zn mobility and the activation of antioxidant mechanisms such as SOD, and corresponded to the levels of oxidized MT. The metallic form of MT was negatively associated with Zn mobility but positively associated with oxidative damage such as LPO. Overall, the oxidized fraction of MT appeared to be more closely related to detoxification, while the metallic form of MT was associated with metal mobility and toxicity via oxidative damage. The protective effect of MT during heavy-metal contamination depends on the availability of metals and on its capacity to sequester reactive oxygen species.

  3. Reducing Eurasian wild boar (Sus scrofa) population density as a measure for bovine tuberculosis control: effects in wild boar and a sympatric fallow deer (Dama dama) population in Central Spain.

    Science.gov (United States)

    García-Jiménez, W L; Fernández-Llario, P; Benítez-Medina, J M; Cerrato, R; Cuesta, J; García-Sánchez, A; Gonçalves, P; Martínez, R; Risco, D; Salguero, F J; Serrano, E; Gómez, L; Hermoso-de-Mendoza, J

    2013-07-01

    Research on management of bovine tuberculosis (bTB) in wildlife reservoir hosts is crucial for the implementation of effective disease control measures and the generation of practical bTB management recommendations. Among the management methods carried out on wild species to reduce bTB prevalence, the control of population density has been frequently used, with hunting pressure a practical strategy to reduce bTB prevalence. However, despite the number of articles about population density control in different bTB wildlife reservoirs, there is little information regarding the application of such measures on the Eurasian wild boar (Sus scrofa), which is considered the main bTB wildlife reservoir within Mediterranean ecosystems. This study shows the effects of a management measure leading to a radical decrease in wild boar population density at a large hunting estate in Central Spain, in order to assess the evolution of bTB prevalence in both the wild boar population and the sympatric fallow deer population. The evolution of bTB prevalence was monitored in populations of the two wild ungulate species over a 5-year study period (2007-2012). The results showed that bTB prevalence decreased in fallow deer, corresponding to an important reduction in the wild boar population. However, this decrease was not homogeneous: in the last season of study there was an increase in bTB-infected male animals. Moreover, bTB prevalence remained high in the remnant wild boar population. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Differential expression of metallothionein isoforms in terrestrial snail embryos reflects early life stage adaptation to metal stress.

    Science.gov (United States)

    Baurand, Pierre-Emmanuel; Pedrini-Martha, Veronika; de Vaufleury, Annette; Niederwanger, Michael; Capelli, Nicolas; Scheifler, Renaud; Dallinger, Reinhard

    2015-01-01

    The aim of this study was to analyze the expression of three metallothionein (MT) isoform genes (CdMT, CuMT and Cd/CuMT), already known from adults, in the Early Life Stage (ELS) of Cantareus aspersus. This was accomplished by detection of the MT isoform-specific transcription adopting Polymerase Chain Reaction (PCR) amplification and quantitative Real Time (qRT)-PCR of the three MT genes. Freshly laid eggs were kept for 24 hours under control conditions or exposed to three cadmium (Cd) solutions of increasing concentration (5, 10, and 15 mg Cd/L). The transcription of the three MT isoform genes was detected via PCR in 1, 6 and 12-day-old control or Cd-exposed embryos. Moreover, the transcription of this isoform genes during development was followed by qRT-PCR in 6 and 12-day-old embryos. Our results showed that the CdMT and Cd/CuMT genes, but not the CuMT gene, are expressed in embryos at the first day of development. The transcription of the 3 MT genes in control embryos increased with development time, suggesting that the capacities of metal regulation and detoxification may have gradually increased throughout embryogenesis. However in control embryos, the most highly expressed MT gene was that of the Cd/CuMT isoform, whose transcription levels greatly exceeded those of the other two MT genes. This contrasts with the minor significance of this gene in adult snails and suggests that in embryos, this isoform may play a comparatively more important role in metal physiology compared to adult individuals. This function in adult snails appears not to be related to Cd detoxification. Instead, snail embryos responded to Cd exposure by over-expression of the CdMT gene in a concentration-dependent manner, whereas the expression of the Cd/CuMT gene remained unaffected. Moreover, our study demonstrates the ability of snail embryos to respond very early to Cd exposure by up-regulation of the CdMT gene.

  5. Subcellular partitioning profiles and metallothionein levels in indigenous clams Moerella iridescens from a metal-impacted coastal bay

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zaosheng, E-mail: zswang@iue.ac.cn [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Boulevard, Xiamen 361021 (China); State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Feng, Chenglian; Ye, Chun [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Wang, Youshao [State Key Laboratory of Tropical Oceanography, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301 (China); Yan, Changzhou, E-mail: czyan@iue.ac.cn [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Boulevard, Xiamen 361021 (China); Li, Rui; Yan, Yijun; Chi, Qiaoqiao [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Boulevard, Xiamen 361021 (China)

    2016-07-15

    Highlights: • Subcellular partitioning profile of metals were investigated in biomonitor organism. • Cu, Zn and Cd levels in main fraction of HSP increase along accumulation gradients. • Despite MTs as the major binding pool, detoxification of Cd and Pb was incomplete. • Induced MTs were sequentially correlated with Cu, Zn and Cd levels in HSP fraction. • Intracellular metal fates highlighted the metabolic availability within organism. - Abstract: In this study, the effect of environmental metal exposure on the accumulation and subcellular distribution of metals in the digestive gland of clams with special emphasis on metallothioneins (MTs) was investigated. Specimens of indigenous Moerella iridescens were collected from different natural habitats in Maluan Bay (China), characterized by varying levels of metal contamination. The digestive glands were excised, homogenized and six subcellular fractions were separated by differential centrifugation procedures and analyzed for their Cu, Zn, Cd and Pb contents. MTs were quantified independently by spectrophotometric measurements of thiols. Site-specific differences were observed in total metal concentrations in the tissues, correlating well with variable environmental metal concentrations and reflecting the gradient trends in metal contamination. Concentrations of the non-essential Cd and Pb were more responsive to environmental exposure gradients than were tissue concentrations of the essential metals, Cu and Zn. Subcellular partitioning profiles for Cu, Zn and Cd were relatively similar, with the heat-stable protein (HSP) fraction as the dominant metal-binding compartment, whereas for Pb this fraction was much less important. The variations in proportions and concentrations of metals in this fraction along with the metal bioaccumulation gradients suggested that the induced MTs play an important role in metal homeostasis and detoxification for M. iridescens in the metal-contaminated bay. Nevertheless

  6. An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels

    Science.gov (United States)

    Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri

    2012-01-01

    Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure–biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0–0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general

  7. The use of insecticide-treated nets for reducing malaria morbidity among children aged 6-59 months, in an area of high malaria transmission in central Côte d'Ivoire

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    Nsanzabana Christian

    2010-09-01

    Full Text Available Abstract Background Long-lasting insecticidal nets (LLINs are an important tool for controlling malaria. Much attention has been devoted to determine both the effect of LLINs on the reduction of Plasmodium infection rate and on clinically-confirmed malaria cases in sub-Saharan Africa. We carried out an epidemiological study to investigate whether LLINs impact on Plasmodium prevalence rate and the proportion of clinically-confirmed malaria cases, in five villages in the district of Toumodi, central Côte d'Ivoire. Methods From April 2007 to November 2008, a community-based malaria control programme was implemented in the study villages, which involved large-scale distribution of LLINs, and training and sensitization activities within the community. We determined the effect of this programme on Plasmodium prevalence rate, clinically-confirmed malaria cases and proportion of high parasitaemia rates in children aged 6-59 months through a series of cross-sectional surveys starting in April 2007 and repeated once every 6 months. Results We observed a significant decrease in the mean P. falciparum prevalence rate from April 2007 to April 2008 (p = 0.029. An opposite trend was observed from November 2007 to November 2008 when P. falciparum prevalence rate increased significantly (p = 0.003. Highly significant decreases in the proportions of clinical malaria cases were observed between April 2007 and April 2008 (p Conclusions Large-scale distribution of LLINs, accompanied by training and sensitization activities, significantly reduced Plasmodium prevalence rates among young children in the first year of the project, whereas overall clinical malaria rates dropped over the entire 18-month project period. A decrease in community motivation to sleep under bed nets, perhaps along with changing patterns of malaria transmission, might explain the observed increase in the Plasmodium prevalence rate between November 2007 and November 2008.

  8. Metallothionein Induction as Indicator of Low Level Metal Exposure to Aquatic Macroinvertebrates from a Relatively Unimpacted River System in South Africa.

    Science.gov (United States)

    Kemp, M; Wepener, V; de Kock, K N; Wolmarans, C T

    2017-12-01

    The Marico River is relatively unaffected by anthropogenic activities. However, metal concentrations-mainly from natural sources-occasionally exceed environmental quality guidelines. Macroinvertebrates are capable to react to these metals through processes such as the induction of metallothioneins (MTs). The aims of this study were to determine whether the induction of MTs can be used as indicator of natural metal exposure in not anthropogenically impacted systems and whether there are relationships between metal concentrations in water, sediment and macroinvertebrates and concomitant MT levels. Positive correlations were found between metals in sediment and macroinvertebrates, while there were no correlations between metal concentrations in water and macroinvertebrates. Even in a not anthropogenically impacted system, a positive correlation existed between trace metal bioaccumulation (e.g. Ni, Pb, Zn) in macroinvertebrates and the induction of MTs. There were, however, no correlations between MTs and bioaccumulation of earth metals (e.g. Al, Fe, Mn, Ti).

  9. IL-6 deficiency leads to reduced metallothionein-I+II expression and increased oxidative stress in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    in brain stem gray matter areas and BM toxicity. In both normal and genetically IL-6-deficient mice (IL-6 knockout (IL-6KO) mice), the extent of astroglial degeneration/cell death in the brain stem was similar as determined from disappearance of GFAP immunoreactivity. In 6-AN-injected normal mice reactive......We examined the effects of interleukin-6 (IL-6) deficiency on brain inflammation and the accompanying bone marrow (BM) leukopoiesis and spleen immune reaction after systemic administration of a niacin antagonist, 6-aminonicotinamide (6-AN), which causes both astroglial degeneration/cell death...... tyrosine and malondialdehyde, was increased by 6-AN to a greater extent in IL-6KO mice. The blood-brain barrier to albumin was only disrupted in 6-AN-injected normal mice, which likely is due to the substantial migration of blood-derived inflammatory cells into the CNS. The present results demonstrate...

  10. M-CSF deficiency leads to reduced metallothioneins I and II expression and increased tissue damage in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, Milena; Poulsen, Christian; Carrasco, Javier

    2002-01-01

    -CSF in neurodegeneration and brain cell death, we have examined the effect of 6-AN on osteopetrotic mice with genetic M-CSF deficiency (op/op mice). The 6-AN-induced degeneration of gray-matter areas was comparable in control and op/op mice, but the numbers of reactive astrocytes, macrophages, and lymphocytes...

  11. M-CSF deficiency leads to reduced metallothioneins I and II expression and increased tissue damage in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, Milena; Poulsen, Christian; Carrasco, Javier

    2002-01-01

    -CSF in neurodegeneration and brain cell death, we have examined the effect of 6-AN on osteopetrotic mice with genetic M-CSF deficiency (op/op mice). The 6-AN-induced degeneration of gray-matter areas was comparable in control and op/op mice, but the numbers of reactive astrocytes, macrophages, and lymphocytes......6-Aminonicotinamide (6-AN) is a niacin antagonist, which leads to degeneration of gray-matter astrocytes followed by a vigorous inflammatory response. Macrophage colony stimulating factor (M-CSF) is important during inflammation, and in order to further clarify the roles for M...

  12. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals

    International Nuclear Information System (INIS)

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min

    2015-01-01

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372 bp in length and had a 237 bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H 2 O 2 , Cu 2+ and Zn 2+ , but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H 2 O 2 . - Highlights: • Cloning an HbMT2a gene from rubber tree. • Analyzing expression patterns of HbMT2a upon abiotic stress and heavy metal stress. • Finding different expression patterns of HbMT2a among two Hevea germplasm. • The expressed protein of HbMT2a enhances copper and zinc tolerance in Escherichia coli

  13. ScMT2-1-3, a Metallothionein Gene of Sugarcane, Plays an Important Role in the Regulation of Heavy Metal Tolerance/Accumulation

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    Jinlong Guo

    2013-01-01

    Full Text Available Plant metallothioneins (MTs, which are cysteine-rich, low-molecular-weight, and metal-binding proteins, play important roles in detoxification, metal ion homeostasis, and metal transport adjustment. In this study, a novel metallothionein gene, designated as ScMT2-1-3 (GenBank Accession number JQ627644, was identified from sugarcane. ScMT2-1-3 was 700 bp long, including a 240 bp open reading frame (ORF encoding 79 amino acid residues. A His-tagged ScMT2-1-3 protein was successfully expressed in Escherichia coli system which had increased the host cell’s tolerance to Cd2+, Cu2+, PEG, and NaCl. The expression of ScMT2-1-3 was upregulated under Cu2+ stress but downregulated under Cd2+ stress. Real-time qPCR demonstrated that the expression levels of ScMT2-1-3 in bud and root were over 14 times higher than those in stem and leaf, respectively. Thus, both the E. coli assay and sugarcane plantlets assay suggested that ScMT2-1-3 is significantly involved in the copper detoxification and storage in the cell, but its functional mechanism in cadmium detoxification and storage in sugarcane cells needs more testification though its expressed protein could obviously increase the host E. coli cell’s tolerance to Cd2+. ScMT2-1-3 constitutes thus a new interesting candidate for elucidating the molecular mechanisms of MTs-implied plant heavy metal tolerance/accumulation and for developing sugarcane phytoremediator varieties.

  14. The potential effect of metallothionein 2A -5A/G single nucleotide polymorphism on blood cadmium, lead, zinc and copper levels.

    Science.gov (United States)

    Kayaaltı, Zeliha; Aliyev, Vugar; Söylemezoğlu, Tülin

    2011-10-01

    Metallothioneins (MTs) are low molecular weight, cysteine-rich, metal-binding proteins. Because of their rich thiol groups, MTs bind to the biologically essential metals and perform these metals' homeostatic regulations; absorb the heavy metals and assist with their transportation and extraction. The aim of this study was to investigate the association between the metallothionein 2A (MT2A) core promoter region -5 A/G single nucleotide polymorphism (SNP) and Cd, Pb, Zn and Cu levels in the blood samples. MT2A polymorphism was determined by the standard polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique using the 616 blood samples and the genotype frequencies were found as 86.6% homozygote typical (AA), 12.8% heterozygote (AG) and 0.6% homozygote atypical (GG). Metal levels were analyzed by dual atomic absorption spectrophotometer system and the average levels of Cd, Pb, Zn and Cu in the blood samples were 1.69±1.57 ppb, 30.62±14.13 ppb, 0.98±0.49 ppm and 1.04±0.45 ppm, respectively. As a result; highly statistically significant associations were detected between the -5 A/G core promoter region SNP in the MT2A gene and Cd, Pb and Zn levels (p=0.004, p=0.012 and p=0.002, respectively), but no association was found with Cu level (p=0.595). Individuals with the GG genotype had statistically lower Zn level and higher Cd and Pb levels in the blood samples than individuals with AA and AG genotypes. This study suggests that having the GG genotype individuals may be more sensitive for the metal toxicity and they should be more careful about protecting their health against the toxic effects of the heavy metals. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min, E-mail: wmtian9110@126.com

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372 bp in length and had a 237 bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H{sub 2}O{sub 2}, Cu{sup 2+} and Zn{sup 2+}, but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H{sub 2}O{sub 2}. - Highlights: • Cloning an HbMT2a gene from rubber tree. • Analyzing expression patterns of HbMT2a upon abiotic stress and heavy metal stress. • Finding different expression patterns of HbMT2a among two Hevea germplasm. • The expressed protein of HbMT2a enhances copper and zinc tolerance in Escherichia coli.

  16. Metallothionein (MT)-III

    DEFF Research Database (Denmark)

    Carrasco, J; Giralt, M; Molinero, A

    1999-01-01

    and renamed as MT-III. In this study we have raised polyclonal antibodies in rabbits against recombinant rat MT-III (rMT-III). The sera obtained reacted specifically against recombinant zinc-and cadmium-saturated rMT-III, and did not cross-react with native rat MT-I and MT-II purified from the liver of zinc...... astrocyte migration in vitro, rMT-III promoted migration to a higher extent than MT-I+II. Thus, MT-III could not only affect neuronal sprouting as previously suggested, but also astrocyte function. Finally, MT-III protein levels of patients with Alzheimer's disease (AD) were, if anything, increased when...

  17. Central Solenoid

    CERN Multimedia

    2002-01-01

    The Central Solenoid (CS) is a single layer coil wound internally in a supporting cylinder housed in the cryostat of the Liquid Argon Calorimeter. It was successfully tested at Toshiba in December 2000 and was delivered to CERN in September 2001 ready for integration in the LAr Calorimeter in 2003. An intermediate test of the chimney and proximity cryogenics was successfully performed in June 2002.

  18. Central sleep apnea

    Science.gov (United States)

    Sleep apnea - central; Obesity - central sleep apnea; Cheyne-Stokes - central sleep apnea; Heart failure - central sleep apnea ... Central sleep apnea results when the brain temporarily stops sending signals to the muscles that control breathing. The condition ...

  19. Does cerebral hypoxia facilitate central fatigue?

    DEFF Research Database (Denmark)

    Siebenmann, Christoph; Rasmussen, Peter

    2016-01-01

    Central fatigue originates within the central nervous system and is characterized by a decreasein voluntary muscle activation. Reduced systemic O2availability can facilitate central fatigue byenhancing the afferent input of the chemosensitive nerves that play a pivotal role in developmentof centr...

  20. Quantitative changes in metallothionein expression in target cell-types in the gills of turbot (Scophthalmus maximus) exposed to Cd, Cu, Zn and after a depuration treatment

    International Nuclear Information System (INIS)

    Alvarado, Nelva E.; Quesada, Iban; Hylland, Ketil; Marigomez, Ionan; Soto, Manu

    2006-01-01

    Turbot (Scophthalmus maximus) were exposed to two sublethal concentrations (1 and 10 mg metal/l) of cadmium (8.9 and 89 μM Cd), copper (15.26 and 152.6 μM Cu) and zinc (15.3 and 153 μM Zn) for 7 days, and afterwards were maintained depurating for 14 days. Immunoreactive metallothioneins (irMTs) and metal ions were localized in the branchial epithelium by immunohistochemistry (using an anti-Cod MT antibody) and autometallography (AMG), respectively. Metal ions were demonstrated by AMG as black silver deposits (BSD), mainly in mucocytes (MC) and to a lesser extent in the other branchial cell-types (respiratory cells (RC), chloride cells (CC) and basal layer cells (BLC)). Irrespective of the metal supplied, BSD were rapidly visualized in MC after 1 h of exposure. This accumulation did not increase with increasing exposure time and concentration. Metallothionein expression was mainly observed in mature CC in the interlamellar space for all exposure conditions and it was shown that all mature cells express the same amount of irMT. The number of CC exhibiting irMT in metal-exposed turbots increased following short exposure times (1 h-1 day) in the filament epithelium and following longer exposure times (1-7 days) in the secondary lamellae. Total levels of irMT in the gills (quantified by image analysis and densitometry) increased significantly in metal-exposed turbot and were related to increased exposure times. It can be concluded that the total content of irMT in the gills of metal-exposed turbot is governed by changes in the number of mature CC expressing the protein. The quantification of total irMT in branchial CC can be considered as a reliable biomarker of metal exposure since reflects changes in metal bioavailability. This approach based on cell-selective immunohistochemistry can be simplified by only quantifying the number of mature CC. In addition, the dramatic increase of CC in the gills that produces epithelial thickening of the FE enhances migration of CC

  1. Metallothionein-I plus II and receptor megalin are altered in relation to oxidative stress in cerebral lymphomas

    DEFF Research Database (Denmark)

    Pedersen, M.O.; Hansen, P.B.; Nielsen, Signe Ledou

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) in immunocompetent patients is highly malignant and has a poor prognosis. The PCNSL molecular features are reminiscent to some degree of diffuse large B-cell lymphoma (DLBCL), yet PCNSL shows unique molecular profiles and a distinct clinical behavior...

  2. Método bundle na redução de infecção de corrente sanguínea relacionada a cateteres centrais: revisão integrativa Método bundle en la redución de infecciones relacionadas a catéteres centrales: una revisión integrativa Care bundle to reduce central venous catheter-related bloodstream infection: an integrative review

    Directory of Open Access Journals (Sweden)

    Juliana Dane Pereira Brachine

    2012-12-01

    éter con su retirada inmediata cuando posible. La mayoría de los estudios analizados mostraron una reducción significante de infección sanguínea relacionadas o asociadas con catéteres intravenosos centrales.This is an integrative review of literature aimed to identify evidence-based interventions which make up care bundles to reduce central venous catheter-related or associated bloodstream infections. To collect data in Brazilian and international databases were used the key word bundle and the descriptors catheter-related infection, infection control and central venous catheterization, resulting in fifteen articles, after inclusion criteria application. This work showed five interventions as those commonly employed in the bundles methods: hand hygiene, chlorhexidine gluconate for skin antisepsis, use of maximal sterile barrier precaution during the catheter insertion, avoid the femoral access and daily review of catheter necessity with prompt removal as no longer essential. The majority of the studies showed a significant reduction in bloodstream infection related to or associated with central venous catheters.

  3. Modulation of metallothionein, pi-GST and Se-GPx mRNA expression in the freshwater bivalve Dreissena polymorpha transplanted into polluted areas

    Directory of Open Access Journals (Sweden)

    Périne Doyen

    2015-04-01

    Full Text Available Glutathione S-transferases (GST, glutathione peroxidases (GPx and metallothioneins (MT are essential components of cellular detoxication systems. We studied the expression of pi-GST, Se-GPx, and MT transcripts in the digestive gland of Dreissena polymorpha exposed to organic and metallic pollutants. Mussels from a control site were transplanted during 3, 15 and 30 days into the Moselle River, upstream and downstream to the confluence with the Fensch River, a tributary highly polluted by polycyclic aromatic hydrocarbons and heavy metals. Se-GPx and pi-GST mRNA expression increased in mussels transplanted into the upstream site, Se-GPx response being the earliest. These genes were also induced after 3-days exposure at the downstream site. These inductions suggest an adaptative response to an alteration of the environment. Moreover, at this site, a significant decrease of the expression of MT, pi-GST and Se-GPx transcripts was observed after 30 days which could correspond to an inefficiency of detoxification mecanisms. The results are in correlation with the levels of pollutants in the sediments and their bioaccumulation in mussels, they confirm the environmental deleterious impact of the pollutants carried by the Fensch River.

  4. Short-term exposure of Nile Tilapia (Oreochromis niloticus) to mercury: histopathological changes, mercury bioaccumulation, and protective role of metallothioneins in different exposure routes.

    Science.gov (United States)

    Kaewamatawong, Theerayuth; Rattanapinyopituk, Kasem; Ponpornpisit, Aranya; Pirarat, Nopadon; Ruangwises, Suthep; Rungsipipat, Anudep

    2013-01-01

    To investigate effects of short-term mercury (Hg) exposure in tilapia (Oreochromis niloticus) including histopathological changes, Hg bioaccumulation, and protective role of metallothionein (MT) in different exposure routes, adult tilapias were intraperitoneally injected, orally intubated, or semistatically exposed to 0.5, 1, 2, 5 µg/g mercuric chloride. Histopathology, autometallography (AMG), inductive coupled plasma-atomic emission spectrometry (ICP-AES), and MT immunohistochemistry were determined at 0, 3, 6, 9, 12, and 15 days postexposure. Microscopic lesions were observed in the kidney, hepatopancreas, spleen, and intestine. AMG positive grains were found in renal tubule epithelium, melanomacrophage centers (MMCs), and intestinal epithelium of treated tilapias. Hg concentrations measured by ICP-AES in abdominal visceral organs were significantly higher than in other organs. All exposure routes caused lesions of increasing severity and Hg accumulations in a dose-dependent manner. Semistatic groups produced the highest intensity of lesions, AMG positive staining, as well as total Hg concentrations. Positive MT expression in renal tubule epithelium, pancreatic acini, and splenic MMCs was observed only in semistatic groups. The semistatic exposure route demonstrated the most significant microscopic lesions, Hg bioaccumulation, and MT expression.

  5. Influence of age, sex and body condition on zinc, copper, cadmium and metallothioneins in common guillemots (Uria aalge) stranded at the Belgian coast.

    Science.gov (United States)

    Debacker, V; Schiettecatte, L S; Jauniaux, T; Bouquegneau, J M

    2001-12-01

    The common guillemots, Uria aalge, found stranded at the Belgian coast, display high levels of Cu in both liver and kidneys. The condition index of the animals, defined as the ratio of liver to kidneys mass (Wenzel & Adelung, 1996, The suitability of oiled Guillemots (Uria aalge) as monitoring organisms for geographical comparisons of trace element contaminants. Archives of Environmental Contamination and Toxicology, 31, 368-377), influences both the metal concentration and its binding to metallothioneins (MT): the lower the condition index, the more emaciated the animals, and the higher the total Cu concentration and the concentration of Cu bound to MT. In less robust individuals, our results suggest that Cu could displace Zn from MT, rendering the Zn ions available to induce a new MT synthesis. Sex-related effects also emerged as significantly higher hepatic MT as well as Cu- and Zn-MT concentrations were found in emaciated male guillemots compared to females. In both organs, Cd concentrations remained low and typically demonstrated an age-dependent renal accumulation, with no noticeable effect of the condition index. As a whole, these results suggest that, for guillemots found stranded at the Belgian coast. Cu binding to hepatic and renal MT could function as a protective mechanism, rendering the metal ions unavailable to exert any cytotoxic activity.

  6. Relationship between metallothioneins and metals in a natural population of the clam Ruditapes decussatus from Sfax coast: a non-linear model using Box-Cox transformation.

    Science.gov (United States)

    Hamza-Chaffai, A; Amiard, J C; Cosson, R P

    1999-06-01

    Cadmium, copper and zinc were determined concomitantly with metallothionein-like proteins (MTLPs) in the subcellular fractions of Ruditapes decussatus digestive gland. This study covered 4 months and aimed to evaluate the effect of metal pollution and other factors such as sex, size and reproductive state on MTLP levels. Copper concentrations did not vary with month, however Cd and Zn concentrations showed high levels during August. Organisms showing low cadmium concentrations presented the highest cadmium percentages in the soluble fraction (SF) containing MTLPs. However for high cadmium concentrations, the insoluble fraction (IF) was implicated in cadmium association. MTLP levels varied according to the month, the sex and the size of the organisms. A non-linear model based on the Box-Cox transformation, was proposed to describe a positive and a significant relationship between MTLPs and the studied metals. A model including sex and size showed that these two factors affected MTLP levels, but were less important than metals. Males of R. decussatus showed higher significant correlations between MTLP levels and cadmium than females. Moreover, the effect of size and reproductive state on MTLP levels was less perceptible in males than in females. As a result, MTLPs in males of R. decussatus could be proposed as suitable biomarker for detecting metal contamination.

  7. Experimental exposure to cadmium affects metallothionein-like protein levels but not survival and growth in wolf spiders from polluted and reference populations

    International Nuclear Information System (INIS)

    Eraly, Debbie; Hendrickx, Frederik; Bervoets, Lieven; Lens, Luc

    2010-01-01

    Both local adaptation and acclimation in tolerance mechanisms may allow populations to persist under metal pollution. However, both mechanisms are presumed to incur (energetic) costs and to trade-off with other life-history traits. To test this hypothesis, we exposed Pardosa saltans (Lycosidae) spiderlings originating from metal-polluted and unpolluted sites to a controlled cadmium (Cd) treatment, and compared contents of metal-binding metallothionein-like proteins (MTLPs), internal metal concentrations, and individual survival and growth rates with a reference treatment. While increased MTLP concentrations in offspring originating from both polluted and unpolluted populations upon exposure indicates a plastic tolerance mechanism, survival and growth rates remain largely unaffected, independent of the population of origin. However, MTLP and Cd concentrations were not significantly correlated. We suggest that MTLP production may be an important mechanism enabling P. saltans populations to persist in ecosystems polluted with heavy metals above a certain level. - Spiders from metal-polluted and unpolluted populations show a similar increase in MTLP production when exposed to Cd, with unaffected growth and survival.

  8. Role of Oxidative Stress in the Induction of Metallothionein-2A and Heme Oxygenase-1 Gene Expression by the Antineoplastic Agent Gallium Nitrate in Human Lymphoma Cells

    Science.gov (United States)

    Yang, Meiying; Chitambar, Christopher R.

    2008-01-01

    The mechanisms of action of gallium nitrate, an antineoplastic drug, are only partly understood. Using a DNA microarray to examine genes induced by gallium nitrate in CCRF-CEM cells, we found that gallium increased metallothionein-2A (MT2A) and heme oxygenase-1 (HO-1) gene expression and altered the levels of other stress-related genes. MT2A and HO-1 were increased after 6 and 16 h of incubation with gallium nitrate. An increase in oxidative stress, evidenced by a decrease in cellular GSH and GSH/GSSG ratio, and an increase in dichlorodihydrofluoroscein (DCF) fluorescence, was seen after 1 – 4 h incubation of cells with gallium nitrate. DCF fluorescence was blocked by the mitochondria-targeted antioxidant mitoquinone. N-acetyl-L-cysteine blocked gallium-induced MT2A and HO-1 expression and increased gallium’s cytotoxicity. Studies with a zinc-specific fluoroprobe suggested that gallium produced an expansion of an intracellular labile zinc pool, suggesting an action of gallium on zinc homeostasis. Gallium nitrate increased the phosphorylation of p38 mitogen-activated protein kinase and activated Nrf-2, a regulator of HO-1 gene transcription. Gallium-induced Nrf-2 activation and HO-1 expression were diminished by a p38 MAP kinase inhibitor. We conclude that gallium nitrate induces cellular oxidative stress as an early event which then triggers the expression of HO-1 and MT2A through different pathways. PMID:18586083

  9. Effects of Two Sublethal Concentrations of Mercury Chloride on the Morphology and Metallothionein Activity in the Liver of Zebrafish (Danio rerio).

    Science.gov (United States)

    Macirella, Rachele; Guardia, Antonello; Pellegrino, Daniela; Bernabò, Ilaria; Tronci, Valentina; Ebbesson, Lars O E; Sesti, Settimio; Tripepi, Sandro; Brunelli, Elvira

    2016-03-11

    Mercury (Hg) is a highly hazardous pollutant widely used in industrial, pharmaceutical and agricultural fields. Mercury is found in the environment in several forms, elemental, inorganic (iHg) and organic, all of which are toxic. Considering that the liver is the organ primarily involved in the regulation of metabolic pathways, homeostasis and detoxification we investigated the morphological and ultrastructural effects in Danio rerio liver after 96 h exposure to two low HgCl₂ concentrations (7.7 and 38.5 μg/L). We showed that a short-term exposure to very low concentrations of iHg severely affects liver morphology and ultrastructure. The main effects recorded in this work were: cytoplasm vacuolization, decrease in both lipid droplets and glycogen granules, increase in number of mitochondria, increase of rough endoplasmic reticulum and pyknotic nuclei. Pathological alterations observed were dose dependent. Trough immunohistochemistry, in situ hybridization and real-time PCR analysis, the induction of metallothionein (MT) under stressor conditions was also evaluated. Some of observed alterations could be considered as a general response of tissue to heavy metals, whereas others (such as increased number of mitochondria and increase of RER) may be considered as an adaptive response to mercury.

  10. A novel, highly conserved metallothionein family in basidiomycete fungi and characterization of two representative SlMTa and SlMTb genes in the ectomycorrhizal fungus Suillus luteus.

    Science.gov (United States)

    Nguyen, Hoai; Rineau, François; Vangronsveld, Jaco; Cuypers, Ann; Colpaert, Jan V; Ruytinx, Joske

    2017-07-01

    The basidiomycete Suillus luteus is an important member of the ectomycorrhizal community that thrives in heavy metal polluted soils covered with pioneer pine forests. This study aimed to identify potential heavy metal chelators in S. luteus. Two metallothionein (MT) coding genes, SlMTa and SlMTb, were identified. When heterologously expressed in yeast, both SlMTa and SlMTb can rescue the Cu sensitive mutant from Cu toxicity. In S. luteus, transcription of both SlMTa and SlMTb is induced by Cu but not Cd or Zn. Several putative Cu-sensing and metal-response elements are present in the promoter sequences. These results indicate that SlMTa and SlMTb function as Cu-thioneins. Homologs of the S. luteus MTs are present in 49 species belonging to 10 different orders of the subphylum Agaricomycotina and are remarkably conserved. The length of the proteins, number and distribution of cysteine residues indicate a novel family of fungal MTs. The ubiquitous and highly conserved features of these MTs suggest that they are important for basic cellular functions in species in the subphylum Agaricomycotina. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Cordyceps sinensis increases hypoxia tolerance by inducing heme oxygenase-1 and metallothionein via Nrf2 activation in human lung epithelial cells.

    Science.gov (United States)

    Singh, Mrinalini; Tulsawani, Rajkumar; Koganti, Praveen; Chauhan, Amitabh; Manickam, Manimaran; Misra, Kshipra

    2013-01-01

    Cordyceps sinensis, an edible mushroom growing in Himalayan regions, is widely recognized in traditional system of medicine. In the present study, we report the efficacy of Cordyceps sinensis in facilitating tolerance to hypoxia using A549 cell line as a model system. Treatment with aqueous extract of Cordyceps sinensis appreciably attenuated hypoxia induced ROS generation, oxidation of lipids and proteins and maintained antioxidant status similar to that of controls via induction of antioxidant gene HO1 (heme oxygenase-1), MT (metallothionein) and Nrf2 (nuclear factor erythroid-derived 2-like 2). In contrast, lower level of NF κ B (nuclear factor kappaB) and tumor necrosis factor- α observed which might be due to higher levels of HO1, MT and transforming growth factor- β . Further, increase in HIF1 (hypoxia inducible factor-1) and its regulated genes; erythropoietin, vascular endothelial growth factor, and glucose transporter-1 was observed. Interestingly, Cordyceps sinensis treatment under normoxia did not regulate the expression HIF1, NF κ B and their regulated genes evidencing that Cordyceps sinensis per se did not have an effect on these transcription factors. Overall, Cordyceps sinensis treatment inhibited hypoxia induced oxidative stress by maintaining higher cellular Nrf2, HIF1 and lowering NF κ B levels. These findings provide a basis for possible use of Cordyceps sinensis in tolerating hypoxia.

  12. Mercury species, selenium, metallothioneins and glutathione in two dolphins from the southeastern Brazilian coast: Mercury detoxification and physiological differences in diving capacity.

    Science.gov (United States)

    Kehrig, Helena A; Hauser-Davis, Rachel A; Seixas, Tercia G; Pinheiro, Ana Beatriz; Di Beneditto, Ana Paula M

    2016-06-01

    In the present study, the concentration of trace elements, total mercury (Hg) and selenium (Se) and mercury forms (MeHg, Hginorg and HgSe) in the vulnerable coastal dolphins Pontoporia blainvillei and Sotalia guianensis were appraised and compared, using metallothioneins (MT) and glutathione (GSH) as biomarkers for trace element exposure. The trace element concentrations varied between muscle and liver tissues, with liver of all dolphin specimens showing higher Hg and Se concentrations than those found in muscle. Hg, MeHg and Hginorg molar concentrations showed a clear increase with Se molar concentrations in the liver of both dolphins, and Se concentrations were higher than those of Hg on a molar basis. Se plays a relevant role in the detoxification of MeHg in the hepatic tissue of both dolphins, forming Hg-Se amorphous crystals in liver. In contrast, MT were involved in the detoxification process of Hginorg in liver. GSH levels in P. blainvillei and S. guianensis muscle tissue suggest that these dolphins have different diving capacities. Muscle Hg concentrations were associated to this tripeptide, which protects dolphin cells against Hg stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Metallothionein from Wild Populations of the African Catfish Clarias gariepinus: From Sequence, Protein Expression and Metal Binding Properties to Transcriptional Biomarker of Metal Pollution.

    Science.gov (United States)

    M'kandawire, Ethel; Mierek-Adamska, Agnieszka; Stürzenbaum, Stephen R; Choongo, Kennedy; Yabe, John; Mwase, Maxwell; Saasa, Ngonda; Blindauer, Claudia A

    2017-07-18

    Anthropogenic pollution with heavy metals is an on-going concern throughout the world, and methods to monitor release and impact of heavy metals are of high importance. With a view to probe its suitability as molecular biomarker of metal pollution, this study has determined a coding sequence for metallothionein of the African sharptooth catfish Clarias gariepinus . The gene product was recombinantly expressed in Escherichia coli in presence of Zn(II), Cd(II), or Cu, and characterised by Electrospray Ionisation Mass Spectrometry and elemental analysis. C. gariepinus MT displays typical features of fish MTs, including 20 conserved cysteines, and seven bound divalent cations (Zn(II) or Cd(II)) when saturated. Livers from wild C. gariepinus fish collected in all three seasons from four different sites on the Kafue River of Zambia were analysed for their metal contents and for MT expression levels by quantitative PCR. Significant correlations were found between Zn and Cu levels and MT expression in livers, with MT expression clearly highest at the most polluted site, Chililabombwe, which is situated in the Copperbelt region. Based on our findings, hepatic expression of MT from C. gariepinus may be further developed as a major molecular biomarker of heavy metal pollution resulting from mining activities in this region.

  14. Metallothionein from Wild Populations of the African Catfish Clarias gariepinus: From Sequence, Protein Expression and Metal Binding Properties to Transcriptional Biomarker of Metal Pollution

    Directory of Open Access Journals (Sweden)

    Ethel M’kandawire

    2017-07-01

    Full Text Available Anthropogenic pollution with heavy metals is an on-going concern throughout the world, and methods to monitor release and impact of heavy metals are of high importance. With a view to probe its suitability as molecular biomarker of metal pollution, this study has determined a coding sequence for metallothionein of the African sharptooth catfish Clarias gariepinus. The gene product was recombinantly expressed in Escherichia coli in presence of Zn(II, Cd(II, or Cu, and characterised by Electrospray Ionisation Mass Spectrometry and elemental analysis. C. gariepinus MT displays typical features of fish MTs, including 20 conserved cysteines, and seven bound divalent cations (Zn(II or Cd(II when saturated. Livers from wild C. gariepinus fish collected in all three seasons from four different sites on the Kafue River of Zambia were analysed for their metal contents and for MT expression levels by quantitative PCR. Significant correlations were found between Zn and Cu levels and MT expression in livers, with MT expression clearly highest at the most polluted site, Chililabombwe, which is situated in the Copperbelt region. Based on our findings, hepatic expression of MT from C. gariepinus may be further developed as a major molecular biomarker of heavy metal pollution resulting from mining activities in this region.

  15. La microfinance en Afrique centrale: Le défi des exclus | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2015-04-20

    Apr 20, 2015 ... Microfinance and reducing poverty in Central Africa. In spite of an abundance of natural resources, including oil and minerals, poverty is increasing in Central Africa. View moreMicrofinance and reducing poverty in Central Africa ...

  16. Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular ...

    African Journals Online (AJOL)

    diseases, primary hypothyroidism, and other disorders of the central nervous, gastrointestinal, genitourinary, and orthopedic systems. In this report, we describe a 3‑month‑old Saudi boy with the rare association of DWS with central diabetes insipidus, congenital central hypothyroidism, and type‑2 renal tubular acidosis.

  17. Dairy Foods in a Moderate Energy Restricted Diet Do Not Enhance Central Fat, Weight, and Intra-Abdominal Adipose Tissue Losses nor Reduce Adipocyte Size or Inflammatory Markers in Overweight and Obese Adults: A Controlled Feeding Study

    Directory of Open Access Journals (Sweden)

    Marta D. Van Loan

    2011-01-01

    Full Text Available Background. Research on dairy foods to enhance weight and fat loss when incorporated into a modest weight loss diet has had mixed results. Objective. A 15-week controlled feeding study to determine if dairy foods enhance central fat and weight loss when incorporated in a modest energy restricted diet of overweight and obese adults. Design. A 3-week run-in to establish energy needs; a 12-week 500 kcal/d energy reduction with 71 low-dairy-consuming overweight and obese adults randomly assigned to diets: ≤1 serving dairy/d (low dairy, LD or ≤4 servings dairy/d (adequate dairy, AD. All foods were weighed and provided by the metabolic kitchen. Weight, fat, intra-abdominal adipose tissue (IAAT, subcutaneous adipose tissue (SAT macrophage number, SAT inflammatory gene expression, and circulating cytokines were measured. Results. No diet differences were observed in weight, fat, or IAAT loss; nor SAT mRNA expression of inflammation, circulating cytokines, fasting lipids, glucose, or insulin. There was a significant increase (P=0.02 in serum 25-hydroxyvitamin D in the AD group. Conclusion. Whether increased dairy intake during weight loss results in greater weight and fat loss for individuals with metabolic syndrome deserves investigation. Assessment of appetite, hunger, and satiety with followup on weight regain should be considered.

  18. Sensitive biomarker responses of the shrimp Palaemonetes argentinus exposed to chlorpyrifos at environmental concentrations: Roles of alpha-tocopherol and metallothioneins.

    Science.gov (United States)

    Bertrand, Lidwina; Monferrán, Magadalena Victoria; Mouneyrac, Catherine; Bonansea, Rocio Inés; Asis, Ramón; Amé, María Valeria

    2016-10-01

    The aim of this study was to evaluate the toxic effects of chlorpyrifos (CPF) at environmental concentrations on the shrimp Palaemonetes argentinus, a South American native species. Organisms were exposed to environmentally relevant concentrations of CPF (from 3.5 to 94.5ngCPFL(-1)) at laboratory conditions for 96h. A wide battery of biochemical responses including bioaccumulation, damage and defense biomarkers were measured in cephalothorax and abdomen of shrimp. The concentration of CPF was below the detection limit of the method in both body sectors (8ngCPFg(-1)ww), probably indicating fast biotransformation of the parental compound. Our results showed that CPF exposure inhibits acetylcholinesterase activity from 3.5ngCPFL(-1), a concentration below the suggested Argentinean guidelines for the protection of aquatic biota. Moreover, oxidative stress was evidenced by increased H2O2 content and increased levels of TBARs and carbonyl groups in proteins. The induction of antioxidant enzymes like catalase, glutathione S-transferase and glutathione peroxidase seems not be sufficient to prevent oxidative damages. In addition, the mobilization of α-tocopherol from abdomen to cephalothorax was observed and reported for the first time in non-reproductive condition. Likewise, a strong diminution of metallothioneins occurred in cephalothorax from the lowest CPF concentration while induction occurred from the same treatment in abdomen as an oxidative stress response. Finally, significant correlation between Integrated Biomarker Response values and exposure concentrations suggest the usefulness of P. argentinus as bioindicator of CPF exposure at concentrations as low as environmental ones. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. ZnT2-overexpression represses the cytotoxic effects of zinc hyper-accumulation in malignant metallothionein-null T47D breast tumor cells.

    Science.gov (United States)

    Lopez, Veronica; Foolad, Farnaz; Kelleher, Shannon L

    2011-05-01

    Human breast tumors accumulate abnormally high levels of zinc (Zn). As a result, numerous studies have implicated Zn hyper-accumulation in the etiology of breast cancer. Zinc accumulation can be cytotoxic, therefore cells have Zn-buffering mechanisms, such as metallothioneins (MT) and vesicular sequestration, which tightly regulate Zn homeostasis. The Zn transporter ZnT2 sequesters Zn into intracellular vesicles and thus can protect cells from Zn cytotoxicity. Herein, we report that malignant breast tumor (T47D) cells do not express MT but have approximately 4-fold greater Zn levels compared with non-malignant breast (MCF-10A) cells. Zinc accumulation coincided with ZnT2 over-expression and increased vesicular Zn pools. In this study, we hypothesized that ZnT2 suppression would eliminate protection from Zn accumulation and result in cytotoxicity in malignant breast tumor cells. Suppression of ZnT2 significantly increased cytoplasmic Zn pools (1.6-fold) as assessed with a Zn-responsive reporter assay containing four metal response elements (4X-MRE) fused to luciferase. Increased cytoplasmic Zn pools activated apoptosis in a caspase-independent manner. We observed significant generation of reactive oxygen species (ROS) (2.3-fold), lysosomal swelling and cathepsin D leakage in ZnT2-attenuated compared with ZnT2-expressing cells. Most importantly, tumor cell viability and tumor formation were significantly decreased (approximately 25%) in ZnT2-attenuated cells compared with ZnT2-expressing cells. Our data indicate that ZnT2 over-expression protects malignant MT-null breast tumor cells from Zn hyper-accumulation by sequestering Zn into intracellular vesicles. Moreover, our results implicate Zn compartmentalizing mechanisms as novel targets for breast cancer therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. [Copper level and metallothionein-like Cu-binding protein in cultured skin fibroblasts from patients with Menkes' disease and Wilson's disease].

    Science.gov (United States)

    Sato, M; Hayashi, A; Ito, H; Tojo, M; Arima, M

    1984-11-01

    Copper concentration, intracellular copper distribution, and inducibility of metallothionein-like metal-binding protein (MLP) by copper or cadmium addition to culture medium were compared among three types of skin fibroblasts derived from patients with Menkes' disease and Wilson's disease, both exhibiting genetic defects of copper metabolism, and from normal subjects (control). Skin fibroblasts were cultivated in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum and antibiotics in 5% CO2 at 37 degrees C. Cells were harvested with rubber-policeman, washed twice with phosphate-buffered saline, pH 7.2, suspended in deionized water, and homogenized. The homogenate from each cell type was used to determine the concentration of copper by atomic absorption spectrophotometry employing graphite-rod atomizer after lyophilization, ashing in HNO3, and coprecipitation with zirconium. Intracellular copper concentration was elevated in Menkes' cells (420 ng Cu/mg of protein) and Wilson's cells (217 ng Cu/mg of protein) than in control cells (90.0 ng Cu/mg of protein), although one of four Wilson's strains showed normal copper level (70.5 ng Cu/mg of protein). Cytosol copper concentration was 5.8-fold higher in Menkes' cells but only 1.3-fold in Wilson's cells than in control cells, and cytosol copper accounted for only 35% of total intracellular copper in Wilson's cells as compared with 68% and 52% in Menkes' and control cells, respectively. These suggest that accumulated copper in each cell type is differently distributed within cells; in Menkes' cells exclusively into cytosol, but in Wilson's cells into particulates rather than cytosol. Elution profiles from Sephadex G-75 columns indicated that most of copper had bound to MLP in Menkes' cells, though no Cu-MLP was detectable in Wilson's or control cells under these experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The physiological role and toxicological significance of the non-metal-selective cadmium/copper-metallothionein isoform differ between embryonic and adult helicid snails.

    Science.gov (United States)

    Pedrini-Martha, Veronika; Schnegg, Raimund; Baurand, Pierre-Emmanuel; deVaufleury, Annette; Dallinger, Reinhard

    2017-09-01

    Metal regulation is essential for terrestrial gastropods to survive. In helicid snails, two metal-selective metallothionein (MT) isoforms with different functions are expressed. A cadmium-selective isoform (CdMT) plays a major role in Cd 2+ detoxification and stress response, whereas a copper-selective MT (CuMT) is involved in Cu homeostasis and hemocyanin synthesis. A third, non-metal-selective isoform, called Cd/CuMT, was first characterized in Cantareus aspersus. The aim of this study was to quantify the transcriptional activity of all three MT genes in unexposed and metal-exposed (Cd, Cu) embryonic Roman snails. In addition, the complete Cd/CuMT mRNA of the Roman snail (Helix pomatia) was characterized, and its expression quantified in unexposed and Cd-treated adult individuals. In embryos of Helix pomatia, the Cd/CuMT gene was induced upon Cu exposure. Its transcription levels were many times higher than that of the other two MT genes, and also exceeded by far the Cd/CuMT mRNA concentrations of adult snails. In the hepatopancreas of adult Roman snails, no Cd/CuMT could be detected at the protein level, irrespective of whether the snails had been exposed to Cd or not. This contrasts with the situation in the near relative, Cantareus aspersus. It appeared that the 3'-UTR of the Cd/CuMT mRNA differed largely between Cantareus aspersus and Helix pomatia, being larger in the latter species, with a number of putative binding sites for proteins and miRNAs known to inhibit mRNA translation. We suggest this as a possible mechanism responsible for the lack of Cd/CuMT protein expression in adult Roman snails. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Physiological relevance and contribution to metal balance of specific and non-specific Metallothionein isoforms in the garden snail, Cantareus aspersus.

    Science.gov (United States)

    Höckner, Martina; Stefanon, Karin; de Vaufleury, Annette; Monteiro, Freddy; Pérez-Rafael, Sílvia; Palacios, Oscar; Capdevila, Mercè; Atrian, Sílvia; Dallinger, Reinhard

    2011-12-01

    Variable environmental availability of metal ions represents a constant challenge for most organisms, so that during evolution, they have optimised physiological and molecular mechanisms to cope with this particular requirement. Metallothioneins (MTs) are proteins that play a major role in metal homeostasis and as a reservoir. The MT gene/protein systems of terrestrial helicid snails are an invaluable model for the study of metal-binding features and MT isoform-specific functionality of these proteins. In the present study, we characterised three paralogous MT isogenes and their expressed products in the escargot (Cantareus aspersus). The metal-dependent transcriptional activation of the three isogenes was assessed using quantitative Real Time PCR. The metal-binding capacities of the three isoforms were studied by characterising the purified native complexes. All the data were analysed in relation to the trace element status of the animals after metal feeding. Two of the three C. aspersus MT (CaMT) isoforms appeared to be metal-specific, (CaCdMT and CaCuMT, for cadmium and copper respectively). A third isoform (CaCd/CuMT) was non-specific, since it was natively recovered as a mixed Cd/Cu complex. A specific role in Cd detoxification for CaCdMT was revealed, with a 80-90% contribution to the Cd balance in snails exposed to this metal. Conclusive data were also obtained for the CaCuMT isoform, which is involved in Cu homeostasis, sharing about 30-50% of the Cu balance of C. aspersus. No apparent metal-related physiological function was found for the third isoform (CaCd/CuMT), so its contribution to the metal balance of the escargot may be, if at all, of only marginal significance, but may enclose a major interest in evolutionary studies.

  3. Bioaccumulation, morphological changes, and induction of metallothionein gene expression in the digestive system of the freshwater crab Sinopotamon henanense after exposure to cadmium.

    Science.gov (United States)

    Wu, Hao; Li, Yingjun; Lang, Xingping; Wang, Lan

    2015-08-01

    To study the responses of digestive system of the freshwater crab Sinopotamon henanense to the exposure with cadmium (Cd), crabs were acutely exposed to 7.25, 14.50, and 29.00 mg/l Cd for 96 h and subchronically exposed to 0.725, 1.450, and 2.900 mg/l for 21 days. Cd bioaccumulation in the hepatopancreas and digestive tract (esophagus and intestine) was examined. Furthermore, histopathological alterations of the esophagus, midgut, hindgut, and hepatopancreas were assessed in animals from the 29.0 and 2.90 mg/l Cd treatment groups, and expression of metallothionein messenger RNA (MT mRNA) in the hepatopancreas and intestine was measured in all treatment groups. The results showed difference in the middle and high concentrations between acute and subchronic treatment groups. Cd content in digestive tract after acute 14.5 and 29.0 mg/l Cd exposure was significantly higher than that at subchronic 1.45 and 2.90 mg/l exposure, but Cd levels in hepatopancreas were not significantly different under the same condition. Acute exposure to Cd induced greater morphological damage than subchronic exposure: large areas of epithelial cells were necrotic in hepatopancreas and midgut, which detached from the basal lamina. Vacuolated muscle cells were observed in the hindgut of animals from the acute exposure group, but the changes of esophageal morphology were not obvious after acute or subchronic treatments. The expression of MT mRNA increased with increasing Cd concentration, and MT mRNA level in acute exposure groups was significantly lower when compared to the subchronic exposure groups. Higher Cd content and lower MT mRNA expression in the acutely exposed groups may be responsible for more severe damage of digestive system in these exposure groups.

  4. Subcellular partitioning kinetics, metallothionein response and oxidative damage in the marine mussel Mytilus galloprovincialis exposed to cadmium-based quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Thiago Lopes [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Gomes, Tânia [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, NO-0349 Oslo (Norway); Durigon, Emerson Giuliani [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal); Bebianno, Maria João, E-mail: mbebian@ualg.pt [CIMA, Faculty of Science and Technology, University of Algarve, Campus de Gambelas, 8005-139 Faro (Portugal)

    2016-06-01

    The environmental health impact of metal-based nanomaterials is of emerging concern, but their metabolism and detoxification pathways in marine bioindicator species remain unclear. This study investigated the role of subcellular partitioning kinetics, metallothioneins (MTs) response and oxidative damage (lipid peroxidation – LPO) in the marine mussel Mytilus galloprovincialis exposed to CdTe quantum dots (QDs) in comparison with its dissolved counterpart. Mussels were exposed to QDs and dissolved Cd for 21 days at 10 μg Cd L{sup −1} followed by a 50 days depuration. Higher Cd concentrations were detected in fractions containing mitochondria, nucleus and lysosomes, suggesting potential subcellular targets of QDs toxicity in mussel tissues. Tissue specific metabolism patterns were observed in mussels exposed to both Cd forms. Although MT levels were directly associated with Cd in both forms, QDs subcellular partitioning is linked to biologically active metal (BAM), but no increase in LPO occurred, while in the case of dissolved Cd levels are in the biologically detoxified metal (BDM) form, indicating nano-specific effects. Mussel gills showed lower detoxification capability of QDs, while the digestive gland is the major tissue for storage and detoxification of both Cd forms. Both mussel tissues were unable to completely eliminate the Cd accumulated in the QDs form (estimated half-life time > 50 days), highlighting the potential source of Cd and QDs toxicity for human and environmental health. Results indicate tissue specific metabolism patterns and nano-specific effects in marine mussel exposed to QDs. - Highlights: • Subcellular partitioning and MT response are Cd form, tissue and time dependent. • Tissue specific metabolism of Cd-based quantum dots (QDs) in marine mussels. • QDs are slower biologically detoxified when compared to dissolved Cd. • Subcellular partitioning and biomarker responses indicate nano-specific effects. • Subcellular

  5. Acquisition of apoptotic resistance in cadmium-induced malignant transformation: specific perturbation of JNK signal transduction pathway and associated metallothionein overexpression.

    Science.gov (United States)

    Qu, Wei; Fuquay, Richard; Sakurai, Teruaki; Waalkes, Michael P

    2006-08-01

    Prior work has shown that chronic cadmium exposed rat liver epithelial cells (CCE-LE) become malignantly transformed after protracted low level cadmium exposure. Acquisition of apoptotic resistance is common in oncogenesis and the present work explores this possibility in CCE-LE cells. CCE-LE cells were resistant to apoptosis induced by etoposide or an acute high concentration of cadmium as assessed by flow cytometry with annexin/FITC. Three key mitogen-activated protein kinases (MAPKs), namely ERK1/2, JNK1/2, and p38, were phosphorylated in CCE-LE cells after acute cadmium exposure. However, the levels of phosphorylated JNK1/2 were markedly decreased in CCE-LE cells compared to control. JNK kinase activity was also suppressed in CCE-LE cells exposed to cadmium. Epidermal growth factor (EGF), used as a positive control for stimulating JNK phosphorylation, was much less effective in CCE-LE cells than control cells. Ro318220 (Ro), a strong activator of JNK, increased phosphorylated JNK1/2 to levels similar to the cadmium-treated control cells and also enhanced apoptosis in response to cadmium in CCE-LE cells. Metallothionein (MT), which is thought to potentially inhibit apoptosis, was strongly overexpressed in CCE-LE cells. Further, in MT knockout (MT-/-) fibroblasts, JNK1/2 phosphorylation was markedly increased after cadmium exposure compared with similarly treated wild-type (MT+/+) cells. These results indicate cadmium-transformed cells acquired apoptotic resistance, which may be linked to the specific suppression of the JNK pathway and is associated with MT overexpression, which, in turn, may impact this signal transduction pathway. The acquisition of apoptotic resistance may play an important role in cadmium carcinogenesis by contributing to both tumor initiation and malignant progression.

  6. Acquired tolerance in cadmium-adapted lung epithelial cells: Roles of the c-Jun N-terminal kinase signaling pathway and basal level of metallothionein

    International Nuclear Information System (INIS)

    Lau, Andy T.Y.; Zhang Jian; Chiu, J.-F.

    2006-01-01

    Cadmium-resistant cells were developed in our laboratory with rat lung epithelial cells (LECs) by stepwise exposure of LECs to cadmium chloride from 1 μM to 20 μM after 20 passages. To investigate the Cd-resistant phenotype in a long-term perspective, cadmium-resistant cells adapted to 20 μM cadmium (Cd R ) were then cultured in the absence of cadmium for various passages [Cd R (-n)]. All these adapted cells were significantly protected from cadmium toxicity as compared to parental cadmium-sensitive LECs (Cd S ). The cadmium-resistant phenotype of adapted cells was relatively stable in the absence of cadmium for as long as 40 passages. Basal mRNA level of metallothionein-1 (MT-1) was dramatically higher in Cd R than in Cd R (-), which may account for the higher Cd-resistance of Cd R than Cd R (-). MT-1 mRNA level decreased drastically in Cd R after cadmium removal, suggesting that the high basal level of MT-1 in Cd R may be only partially responsible for cadmium-resistance. Treatment of cells with high levels of cadmium resulted in decreased phosphorylation of c-Jun N-terminal kinase (JNK1/2) in adapted cells than in sensitive cells and this cadmium-induced JNK activity was blocked by JNK inhibitor II, SP600125. Ro318220, a strong activator of JNK, reverted cadmium-sensitive phenotype in adapted cells. Taken together, our results suggest that during cadmium adaptation, cells develop tolerance to cell death, generally due to perturbation of the JNK signaling pathway and the nonresponsiveness of JNK phosphorylation is critical for the Cd-tolerance in these cells

  7. Modulation of metallothionein and metal partitioning in liver and kidney of Solea senegalensis after long-term acclimation to two environmental temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Siscar, R.; Torreblanca, A.; Ramo, J. del [Departamento Biología Funcional y Antropología Física, Universitat de València, Dr. Moliner 50 Burjassot, 46100 València (Spain); Solé, M., E-mail: msole@icm.csic.es [Institut de Ciencies del Mar (ICM-CSIC), Passeig marítim de la Barceloneta 37-49, 08003 Barcelona (Spain)

    2014-07-15

    Juveniles of Solea senegalensis were fed with commercial pellets under controlled conditions at two environmental Mediterranean temperatures (15 and 20 °C) for two months. After this period, the accumulation of essential and non-essential metals and metallothionein (MT) levels was measured in liver and kidney by inductively coupled plasma mass spectrometry (ICP-MS) and pulse polarography, respectively. The bioaccumulation factor (BAF) for selected metals in both tissues was calculated in relation to levels present in the feed. Tissue partitioning (liver/kidney) and molar ratios, considering the metal protective mechanisms: MT and Selenium (Se), were included for evaluating the detoxification capacity of each tissue. Ag, Cd, Cu and Mn were preferentially accumulated in the liver whereas Co, Fe, Hg, Se and Zn were found in larger concentrations in the kidney, and higher temperature enhanced the accumulation of some of them, but not all. MT content in liver, but not in kidney, was also influenced by temperature changes and by length of exposure. The BAF revealed that Cu was taken up mainly by the liver whereas Se was efficiently taken up by both tissues. The high molar ratios of MT and most metals denoted the kidney's remarkable spare capacity for metal detoxification through MT binding. Moreover, the potential protective role of Se was also more evident in kidney as a higher Se:Cd and Se:Ag molar ratios were reached in this organ. In contrast to other fish, the storage of Cd in kidney was particularly low. - Highlights: • Long-term increases in temperature entailed changes in MT and metal content in liver. • The liver is the preferred storage organ for most metals. • Se assimilation from feed results in a high BAF in the liver and kidney. • MT/metal and Se/metal are higher in kidney than in liver for most metals, except Cd.

  8. Tissue- and cell-specific expression of metallothionein genes in cadmium- and copper-exposed mussels analyzed by in situ hybridization and RT-PCR

    International Nuclear Information System (INIS)

    Zorita, I.; Bilbao, E.; Schad, A.; Cancio, I.; Soto, M.; Cajaraville, M.P.

    2007-01-01

    Metallothioneins (MTs) are metal-inducible proteins that can be used as biomarkers of metal exposure. In mussels two families of MT isoforms (MT10 and MT20) have been characterized. In this study, mussels (Mytilus galloprovincialis) were exposed to 200 ppb Cd and 40 ppb Cu for 2 and 9 days to characterize the tissue and isoform specificity of metal-induced MT expression. Non-radioactive in situ hybridization demonstrated that both MT isoforms were mainly transcribed in digestive tubule epithelial cells, especially in basophilic cells. Weaker MT expression was detected in non-ciliated duct cells, stomach and gill epithelial cells, haemocytes, adipogranular cells, spermatic follicles and oocytes. RT-PCR resulted in cloning of a novel M. galloprovincialis isoform homologous to recently cloned Mytilus edulis intron-less MT10B isoform. In gills, Cd only affected MT10 gene expression after 2 days of exposure while increases in MT protein levels occurred at day 9. In the digestive gland, a marked increase of both isoforms, but especially of MT20, was accompanied by increased levels of MT proteins and basophilic cell volume density (Vv BAS ) after 2 and 9 days and of intralysosomal metal accumulation in digestive cells after 9 days. Conversely, although metal was accumulated in digestive cells lysosomes and the Vv BAS increased in Cu-exposed mussels, Cu exposure did not produce an increase of MT gene expression or MT protein levels. These data suggest that MTs are expressed in a tissue-, cell- and isoform-specific way in response to different metals

  9. Metallothionein and Hsp70 trade-off against one another in Daphnia magna cross-tolerance to cadmium and heat stress

    Energy Technology Data Exchange (ETDEWEB)

    Haap, Timo, E-mail: timo.haap@gmx.de; Schwarz, Simon; Köhler, Heinz-R.

    2016-01-15

    Highlights: • Cadmium acclimation of two Daphnia magna clones which differed in Cd sensitivity and Hsp70 levels. • Two distinct metal-handling strategies regarding Hsp70 and MT expression were observed. • High Hsp70 levels did not confer an increase in Cd and heat stress tolerance. • Our results indicate a trade-off between Hsp70 and MT. - Abstract: The association between the insensitivity of adapted ecotypes of invertebrates to environmental stress, such as heavy metal pollution, and overall low Hsp levels characterizing these organisms has been attracting attention in various studies. The present study seeks to induce and examine this phenomenon in Daphnia magna by multigenerational acclimation to cadmium in a controlled laboratory setting. In this experiment, interclonal variation was examined: two clones of D. magna that have previously been characterized to diverge regarding their cadmium resistance and levels of the stress protein Hsp70, were continuously exposed to a sublethal concentration of Cd over four generations to study the effects of acclimation on Hsp70, metallothionein (MT), reproduction and cross-tolerance to heat stress. The two clones differed in all the measured parameters in a characteristic way, clone T displaying Cd and heat resistance, lower Hsp70 levels and offspring numbers on the one hand and higher MT expression on the other hand, clone S the opposite for all these parameters. We observed only slight acclimation-induced changes in constitutive Hsp70 levels and reproductive output. The differences in MT expression between clones as well as between acclimated organisms and controls give evidence for MT accounting for the higher Cd tolerance of clone T. Overall high Hsp70 levels of clone S did not confer cross tolerance to heat stress, contrary to common expectations. Our results suggest a trade-off between the efforts to limit the proteotoxic symptoms of Cd toxicity by Hsp70 induction and those to sequester and detoxify Cd by

  10. Analysis of Metal-Binding Features of the Wild Type and Two Domain-Truncated Mutant Variants of Littorina littorea Metallothionein Reveals Its Cd-Specific Character

    Directory of Open Access Journals (Sweden)

    Òscar Palacios

    2017-07-01

    Full Text Available After the resolution of the 3D structure of the Cd9-aggregate of the Littorina littorea metallothionein (MT, we report here a detailed analysis of the metal binding capabilities of the wild type MT, LlwtMT, and of two truncated mutants lacking either the N-terminal domain, Lltr2MT, or both the N-terminal domain, plus four extra flanking residues (SSVF, Lltr1MT. The recombinant synthesis and in vitro studies of these three proteins revealed that LlwtMT forms unique M9-LlwtMT complexes with Zn(II and Cd(II, while yielding a complex mixture of heteronuclear Zn,Cu-LlwtMT species with Cu(I. As expected, the truncated mutants gave rise to unique M6-LltrMT complexes and Zn,Cu-LltrMT mixtures of lower stoichiometry with respect to LlwtMT, with the SSVF fragment having an influence on their metal binding performance. Our results also revealed a major specificity, and therefore a better metal-coordinating performance of the three proteins for Cd(II than for Zn(II, although the analysis of the Zn(II/Cd(II displacement reaction clearly demonstrates a lack of any type of cooperativity in Cd(II binding. Contrarily, the analysis of their Cu(I binding abilities revealed that every LlMT domain is prone to build Cu4-aggregates, the whole MT working by modules analogously to, as previously described, certain fungal MTs, like those of C. neoformans and T. mesenterica. It is concluded that the Littorina littorea MT is a Cd-specific protein that (beyond its extended binding capacity through an additional Cd-binding domain confers to Littorina littorea a particular adaptive advantage in its changeable marine habitat.

  11. Effects of cadmium exposure on sea urchin development assessed by SSH and RT-qPCR: metallothionein genes and their differential induction.

    Science.gov (United States)

    Ragusa, Maria Antonietta; Costa, Salvatore; Gianguzza, Marco; Roccheri, Maria Carmela; Gianguzza, Fabrizio

    2013-03-01

    In order to study the defense strategies activated by Paracentrotus lividus embryos in response to sub-lethal doses of CdCl2, we compared the induced transcripts to that of control embryos by suppression subtractive hybridization technique. We isolated five metallothionein (MT) cDNAs and other genes related to detoxification, to signaling pathway components, to oxidative, reductive and conjugative biotransformation, to RNA maturation and protein synthesis. RT-qPCR analysis revealed that two of the five P. lividus MT (PlMT7 and PlMT8) genes appeared to be constitutively expressed and upregulated following cadmium treatment, whereas the other three genes (PlMT4, PlMT5, PlMT6) are specifically switched-on in response to cadmium treatment. Moreover, we found that this transcriptional induction is concentration dependent and that the cadmium concentration threshold for the gene activation is distinct for every gene. RT-qPCR experiments showed in fact that, among induced genes, PlMT5 gene is activated at a very low cadmium concentration (0.1 μM) whereas PlMT4 and PlMT6 are activated at intermediate doses (1-10 μM). Differently, PlMT7 and PlMT8 genes increase significantly their expression only in embryos treated with the highest dose (100 μM CdCl2). We found also that, in response to a lethal dose of cadmium (1 μM), only PlMT5 and PlMT6 mRNA levels increased further. These data suggest a hierarchical and orchestrated response of the P. lividus embryo to overcome differential environmental stressors that could interfere with a normal development.

  12. Surface display of monkey metallothionein {alpha} tandem repeats and EGFP fusion protein on Pseudomonas putida X4 for biosorption and detection of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    He, Xiaochuan; Chen, Wenli; Huang, Qiaoyun [Huazhong Agricultural Univ., Wuhan (China). State Key Lab. of Agricultural Microbiology

    2012-09-15

    Monkey metallothionein {alpha} domain tandem repeats (4mMT{alpha}), which exhibit high cadmium affinity, have been displayed for the first time on the surface of a bacterium using ice nucleation protein N-domain (inaXN) protein from the Xanthomonas campestris pv (ACCC - 10049) as an anchoring motif. The shuttle vector pIME, which codes for INAXN-4mMT{alpha}-EGFP fusion, was constructed and used to target 4mMT{alpha} and EGFP on the surface of Pseudomonas putida X4 (CCTCC - 209319). The surface location of the INAXN-4mMT{alpha}-EGFP fusion was further verified by western blot analysis and immunofluorescence microscopy. The growth of X4 showed resistance to cadmium presence. The presence of surface-exposed 4mMT{alpha} on the engineered strains was four times higher than that of the wild-type X4. The Cd{sup 2+} accumulation by X4/pIME was not only four times greater than that of the original host bacterial cells but was also remarkably unaffected by the presence of Cu{sup 2+} and Zn{sup 2+}. Moreover, the surface-engineered strains could effectively bind Cd{sup 2+} under a wide range of pH levels, from 4 to 7. P. putida X4/pIME with surface-expressed 4mMT{alpha}-EGFP had twice the cadmium binding capacity as well as 1.4 times the fluorescence as the cytoplasmic 4mMTa-EGFP. These results suggest that P. putida X4 expressing 4mMT{alpha}-EGFP with the INAXN anchor motif on the surface would be a useful tool for the remediation and biodetection of environmental cadmium contaminants. (orig.)

  13. Chromatographic separation of similar post-translationally modified metallothioneins reveals the changing conformations of apo-MT upon cysteine alkylation by high resolution LC-ESI-MS.

    Science.gov (United States)

    Irvine, Gordon W; Stillman, Martin J

    2018-03-05

    Metallothioneins (MTs) are a class of small cysteine-rich proteins essential for Zn and Cu homeostasis, heavy metal detoxification, and cellular redox chemistry. Herein, we describe the separation and characterization of MTs differentially modified with N-ethylmaleimide (NEM) by liquid chromatography-mass spectrometry (LC-MS). The full-length recombinant MT isoform 1a as well as is isolated domain fragments were first alkylated, then separated on column with subsequent detection by MS. Different behavior was observed for the three peptides with the full-length protein and the isolated α-domain exhibiting similar separation characteristics. For the isolated β-domain, the smallest peptide, each alkylated species was well separated, indicating large changes in protein conformation. For the full-length and α-domain peptides, the apo- and lightly alkylated species co-eluted, indicating similar structural properties. However, the more extensively alkylated species were well separated from each other, indicating the sequential unfolding of the apo-MT peptides and providing evidence for the mechanistic explanation for the cooperative alkylation reaction observed for NEM and other bulky and hydrophobic alkylation reagents. We show for the first time clear separation of highly similar MTs, differing by only +125 Da, and can infer structural properties from the LC-MS data, analogous to more complicated and less ubiquitous ion-mobility experiments. The data suggest a compact globular structure of apo-MTs, wherein the β-domain is more easily denatured. This may have biological implications in terms of domain-specific participation in cellular redox chemistry and resulting metal release. Copyright © 2018. Published by Elsevier B.V.

  14. Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, M.; Thomsen, Pernille Sjølin

    2001-01-01

    damage to neurons as indicated by neuron specific enolase (NSE) ir, and the number of cells undergoing apoptosis (measured by TUNEL) was dramatically increased. Zinc deficiency significantly altered brain response to TBI, potentiating the microgliosis and reducing the astrogliosis, while increasing...

  15. Central Nervous System Vasculitis

    Science.gov (United States)

    ... Forms of Vasculitis / Central Nervous System (CNS) Vasculitis Central Nervous System (CNS) Vasculitis Swap out your current Facebook Profile ... your Facebook personal page. Replace with this image. Central nervous system (CNS) vasculitis is inflammation of blood vessel walls ...

  16. Intervention Packages to Reduce the Impact of HIV and HCV Infections Among People Who Inject Drugs in Eastern Europe and Central Asia: A Modeling and Cost-effectiveness Study.

    Science.gov (United States)

    Mabileau, Guillaume; Scutelniciuc, Otilia; Tsereteli, Maia; Konorazov, Ivan; Yelizaryeva, Alla; Popovici, Svetlana; Saifuddin, Karimov; Losina, Elena; Manova, Manoela; Saldanha, Vinay; Malkin, Jean-Elie; Yazdanpanah, Yazdan

    2018-03-01

    We evaluated the effectiveness and cost-effectiveness of interventions targeting hepatitis C virus (HCV) and HIV infections among people who inject drugs (PWID) in Eastern Europe/Central Asia. We specifically considered the needle-syringe program (NSP), opioid substitution therapy (OST), HCV and HIV diagnosis, antiretroviral therapy (ART), and/or new HCV treatment (direct acting antiviral [DAA]) in Belarus, Georgia, Kazakhstan, Republic of Moldova, and Tajikistan. We developed a deterministic dynamic compartmental model and evaluated the number of infections averted, costs, and incremental cost-effectiveness ratios (ICERs) of interventions. OST decreased frequencies of injecting by 85% and NSP needle sharing rates by 57%; ART was introduced at CD4 impact on transmissions (infections averted in PWID: 42% in Tajikistan to 55% in Republic of Moldova for HCV; 30% in Belarus to 61% in Kazakhstan for HIV over 20 years). Increasing NSP+OST+ART was very cost-effective in Georgia (ICER = $910/year of life saved [YLS]), and was cost-saving in Kazakhstan and Republic of Moldova. NSP+OST+ART and HIV diagnosis was very cost-effective in Tajikistan (ICER = $210/YLS). Increasing the coverage of all interventions was always the most effective strategy and was cost-effective in Belarus and Kazakhstan (ICER = $12 960 and $21 850/YLS); it became cost-effective/cost-saving in all countries when we decreased DAA costs. Increasing NSP+OST coverage, in addition to ART and HIV diagnosis, had a high impact on both epidemics and was very cost-effective and even cost-saving. When HCV diagnosis was improved, increased DAA averted a high number of new infections if associated with NSP+OST.

  17. Unsaturated fatty acids supplementation reduces blood lead level in rats.

    Science.gov (United States)

    Skoczyńska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, Łukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100 ppm Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2 mL/kg b.w.) or egg derived lecithin fraction: "super lecithin" (50 g/kg b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05).

  18. Tamarix hispida metallothionein-like ThMT3, a reactive oxygen species scavenger, increases tolerance against Cd(2+), Zn(2+), Cu(2+), and NaCl in transgenic yeast.

    Science.gov (United States)

    Yang, Jingli; Wang, Yucheng; Liu, Guifeng; Yang, Chuanping; Li, Chenghao

    2011-03-01

    A metallothionein-like gene, ThMT3, encoding a type 3 metallothionein, was isolated from a Tamarix hispida leaf cDNA library. Expression analysis revealed that mRNA of ThMT3 was upregulated by high salinity as well as by heavy metal ions, and that ThMT3 was predominantly expressed in the leaf. Transgenic yeast (Saccharomyces cerevisiae) expressing ThMT3 showed increased tolerance to Cd(2+), Zn(2+), Cu(2+), and NaCl stress. Transgenic yeast also accumulated more Cd(2+), Zn(2+), and NaCl, but not Cu(2+). Analysis of the expression of four genes (GLR1, GTT2, GSH1, and YCF1) that aid in transporting heavy metal (Cd(2+)) from the cytoplasm to the vacuole demonstrated that none of these genes were induced under Cd(2+), Zn(2+), Cu(2+), and NaCl stress in ThMT3-transgenic yeast. H(2)O(2) levels in transgenic yeast under such stress conditions were less than half those in control yeast under the same conditions. Three antioxidant genes (SOD1, CAT1, and GPX1) were specifically expressed under Cd(2+), Zn(2+), Cu(2+), and NaCl stress in the transgenic yeast. Cd(2+), Zn(2+), and Cu(2+) increased the expression levels of SOD1, CAT1, and GPX1, respectively, whereas NaCl induced the expression of SOD1 and GPX1.

  19. Equipe interdisciplinar reduz infecção sanguínea relacionada ao cateter venoso central em Unidade de Terapia Intensiva Pediátrica Interdisciplinary task-force reduces catheter-related bloodstream infection in a Pediatric Intensive Care Unit

    Directory of Open Access Journals (Sweden)

    Ricardo Vilela

    2010-12-01

    respectively (Phase 1 vs Phase 2 and 3; p<0.001. Gram-positive organisms were isolated in 57% of bloodstream infections in Phase 1, and 45 and 58% in Phases 2 and 3, respectively. CONCLUSIONS: The interdisciplinary educational approach and the central venous catheter insertion policies were effective to reduce central venous catheter-related bloodstream infections in the Pediatric Intensive Care Unit.

  20. Preliminary analysis of the inclusion of security passive systems to reduce the impact of accidents in nuclear power plants; Analisis preliminar de la inclusion de sistemas pasivos de seguridad para reducir el impacto de accidentes en centrales nucleares

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez J, J.; Morales S, J. B. [UNAM, Facultad de Ingenieria, Circuito Interior, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Espinosa P, G., E-mail: jersonsanchez@gmail.com [Universidad Autonoma Metropolitana, Unidad Iztapalapa, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 Mexico D. F. (MX)

    2011-11-15

    In this work is presented a conceptual analysis of possible benefits and limitations that potentially represents the introduction of security passive systems to reduce the events impact of very low probability and high risk to the systems of radioactive material confinement of a light water reactor. These events are related with the possibility that a hydrogen explosion is presented as consequence of the accumulation of the same hydrogen in the contention of the reactor, in a scenario of severe accident. This accumulated hydrogen can be liberated in the reactor building or primary contention, where the conditions of their atmosphere make but prone the combustion. The catalytic recombination represents a viable option for the hydrogen concentrations decrease and because this recombination is highly exothermic, is important to analyze and to know if the recombined vapor to high temperature can be used in combination with vapor injectors that in turn, they are passive systems. In the following sections an explanation is presented about the use of the mentioned systems, as well as some results on the behavior of the vapor injectors. (Author)

  1. Central solar energy receiver

    Science.gov (United States)

    Drost, M. Kevin

    1983-01-01

    An improved tower-mounted central solar energy receiver for heating air drawn through the receiver by an induced draft fan. A number of vertically oriented, energy absorbing, fin-shaped slats are radially arranged in a number of concentric cylindrical arrays on top of the tower coaxially surrounding a pipe having air holes through which the fan draws air which is heated by the slats which receive the solar radiation from a heliostat field. A number of vertically oriented and wedge-shaped columns are radially arranged in a number of concentric cylindrical clusters surrounding the slat arrays. The columns have two mirror-reflecting sides to reflect radiation into the slat arrays and one energy absorbing side to reduce reradiation and reflection from the slat arrays.

  2. Effects of heavy metals on population growth and metallothionein gene expression in the mosquito Culex quinquefasciatus, from Calcutta, India

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Sagartirtha; Duttagupta, Asish K.; Mal, Tarun K

    2004-01-01

    Major water bodies in and around the city of Calcutta (India) receive heavy metal contaminated effluents from industries, households, and vehicular traffic through sewage or drainage. We quantified concentrations of Cu, Zn, and Cd from three water bodies at Kalighat, Tangra, and VIP Road, respectively. The concentrations of these heavy metals were significantly greater in the summer than in monsoon when heavy downpours resulted in reduced metal concentrations. Concentrations of metals in the mosquito Culex quinquefasciatus also reflected such seasonal fluctuations. Hatchability and survivorship of C. quinquefasciatus significantly differed among the sites and were reduced significantly from the control. Exposure to heavy metals also induced MT-gene expression in C. quinquefasciatus, likely helping them to survive in the water bodies stressed with heavy metals. MT-gene activity demonstrated significant variation among sites and seasons with the highest activity in the summer in the VIP Road population. This study suggests that C. quinquefasciatus could be used as an ecological indicator of heavy metal pollution by monitoring its MT-gene expression. - The mosquito, Culex quinquefasciatus, might be useful as an indicator of trace metals.

  3. Effects of heavy metals on population growth and metallothionein gene expression in the mosquito Culex quinquefasciatus, from Calcutta, India

    International Nuclear Information System (INIS)

    Sarkar, Sagartirtha; Duttagupta, Asish K.; Mal, Tarun K.

    2004-01-01

    Major water bodies in and around the city of Calcutta (India) receive heavy metal contaminated effluents from industries, households, and vehicular traffic through sewage or drainage. We quantified concentrations of Cu, Zn, and Cd from three water bodies at Kalighat, Tangra, and VIP Road, respectively. The concentrations of these heavy metals were significantly greater in the summer than in monsoon when heavy downpours resulted in reduced metal concentrations. Concentrations of metals in the mosquito Culex quinquefasciatus also reflected such seasonal fluctuations. Hatchability and survivorship of C. quinquefasciatus significantly differed among the sites and were reduced significantly from the control. Exposure to heavy metals also induced MT-gene expression in C. quinquefasciatus, likely helping them to survive in the water bodies stressed with heavy metals. MT-gene activity demonstrated significant variation among sites and seasons with the highest activity in the summer in the VIP Road population. This study suggests that C. quinquefasciatus could be used as an ecological indicator of heavy metal pollution by monitoring its MT-gene expression. - The mosquito, Culex quinquefasciatus, might be useful as an indicator of trace metals

  4. Parallelization of game theoretic centrality algorithms

    Indian Academy of Sciences (India)

    of a class of node centrality algorithms based on cooperative game theory. These were proposed earlier as an efficient alternatives to traditional measure of information diffusion centrality. We present here distributed versions of these algorithms in a Map-. Reduce framework, currently the most popular distributed computing ...

  5. Short-term metallothionein inductions in the edible cockle Cerastoderma edule after cadmium or mercury exposure: Discrepancy between mRNA and protein responses

    Energy Technology Data Exchange (ETDEWEB)

    Paul-Pont, Ika, E-mail: i.paulpont@epoc.u-bordeaux1.fr [Universite Bordeaux 1 - CNRS, UMR 5805 EPOC, CNRS, Station Marine d' Arcachon, Place du Dr. Peyneau, Arcachon 33120 (France); Gonzalez, Patrice, E-mail: p.gonzalez@epoc.u-bordeaux1.fr [Universite Bordeaux 1 - CNRS, UMR 5805 EPOC, CNRS, Station Marine d' Arcachon, Place du Dr. Peyneau, Arcachon 33120 (France); Baudrimont, Magalie, E-mail: m.baudrimont@epoc.u-bordeaux1.fr [Universite Bordeaux 1 - CNRS, UMR 5805 EPOC, CNRS, Station Marine d' Arcachon, Place du Dr. Peyneau, Arcachon 33120 (France); Nili, Hanane, E-mail: h.nili@etu.u-bordeaux1.fr [Universite Bordeaux 1 - CNRS, UMR 5805 EPOC, CNRS, Station Marine d' Arcachon, Place du Dr. Peyneau, Arcachon 33120 (France); Montaudouin, Xavier de, E-mail: x.de-montaudouin@epoc.u-bordeaux1.fr [Universite Bordeaux 1 - CNRS, UMR 5805 EPOC, CNRS, Station Marine d' Arcachon, Place du Dr. Peyneau, Arcachon 33120 (France)

    2010-05-05

    Metallothioneins (MT) are essential metal binding proteins involved in metal homeostasis and detoxification in living organisms. Numerous studies have focused on MT response to metal exposure and showed an important variability according to species, metal, concentration and time of exposure. In this study, the expression of one isoform of MT gene (Cemt1) and associated MT protein synthesis were determined after 1, 3, 9, 24, 72 and 168 h of cadmium (Cd) or mercury (Hg) exposures in gills of the cockle Cerastoderma edule. This experiment, carried out in laboratory conditions, revealed that in Cd-exposed cockles, induction of Cemt1 is time-dependent following a 'pulse-scheme' with significant upregulation at 24 h and 168 h intersected by time point (72 h) with significant downregulation. MT protein concentration increases with time in gills of exposed cockles in relation with the progressive accumulation of Cd in soluble fraction. On contrary, Hg exposure does not lead to any induction of Cemt1 mRNA expression or MT protein synthesis compared to control, despite a higher accumulation of this metal in gills of cockles compared to Cd. The localization of Hg (85-90%) is in insoluble fraction, whereas MT was located in the cytoplasm of cells. This gives us a first clue to understand the inability of Hg to activate MT synthesis. However, other biochemical processes probably occur in gills of C. edule since the remaining soluble fraction of Hg exceeds MT sequestration ability. Finally, since one of the first main targets of metal toxicity in cells was the mitochondria, some genes involved in mitochondria metabolism were also analyzed in order to assess potential differences in cellular damages between two metal exposures. Indeed, until T{sub 168}, no impact on mitochondrial genes was shown following Hg exposure, despite the complete lack of MT response. This result indicated the presence of other effective cellular ligands which sequester the cytosolic fraction of

  6. The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues

    Energy Technology Data Exchange (ETDEWEB)

    Starska, Katarzyna, E-mail: katarzyna.starska@umed.lodz.pl [I Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Kopcinskiego 22, 90-153 Łódź (Poland); Bryś, Magdalena; Forma, Ewa [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland); Olszewski, Jurek; Pietkiewicz, Piotr [II Department of Otolaryngology and Laryngological Oncology, Medical University of Łódź, Żeromskiego 113, 90-549 Łódź (Poland); Lewy-Trenda, Iwona; Danilewicz, Marian [Department of Pathology, Medical University of Łódź, Pomorska 251, 92-213 Łódź (Poland); Krześlak, Anna [Department of Cytobiochemistry, University of Łódź, Pomorska 142/143, 90-236 Łódź (Poland)

    2015-06-15

    Metallothioneins (MTs) are intracellular thiol-rich heavy metal-binding proteins which join trace metal ions protecting cells against heavy metal toxicity and regulate metal distribution and donation to various enzymes and transcription factors. The goal of this study was to identify the − 5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene, and to investigate its effect on allele-specific gene expression and Cd, Zn, Cu and Ni content in sinonasal inverted papilloma tissue (IP), with non-cancerous sinonasal mucosa (NCM) as a control. The MT2A promoter region − 5 A/G SNP was identified by restriction fragment length polymorphism using 117 IP and 132 NCM. MT2A gene analysis was performed by quantitative real-time PCR. Metal levels were analyzed by flame atomic absorption spectrometry. The frequency of A allele carriage was 99.2% and 100% in IP and NCM, respectively. The G allele carriage was detected in 23.9% of IP and in 12.1% of the NCM samples. As a result, a significant association of − 5 A/G SNP in MT2A gene with mRNA expression in both groups was determined. A significant association was identified between the − 5 A/G SNP in the MT2A gene with mRNA expression in both groups. A highly significant association was detected between the rs28366003 genotype and Cd and Zn content in IP. Furthermore, significant differences were identified between A/A and A/G genotype with regard to the type of metal contaminant. The Spearman rank correlation results showed the MT2A gene expression and both Cd and Cu levels were negatively correlated. The results obtained in this study suggest that the − 5 A/G SNP in the MT2A gene may have an effect on allele-specific gene expression and toxic metal accumulation in sinonasal inverted papilloma. - Highlights: • MT2A gene expression and metal content in sinonasal inverted papilloma tissues • Association between SNP (rs28366003) and expression of MT2A • Significant

  7. Characterization of the rubber tree metallothionein family reveals a role in mitigating the effects of reactive oxygen species associated with physiological stress.

    Science.gov (United States)

    Huang, Yacheng; Fang, Yongjun; Long, Xiangyu; Liu, Linya; Wang, Jia; Zhu, Jinheng; Ma, Yanyan; Qin, Yunxia; Qi, Jiyan; Hu, Xinwen; Tang, Chaorong

    2018-02-07

    Metallothioneins (MTs) as reactive oxygen species (ROS) scavengers play important roles in stress response and heavy metal homeostasis. In Hevea brasiliensis (the para rubber tree that is the source of commercial natural rubber) and in other trees, the functions of MTs are not well understood. Latex exudes when the rubber tree is tapped. The flow of latex and its regeneration can be enhanced by tapping, wounding and ethylene treatment, all of which produce ROS as a by-product. Here, we show the presence of four MT genes in H. brasiliensis, comprising three Type 2 (HbMT2, -2a and -2b) and one Type 3 (HbMT3L) isoforms, representing one of the smallest MT gene families among angiosperms. The four HbMTs exhibited distinct tissue expression patterns: HbMT2 and HbMT3L mainly in leaves, HbMT2a specifically in flowers and HbMT2b in diverse tissues. The expression of HbMT2b, an isoform present in latex, decreased significantly in the latex following the stress-inducing treatments of tapping, wounding and ethephon (an ethylene generator). The expressions of the leaf-abundant isoforms, HbMT2 and -3L were up-regulated following pathogenic fungus infection and high-temperature stress, but down-regulated by low-temperature stress. These reactions were consistent with multiple defense- and hormone-responsive cis-acting elements in the HbMT promoters. Nine transcription factors were shown to implicate in the high-temperature responsiveness of HbMT2 and -3L in leaves. Overexpression of HbMT2 in Escherichia coli enhanced the bacterium's tolerance to heavy metals and ROS, consistent with its predicted role as an ROS scavenger. Taken together, our results, along with other relevant studies, suggest an important role of HbMTs in latex regeneration as well as species adaptation via the regulation of ROS homeostasis. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. miR-122 promotes hepatic antioxidant defense of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium by directly targeting a metallothionein gene

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, Jun, E-mail: Qiangj@ffrc.cn [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China); Tao, Yi-Fan [Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081 (China); He, Jie [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China); Xu, Pao, E-mail: Xup@ffrc.cn [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China); Bao, Jin-Wen [Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081 (China); Sun, Yi-Lan [Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, Jiangsu (China)

    2017-01-15

    Highlights: • MiR-122 regulated tilapia MT by directly targeting MT 3′UTR. • MiR-122 level was negatively related to MT level under Cd stress. • MiR-122 silencing caused up-regulation of MT expression. • MiR-122 loss relieved liver stress and stimulated antioxidant enzymes. - Abastract: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3′untranslated region (3′UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver homeostasis and energy metabolism. Down-regulated levels of hepatic miR-122 were found in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium (Cd) stress. Here, we report for the first time that reduction of miR-122 post-transcriptionally increased metallothionein (MT) mRNA levels by binding to its 3′UTR, as shown by a 3′ UTR luciferase reporter assay. The expression levels of miR-122 were negatively related to MT levels in GIFT under Cd stress. We performed in vivo functional analysis of miR-122 by injecting the fish with a miR-122 antagomir. Inhibition of miR-122 levels in GIFT liver caused a significant increase in MT expression, affected white blood cell and red blood cell counts, and serum alanine and aspartate aminotransferase activities, and glucose levels, all of which may help to relieve Cd stress-related liver stress. miR-122 silencing modulated oxidative stress and stimulated the activity of antioxidant enzymes. Our findings indicate that miR-122 regulated MT levels by binding to the 3′UTR of MT mRNA, and this interaction affected Cd stress induction and the resistance response in GIFT. We concluded that miR-122 plays an important role in regulating the stress response in GIFT liver. Our findings may contribute to understanding the mechanisms of miRNA-mediated gene regulation in tilapia in response to environmental stresses.

  9. miR-122 promotes hepatic antioxidant defense of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium by directly targeting a metallothionein gene

    International Nuclear Information System (INIS)

    Qiang, Jun; Tao, Yi-Fan; He, Jie; Xu, Pao; Bao, Jin-Wen; Sun, Yi-Lan

    2017-01-01

    Highlights: • MiR-122 regulated tilapia MT by directly targeting MT 3′UTR. • MiR-122 level was negatively related to MT level under Cd stress. • MiR-122 silencing caused up-regulation of MT expression. • MiR-122 loss relieved liver stress and stimulated antioxidant enzymes. - Abastract: MicroRNAs (miRNAs) are small, non-coding RNAs that regulate target gene expression by binding to the 3′untranslated region (3′UTR) of the target mRNA. MiRNAs regulate a large variety of genes, including those involved in liver homeostasis and energy metabolism. Down-regulated levels of hepatic miR-122 were found in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) exposed to cadmium (Cd) stress. Here, we report for the first time that reduction of miR-122 post-transcriptionally increased metallothionein (MT) mRNA levels by binding to its 3′UTR, as shown by a 3′ UTR luciferase reporter assay. The expression levels of miR-122 were negatively related to MT levels in GIFT under Cd stress. We performed in vivo functional analysis of miR-122 by injecting the fish with a miR-122 antagomir. Inhibition of miR-122 levels in GIFT liver caused a significant increase in MT expression, affected white blood cell and red blood cell counts, and serum alanine and aspartate aminotransferase activities, and glucose levels, all of which may help to relieve Cd stress-related liver stress. miR-122 silencing modulated oxidative stress and stimulated the activity of antioxidant enzymes. Our findings indicate that miR-122 regulated MT levels by binding to the 3′UTR of MT mRNA, and this interaction affected Cd stress induction and the resistance response in GIFT. We concluded that miR-122 plays an important role in regulating the stress response in GIFT liver. Our findings may contribute to understanding the mechanisms of miRNA-mediated gene regulation in tilapia in response to environmental stresses.

  10. Influence of water temperature and waterborne cadmium toxicity on growth performance and metallothionein-cadmium distribution in different organs of Nile tilapia, Oreochromis niloticus (L.).

    Science.gov (United States)

    Abdel-Tawwab, Mohsen; Wafeek, Mohammed

    2014-10-01

    Cadmium (Cd) is believed to be one of the most abundant and ubiquitously distributed toxins in the aquatic system. This metal is released to the aquatic environment from both anthropogenic sources, such as industrial, agricultural and urban effluents as well as natural sources, such as rocks and soils. Otherwise, the temperature increase of water bodies, which has been observed due to global climatic changes, has been shown to increase Cd toxicity for several aquatic animal species including fish. In the present study, Nile tilapia, Oreochromis niloticus (L.), (26.0 ± 0.38 g) were reared at 20, 24, 28, or 32 °C and exposed to 0.0 or 0.5mg Cd/L for 8 weeks to investigate effects of water temperature, Cd toxicity and their interaction on fish performance as well as metallothionein (MT) and Cd distribution in different fish organs. It was found that fish reared in Cd-free group at 28 °C showed the optimum growth and feed intake, while Cd-exposed fish showed low growth and feed intake irrespective to water temperature. A synergetic relationship between water temperature and Cd toxicity was observed where Cd toxicity increased as water temperature increased and the worse growth was obtained in Cd-exposed fish reared at 32 °C. Additionally, the highest Cd residues in different fish organs were detected in Cd-exposed fish reared at 32 °C. Similarly, MT concentrations in different fish organs increased as water temperature increased especially in Cd-exposed fish groups. A high positive correlation between MT and Cd concentrations in fish organs was detected. The distribution of MT and Cd levels was in the order of liver>kidney>gills>muscles. The present study revealed that the optimum water temperature suitable for Nile tilapia growth is 28 °C. Additionally, Cd exposure had a deteriorate effect on the growth and health of Nile tilapia. This hazardous effect increased as water temperature increased. Further, liver and kidney were the prime sites of Cd accumulation

  11. Determination of metallothionein levels in tissues of young rats fed zinc-enriched diets Determinação dos níveis de metalotioneínas em tecidos de ratos jovens alimentados com dietas enriquecidas com zinco

    Directory of Open Access Journals (Sweden)

    Gilberto Simeone HENRIQUES

    2001-12-01

    Full Text Available The objective of this work was to quantify metallothioneins (MT's in tissues of rats fed different concentrations of zinc, in order to observe the animal response to the metal in relation to different types of diets, and to assess the nutritional status relating to zinc in the diets. Thirty-two Wistar newly-weaned male rats were distributed into four experimental groups and housed in individual cages. They had free access to water and diet containing different zinc concentrations, named RC (AIN 93-like diet, RH (customary diet of the university restaurant, both non-supplemented, and RCS and RHS, supplemented. After four weeks, the animals were killed and liver, kidneys, femurs and testes were isolated to determine metallothionein levels by a Cd/Hb affinity assay. Zinc content was determined by Flame Atomic Absorption Spectroscopy (FAAS. The results showed that zinc supplementation produced no change in the tissue metallothionein profile in the doses under analysis. The highest metallothionein mean concentration was found in the liver - 36.21 ± 0.88 µg/g (mean for RC-RCS groups, and 28.92 ± 5.32 µg/g (mean for RH-RHS groups. Metallothionein concentrations in testes were quite high, considering the small volume of the organ - 19.29 ± 0.54 µg/g (mean for RC-RCS groups, and 17.22 ± 1.07 µg/g (mean for RH-RHS groups. Significant increases in zinc concentration were observed in the liver of young supplemented rats - 38.94 ± 3.43 µg/g of tissue for RCS, and 42.83 ± 2.78 µg/g of tissue for RHS, and in the femurs - 140.04 ± 6.03 µg/g of tissue for RCS, and 86.57 ± 6.95 µg/g of tissue for RHS. The different carrying zinc food matrices caused no change in the adaptive response to metallothionein metabolism, and the lack of responsiveness towards metallothionein synthesis did not invalidate the results of tissue zinc concentration parameters, which suggest different degrees for zinc bioavailability.O objetivo deste trabalho foi quantificar

  12. Observations of central stars

    International Nuclear Information System (INIS)

    Lutz, J.H.

    1978-01-01

    Difficulties occurring in the observation of central stars of planetary nebulae are reviewed with emphasis on spectral classifications and population types, and temperature determination. Binary and peculiar central stars are discussed. (U.M.G.)

  13. NIDDK Central Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  14. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  15. Reducing sedentarism

    DEFF Research Database (Denmark)

    Brown, Wendy; Andersen, Lars Bo; Sigmund, Anderssen

    being a health risk will be briefly considered. Second, a review of the evidence on the health effects of sitting will be presented. This will include results from observational cohort studies on the relationships between sitting and diabetes, cardiovascular diseases, cancers, depression, obesity...... include sitting during leisure time, at work, and during commuting. Sedentary behaviors such as TV viewing, using a computer or driving a car typically demands low levels of energy expenditure. Youth and adults spend most of their waking time sitting or doing light activities, and most of them do little......, type 2 diabetes, musculoskeletal diseases, and psychological disorders. In addition, low level of energy expenditure is one of the key determinants of the current epidemic of overweight and obesity in Europe. In order to both reduce sitting time and to increase the level of physical activity...

  16. Central America's shrinking forests.

    Science.gov (United States)

    1992-01-01

    This news brief reports that 66% of deforestation in Central America has happened in the past 40 years, based on World Conservation Union (WCU) data. Deforestation is expected to continue. The population of Central America and Mexico grew by 28% between 1977 and 1987. Growth is decreasing but remains high at 2.5% in all countries of the region except Panama. 29 million was the regional population in 1990; the projection is for 63 million by 2025. Population is migrating to urban centers. Forests declined by 13% and croplands increased from 4% to 13% of total land area and pasture land from 2% to 37%. There was an increase in unproductive land from 145 to 24%, i.e., 50% of El Salvador's land had soil degradation as does 30% of Guatemala's. In addition to deforestation and soil degradation, there has been soil erosion leading to sedimentation buildup near dam sites and in rivers, which diminishes hydroelectric power capability. Silting also affects groundwater resources, which impact on a safe drinking water supply. Population growth results in increased demand for fuelwood, urban land, and agricultural land. New techniques practiced widely are needed in order to meet the region's needs or demands. Slowing population growth buys time for adjusting to the necessary changes needed for sustaining the region's population. WCU urges conservation organizations to raise awareness about the role population plays in environmental degradation, and to support efforts to reduce birth rates. Women's status needs to be improved through income-generating projects, for instance, and cooperation is needed between conservation groups and organizations involved with improving maternal and child health.

  17. Youth employment to reduce violence in Central America | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    By combining quantitative and qualitative approaches, mapping out initiatives and outcomes, and focusing both on beneficiaries of employment programs for vulnerable youth and policymakers in charge of program design and implementation, the project aims to uncover the strengths and weaknesses of these interventions ...

  18. Microfinance and reducing poverty in Central Africa | CRDI - Centre ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... to the role of microfinance institutions in the region, where the poor rely on microfinance for access to a livelihood, and micro-insurance to buffer risk. This grant will allow research centres in the four aforementioned countries to evaluate the contribution of microfinance institutions to economic growth and poverty reduction.

  19. Do minimum wages reduce poverty? Evidence from Central America ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Minimum wage legislation applies to all private-sector employees, but in all three countries a large part of the work force is self-employed or works as unpaid family workers and is therefore not covered by the legal minimum. Self-employed and unpaid family workers account for 20% of workers in Costa Rica, 41.4% in El ...

  20. Do minimum wages reduce poverty? Evidence from Central America ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2010-12-16

    Dec 16, 2010 ... Minimum wage legislation applies to all private-sector employees, but in all three countries a large part of the work force is self-employed or works as ... firms in the private formal sector from hiring new workers and trigger layoffs from jobs that usually offer other benefits such as social security coverage.

  1. Reducing costs by reducing size

    International Nuclear Information System (INIS)

    Hayns, M.R.; Shepherd, J.

    1991-01-01

    The present paper discusses briefly the many factors, including capital cost, which have to be taken into account in determining whether a series of power stations based on a small nuclear plant can be competitive with a series based on traditional large unit sizes giving the guaranteed level of supply. The 320 MWe UK/US Safe Integral Reactor is described as a good example of how the factors discussed can be beneficially incorporated into a design using proven technology. Finally it goes on to illustrate how the overall costs of a generating system can indeed by reduced by use of the 320 MWe Safe Integral Reactor rather than conventional units of around 1200 MWe. (author). 9 figs

  2. Do central bank law reforms affect the term in office of central bank governors?

    NARCIS (Netherlands)

    Klomp, J.G.; de Haan, J.

    In this paper we confirm the hypothesis that central bank independence reforms reduce the likelihood that a central bank governor will be replaced. However, the strength of this effect depends on the rule of law and the degree of political polarization. (c) 2009 Elsevier B.V. All rights reserved.

  3. Do central bank law reforms affect the term in office of central bank governors?

    NARCIS (Netherlands)

    Klomp, J.G.; Haan, de J.

    2010-01-01

    In this paper we confirm the hypothesis that central bank independence reforms reduce the likelihood that a central bank governor will be replaced. However, the strength of this effect depends on the rule of law and the degree of political polarization. (c) 2009 Elsevier B.V. All rights reserved.

  4. MODULACIÓN DE LA SINTESIS DE METALOTIONINAS EN Perna viridis PREEXPUESTOS A COBRE Y EXPUESTOS A CADMIO | MODULATION OF METALLOTHIONEIN SYNTHESIS IN Perna viridis PRE EXPOSED TO COPPER AND EXPOSED TO CADMIUM

    Directory of Open Access Journals (Sweden)

    Marín Lemus,

    2014-02-01

    Full Text Available The metallothioneins (Mts have been used as biomarkers because toxic metals such as Hg, Cd, Cu can induce their synthesis; however, environmental factors and the presence of other xenobiotics can determine the magnitude of the response in future exposures to metal ions. Metallothionein concentration was determinate in the soft tissue of Perna viridis juveniles pre-exposed to Cu and exposed to Cd (Cu/Cd for 21 days. For this, three experimental groups were established: exposed to Cd, pre-exposed to Cu and exposed to Cd and the control group (no metal. Cadmium accumulation in tissues of P. viridis was significantly higher in pre-exposed organisms to Cu, with an average value of 6.6 ± 1.9 mg/g, while in those exposed to Cd, was 4.7 ± 2.4 mg/g. Mts concentrations were also higher in the Cu/Cd experimental group, with a value of 1.36 ± 0.52 mg/g in relation to those exposed to Cd which had a value of 0.79 ± 0.47 mg/g. The relationship between Mts and bioaccumulation of Cd was significant in the group exposed to Cd, but not in the exposed Cu/Cd. These results suggest that Cu possibly acted as an inducer of Mts in the body, which led to increased accumulation of Cd in P. viridis and increase in Mts concentration. Tolerance and bioaccumulation of Cd in P. viridis was determined by previous exposure of the organism and hence its response on levels of MTs also depends on it.

  5. The promoter and the 5'-untranslated region of rice metallothionein OsMT2b gene are capable of directing high-level gene expression in germinated rice embryos.

    Science.gov (United States)

    Wu, Chung-Shen; Chen, Dai-Yin; Chang, Chung-Fu; Li, Min-Jeng; Hung, Kuei-Yu; Chen, Liang-Jwu; Chen, Peng-Wen

    2014-05-01

    Critical regions within the rice metallothionein OsMT2b gene promoter are identified and the 5'-untranslated region (5'-UTR) is found essential for the high-level promoter activity in germinated transgenic rice embryos. Many metallothionein (MT) genes are highly expressed in plant tissues. A rice subfamily p2 (type 2) MT gene, OsMT2b, has been shown previously to exhibit the most abundant gene expression in young rice seedling. In the present study, transient expression assays and a transgenic approach were employed to characterize the expression of the OsMT2b gene in rice. We found that the OsMT2b gene is strongly and differentially expressed in germinated rice embryos during seed germination and seedling development. Histochemical staining analysis of transgenic rice carrying OsMT2b::GUS chimeric gene showed that high-level GUS activity was detected in germinated embryos and at the meristematic part of other tissues during germination. Deletion analysis of the OsMT2b promoter revealed that the 5'-flanking region of the OsMT2b between nucleotides -351 and -121 relative to the transcriptional initiation site is important for promoter activity in rice embryos, and this region contains the consensus sequences of G box and TA box. Our study demonstrates that the 5'-untranslated region (5'-UTR) of OsMT2b gene is not only necessary for the OsMT2b promoter activity, but also sufficient to augment the activity of a minimal promoter in both transformed cell cultures and germinated transgenic embryos in rice. We also found that addition of the maize Ubi intron 1 significantly enhanced the OsMT2b promoter activity in rice embryos. Our studies reveal that OsMT2b351-ubi(In) promoter can be applied in plant transformation and represents potential for driving high-level production of foreign proteins in transgenic rice.

  6. Intraneuronal signaling pathways of metallothionein

    DEFF Research Database (Denmark)

    Asmussen, Johanne Wirenfeldt; Von Sperling, Marie Louise; Penkowa, Milena

    2009-01-01

    -protein-coupled pathway but not on protein tyrosine kinases or on receptor tyrosine kinases. Activation of phospholipase C was necessary for MT-induced neurite outgrowth, and furthermore it was shown that inhibition of several intracellular protein kinases, such as protein kinase A, protein kinase C, phosphatidylinositol...

  7. Central blood pressure and chronic kidney disease

    Science.gov (United States)

    Ohno, Yoichi; Kanno, Yoshihiko; Takenaka, Tsuneo

    2016-01-01

    In this review, we focused on the relationship between central blood pressure and chronic kidney diseases (CKD). Wave reflection is a major mechanism that determines central blood pressure in patients with CKD. Recent medical technology advances have enabled non-invasive central blood pressure measurements. Clinical trials have demonstrated that compared with brachial blood pressure, central blood pressure is a stronger risk factor for cardiovascular (CV) and renal diseases. CKD is characterized by a diminished renal autoregulatory ability, an augmented direct transmission of systemic blood pressure to glomeruli, and an increase in proteinuria. Any elevation in central blood pressure accelerates CKD progression. In the kidney, interstitial inflammation induces oxidative stress to handle proteinuria. Oxidative stress facilitates atherogenesis, increases arterial stiffness and central blood pressure, and worsens the CV prognosis in patients with CKD. A vicious cycle exists between CKD and central blood pressure. To stop this cycle, vasodilator antihypertensive drugs and statins can reduce central blood pressure and oxidative stress. Even in early-stage CKD, mineral and bone disorders (MBD) may develop. MBD promotes oxidative stress, arteriosclerosis, and elevated central blood pressure in patients with CKD. Early intervention or prevention seems necessary to maintain vascular health in patients with CKD. PMID:26788468

  8. Central Laboratories Services

    Data.gov (United States)

    Federal Laboratory Consortium — The TVA Central Laboratories Services is a comprehensive technical support center, offering you a complete range of scientific, engineering, and technical services....

  9. Credibility of Central Bank Independence Revisited

    OpenAIRE

    Timo T Valila

    1999-01-01

    The specific role of central bank independence in determining the overall credibility of monetary policy is addressed in this paper. It is argued that the credibility of delegating monetary policy to an independent central bank is endogenous to the credibility of the inflation target because a “conservative” inflation target may not be compatible with the fiscal policy stance. Also, lack of transparency in designing the institutional set-up is shown to be welfare-reducing.

  10. Central venous catheters and catheter locks in children with cancer

    DEFF Research Database (Denmark)

    Handrup, Mette Møller; Møller, Jens Kjølseth; Schrøder, Henrik

    2013-01-01

    To determine if the catheter lock taurolidine can reduce the number of catheter-related bloodstream infections (CRBSI) in pediatric cancer patients with tunneled central venous catheters (CVC).......To determine if the catheter lock taurolidine can reduce the number of catheter-related bloodstream infections (CRBSI) in pediatric cancer patients with tunneled central venous catheters (CVC)....

  11. Central nervous system tumors

    International Nuclear Information System (INIS)

    Gavin, P.R.; Fike, J.R.; Hoopes, P.J.

    1995-01-01

    Central nervous system (CNS) tumors are relatively common in veterinary medicine, with most diagnoses occurring in the canine and feline species. Numerous tumor types from various cells or origins have been identified with the most common tumors being meningiomas and glial cell tumors. Radiation therapy is often used as an aid to control the clinical signs associated with these neoplasms. In general, these tumors have a very low metastatic potential, such that local control offers substantial benefit. Experience in veterinary radiation oncology would indicate that many patients benefit from radiation treatment. Current practice indicates the need for computed tomography or magnetic resonance imaging studies. These highly beneficial studies are used for diagnosis, treatment planning, and to monitor treatment response. Improvements in treatment planning and radiation delivered to the tumor, while sparing the normal tissues, should improve local control and decrease potential radiation related problems to the CNS. When possible, multiple fractions of 3 Gy or less should be used. The tolerance dose to the normal tissue with this fractionation schedule is 50 to 55 Gy. The most common and serious complications of radiation for CNS tumors is delayed radiation myelopathy and necrosis. Medical management of the patient during radiation therapy requires careful attention to anesthetic protocols, and medications to reduce intracranial pressure that is often elevated in these patients. Canine brain tumors have served as an experimental model to test numerous new treatments. Increased availability of advanced imaging modalities has spawned increased detection of these neoplasms. Early detection of these tumors with appropriate aggressive therapy should prove beneficial to many patients

  12. Central Diffraction at ALICE

    CERN Document Server

    Lämsä, Jerry W

    2011-01-01

    The ALICE experiment is shown to be well suited for studies of exclusive final states from central diffractive reactions. The gluon-rich environment of the central system allows detailed QCD studies and searches for exotic meson states, such as glueballs, hybrids and new charmonium-like states. It would also provide a good testing ground for detailed studies of heavy quarkonia. Due to its central barrel performance, ALICE can accurately measure the low-mass central systems with good purity. The efficiency of the Forward Multiplicity Detector (FMD) and the Forward Shower Counter (FSC) system for detecting rapidity gaps is shown to be adequate for the proposed studies. With this detector arrangement, valuable new data can be obtained by tagging central diffractive processes.

  13. Multidisciplinary team review of best practices for collection and handling of blood cultures to determine effective interventions for increasing the yield of true-positive bacteremias, reducing contamination, and eliminating false-positive central line-associated bloodstream infections.

    Science.gov (United States)

    Garcia, Robert A; Spitzer, Eric D; Beaudry, Josephine; Beck, Cindy; Diblasi, Regina; Gilleeny-Blabac, Michelle; Haugaard, Carol; Heuschneider, Stacy; Kranz, Barbara P; McLean, Karen; Morales, Katherine L; Owens, Susan; Paciella, Mary E; Torregrosa, Edwin

    2015-11-01

    A literature search was conducted using keywords for articles published in English from January 1990 to March 2015. Using criteria related to blood culture collection and handling, the search yielded 101 articles. References used also included Microbiology Laboratory standards, guidelines, and textbook information. The literature identified diverse and complex issues surrounding blood culture practices, including the impact of false-positive results, laboratory definition of contamination, effect on central line-associated bloodstream infection (CLABSI) reporting, indications for collecting blood cultures, drawing from venipuncture sites versus intravascular catheters, selection of antiseptics, use of needleless connectors, inoculation of blood culture bottles, and optimizing program management in emergency departments, education, and implementation of bundled practice initiatives. Hospitals should optimize best practice in the collection, handling, and management of blood culture specimens, an often overlooked but essential component in providing optimal care of patients in all settings and populations, reducing financial burdens, and increasing the accuracy of reportable CLABSI. Although universal concepts exist in blood culture practices, some issues require further research to determine benefit. Institutions undertaking a review of their blood culture programs are encouraged to use a checklist that addresses elements that encompass the research contained in this review. Copyright © 2015 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

  14. "Central Station" Londonis

    Index Scriptorium Estoniae

    2000-01-01

    Londoni galeriis Milch seitsme läti, leedu ja eesti kunstniku projekt "Central Station". Kuraatorid Lisa Panting, Sally Tallant. Eestist osalevad Hanno Soans (Catarina Campinoga koostöös valminud video), Kiwa, Kai Kaljo

  15. Central nervous system resuscitation

    DEFF Research Database (Denmark)

    McIntosh, T K; Garde, E; Saatman, K E

    1997-01-01

    Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities...

  16. Outsourcing central banking

    DEFF Research Database (Denmark)

    Khoury, Sarkis Joseph; Wihlborg, Clas

    2005-01-01

    The literature on Currency Boards (CB) stops at the water edge in terms of dealing with the totality of the functions of a central bank. Monetary policy, and banking supervisioncan be "outsourced" in an open economy with substantial foreign direct investment (FDI)in the banking sector if political...... nationalism does not trump economic rationality. An orthodox CB renders the central banking function redundant in terms of interest rate and exchange rate determination. FDI in banking could perform the same role for the supervisory function of central banks. We use the case of Estonia to illustrate...... the feasibility of, and constraints on, outsourcing of central bank functions. A brief discussion of the Argentinian experience is used for contrast.Key words: Currency Board, Foreign Banks, Supervision, Regional Integration,outsourcing....

  17. Central nervous system

    Science.gov (United States)

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  18. Isolated central vestibular syndrome.

    Science.gov (United States)

    Kim, Sung-Hee; Park, Seong-Ho; Kim, Hyo-Jung; Kim, Ji-Soo

    2015-04-01

    Isolated vestibular syndrome may occur all along the vestibular pathways from the peripheral labyrinth to the brain. By virtue of recent developments in clinical neurotology and neuroimaging, however, diagnosis of isolated central vestibulopathy is increasing. Here, we review five distinct syndromes of isolated central vestibular syndrome from lesions restricted to the vestibular nuclei, the nucleus prepositus hypoglossi, the flocculus, the tonsil, and the nodulus, and introduce a new vestibular syndrome from isolated involvement of the inferior cerebellar peduncle. Decreased responses to head impulses do not exclude a central lesion as a cause of isolated vestibular syndrome. Brain imaging, including diffusion-weighted magnetic resonance imaging (MRI), may be falsely negative during the acute phase in patients with isolated vestibular syndrome because of a stroke. Central signs should be sought carefully in patients with isolated vertigo, even when the patients show the features of peripheral vestibulopathy and negative MRIs. Recognition of these isolated central vestibular syndromes would aid in defining the lesions responsible for various vestibular manifestations in central vestibulopathy. © 2015 New York Academy of Sciences.

  19. Central Hemodynamics for Management of Arteriosclerotic Diseases.

    Science.gov (United States)

    Hashimoto, Junichiro

    2017-08-01

    Arteriosclerosis, particularly aortosclerosis, is the most critical risk factor associated with cardiovascular, cerebrovascular, and renal diseases. The pulsatile hemodynamics in the central aorta consists of blood pressure, flow, and stiffness and substantially differs from the peripheral hemodynamics in muscular arteries. Arteriosclerotic changes with age appear earlier in the elastic aorta, and age-dependent increases in central pulse pressure are more marked than those apparent from brachial pressure measurement. Central pressure can be affected by lifestyle habits, metabolic disorders, and endocrine and inflammatory diseases in a manner different from brachial pressure. Central pulse pressure widening due to aortic stiffening increases left ventricular afterload in systole and reduces coronary artery flow in diastole, predisposing aortosclerotic patients to myocardial hypertrophy and ischemia. The widened pulse pressure is also transmitted deep into low-impedance organs such as the brain and kidney, causing microvascular damage responsible for lacunar stroke and albuminuria. In addition, aortic stiffening increases aortic blood flow reversal, which can lead to retrograde embolic stroke and renal function deterioration. Central pressure has been shown to predict cardiovascular events in most previous studies and potentially serves as a surrogate marker for intervention. Quantitative and comprehensive evaluation of central hemodynamics is now available through various noninvasive pressure/flow measurement modalities. This review will focus on the clinical usefulness and mechanistic rationale of central hemodynamic measurements for cardiovascular risk management.