Gaharu Leaf Extract Water Reduce MDA and 8-OHdG Levels and Increase Activities SOD and Catalase in Wistar Rats Provided Maximum Physical Activity

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I Made Oka Adi Parwata

2016-09-01

Full Text Available Background: Oxidative stress occurs due to an imbalance of the number of free radicals by the number of endogenous antioxidant produced by the body i.e. Superoxide Dismutase (SOD, Gluthathione Peroxidase (GPx, and Catalase. The imbalance between the number of free radicals and antioxidants can be overcome with the endogenous antioxidant intake that exogenous oxidative stress can be reduced. One of exogenous antioxidants is natural Gaharu leaf water extract. Objective: This research focus on the effect of Gaharu leaf water extract in reducing MDA and 8-OHdG and increase the activity of SOD and Catalase. Methods: This study was an experimental with post only controls group design. Experiment was divided  into 5 groups of wistar rats, each consisting of 5 animals, i.e. negative control group without extract [K (-], treatment 1 treated 50 mg/kg BW/day of the extract (T1, treatment 2 treated 100 mg/kg BW/day of the extract (T2, treatment 3 treated 200 mg/ kg BW/day of the extract (T3, and positive control group [K (+] treated with vitamin Cat a dose 50 mg/kg BW/day. All groups treated for 10 weeks. Every day, before treatment, each group was given a maximum swimming activity for 1.5 hours for 10 weeks. ELISA was used to measure MDA, 8-OHdG, SOD, and Catalase activities. Result: The research results showed that treatment of extract of  leaves of Gaharu with an higher dose from 50 mg/kg BW up to 200 mg/ kg BW significantly decline (p <0.05 levels of MDA with the average ranging from 6.37±0.23, 5,56±0.27 and 4.32±0.27, 8-OHdG with a mean of 1.64±0.11, 1.26±0.46, and 1.09±0.17. On the other hand the treatment also increase SOD activity with less ranging from 12.15±1.04, 15.70±2.02, and 18.84±1.51, and Catalase ranging from 6,68±0.63, 8.20±1.14 and 9.29±0,79 in the blood of Wistar rats were given a maximum activity compared to the negative control group. This is probably higher phenol compounds (bioflavonoids quantity content of the extract

PGC-1 silencing compounds the perturbation of mitochondrial function caused by mutant SOD1 in skeletal muscle of ALS mouse model

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Yan eQi

2015-10-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a lethal neurodegenerative disease causing death of motor neurons. This study investigated the roles of energy metabolism in the pathogenesis of ALS in the SOD1(G93A transgenic mouse model. Control and SOD1(G93A mice were administered with shcontrol or shPGC-1α in combination with PBS or TZD for 8 weeks. Gene expression was analyzed by quantitative real-time PCR and western blot. ROS and fibrosis were assessed with a colorimetric kit and Sirius staining respectively. Inflammatory cytokines were measured using ELISA kits. The levels of tissue ROS and serum inflammatory cytokines were significantly higher in SOD1(G93A mice compared to control mice, and knocking down PGC-1α drastically increased cytokine levels in both control and SOD1(G93A mice. Muscle fibrosis was much severer in SOD1(G93A mice, and worsened by silencing PGC-1α and attenuate d by TZD. The expression levels of PGC-1α, SOD1, UCP2, and cytochrome C were substantially reduced by shPGC-1α and increased by TZD in muscle of both control and SOD1(G93A mice whereas the level of NF-B was significantly elevated in SOD1(G93A mice, which was further increased by PGC-1α silencing. These data indicated that disruption of energy homeostasis would exacerbate the pathological changes caused by SOD1 mutations to promote the pathogenesis of ALS.

Spinal cord homogenates from SOD1 familial amyotrophic lateral sclerosis induce SOD1 aggregation in living cells.

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Edward Pokrishevsky

Full Text Available Mutant Cu/Zn superoxide dismutase (SOD1 can confer its misfolding on wild-type SOD1 in living cells; the propagation of misfolding can also be transmitted between cells in vitro. Recent studies identified fluorescently-tagged SOD1G85R as a promiscuous substrate that is highly prone to aggregate by a variety of templates, in vitro and in vivo. Here, we utilized several SOD1-GFP reporter proteins with G37R, G85R, or G93A mutations in SOD1. We observed that human spinal cord homogenates prepared from SOD1 familial ALS (FALS can induce significantly more intracellular reporter protein aggregation than spinal cord homogenates from sporadic ALS, Alzheimer's disease, multiple system atrophy or healthy control individuals. We also determined that the induction of reporter protein aggregation by SOD1-FALS tissue homogenates can be attenuated by incubating the cells with the SOD1 misfolding-specific antibody 3H1, or the small molecule 5-fluorouridine. Our study further implicates SOD1 as the seeding particle responsible for the spread of SOD1-FALS neurodegeneration from its initial onset site(s, and demonstrates two potential therapeutic strategies for SOD1-mediated disease. This work also comprises a medium-throughput cell-based platform of screening potential therapeutics to attenuate propagated aggregation of SOD1.

SOD1 Transcriptional and Posttranscriptional Regulation and Its Potential Implications in ALS

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Pamela Milani

2011-01-01

Full Text Available Copper-zinc superoxide dismutase (SOD1 is a detoxifying enzyme localized in the cytosol, nucleus, peroxisomes, and mitochondria. The discovery that mutations in SOD1 gene cause a subset of familial amyotrophic lateral sclerosis (FALS has attracted great attention, and studies to date have been mainly focused on discovering mutations in the coding region and investigation at protein level. Considering that changes in SOD1 mRNA levels have been associated with sporadic ALS (SALS, a molecular understanding of the processes involved in the regulation of SOD1 gene expression could not only unravel novel regulatory pathways that may govern cellular phenotypes and changes in diseases but also might reveal therapeutic targets and treatments. This review seeks to provide an overview of SOD1 gene structure and of the processes through which SOD1 transcription is controlled. Furthermore, we emphasize the importance to focus future researches on investigating posttranscriptional mechanisms and their relevance to ALS.

Oxidized SOD1 alters proteasome activities in vitro and in the cortex of SOD1 overexpressing mice.

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Le Pecheur, Marie; Bourdon, Emmanuel; Paly, Evelyne; Farout, Luc; Friguet, Bertrand; London, Jacqueline

2005-07-04

Premature ageing, one of the characteristics of Down syndrome (DS), may involve oxidative stress and impairment of proteasome activity. Transgenic mice overexpressing the human copper/zinc superoxide dismutase (SOD1) gene are one of the first murine models for DS and it has been shown that SOD1 overexpression might be either deleterious or beneficial. Here, we show a reduction in proteasome activities in the cortex of SOD1 transgenic mice and an associated increase in the content of oxidized SOD1 protein. As we demonstrate that in vitro oxidized SOD can inhibit purified proteasome peptidase activities, modified SOD1 might be partially responsible for proteasome inhibition shown in SOD1 transgenic mice.

Manganese superoxide dismutase (MnSOD catalyzes NO-dependent tyrosine residue nitration

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SRDJAN STOJANOVIC

2005-04-01

Full Text Available The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD tyrosine residue, which causes enzyme inactivation, is well established. This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO, conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous in vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+ and nitroxyl (NO– species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation in vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels.

Article Expression, Purification, and Characterization of Cu/ZnSOD from Panax Ginseng

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Dayong Ding

2014-06-01

Full Text Available Superoxide dismutase (SOD has a strong antioxidant effect, but the traditional SOD extraction method is not the most efficient method of SOD amplification. In this study, we report the cloning of the Cu/ZnSOD gene from Panax ginseng into a temperature-regulated expression plasmid, pBV220. Cu/ZnSOD inclusion bodies were expressed in E. coli at a high level. Then, the inclusion bodies were purified by ion-exchange chromatography and molecular sieve chromatography. Finally, we obtained stable SOD in the bacterial broth, with a protein content of 965 mg/L and enzyme specific activity of 9389.96 U/mg. These results provide a foundation for future studies on the antioxidant mechanisms of ginseng and the development and application of ginseng Cu/ZnSOD.

Increased Zn/Glutathione Levels and Higher Superoxide Dismutase-1 Activity as Biomarkers of Oxidative Stress in Women with Long-Term Dental Amalgam Fillings: Correlation between Mercury/Aluminium Levels (in Hair) and Antioxidant Systems in Plasma

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Cabaña-Muñoz, María Eugenia; Parmigiani-Izquierdo, José María; Bravo-González, Luis Alberto; Kyung, Hee-Moon; Merino, José Joaquín

2015-01-01

Background The induction of oxidative stress by Hg can affect antioxidant enzymes. However, epidemiological studies have failed to establish clear association between dental fillings presence and health problems. Objectives To determine whether heavy metals (in hair), antioxidant enzymes (SOD-1) and glutathione levels could be affected by the chronic presence of heavy metals in women who had dental amalgam fillings. Materials and Methods 55 hair samples (42 females with amalgam fillings and 13 female control subjects) were obtained. All subjects (mean age 44 years) who had dental amalgam filling for more than 10 years (average 15 years). Certain metals were quantified by ICP-MS (Mass Spectrophotometry) in hair (μg/g: Al, Hg, Ba, Ag, Sb, As, Be, Bi, Cd, Pb, Pt, Tl, Th, U, Ni, Sn, Ti) and SOD-1 and Glutathione (reduced form) levels in plasma. Data were compared with controls without amalgams, and analyzed to identify any significant relation between metals and the total number of amalgam fillings, comparing those with four or less (n = 27) with those with more than four (n = 15). As no significant differences were detected, the two groups were pooled (Amlgam; n = 42). Findings Hg, Ag, Al and Ba were higher in the amalgam group but without significant differences for most of the heavy metals analyzed. Increased SOD-1 activity and glutathione levels (reduced form) were observed in the amalgam group. Aluminum (Al) correlated with glutathione levels while Hg levels correlated with SOD-1. The observed Al/glutathione and Hg/SOD-1 correlation could be adaptive responses against the chronic presence of mercury. Conclusions Hg, Ag, Al and Ba levels increased in women who had dental amalgam fillings for long periods. Al correlated with glutathione, and Hg with SOD-1. SOD-1 may be a possible biomarker for assessing chronic Hg toxicity. PMID:26076368

Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS protein.

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Son, Marjatta; Leary, Scot C; Romain, Nadine; Pierrel, Fabien; Winge, Dennis R; Haller, Ronald G; Elliott, Jeffrey L

2008-05-02

G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1. Because these results suggest an effect of mutant SOD1 on mitochondrial function, we assessed the enzymatic activities of mitochondrial respiratory chain complexes in the spinal cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast, CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II, or III. Blue native gel analysis further demonstrates a marked reduction in the levels of complex IV but not of complex I, II, III, or V in spinal cords of CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1 controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed significant decreases in the levels of two structural subunits of cytochrome c oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse spinal cord showed no reduction in levels of selected subunits from complexes I, II, III, or V. Heme A analyses of spinal cord further support the existence of cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these results establish that CCS/G93A SOD1 mice manifest an isolated complex IV deficiency which may underlie a substantial part of mutant SOD1-induced mitochondrial cytopathy.

Molecular identification of Nocardia species using the sodA gene: Identificación molecular de especies de Nocardia utilizando el gen sodA.

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Sánchez-Herrera, K; Sandoval, H; Mouniee, D; Ramírez-Durán, N; Bergeron, E; Boiron, P; Sánchez-Saucedo, N; Rodríguez-Nava, V

2017-09-01

Currently for bacterial identification and classification the rrs gene encoding 16S rRNA is used as a reference method for the analysis of strains of the genus Nocardia. However, it does not have enough polymorphism to differentiate them at the species level. This fact makes it necessary to search for molecular targets that can provide better identification. The sod A gene (encoding the enzyme superoxide dismutase) has had good results in identifying species of other Actinomycetes. In this study the sod A gene is proposed for the identification and differentiation at the species level of the genus Nocardia. We used 41 type species of various collections; a 386 bp fragment of the sod A gene was amplified and sequenced, and a phylogenetic analysis was performed comparing the genes rrs (1171 bp), hsp 65 (401 bp), sec A1 (494 bp), gyr B (1195 bp) and rpo B (401 bp). The sequences were aligned using the Clustal X program. Evolutionary trees according to the neighbour-joining method were created with the programs Phylo_win and MEGA 6. The specific variability of the sod A genus of the genus Nocardia was analysed. A high phylogenetic resolution, significant genetic variability, and specificity and reliability were observed for the differentiation of the isolates at the species level. The polymorphism observed in the sod A gene sequence contains variable regions that allow the discrimination of closely related Nocardia species. The clear specificity, despite its small size, proves to be of great advantage for use in taxonomic studies and clinical diagnosis of the genus Nocardia.

The SOD gene family in tomato: identification, phylogenetic relationships and expression patterns

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kun feng

2016-08-01

Full Text Available Superoxide dismutases (SODs are critical antioxidant enzymes that protect organisms from reactive oxygen species (ROS caused by adverse conditions, and have been widely found in the cytoplasm, chloroplasts, and mitochondria of eukaryotic and prokaryotic cells. Tomato (Solanum lycopersicum L. is an important economic crop and is cultivated worldwide. However, abiotic and biotic stresses severely hinder growth and development of the plant, which affects the production and quality of the crop. To reveal the potential roles of SOD genes under various stresses, we performed a systematic analysis of the tomato SOD gene family and analyzed the expression patterns of SlSOD genes in response to abiotic stresses at the whole-genome level. The characteristics of the SlSOD gene family were determined by analyzing gene structure, conserved motifs, chromosomal distribution, phylogenetic relationships, and expression patterns. We determined that there are at least nine SOD genes in tomato, including four Cu/ZnSODs, three FeSODs, and one MnSOD, and they are unevenly distributed on 12 chromosomes. Phylogenetic analyses of SOD genes from tomato and other plant species were separated into two groups with a high bootstrap value, indicating that these SOD genes were present before the monocot-dicot split. Additionally, many cis-elements that respond to different stresses were found in the promoters of nine SlSOD genes. Gene expression analysis based on RNA-seq data showed that most genes were expressed in all tested tissues, with the exception of SlSOD6 and SlSOD8, which were only expressed in young fruits. Microarray data analysis showed that most members of the SlSOD gene family were altered under salt- and drought-stress conditions. This genome-wide analysis of SlSOD genes helps to clarify the function of SlSOD genes under different stress conditions and provides information to aid in further understanding the evolutionary relationships of SOD genes in plants.

Tempol moderately extends survival in a hSOD1(G93A ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A forms.

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Edlaine Linares

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.

Molecular identification of Nocardia species using the sodA gene

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K. Sánchez-Herrera

2017-09-01

Full Text Available Currently for bacterial identification and classification the rrs gene encoding 16S rRNA is used as a reference method for the analysis of strains of the genus Nocardia. However, it does not have enough polymorphism to differentiate them at the species level. This fact makes it necessary to search for molecular targets that can provide better identification. The sodA gene (encoding the enzyme superoxide dismutase has had good results in identifying species of other Actinomycetes. In this study the sodA gene is proposed for the identification and differentiation at the species level of the genus Nocardia. We used 41 type species of various collections; a 386 bp fragment of the sodA gene was amplified and sequenced, and a phylogenetic analysis was performed comparing the genes rrs (1171 bp, hsp65 (401 bp, secA1 (494 bp, gyrB (1195 bp and rpoB (401 bp. The sequences were aligned using the Clustal X program. Evolutionary trees according to the neighbour-joining method were created with the programs Phylo_win and MEGA 6. The specific variability of the sodA genus of the genus Nocardia was analysed. A high phylogenetic resolution, significant genetic variability, and specificity and reliability were observed for the differentiation of the isolates at the species level. The polymorphism observed in the sodA gene sequence contains variable regions that allow the discrimination of closely related Nocardia species. The clear specificity, despite its small size, proves to be of great advantage for use in taxonomic studies and clinical diagnosis of the genus Nocardia.

Molecular Cloning and Expression Analysis of Cu/Zn SOD Gene from Gynura bicolor DC.

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Xin Xu

2017-01-01

Full Text Available Superoxide dismutase is an important antioxidant enzyme extensively existing in eukaryote, which scavenges reactive oxygen species (ROS and plays an essential role in stress tolerance of higher plants. A full-length cDNA encoding Cu/Zn SOD was cloned from leaves of Gynura bicolor DC. by rapid amplification of cDNA ends (RACE. The full-length cDNA of Cu/Zn SOD is 924 bp and has a 681 bp open reading frame encoding 227 amino acids. Bioinformatics analysis revealed that belonged to the plant SOD super family. Cu/Zn SODs of the Helianthus annuus, Mikania micrantha, and Solidago canadensis var. scabra all have 86% similarity to the G. bicolor Cu/Zn SOD. Analysis of the expression of Cu/Zn SOD under different treatments revealed that Cu/Zn SOD was a stress-responsive gene, especially to 1-MCP. It indicates that the Cu/Zn SOD gene would be an important gene in the resistance to stresses and will be helpful in providing evidence for future research on underlying molecular mechanism and choosing proper postharvest treatments for G. bicolor.

Mice overexpressing both non-mutated human SOD1 and mutated SOD1G93A genes: a competent experimental model for studying iron metabolism in amyotrophic lateral sclerosis

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Anna eGajowiak

2016-01-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease characterized by degeneration and loss of motor neurons in the spinal cord, brainstem and motor cortex. Up to 10% of ALS cases are inherited (familial, fALS and associated with mutations, frequently in the superoxide dismutase 1 (SOD1 gene. Rodent transgenic models of ALS are often used to elucidate a complex pathogenesis of this disease. Of importance, both ALS patients and animals carrying mutated human SOD1 gene show symptoms of oxidative stress and iron metabolism misregulation. The aim of our study was to characterize changes in iron metabolism in one of the most commonly used models of ALS – transgenic mice overexpressing human mutated SOD1G93A gene. We analyzed the expression of iron-related genes in asymptomatic, 2-month old and symptomatic, 4-month old SOD1G93A mice. In parallel, respective age-matched mice overexpressing human non-mutated SOD1 transgene and control mice were analyzed. We demonstrate that the overexpression of both SOD1 and SOD1G93A genes account for a substantial increase in SOD1 protein levels and activity in selected tissues and that not all the changes in iron metabolism genes expression are specific for the overexpression of the mutated form of SOD1.

Deregulation of manganese superoxide dismutase (SOD2) expression and lymph node metastasis in tongue squamous cell carcinoma

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Liu, Xiqiang; Crowe, David L; Zhou, Xiaofeng; Wang, Anxun; Muzio, Lorenzo Lo; Kolokythas, Antonia; Sheng, Shihu; Rubini, Corrado; Ye, Hui; Shi, Fei; Yu, Tianwei

2010-01-01

Lymph node metastasis is a critical event in the progression of tongue squamous cell carcinoma (TSCC). The identification of biomarkers associated with the metastatic process would provide critical prognostic information to facilitate clinical decision making. Previous studies showed that deregulation of manganese superoxide dismutase (SOD2) expression is a frequent event in TSCC and may be associated with enhanced cell invasion. The purpose of this study is to further evaluate whether the expression level of SOD2 is correlated with the metastatic status in TSCC patients. We first examined the SOD2 expression at mRNA level on 53 TSCC and 22 normal control samples based on pooled-analysis of existing microarray datasets. To confirm our observations, we examined the expression of SOD2 at protein level on an additional TSCC patient cohort (n = 100), as well as 31 premalignant dysplasias, 15 normal tongue mucosa, and 32 lymph node metastatic diseases by immunohistochemistry (IHC). The SOD2 mRNA level in primary TSCC tissue is reversely correlated with lymph node metastasis in the first TSCC patient cohort. The SOD2 protein level in primary TSCC tissue is also reversely correlated with lymph node metastasis in the second TSCC patient cohort. Deregulation of SOD2 expression is a common event in TSCC and appears to be associated with disease progression. Statistical analysis revealed that the reduced SOD2 expression in primary tumor tissue is associated with lymph node metastasis in both TSCC patient cohorts examined. Our study suggested that the deregulation of SOD2 in TSCC has potential predictive values for lymph node metastasis, and may serve as a therapeutic target for patients at risk of metastasis

Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations.

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Lange, Dale J; Shahbazi, Mona; Silani, Vincenzo; Ludolph, Albert C; Weishaupt, Jochen H; Ajroud-Driss, Senda; Fields, Kara G; Remanan, Rahul; Appel, Stanley H; Morelli, Claudia; Doretti, Alberto; Maderna, Luca; Messina, Stefano; Weiland, Ulrike; Marklund, Stefan L; Andersen, Peter M

2017-06-01

Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). A multicenter (5 sites), open-label, 9-month-duration, dose-ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale-Revised, and McGill Quality of Life Single-Item Scale were measured at screening, visit 6, and visit 9. We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p < 0.001) with a mean reduction of 13.5% (95% confidence interval [CI] = 8.4-18.5) and at visit 9 (p < 0.001) with a mean reduction of 10.5% (95% CI = 5.2-15.8). Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy. Ann Neurol 2017;81:837-848. © 2017 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

Metallochaperone for Cu,Zn-superoxide dismutase (CCS) protein but not mRNA is higher in organs from copper-deficient mice and rats.

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Prohaska, Joseph R; Broderius, Margaret; Brokate, Bruce

2003-09-15

Cu,Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats and mice have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. SOD1 interacts with and requires its metallochaperone CCS for donating copper. We produced dietary Cu deficiency in rodents to determine if the reduction in SOD1 was related to the level of its specific metallochaperone CCS. CCS levels determined by immunoblot were 2- to 3-fold higher in liver, heart, kidney, and brain from male Cu-deficient rats and mice under a variety of conditions. CCS was also higher in livers of Cu-deficient dams. Interestingly, CCS levels in brain of Cu-deficient mice were also higher even though SOD1 activity and protein were not altered, suggesting that the rise in CCS is correlated with altered Cu status rather than a direct result of lower SOD1. A DNA probe specific for rat CCS detected a single transcript by Northern blot hybridization with liver RNA. CCS mRNA levels in mouse and rat liver were not altered by dietary treatment. These results suggest a posttranscriptional mechanism for higher CCS protein when Cu is limiting in the cell, perhaps due to slower protein turnover. Elevation in CCS level is one of the most dramatic alterations in Cu binding proteins accompanying Cu deficiency and may be useful to assess Cu status.

Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice

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Ibrahim, Osama M. A.; Dogru, Murat; Matsumoto, Yukihiro; Igarashi, Ayako; Kojima, Takashi; Wakamatsu, Tais Hitomi; Inaba, Takaaki; Shimizu, Takahiko; Shimazaki, Jun; Tsubota, Kazuo

2014-01-01

Purpose The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 −/−) mouse. Methods Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 −/− male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild–type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. Results Corneal vital staining scores in the Sod1 −/− mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1 −/− mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1 −/− mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1 −/− mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1 −/− mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1 −/− mice. Conclusions Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1 −/− mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations. PMID:25036096

Superoxide Dismutase (SOD Enzyme Activity Assay in Fasciola spp. Para-sites and Liver Tissue Extract

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M Assady

2011-09-01

Full Text Available Background: The purpose of this comparative study was to detect superoxide dismutase (SOD activities in Fasciola hepatica, F. gigantica parasites, infected and healthy liver tissues in order to determine of species effects and liver infection on SODs activity level.Methods: Fasciola spp. parasites and sheep liver tissues (healthy and infected liver tissues, 10 samples for each, were collected, homogenized and investigated for protein measurement, protein detection and SOD enzyme activity assay. Protein concentration was measured by Bradford method and SODs band protein was detected on SDS-PAGE. SODs activity was determined by iodonitrotetrazolium chloride, INT, and xanthine substrates. Independent samples t-test was conducted for analysis of SODs activities difference.Results: Protein concentration means were detected for F. hepatica 1.3 mg/ ml, F. gigantica 2.9 mg/ml, healthy liver tissue 5.5 mg/ml and infected liver tissue 1.6 mg/ml (with similar weight sample mass. Specific enzyme activities in the samples were obtained 0.58, 0.57, 0.51, 1.43 U/mg for F. hepatica, F. gigantica, healthy liver and infected liver respectively. Gel electrophoresis of Fasciola spp. and sheep liver tissue extracts revealed a band protein with MW of 60 kDa. The statistical analysis revealed significant difference between SOD activities of Fasciola species and also between SOD activity of liver tissues (P<.05.Conclusion: Fasciola species and liver infection are effective causes on SOD enzyme activity level.

A Comparison of Two Yeast MnSODs: Mitochondrial Saccharomyces cerevisiae versus Cytosolic Candida albicans

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Sheng, Y.; Cabelli, D.; Stich, T.A.; Barnese, K.; Gralla, E.B.; Cascio, D.; Britt, R.D.; Valentine, J.S.

2011-01-01

Human MnSOD is significantly more product-inhibited than bacterial MnSODs at high concentrations of superoxide (O 2 - ). This behavior limits the amount of H 2 O 2 produced at high [O 2 - ]; its desirability can be explained by the multiple roles of H 2 O 2 in mammalian cells, particularly its role in signaling. To investigate the mechanism of product inhibition in MnSOD, two yeast MnSODs, one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), were isolated and characterized. ScMnSOD and CaMnSODc are similar in catalytic kinetics, spectroscopy, and redox chemistry, and they both rest predominantly in the reduced state (unlike most other MnSODs). At high [O 2 - ], the dismutation efficiencies of the yeast MnSODs surpass those of human and bacterial MnSODs, due to very low level of product inhibition. Optical and parallel-mode electron paramagnetic resonance (EPR) spectra suggest the presence of two Mn 3+ species in yeast Mn 3+ SODs, including the well-characterized 5-coordinate Mn 3+ species and a 6-coordinate L-Mn 3+ species with hydroxide as the putative sixth ligand (L). The first and second coordination spheres of ScMnSOD are more similar to bacterial than to human MnSOD. Gln154, an H-bond donor to the Mn-coordinated solvent molecule, is slightly further away from Mn in yeast MnSODs, which may result in their unusual resting state. Mechanistically, the high efficiency of yeast MnSODs could be ascribed to putative translocation of an outer-sphere solvent molecule, which could destabilize the inhibited complex and enhance proton transfer from protein to peroxide. Our studies on yeast MnSODs indicate the unique nature of human MnSOD in that it predominantly undergoes the inhibited pathway at high [O 2 - ].

An Adaptation to Low Copper in Candida albicans Involving SOD Enzymes and the Alternative Oxidase.

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Chynna N Broxton

Full Text Available In eukaryotes, the Cu/Zn superoxide dismutase (SOD1 is a major cytosolic cuproprotein with a small fraction residing in the mitochondrial intermembrane space (IMS to protect against respiratory superoxide. Curiously, the opportunistic human fungal pathogen Candida albicans is predicted to express two cytosolic SODs including Cu/Zn containing SOD1 and manganese containing SOD3. As part of a copper starvation response, C. albicans represses SOD1 and induces the non-copper alternative SOD3. While both SOD1 and SOD3 are predicted to exist in the same cytosolic compartment, their potential role in mitochondrial oxidative stress had yet to be investigated. We show here that under copper replete conditions, a fraction of the Cu/Zn containing SOD1 localizes to the mitochondrial IMS to guard against mitochondrial superoxide. However in copper starved cells, localization of the manganese containing SOD3 is restricted to the cytosol leaving the mitochondrial IMS devoid of SOD. We observe that during copper starvation, an alternative oxidase (AOX form of respiration is induced that is not coupled to ATP synthesis but maintains mitochondrial superoxide at low levels even in the absence of IMS SOD. Surprisingly, the copper-dependent cytochrome c oxidase (COX form of respiration remains high with copper starvation. We provide evidence that repression of SOD1 during copper limitation serves to spare copper for COX and maintain COX respiration. Overall, the complex copper starvation response of C. albicans involving SOD1, SOD3 and AOX minimizes mitochondrial oxidative damage whilst maximizing COX respiration essential for fungal pathogenesis.

S-acylation of SOD1, CCS, and a stable SOD1-CCS heterodimer in human spinal cords from ALS and non-ALS subjects.

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Antinone, Sarah E; Ghadge, Ghanashyam D; Ostrow, Lyle W; Roos, Raymond P; Green, William N

2017-01-25

Previously, we found that human Cu, Zn-superoxide dismutase (SOD1) is S-acylated (palmitoylated) in vitro and in amyotrophic lateral sclerosis (ALS) mouse models, and that S-acylation increased for ALS-causing SOD1 mutants relative to wild type. Here, we use the acyl resin-assisted capture (acyl-RAC) assay to demonstrate S-acylation of SOD1 in human post-mortem spinal cord homogenates from ALS and non-ALS subjects. Acyl-RAC further revealed that endogenous copper chaperone for SOD1 (CCS) is S-acylated in both human and mouse spinal cords, and in vitro in HEK293 cells. SOD1 and CCS formed a highly stable heterodimer in human spinal cord homogenates that was resistant to dissociation by boiling, denaturants, or reducing agents and was not observed in vitro unless both SOD1 and CCS were overexpressed. Cysteine mutations that attenuate SOD1 maturation prevented the SOD1-CCS heterodimer formation. The degree of S-acylation was highest for SOD1-CCS heterodimers, intermediate for CCS monomers, and lowest for SOD1 monomers. Given that S-acylation facilitates anchoring of soluble proteins to cell membranes, our findings suggest that S-acylation and membrane localization may play an important role in CCS-mediated SOD1 maturation. Furthermore, the highly stable S-acylated SOD1-CCS heterodimer may serve as a long-lived maturation intermediate in human spinal cord.

Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress response in HeLa cells

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Hosoki, Ayaka; Yonekura, Shin-Ichiro; Zhao, Qing-Li

2012-01-01

Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable HeLa cell lines overexpressing SOD2, HeLa S3/SOD2 and T-REx HeLa/SOD2, to elucidate the mechanisms underlying the protection against radiation by SOD2. SOD2 overexpression in mitochondria enhanced the survival of HeLa S3 and T-REx HeLa cells following γ-irradiation. The levels of γH2AX significantly decreased in HeLa S3/SOD2 and T-REx HeLa/SOD2 cells compared with those in the control cells. MitoSox TM Red assays showed that both lines of SOD2-expressing cells showed suppression of the superoxide generation in mitochondria. Furthermore, flow cytometry with a fluorescent probe (2',7'-dichlorofluorescein) revealed that the cellular levels of ROS increased in HeLa S3 cells during post-irradiation incubation, but the increase was markedly attenuated in HeLa S3/SOD2 cells. DNA microarray analysis revealed that, of 47,000 probe sets analyzed, 117 and 166 probes showed more than 2-fold changes after 5.5 Gy of γ-irradiation in control and HeLa S3/SOD2 cells, respectively. Pathway analysis revealed different expression profiles in irradiated control cells and irradiated SOD2-overexpressing cells. These results indicate that SOD2 protects HeLa cells against cellular effects of γ-rays through suppressing oxidative stress in irradiated cells caused by ROS generated in the mitochondria and through regulating the expression of genes which play a critical role in protection against ionizing radiation. (author)

Tolerance analysis of chloroplast OsCu/Zn-SOD overexpressing rice under NaCl and NaHCO3 stress.

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Qingjie Guan

Full Text Available The 636-bp-long cDNA sequence of OsCu/Zn-SOD (AK059841 was cloned from Oryza sativa var. Longjing11 via reverse transcription polymerase chain reaction (RT-PCR. The encoded protein comprised of 211 amino acids is highly homologous to Cu/Zn-SOD proteins from tuscacera rice and millet. Quantitative RT-PCR revealed that in rice, the level of OsCu/Zn-SOD gene expression was lowest in roots and was highest in petals and during the S5 leaf stage. Moreover, the expression level of OsCu/Zn-SOD gene expression decreased during the L5 leaf stage to maturity. The level of OsCu/Zn-SOD gene expression, however, was increased under saline-sodic stress and NaHCO3 stress. Germination tests under 125, 150, and 175 mM NaCl revealed that OsCu/Zn-SOD-overexpressing lines performed better than the non-transgenic (NT Longjing11 lines in terms of germination rate and height. Subjecting seedlings to NaHCO3 and water stress revealed that OsCu/Zn-SOD-overexpressing lines performed better than NT in terms of SOD activity, fresh weight, root length, and height. Under simulated NaHCO3 stress, OsCu/Zn-SOD-overexpressing lines performed better than NT in terms of survival rate (25.19% > 6.67% and yield traits (average grain weight 20.6 > 18.15 g. This study showed that OsCu/Zn-SOD gene overexpression increases the detoxification capacity of reactive oxygen species in O. sativa and reduces salt-induced oxidative damage. We also revealed the regulatory mechanism of OsCu/Zn-SOD enzyme in saline-sodic stress resistance in O. sativa. Moreover, we provided an experimental foundation for studying the mechanism of OsCu/Zn-SOD enzymes in the chloroplast.

Identification of a single-nucleotide insertion in the promoter region affecting the sodC promoter activity in Brucella neotomae.

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Dina A Moustafa

Full Text Available Brucella neotomae is not known to be associated with clinical disease in any host species. Previous research suggested that B. neotomae might not express detectable levels of Cu/Zn superoxide dismutase (SOD, a periplasmic enzyme known to be involved in protecting Brucella from oxidative bactericidal effects of host phagocytes. This study was undertaken to investigate the genetic basis for the disparity in SOD expression in B. neotomae. Our Western blot and SOD enzyme assay analyses indicated that B. neotomae does express SOD, but at a substantially reduced level. Nucleotide sequence analysis of region upstream to the sodC gene identified a single-nucleotide insertion in the potential promoter region. The same single-nucleotide insertion was also detected in the sodC promoter of B. suis strain Thomsen, belonging to biovar 2 in which SOD expression was undetectable previously. Examination of the sodC promoter activities using translational fusion constructs with E. coli β-galactosidase demonstrated that the B. neotomae and B. suis biovar 2 promoters were very weak in driving gene expression. Site-directed mutation studies indicated that the insertion of A in the B. neotomae sodC promoter reduced the promoter activity. Increasing the level of SOD expression in B. neotomae through complementation with B. abortus sodC gene did not alter the bacterial survival in J774A.1 macrophage-like cells and in tissues of BALB/c and C57BL/6 mice. These results for the first time demonstrate the occurrence of a single-nucleotide polymorphism affecting promoter function and gene expression in Brucella.

Irradiation effect on the seed vigor, SOD activity and MDA content in germinating seeds of yellow-seeded and black-seeded rape seed (Brassica napus L.)

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Han Jixiang; Hu Danhong; Liu Houli

1993-01-01

Seeds of a set of near-isogenic lines (Brassica napus L.) with different seed coat color from yellow to black were irradiated by 60 Co γ-rays of 150 krad. Seed vigor, superoxide dismutase (SOD) and malondialdehyde (MDA) in germinating seeds were analysed. In these characters, no significant difference between yellow-seeded lines (YLs) and black-seeded lines (BLs) showed before irradiation. But after irradiation, SOD activity in YLs was lower than that in BLs. While MDA content in YLs was obviously higher that that in DLs. As a result of irradiation, seed vigor of YLs was lower than that in BLs. these results indicated that the irradiation resistance of rape seed was related to the level of SOD as well as protective structure or substances in seed coat and that the radiosensitivity of YLs was higher than that of DLs

TFE-induced local unfolding and fibrillation of SOD1: bridging the experiment and simulation studies.

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Kumar, Vijay; Prakash, Amresh; Pandey, Preeti; Lynn, Andrew M; Hassan, Md Imtaiyaz

2018-05-18

Misfolding and aggregation of Cu, Zn Superoxide dismutase (SOD1) is involved in the neurodegenerative disease, amyotrophic lateral sclerosis. Many studies have shown that metal-depleted, monomeric form of SOD1 displays substantial local unfolding dynamics and is the precursor for aggregation. Here, we have studied the structure and dynamics of different apo monomeric SOD1 variants associated with unfolding and aggregation in aqueous trifluoroethanol (TFE) through experiments and simulation. TFE induces partially unfolded β-sheet-rich extended conformations in these SOD1 variants, which subsequently develops aggregates with fibril-like characteristics. Fibrillation was achieved more easily in disulfide-reduced monomeric SOD1 when compared with wild-type and mutant monomeric SOD1. At higher concentrations of TFE, a native-like structure with the increase in α-helical content was observed. The molecular dynamics simulation results illustrate distinct structural dynamics for different regions of SOD1 variants and show uniform local unfolding of β-strands. The strands protected by the zinc-binding and electrostatic loops were found to unfold first in 20% (v/v) TFE, leading to a partial unfolding of β-strands 4, 5, and 6 which are prone to aggregation. Our results thus shed light on the role of local unfolding and conformational dynamics in SOD1 misfolding and aggregation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Superoxide dismutase levels and peak expiratory flow in asthmatic children

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Arie Kurniasih

2016-11-01

Full Text Available Background Asthma is a chronic inflammatory process which involve variety of cells such as inflammatory mediators, reactive oxygen species (ROS, and cytokines. The inflammatory process would be exacerbated in the presence of oxidative stress. Superoxide dismutase (SOD is the first important enzyme to protect the respiratory tract against oxidative stress. The decreased of SOD has a correlation with increased of airway obstruction and bronchospasm. Objective To assess for a correlation between superoxide dismutase (SOD levels and peak expiratory flow, as well as to determine the impact of SOD levels for predicting asthma attacks. Methods We conducted a prospective cohort study at Dr. Sardjito Hospital, Yogyakarta, between February and April 2011 involving asthmatic children aged 5-18 years. Subjects’ serum SOD levels and peak expiratory flow were measured at the same time point. We then performed a prospective study following up on the same subjects to find out if they had a recurrent asthma attack within one month of the tests. We also reassessed their peak expiratory flow one month after blood specimens were obtained. Results Thirty-nine patients were enrolled in this study. There was no significant correlation between SOD level and peak expiratory flow [r=0.289; 95%CI -0.025 to 0.47; P=0.074]. However, older age was significantly associated with higher peak expiratory flow (=0.5; 95%CI 3.10 to 11.57; P=0.01. Lower levels of SOD increased the risk of asthma attacks in a month following the initial measurements (RR=5.5; 95%CI 1.6 to 18.9; P=0.009. Conclusion Superoxide dismutase (SOD level is not significantly associated with peak expiratory flow. However, we find a relationship between older age and higher peak expiratory flow and a relationship between lower SOD levels and risk of asthma attacks within one month following the tests.

Molecular Cloning, Characterization and Predicted Structure of a Putative Copper-Zinc SOD from the Camel, Camelus dromedarius

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Ajamaluddin Malik

2012-01-01

Full Text Available Superoxide dismutase (SOD is the first line of defense against oxidative stress induced by endogenous and/or exogenous factors and thus helps in maintaining the cellular integrity. Its activity is related to many diseases; so, it is of importance to study the structure and expression of SOD gene in an animal naturally exposed most of its life to the direct sunlight as a cause of oxidative stress. Arabian camel (one humped camel, Camelus dromedarius is adapted to the widely varying desert climatic conditions that extremely changes during daily life in the Arabian Gulf. Studying the cSOD1 in C. dromedarius could help understand the impact of exposure to direct sunlight and desert life on the health status of such mammal. The full coding region of a putative CuZnSOD gene of C. dromedarius (cSOD1 was amplified by reverse transcription PCR and cloned for the first time (gene bank accession number for nucleotides and amino acids are JF758876 and AEF32527, respectively. The cDNA sequencing revealed an open reading frame of 459 nucleotides encoding a protein of 153 amino acids which is equal to the coding region of SOD1 gene and protein from many organisms. The calculated molecular weight and isoelectric point of cSOD1 was 15.7 kDa and 6.2, respectively. The level of expression of cSOD1 in different camel tissues (liver, kidney, spleen, lung and testis was examined using Real Time-PCR. The highest level of cSOD1 transcript was found in the camel liver (represented as 100% followed by testis (45%, kidney (13%, lung (11% and spleen (10%, using 18S ribosomal subunit as endogenous control. The deduced amino acid sequence exhibited high similarity with Cebus apella (90%, Sus scrofa (88%, Cavia porcellus (88%, Mus musculus (88%, Macaca mulatta (87%, Pan troglodytes (87%, Homo sapiens (87%, Canis familiaris (86%, Bos taurus (86%, Pongo abelii (85% and Equus caballus (82%. Phylogenetic analysis revealed that cSOD1 is grouped together with S. scrofa. The

Molecular cloning, characterization and predicted structure of a putative copper-zinc SOD from the camel, Camelus dromedarius.

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Ataya, Farid S; Fouad, Dalia; Al-Olayan, Ebtsam; Malik, Ajamaluddin

2012-01-01

Superoxide dismutase (SOD) is the first line of defense against oxidative stress induced by endogenous and/or exogenous factors and thus helps in maintaining the cellular integrity. Its activity is related to many diseases; so, it is of importance to study the structure and expression of SOD gene in an animal naturally exposed most of its life to the direct sunlight as a cause of oxidative stress. Arabian camel (one humped camel, Camelus dromedarius) is adapted to the widely varying desert climatic conditions that extremely changes during daily life in the Arabian Gulf. Studying the cSOD1 in C. dromedarius could help understand the impact of exposure to direct sunlight and desert life on the health status of such mammal. The full coding region of a putative CuZnSOD gene of C. dromedarius (cSOD1) was amplified by reverse transcription PCR and cloned for the first time (gene bank accession number for nucleotides and amino acids are JF758876 and AEF32527, respectively). The cDNA sequencing revealed an open reading frame of 459 nucleotides encoding a protein of 153 amino acids which is equal to the coding region of SOD1 gene and protein from many organisms. The calculated molecular weight and isoelectric point of cSOD1 was 15.7 kDa and 6.2, respectively. The level of expression of cSOD1 in different camel tissues (liver, kidney, spleen, lung and testis) was examined using Real Time-PCR. The highest level of cSOD1 transcript was found in the camel liver (represented as 100%) followed by testis (45%), kidney (13%), lung (11%) and spleen (10%), using 18S ribosomal subunit as endogenous control. The deduced amino acid sequence exhibited high similarity with Cebus apella (90%), Sus scrofa (88%), Cavia porcellus (88%), Mus musculus (88%), Macaca mulatta (87%), Pan troglodytes (87%), Homo sapiens (87%), Canis familiaris (86%), Bos taurus (86%), Pongo abelii (85%) and Equus caballus (82%). Phylogenetic analysis revealed that cSOD1 is grouped together with S. scrofa. The

A Manganese Superoxide Dismutase (SOD2 Gene Polymorphism in Insulin-Dependent Diabetes Mellitus

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Flemming Pociot

1993-01-01

Full Text Available Interleukin I (lL-I is selectively cytotoxic to the insulin producing beta cell of pancreatic islets. This effect may be due to IL-I induced generation of reactive oxygen species and nitric oxide. Since beta cells contain low amounts of the superoxide radical scavenger enzyme manganese superoxide dismutase (MnSOD, this may leave beta cells more susceptible to IL-I than other cell types. Genetic variation in the MnSOD locus could reflect differences in scavenger potential. We, therefore, studied possible restriction fragment length polymorphisms (RFLPs of this locus in patients with insulin-dependent diabetes mellitus (100M (n= 154 and control individuals (n=178, Taql revealed a double diallelic RFLP in patients as well as in controls. No overall difference in allelic or genotype frequencies were observed between 100M patients and control individuals (p=0.11 and no significant association of any particular RFLP pattern with 100M was found. Structurally polymorphic MnSOD protein variants with altered activities have been reported. If genetic variation results in MnSOD variants with reduced activities, the MnSOD locus may still be a candidate gene for 100M susceptibility. Whether the RFLPs reported in this study reflects differences in gene expression level, protein level and/or specific activity of the protein is yet to be studied.

Size and targeting to PECAM vs ICAM control endothelial delivery, internalization and protective effect of multimolecular SOD conjugates.

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Shuvaev, Vladimir V; Muro, Silvia; Arguiri, Evguenia; Khoshnejad, Makan; Tliba, Samira; Christofidou-Solomidou, Melpo; Muzykantov, Vladimir R

2016-07-28

Controlled endothelial delivery of SOD may alleviate abnormal local surplus of superoxide involved in ischemia-reperfusion, inflammation and other disease conditions. Targeting SOD to endothelial surface vs. intracellular compartments is desirable to prevent pathological effects of external vs. endogenous superoxide, respectively. Thus, SOD conjugated with antibodies to cell adhesion molecule PECAM (Ab/SOD) inhibits pro-inflammatory signaling mediated by endogenous superoxide produced in the endothelial endosomes in response to cytokines. Here we defined control of surface vs. endosomal delivery and effect of Ab/SOD, focusing on conjugate size and targeting to PECAM vs. ICAM. Ab/SOD enlargement from about 100 to 300nm enhanced amount of cell-bound SOD and protection against extracellular superoxide. In contrast, enlargement inhibited endocytosis of Ab/SOD and diminished mitigation of inflammatory signaling of endothelial superoxide. In addition to size, shape is important: endocytosis of antibody-coated spheres was more effective than that of polymorphous antibody conjugates. Further, targeting to ICAM provides higher endocytic efficacy than targeting to PECAM. ICAM-targeted Ab/SOD more effectively mitigated inflammatory signaling by intracellular superoxide in vitro and in animal models, although total uptake was inferior to that of PECAM-targeted Ab/SOD. Therefore, both geometry and targeting features of Ab/SOD conjugates control delivery to cell surface vs. endosomes for optimal protection against extracellular vs. endosomal oxidative stress, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK cells

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Akira Marine

2014-01-01

Full Text Available Superoxide is widely regarded as the primary reactive oxygen species (ROS which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1α expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ, a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS inhibitor demonstrated that peroxynitrite (at low micromolar levels induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation.

Defining SOD1 ALS natural history to guide therapeutic clinical trial design.

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Bali, Taha; Self, Wade; Liu, Jingxia; Siddique, Teepu; Wang, Leo H; Bird, Thomas D; Ratti, Elena; Atassi, Nazem; Boylan, Kevin B; Glass, Jonathan D; Maragakis, Nicholas J; Caress, James B; McCluskey, Leo F; Appel, Stanley H; Wymer, James P; Gibson, Summer; Zinman, Lorne; Mozaffar, Tahseen; Callaghan, Brian; McVey, April L; Jockel-Balsarotti, Jennifer; Allred, Peggy; Fisher, Elena R; Lopate, Glenn; Pestronk, Alan; Cudkowicz, Merit E; Miller, Timothy M

2017-02-01

Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALS SOD1 ) will provide key information for optimising clinical trials in this patient population. To establish an updated natural history of ALS SOD1 . Retrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000. Age of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1 A4V ), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1 non-A4V ) for analysis. Mean age of disease onset was 49.7±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1 A4V and SOD1 non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1 A4V . SOD1 A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1 non-A4V (median survival 6.8 years; p<0.0001, log-rank). A statistically significant increase in ALS-FRS decline in SOD1 A4V compared with SOD1 non-A4V participants (p=0.02) was observed, as well as a statistically significant increase in ALS-forced vital capacity decline in SOD1 A4V compared with SOD1 non-A4V (p=0.02). SOD1 A4V is an aggressive, but relatively homogeneous form of ALS. These SOD1-specific ALS natural history data will be important for the design and implementation of clinical trials in the ALS SOD1 patient population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Overexpression of survival motor neuron improves neuromuscular function and motor neuron survival in mutant SOD1 mice.

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Turner, Bradley J; Alfazema, Neza; Sheean, Rebecca K; Sleigh, James N; Davies, Kay E; Horne, Malcolm K; Talbot, Kevin

2014-04-01

Spinal muscular atrophy results from diminished levels of survival motor neuron (SMN) protein in spinal motor neurons. Low levels of SMN also occur in models of amyotrophic lateral sclerosis (ALS) caused by mutant superoxide dismutase 1 (SOD1) and genetic reduction of SMN levels exacerbates the phenotype of transgenic SOD1(G93A) mice. Here, we demonstrate that SMN protein is significantly reduced in the spinal cords of patients with sporadic ALS. To test the potential of SMN as a modifier of ALS, we overexpressed SMN in 2 different strains of SOD1(G93A) mice. Neuronal overexpression of SMN significantly preserved locomotor function, rescued motor neurons, and attenuated astrogliosis in spinal cords of SOD1(G93A) mice. Despite this, survival was not prolonged, most likely resulting from SMN mislocalization and depletion of gems in motor neurons of symptomatic mice. Our results reveal that SMN upregulation slows locomotor deficit onset and motor neuron loss in this mouse model of ALS. However, disruption of SMN nuclear complexes by high levels of mutant SOD1, even in the presence of SMN overexpression, might limit its survival promoting effects in this specific mouse model. Studies in emerging mouse models of ALS are therefore warranted to further explore the potential of SMN as a modifier of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans

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Vandesompele Jo

2008-01-01

Full Text Available Abstract Background In the nematode Caenorhabditis elegans the conserved Ins/IGF-1 signaling pathway regulates many biological processes including life span, stress response, dauer diapause and metabolism. Detection of differentially expressed genes may contribute to a better understanding of the mechanism by which the Ins/IGF-1 signaling pathway regulates these processes. Appropriate normalization is an essential prerequisite for obtaining accurate and reproducible quantification of gene expression levels. The aim of this study was to establish a reliable set of reference genes for gene expression analysis in C. elegans. Results Real-time quantitative PCR was used to evaluate the expression stability of 12 candidate reference genes (act-1, ama-1, cdc-42, csq-1, eif-3.C, mdh-1, gpd-2, pmp-3, tba-1, Y45F10D.4, rgs-6 and unc-16 in wild-type, three Ins/IGF-1 pathway mutants, dauers and L3 stage larvae. After geNorm analysis, cdc-42, pmp-3 and Y45F10D.4 showed the most stable expression pattern and were used to normalize 5 sod expression levels. Significant differences in mRNA levels were observed for sod-1 and sod-3 in daf-2 relative to wild-type animals, whereas in dauers sod-1, sod-3, sod-4 and sod-5 are differentially expressed relative to third stage larvae. Conclusion Our findings emphasize the importance of accurate normalization using stably expressed reference genes. The methodology used in this study is generally applicable to reliably quantify gene expression levels in the nematode C. elegans using quantitative PCR.

Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study.

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Lefaix, J L; Delanian, S; Leplat, J J; Tricaud, Y; Martin, M; Nimrod, A; Baillet, F; Daburon, F

1996-05-01

To establish how far liposomal copper/zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD), respectively, reduce radiation-induced fibrosis (RIF), using a well-characterized pig model of RIF permitting the design of a controlled laboratory experiment. In this model of acute localized gamma irradiation simulating accidental overexposure in humans, three groups of five large white pigs were irradiated using a collimated 192Ir source to deliver a single dose of 160 Gy onto the skin surface (100%) of the outer side of the thigh. A well-defined block of subcutaneous fibrosis involving skin and skeletal muscle developed 6 months after irradiation. One experimental group of five pigs was then injected i.m. with 10 mg/10 kg b.wt. of Cu/Zn-SOD, twice a week for 3 weeks, and another experimental group of five was injected with 10 mg/10 kg b.wt. of Mn-SOD, three times a week for 3 weeks. Five irradiated control pigs were injected with physiological serum. Animals were assessed for changes in the density of the palpated fibrotic block and in the dimensions of the projected cutaneous surface. Block depth was determined by ultrasound. Physical and sonographic findings were confirmed by autopsy 12-14 weeks after completing SOD injections. The density, length, width, and depth of the fibrotic block, and the areas and volume of its projected cutaneous surface were compared before treatment, 1, 3, and 6 weeks thereafter, and at autopsy, 12-14 weeks after treatment ended. The experimental animals exhibited no change in behavior and no abnormal clinical or anatomic signs. Whether they were given Cu/Zn- or Mn-SOD, significant and roughly equivalent softening and shrinking of the fibrotic block were noted in all treated animals between the first week after treatment ended and autopsy, when mean regression was 45% for length and width, 30% for depth, and 70% for area and volume. Histologic examination showed completely normal muscle and subcutaneous tissue

Effect of irradiation on sod activity and selenium content in garlic

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Xu Weimin; Zheng Anjian; Yan Jianmin; Cao Qingsui; Wu Haihong; Cao Shifeng

2006-01-01

The effects of irradiation at 0.1 kGy, 1.0 kGy on SOD activity and the content of total selenium, inorganic selenium, organic selenium in garlic (Allium sativum L.) stored at 10 degree C or 25 degree C were investigated. The results indicated that irradiation treatment with 0.1 kGy, 1 kGy significantly slowed the reduction of SOD activities in garlic stored at 10 degree C or 25 degree C, while the treatment irradiation had no influence on the content of all kinds of selenium. But the garlic stored at 25 degree C had higher content of total selenium, inorganic selenium, organic selenium than that in garlic stored at 10 degree C. (authors)

Immunization with a DNA vaccine encoding Toxoplasma gondii Superoxide dismutase (TgSOD) induces partial immune protection against acute toxoplasmosis in BALB/c mice.

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Liu, Yuan; Cao, Aiping; Li, Yawen; Li, Xun; Cong, Hua; He, Shenyi; Zhou, Huaiyu

2017-06-07

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects all warm-blooded animals including humans and causes toxoplasmosis. An effective vaccine could be an ideal choice for preventing and controlling toxoplasmosis. T. gondii Superoxide dismutase (TgSOD) might participate in affecting the intracellular growth of both bradyzoite and tachyzoite forms. In the present study, the TgSOD gene was used to construct a DNA vaccine (pEGFP-SOD). TgSOD gene was amplified and inserted into eukaryotic vector pEGFP-C1 and formed the DNA vaccine pEGFP-SOD. Then the BALB/c mice were immunized intramuscularly with the DNA vaccine and those injected with pEGFP-C1, PBS or nothing were treated as controls. Four weeks after the last immunization, all mouse groups followed by challenging intraperitoneally with tachyzoites of T. gondii ME49 strain. Results showed higher levels of total IgG, IgG2α in the sera and interferon gamma (IFN-γ) in the splenocytes from pEGFP-SOD inoculated mice than those unvaccinated, or inoculated with either empty plasmid vector or PBS. The proportions of CD4 + T cells and CD8 + T cells in the spleen from pEGFP-SOD inoculated mice were significantly (p < 0.05) increased compared to control groups. In addition, the survival time of mice immunized with pEGFP-SOD was significantly prolonged as compared to the controls (p < 0.05) although all the mice died. The present study revealed that the DNA vaccine triggered strong humoral and cellular immune responses, and aroused partial protective immunity against acute T. gondii infection in BALB/c mice. The collective data suggests the SOD may be a potential vaccine candidate for further development.

SOD1 aggregation in ALS mice shows simplistic test tube behavior.

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Lang, Lisa; Zetterström, Per; Brännström, Thomas; Marklund, Stefan L; Danielsson, Jens; Oliveberg, Mikael

2015-08-11

A longstanding challenge in studies of neurodegenerative disease has been that the pathologic protein aggregates in live tissue are not amenable to structural and kinetic analysis by conventional methods. The situation is put in focus by the current progress in demarcating protein aggregation in vitro, exposing new mechanistic details that are now calling for quantitative in vivo comparison. In this study, we bridge this gap by presenting a direct comparison of the aggregation kinetics of the ALS-associated protein superoxide dismutase 1 (SOD1) in vitro and in transgenic mice. The results based on tissue sampling by quantitative antibody assays show that the SOD1 fibrillation kinetics in vitro mirror with remarkable accuracy the spinal cord aggregate buildup and disease progression in transgenic mice. This similarity between in vitro and in vivo data suggests that, despite the complexity of live tissue, SOD1 aggregation follows robust and simplistic rules, providing new mechanistic insights into the ALS pathology and organism-level manifestation of protein aggregation phenomena in general.

Molecular and expression analysis of manganese superoxide dismutase (Mn-SOD) gene under temperature and starvation stress in rotifer Brachionus calyciflorus.

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Yang, Jianghua; Dong, Siming; Zhu, Huanxi; Jiang, Qichen; Yang, Jiaxin

2013-04-01

Superoxide dismutase (SOD) is an important antioxidant enzyme that protects organs from damage by reactive oxygen species. We cloned cDNA encoding SOD activated with manganese (Mn-SOD) from the rotifer Brachionus calyciflorus Pallas. The full-length cDNA of Mn-SOD was 1,016 bp and had a 669 bp open reading frame encoding 222 amino acids. The deduced amino acid sequence of B. calyciflorus Mn-SOD showed 89.1, 71.3, and 62.1 % similarity with the Mn-SOD of the marine rotifer Brachionus plicatilis, the nematode Caenorhabditis elegans, and the fruit fly Drosophila melanogaster, respectively. The phylogenetic tree constructed based on the amino acid sequences of Mn-SODs from B. calyciflorus and other organisms revealed that this rotifer is closely related to nematodes. Analysis of the mRNA expression of Mn-SOD under different conditions revealed that expression was enhanced 5.6-fold (p 0.05). Moderate starvation promoted Mn-SOD mRNA expression (p 12 < 0.01, p 36 < 0.05), which reached a maximum value (15.3 times higher than control, p 24 < 0.01) at 24 h. SOD and CAT activities also elevated at the 12 h-starved group. These results indicate that induction of Mn-SOD expression by stressors likely plays an important role in aging of B. calyciflorus.

Association of the SOD2 polymorphism (Val6Ala and SOD activity with vaso-occlusive crisis and acute splenic sequestration in children with sickle cell anemia

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Isabela Cristina Cordeiro Farias

2018-02-01

Full Text Available The SOD2 polymorphism Val16Ala TàC influences the antioxidative response. This study investigated the association of the SOD2 polymorphism and superoxide dismutase (SOD activity with vaso-occlusive crisis (VOC and acute splenic sequestration (ASS in children with sickle cell anemia (SCA. One hundred ninety-five children aged 1-9 years old were analyzed. The TC and CC genotypes were associated with lower SOD activity compared with the TT genotype (p=0.0321; p=0.0253, respectively. Furthermore, TC/CC were more frequent in patients with VOC or ASS (p=0.0285; p=0.0090, respectively. These results suggest that the SOD2 polymorphism associated with low SOD activity could be involved in SCA physiopathology.

Influence of radiation damage repair inhibitor on superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) in different sensitive crops

International Nuclear Information System (INIS)

Song Daojun; Xu Dengyi; Wan Zhaoliang; He Shoulin

1997-01-01

The activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were affected remarkably by 60 Co γ-ray irradiation and radiation damage repair inhibitor (Caf, EDTA). SOD, CAT and POD activities showed the similar change pattern in both soybean (sensitive to radiation) and Brassica napus L. (resistant to radiation) seedlings in all treatments. After reaching the maximum value, SOD activity decreased with the increase of doses. CAT activity had the same change pattern as that of SOD in soybean, while with Brassica napus L., CAT activity remained relatively steady from 300 Gy to 1000 Gy. And POD activity increased with the increase of doses. Compared with H 2 O-treatments, CaF, EDAT post-treatments obviously enhanced SOD, CAT and POD activities. With all the treatments, the three enzyme activities were higher in Brassica napus L. than those in soybean seedlings

Overexpression of human SOD1 improves survival of mice susceptible to endotoxic shock

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Charchaflieh J

2012-07-01

Full Text Available Jean Charchaflieh,1,2 Georges I Labaze,1 Pulsar Li,1 Holly Van Remmen,3 Haekyung Lee,1 Helen Stutz,1 Arlan Richardson,3 Asher Emanuel,1 Ming Zhang1,41Department of Anesthesiology, State University of New York (SUNY Downstate Medical Center, New York, NY, USA; 2Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA; 3Barshop Center for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 4Department of Cell Biology, State University of New York (SUNY Downstate Medical Center, New York, NY, USABackground: Protective effects of the antioxidant enzyme Cu-Zn superoxide dismutase (SOD1 against endotoxic shock have not been demonstrated in animal models. We used a murine model to investigate whether overexpression of SOD1 protects against endotoxic shock, and whether the genetic background of SOD1 affects its effective protective effects and susceptibility to endotoxic shock.Methods: Transgenic (tg mice overexpressing human SOD1 and control mice were divided into four groups based on their genetic background: (1 tg mice with mixed genetic background (tg-JAX; (2 wild-type (WT littermates of tg-JAX strain (WT-JAX; (3 tg mice with C57BL/6J background (tg-TX; (4 WT littermates of tg-TX strain (WT-TX. Activity of SOD1 in the intestine, heart, and liver of tg and control mice was confirmed using a polyacrylamide activity gel. Endotoxic shock was induced by intraperitoneal injection of lipopolysaccharide. Survival rates over 120 hours (mean, 95% confidence interval were analyzed using Kaplan–Meier survival curves.Results: Human SOD1 enzymatic activities were significantly higher in the intestine, heart, and liver of both tg strains (tg-JAX and tg-TX compared with their WT littermates (WT-JAX and WT-TX, respectively. Interestingly, the endogenous SOD1 activities in tg-JAX mice were decreased compared with their WT littermates (WT-JAX, but such aberrant changes were not

Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK.

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Wang, T H; Wang, S Y; Wang, X D; Jiang, H Q; Yang, Y Q; Wang, Y; Cheng, J L; Zhang, C T; Liang, W W; Feng, H L

2018-05-21

Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro, as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

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Jankovic, Aleksandra; Ferreri, Carla; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Stancic, Ana; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2016-11-01

Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

Maximization of the sod peat load and treatment; Palaturpeen kuormituksen maksimointi ja kaesittely

Energy Technology Data Exchange (ETDEWEB)

Erkkilae, A.; Nurmi, H.; Paappanen, T.; Frilander, P.

1996-12-31

The objective of this two year (1994-1995) project was to improve especially the efficiency of sod peat production, carried out using a spreading wagon, by increasing the sod peat load set for the field to value 20 kgDS/m{sup 2} (original value 10-14 kgDS/m{sup 2}), and by studying and developing a collection method for ridging and ridge processing, suitable for high-loads. The research was emphasized to laboratory tests, but some field test were also made. It was possible to increase the sod peat load most accurately to 20 kgDS/m{sup 2} by using wave-like sod peat. The drying speeds of horizontal and vertical wave-like sod peats were near to each other. The functioning of active-sod was rendered by the unevenness of the field. Production of active-sod requires less energy than production of wave-like sod. Horizontal wave-like sod was scaled using Malkov`s drying model, adjusted in cooperation with the researchers of the Russian research centre NIITP to suit better for wave-like sod peat. The best dimensions for wave were calculated for the horizontal wave-like sod using long-term weather conditions data (Pudasjaervi 1971-1990). The picking device of the ridger, developed using laboratory tests, consisted of a grid moving on the field, standing the sod up, above which there is a rotating truncheon coil which transfers the sod along the grid for further processing. The share of the fines by weight, loosened from the field during picking up the sod was 0.5 % of the sod-mass, and the losses were 11 % of the number of the sod. At the driving speed 2.9 km/h the suitable coil rotation speed was about 20 r/min, hence the rotation speed of the truncheons was twice as high as the driving speed

Additive contributions of two manganese-cored superoxide dismutases (MnSODs to antioxidation, UV tolerance and virulence of Beauveria bassiana.

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Xue-Qin Xie

Full Text Available The biocontrol potential of entomopathogenic fungi against arthropod pests depends on not only their virulence to target pests but tolerance to outdoor high temperature and solar UV irradiation. Two Beauveria bassiana superoxide dismutases (SODs, BbSod2 and BbSod3, were characterized as cytosolic and mitochondrial manganese-cored isoenzymes (MnSODs dominating the total SOD activity of the fungal entomopathogen under normal growth conditions. To probe their effects on the biocontrol potential of B. bassiana, ΔBbSod2, ΔBbSod3, and three hairpin RNA-interfered (RNAi mutants with the transcripts of both BbSod2 and BbSod3 being suppressed by 91-97% were constructed and assayed for various phenotypic parameters in conjunction with ΔBbSod2/BbSod2, ΔBbSod3/BbSod3 and wild-type (control strains. In normal cultures, the knockout and RNAi mutants showed significant phenotypic alterations, including delayed sporulation, reduced conidial yields, and impaired conidial quality, but little change in colony morphology. Their mycelia or conidia became much more sensitive to menadione or H(2O(2-induced oxidative stress but had little change in sensitivity to the hyperosmolarity of NaCl and the high temperature of 45°C. Accompanied with the decreased antioxidative capability, conidial tolerances to UV-A and UV-B irradiations were reduced by 16.8% and 45.4% for ΔBbSod2, 18.7% and 44.7% for ΔBbSod3, and ∼33.7% and ∼63.8% for the RNAi mutants, respectively. Their median lethal times (LT(50s against Myzus persicae apterae, which were topically inoculated under a standardized spray, were delayed by 18.8%, 14.5% and 37.1%, respectively. Remarkably, the effects of cytosolic BbSod2 and mitochondrial BbSod3 on the phenotypic parameters important for the fungal bioncontrol potential were additive, well in accordance with the decreased SOD activities and the increased superoxide levels in the knockout and RNAi mutants. Our findings highlight for the first time that

A fused selenium-containing protein with both GPx and SOD activities

International Nuclear Information System (INIS)

Yu, Huijun; Ge, Yan; Wang, Ying; Lin, Chi-Tsai; Li, Jing; Liu, Xiaoman; Zang, Tianzhu; Xu, Jiayun; Liu, Junqiu; Luo, Guimin; Shen, Jiacong

2007-01-01

As a safeguard against oxidative stress, the balance between the main antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) was believed to be more important than any single one, for example, dual-functional SOD/CAT enzyme has been proved to have better antioxidant ability than either single enzyme. By combining traditional fusion protein technology with amino acid auxotrophic expression system, we generated a bifunctional enzyme with both GPx and SOD activities. It displayed better antioxidant ability than GPx or SOD. Such dual-functional enzymes could facilitate further studies of the cooperation of GPx and SOD and generation of better therapeutic agents

ALS-associated mutation SOD1G93A leads to abnormal mitochondrial dynamics in osteocytes.

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Wang, Huan; Yi, Jianxun; Li, Xuejun; Xiao, Yajuan; Dhakal, Kamal; Zhou, Jingsong

2018-01-01

While the death of motor neuron is a pathological hallmark of amyotrophic lateral sclerosis (ALS), defects in other cell types or organs may also actively contribute to ALS disease progression. ALS patients experience progressive skeletal muscle wasting that may not only exacerbate neuronal degeneration, but likely has a significant impact on bone function. In our previous published study, we have discovered severe bone loss in an ALS mouse model with overexpression of ALS-associated mutation SOD1 G93A (G93A). Here we further provide a mechanistic understanding of the bone loss in ALS animal and cellular models. Combining mitochondrial fluorescent indicators and confocal live cell imaging, we discovered abnormalities in mitochondrial network and dynamics in primary osteocytes derived from the same ALS mouse model G93A. Those mitochondrial defects occur in ALS mice after the onset of neuromuscular symptoms, indicating that mitochondria in bone cells respond to muscle atrophy during ALS disease progression. To examine whether ALS mutation has a direct contribution to mitochondrial dysfunction independent of muscle atrophy, we evaluated mitochondrial morphology and motility in cultured osteocytes (MLO-Y4) with overexpression of mitochondrial targeted SOD1 G93A . Compared with osteocytes overexpressing the wild type SOD1 as a control, the SOD1 G93A osteocytes showed similar defects in mitochondrial network and dynamic as that of the primary osteocytes derived from the ALS mouse model. In addition, we further discovered that overexpression of SOD1 G93A enhanced the expression level of dynamin-related protein 1 (Drp1), a key protein promoting mitochondrial fission activity, and reduced the expression level of optic atrophy protein 1 (OPA1), a key protein related to mitochondrial fusion. A specific mitochondrial fission inhibitor (Mdivi-1) partially reversed the effect of SOD1 G93A on mitochondrial network and dynamics, indicating that SOD1 G93A likely promotes

Carbon dioxide adsorption over zeolite-like metal organic frameworks (ZMOFs) having a sod topology: Structure and ion-exchange effect

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Chen, C.; Kim, J.; Yang, D.A.; Ahn, W.S. [Inha University, Inchon (Republic of Korea). Dept. of Chemical Engineering

2011-04-15

Zeolite-like metal organic framework (ZMOF) materials having rho and sod topologies were experimentally investigated as CO{sub 2} adsorbents for the first time. As-prepared ZMOF materials showed reasonably high CO{sub 2} adsorption capacities (ca. 51 and 53 mg/g(adsorbent) for rho- and sod-ZMOF, respectively) and high CO{sub 2}/N{sub 2} selectivity (> 20) at 298 K and 1 bar. The latter showed a higher heat of adsorption (27-45 kJ/mol). These ZMOFs exhibited better CO{sub 2} adsorption than ZIF-8, a commonly investigated zeolitic imidazolate framework (ZIF) material having the same sod topology but in a neutral framework. Partially ion-exchanged sod-ZMOFs by alkali-metals resulted in improved CO{sub 2} adsorption performance compared with the as-prepared ZMOF. The highest CO{sub 2} adsorption was obtained with K{sup +}-exchanged sod-ZMOF (61 mg/g(adsorbent)), representing a ca. 15% increase in adsorption capacity. Complete desorption of CO{sub 2} in the K{sup +}-sod-ZMOF was attained at mild conditions (40{sup o}C, He purging), and reversible and sustainable CO{sub 2} adsorption performance was demonstrated in 5 sets of recycling runs.

ATM is required for SOD2 expression and homeostasis within the mammary gland.

Science.gov (United States)

Dyer, Lisa M; Kepple, Jessica D; Ai, Lingbao; Kim, Wan-Ju; Stanton, Virginia L; Reinhard, Mary K; Backman, Lindsey R F; Streitfeld, W Scott; Babu, Nivetha Ramesh; Treiber, Nicolai; Scharffetter-Kochanek, Karin; McKinnon, Peter J; Brown, Kevin D

2017-12-01

ATM activates the NF-κB transcriptional complex in response to genotoxic and oxidative stress. The purpose of this study was to examine if the NF-κB target gene and critical antioxidant SOD2 (MnSOD) in cultured mammary epithelium is also ATM-dependent, and what phenotypes arise from deletion of ATM and SOD2 within the mammary gland. SOD2 expression was studied in human mammary epithelial cells and MCF10A using RNAi to knockdown ATM or the NF-κB subunit RelA. To study ATM and SOD2 function in mammary glands, mouse lines containing Atm or Sod2 genes containing LoxP sites were mated with mice harboring Cre recombinase under the control of the whey acidic protein promoter. Quantitative PCR was used to measure gene expression, and mammary gland structure was studied using histology. SOD2 expression is ATM- and RelA-dependent, ATM knockdown renders cells sensitive to pro-oxidant exposure, and SOD mimetics partially rescue this sensitivity. Mice with germline deletion of Atm fail to develop mature mammary glands, but using a conditional knockout approach, we determined that Atm deletion significantly diminished the expression of Sod2. We also observed that these mice (termed Atm Δ/Δ ) displayed a progressive lactation defect as judged by reduced pup growth rate, aberrant lobulo-alveolar structure, diminished milk protein gene expression, and increased apoptosis within lactating glands. This phenotype appears to be linked to dysregulated Sod2 expression as mammary gland-specific deletion of Sod2 phenocopies defects observed in Atm Δ/Δ dams. We conclude that ATM is required to promote expression of SOD2 within the mammary epithelium, and that both ATM and SOD2 play a crucial role in mammary gland homeostasis.

Comparative proteomic analyses reveal that FlbA down-regulates gliT expression and SOD activity in Aspergillus fumigatus.

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Shin, Kwang-Soo; Park, Hee-Soo; Kim, Young-Hwan; Yu, Jae-Hyuk

2013-07-11

FlbA is a regulator of G-protein signaling protein that plays a central role in attenuating heterotrimeric G-protein mediated vegetative growth signaling in Aspergillus. The deletion of flbA (∆flbA) in the opportunistic human pathogen Aspergillus fumigatus results in accelerated cell death and autolysis in submerged culture. To further investigate the effects of ∆flbA on intracellular protein levels we carried out 2-D proteome analyses of 2-day old submerged cultures of ∆flbA and wild type (WT) strains and observed 160 differentially expressed proteins. Via nano-LC-ESI-MS/MS analyses, we revealed the identity of 10 and 2 proteins exhibiting high and low level accumulation, respectively, in ∆flbA strain. Notably, the GliT protein is accumulated at about 1800-fold higher levels in ∆flbA than WT. Moreover, GliT is secreted at high levels from ∆flbA strain, whereas Sod1 (superoxide dismutase) is secreted at a higher level in WT. Northern blot analyses reveal that ∆flbA results in elevated accumulation of gliT mRNA. Consequently, ∆flbA strain exhibits enhanced tolerance to gliotoxin toxicity. Finally, ∆flbA strain displayed enhanced SOD activity and elevated resistance to menadione and paraquat. In summary, FlbA-mediated signaling control negatively affects cellular responses associated with detoxification of reactive oxygen species and of exogenous gliotoxin in A. fumigatus. Regulator of G protein Signaling (RGS) proteins play crucial roles in fundamental biological processes in filamentous fungi. FlbA is the first studied filamentous fungal RGS protein, yet much remains to be understood about its roles in the opportunistic human pathogen Aspergillus fumigatus. In the present study, we examined the effects of the deletion of flbA using comprehensive analyses of the intra- and extracellular proteomes of A. fumigatus wild type and the flbA deletion mutant. Via MS analyses, we identified 10 proteins exhibiting high level accumulation in the flbA deletion

Oxidant production and SOD1 protein expression in single skeletal myofibers from Down syndrome mice

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Patrick M. Cowley

2017-10-01

Full Text Available Down syndrome (DS is a genetic condition caused by the triplication of chromosome 21. Persons with DS exhibit pronounced muscle weakness, which also occurs in the Ts65Dn mouse model of DS. Oxidative stress is thought to be an underlying factor in the development of DS-related pathologies including muscle dysfunction. High-levels of oxidative stress have been attributed to triplication and elevated expression of superoxide dismutase 1 (SOD1; a gene located on chromosome 21. The elevated expression of SOD1 is postulated to increase production of hydrogen peroxide and cause oxidative injury and cell death. However, it is unknown whether SOD1 protein expression is associated with greater oxidant production in skeletal muscle from Ts65Dn mice. Thus, our objective was to assess levels of SOD1 expression and oxidant production in skeletal myofibers from the flexor digitorum brevis obtained from Ts65Dn and control mice. Measurements of oxidant production were obtained from myofibers loaded with 2′,7′-dichlorodihydrofluorescein diacetate (DCFH2-DA in the basal state and following 15 min of stimulated unloaded contraction. Ts65Dn myofibers exhibited a significant decrease in basal DCF emissions (p 0.05. Myofibers from Ts65Dn mice tended to be smaller and myonuclear domain was lower (p < 0.05. In summary, myofibers from Ts65Dn mice exhibited decreased basal DCF emissions that were coupled with elevated protein expression of SOD1. Stimulated contraction in isolated myofibers did not affect DCF emissions in either group. These findings suggest the skeletal muscle dysfunction in the adult Ts65Dn mouse is not associated with skeletal muscle oxidative stress.

Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis.

Science.gov (United States)

Roberts, Blaine R; Lim, Nastasia K H; McAllum, Erin J; Donnelly, Paul S; Hare, Dominic J; Doble, Philip A; Turner, Bradley J; Price, Katherine A; Lim, Sin Chun; Paterson, Brett M; Hickey, James L; Rhoads, Timothy W; Williams, Jared R; Kanninen, Katja M; Hung, Lin W; Liddell, Jeffrey R; Grubman, Alexandra; Monty, Jean-Francois; Llanos, Roxana M; Kramer, David R; Mercer, Julian F B; Bush, Ashley I; Masters, Colin L; Duce, James A; Li, Qiao-Xin; Beckman, Joseph S; Barnham, Kevin J; White, Anthony R; Crouch, Peter J

2014-06-04

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1. Copyright © 2014 the authors 0270-6474/14/348021-11$15.00/0.

Engineering of a novel tri-functional enzyme with MnSOD, catalase and cell-permeable activities.

Science.gov (United States)

Luangwattananun, Piriya; Yainoy, Sakda; Eiamphungporn, Warawan; Songtawee, Napat; Bülow, Leif; Ayudhya, Chartchalerm Isarankura Na; Prachayasittikul, Virapong

2016-04-01

Cooperative function of superoxide dismutase (SOD) and catalase (CAT), in protection against oxidative stress, is known to be more effective than the action of either single enzyme. Chemical conjugation of the two enzymes resulted in molecules with higher antioxidant activity and therapeutic efficacy. However, chemical methods holds several drawbacks; e.g., loss of enzymatic activity, low homogeneity, time-consuming, and the need of chemical residues removal. Yet, the conjugated enzymes have never been proven to internalize into target cells. In this study, by employing genetic and protein engineering technologies, we reported designing and production of a bi-functional protein with SOD and CAT activities for the first time. To enable cellular internalization, cell penetrating peptide from HIV-1 Tat (TAT) was incorporated. Co-expression of CAT-MnSOD and MnSOD-TAT fusion genes allowed simultaneous self-assembly of the protein sequences into a large protein complex, which is expected to contained one tetrameric structure of CAT, four tetrameric structures of MnSOD and twelve units of TAT. The protein showed cellular internalization and superior protection against paraquat-induced cell death as compared to either complex bi-functional protein without TAT or to native enzymes fused with TAT. This study not only provided an alternative strategy to produce multifunctional protein complex, but also gained an insight into the development of therapeutic agent against oxidative stress-related conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Noziegums un sods Grama Svifta romānā "Dienas gaisma" un Fjodora Dostojevska romānā "Noziegums un sods"

OpenAIRE

Hohlova, Marija

2008-01-01

Šis bakalaura darbs pēta nozieguma un soda tēmu Fjodora Dostojevska romānā "Noziegums un sods" un Grema Svifta romānā "Dienas gaisma". Darbs sastāv no četrām nodaļām. Pirmajā nodaļā, kura pamatīgi aplūko nozieguma folozofiju, autore piemin integrēto pieeju nozieguma parādībai folozofijas skatījumā, kā arī analīzē nozieguma metafiziskās un socioloģiskās īpatnības uz Fjodora Dostojevska romāna "Noziegums un sods" pamata. Otrā nodaļa apraksta Fjodora Dostojevska romāna "Noziegums un sods" un Gre...

Serum and Ascitic Fluid Superoxide Dismutase and Malondialdehyde Levels in Patients with Cirrhosis

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Ugur Coskun

2008-01-01

Full Text Available Serum and ascitic fluid superoxide dismutase (SOD and malondialdehyde (MDA levels were measured in 43 patients with cirrhosis and in a 10 healthy control group. Compensated cirrhotic patients had no clinically detectable ascites, but decompensated patients had massive ascites. Cirrhotic patients were divided into three groups: patients with compensated cirrhosis (n = 16, patients with decompensated cirrhosis with Spontaneous bacterial peritonitis (SBP (n = 14, and patients with decompensated cirrhosis without SBP (n = 13. All cirrhotic patients in the experimental group had significantly higher serum SOD (p 0.05. These results suggest that the increase in serum SOD and MDA levels are not related to the presence of SBP and the status of liver cirrhosis. To sum up, clarifying the impact of increased serum SOD and MDA levels in cirrhotic patients needs further investigation.

The Effect of Seaweed Eucheuma cottonii on Superoxide Dismutase (SOD Liver of Hypercholesterolemic Rats

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TUTIK WRESDIYATI

2008-09-01

Full Text Available Intracellular antioxidant superoxide dismutase (SOD was reported decreased in the liver and kidney of hypercholesterolemic rats. This study was conducted to observe the effect of seaweed Eucheuma cottonii powder on the profile of blood cholesterol and the level of SOD in liver tissues of hypercholesterolemic rats by using immunohistochemical technique. Twenty male Wistar rats were used for this study. Those rats were divided into four groups; (i negative control group (A, (ii hypercholesterolemia group treated by 5% seaweed powder (B, (iii hypercholesterolemia group treated by 10% seaweed powder (C, and (iv Positive control group or hypercholesterolemia group (D. The experiment was carried out for 35 days. Hypercholesterolemia condition (> 130 mg/dl, except group A, was achieved by feeding the rats with commercial diet containing 1% cholesterol. Drinking water was given ad libitum for 40 days. The results showed that seaweed powder decreased the total cholesterol, low density lipoprotein (LDL, triglyceride, and increased the level of high density lipoprotein (HDL and SOD status in the liver tissues of hypercholesterolemic rats. The treatment of 10% seaweed powder gave better results than that of 5%. These results suggested that dietary fiber such in the seaweed powder has antioxidant activity.

Effect of fluorozis on the erythrocyte antioxidant enzyme activity levels

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Akdogan, M.; YiImaz, D.; Yontem, M.; Kalei, S.; Kilic, I.

2011-01-01

While the flourine level of (drinking) water was higher than normal ranges in the center of Isparta region before 1995 year, this problematic situation is solved in later years. (However) the individuals who are staying in Yenice district are still expose to high levels of fluorine because of the usage of Andik spring water (3.8 mg/L flour level) as drinking water. In this study we aimed to investigate the harmful effect of floride on human erythrocytes via antioxidant defence system and lipid peroxidation. Therefore, we studied the activities of erythrocyte antioxidant enzymes such as Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px) and Catalase (CAT), and the level of erythrocyte Glutathione (GSH), thiobarbituric acid reactive substance (TBARS) and the level of urine floride in high floride exposed people (children, adult and elderly). The activities of SOD, GSH-Px and CAT and the level of GSH, TBARS and urine floride were higher in 3.8 mg/L floride exposed children (Group II) than 0.8 mg/L floride exposed control children (Group I) (p 0.05). The activities of SOD, GSH-Px and CAT were lower and the levels of TBARS and urine floride were higher in 3.8 mg/L floride exposed elderly people (Group VI) than 0.8 mg/L floride exposed control elderly people (Group V) (p 0.05). As a result we thought that increased SOD, GSH-Px and CAT activities in floride exposed children and adult people, decreased activities of these enzymes in floride exposed elderly people, and increased TBARS in all groups may indicate floride caused oxidative damage in erythrocytes. (author)

Association SOD2 Polymorphism(-9C/T and Senile Cataract

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A.R. Nakhaee

2017-01-01

Full Text Available Introduction: One of the most common causes of blindness around the world is cataract, which is a multifactorial eye disease and a major cause the loss lens transparency in the aging population. Oxidative stress is a major factor that often leads to cataract formation. Oxidative stress is defined as a disturbance in the balance of reactive oxygen species (ROS production  and antioxidant defenses, including enzymatic and non-enzymatic systems. One of the defense systems against free radicals is superoxide dismutase II (Mn SOD enzyme. SOD enzyme catalyses the dismutation of superoxide anion to O2 and H2O2. Several polymorphism  have been found associated with SOD2 gene. Present study has been done to evaluaet effects of genetic polymorphism, including SOD2 C/T polymorphism in the -9 position in senile cataract patiens and normal individuals. Material and methods: in this case- control study, there are 120 patients with senile cataract and 104 healthy people. We collected 2ml of whole blood in tubes containing EDTA, and then DNA extraction was performed. Polymorphisms were detected by PCR–RFLP technique. Findings: The distribution of CC, CT, TT genotypes of SOD2 gene were 28.3%, 43.3% and 28.3% in the patient group and 24%, 48.1% and 27.9% in the healthy group, respectively. Conclusion: No significant difference in the distribution SOD2 C/T polymorphism was observed between cases and controls. 

The impact of partial manganese superoxide dismutase (SOD2)-deficiency on mitochondrial oxidant stress, DNA fragmentation and liver injury during acetaminophen hepatotoxicity

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Ramachandran, Anup; Lebofsky, Margitta; Weinman, Steven A.; Jaeschke, Hartmut

2011-01-01

Acetaminophen (APAP) hepatotoxicity is the most frequent cause of acute liver failure in many countries. The mechanism of cell death is initiated by formation of a reactive metabolite that binds to mitochondrial proteins and promotes mitochondrial dysfunction and oxidant stress. Manganese superoxide dismutase (SOD2) is a critical defense enzyme located in the mitochondrial matrix. The objective of this investigation was to evaluate the functional consequences of partial SOD2-deficiency (SOD2+/-) on intracellular signaling mechanisms of necrotic cell death after APAP overdose. Treatment of C57Bl/6J wild type animals with 200 mg/kg APAP resulted in liver injury as indicated by elevated plasma alanine aminotransferase activities (2870 ± 180 U/L) and centrilobular necrosis at 6 h. In addition, increased tissue glutathione disulfide (GSSG) levels and GSSG-to-GSH ratios, delayed mitochondrial GSH recovery, and increased mitochondrial protein carbonyls and nitrotyrosine protein adducts indicated mitochondrial oxidant stress. In addition, nuclear DNA fragmentation (TUNEL assay) correlated with translocation of Bax to the mitochondria and release of apoptosis-inducing factor (AIF). Furthermore, activation of c-jun-N-terminal kinase (JNK) was documented by the mitochondrial translocation of phospho-JNK. SOD2+/- mice showed 4-fold higher ALT activities and necrosis, an enhancement of all parameters of the mitochondrial oxidant stress, more AIF release and more extensive DNA fragmentation and more prolonged JNK activation. Conclusions: the impaired defense against mitochondrial superoxide formation in SOD2+/- mice prolongs JNK activation after APAP overdose and consequently further enhances the mitochondrial oxidant stress leading to exaggerated mitochondrial dysfunction, release of intermembrane proteins with nuclear DNA fragmentation and more necrosis.

ALS-linked mutant SOD1 proteins promote Aβ aggregates in ALS through direct interaction with Aβ.

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Jang, Ja-Young; Cho, Hyungmin; Park, Hye-Yoon; Rhim, Hyangshuk; Kang, Seongman

2017-11-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motor neurons. Aggregation of ALS-linked mutant Cu/Zn superoxide dismutase (SOD1) is a hallmark of a subset of familial ALS (fALS). Recently, intracellular amyloid-β (Aβ) is detected in motor neurons of both sporadic and familial ALS. We have previously shown that intracellular Aβ specifically interacts with G93A, an ALS-linked SOD1 mutant. However, little is known about the pathological and biological effect of this interaction in neurons. In this study, we have demonstrated that the Aβ-binding region is exposed on the SOD1 surface through the conformational changes due to misfolding of SOD1. Interestingly, we found that the intracellular aggregation of Aβ is enhanced through the direct interaction of Aβ with the Aβ-binding region exposed to misfolded SOD1. Ultimately, increased Aβ aggregation by this interaction promotes neuronal cell death. Consistent with this result, Aβ aggregates was three-fold higher in the brains of G93A transgenic mice than those of non Tg. Our study provides the first direct evidence that Aβ, an AD-linked factor, is associated to the pathogenesis of ALS and provides molecular clues to understand common aggregation mechanisms in the pathogenesis of neurodegenerative diseases. Furthermore, it will provide new insights into the development of therapeutic approaches for ALS. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical significance of determination of changes of serum SOD and T-cell subsets distribution type after leukocyte-deduced red blood cell transfusion in patients with lung cancer

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Yu Zhengqin; Li Keqin; Xiang Hengquan

2006-01-01

Objective: To investigate the changes of serum SOD contents and T-cell subsets distribution type after leukocyte-deduced red blood cell transfusion in patients with lung cancer. Methods: Serum SOD levels was measured with RIA and T-cell subsets distribution type was detected with monoclonal antibody technic both before and after leukocyte-deduced red blood cell transfusion in 32 patients with lung cancer and 35 normal controls. Results: Before treatment, the serum levels of SOD and T-cell CIM/ CD8 value were significantly lower in the patients than those in controls (P 0.05). Conclusion: Determination of serum SOD level and T-cell subsets distribution type is clinically useful in the management of patients with lung cancer. (authors)

Effect of CCS on the accumulation of FALS SOD1 mutant-containing aggregates and on mitochondrial translocation of SOD1 mutants: implication of a free radical hypothesis.

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Kim, Ha Kun; Chung, Youn Wook; Chock, P Boon; Yim, Moon B

2011-05-15

Missense mutations of SOD1 are linked to familial amyotrophic lateral sclerosis (FALS) through a yet-to-be identified toxic-gain-of-function. One of the proposed mechanisms involves enhanced aggregate formation. However, a recent study showed that dual transgenic mice overexpressing both G93A and CCS copper chaperone (G93A/CCS) exhibit no SOD1-positive aggregates yet show accelerated FALS symptoms with enhanced mitochondrial pathology compared to G93A mice. Using a dicistronic mRNA to simultaneously generate hSOD1 mutants, G93A, A4V and G85R, and hCCS in AAV293 cells, we revealed: (i) CCS is degraded primarily via a macroautophagy pathway. It forms a stable heterodimer with inactive G85R, and via its novel copper chaperone-independent molecular chaperone activity facilitates G85R degradation via a macroautophagy-mediated pathway. For active G93A and A4V, CCS catalyzes their maturation to form active and soluble homodimers. (ii) CCS reduces, under non-oxidative conditions, yet facilitates in the presence of H(2)O(2), mitochondrial translocation of inactive SOD1 mutants. These results, together with previous reports showing FALS SOD1 mutants enhanced free radical-generating activity, provide a mechanistic explanation for the observations with G93A/CCS dual transgenic mice and suggest that free radical generation by FALS SOD1, enhanced by CCS, may, in part, be responsible for the FALS SOD1 mutant-linked aggregation, mitochondrial translocation, and degradation. Published by Elsevier Inc.

Cytoplasmic Copper Detoxification in Salmonella Can Contribute to SodC Metalation but Is Dispensable during Systemic Infection.

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Fenlon, Luke A; Slauch, James M

2017-12-15

Salmonella enterica serovar Typhimurium is a leading cause of foodborne disease worldwide. Severe infections result from the ability of S Typhimurium to survive within host immune cells, despite being exposed to various host antimicrobial factors. SodCI, a copper-zinc-cofactored superoxide dismutase, is required to defend against phagocytic superoxide. SodCII, an additional periplasmic superoxide dismutase, although produced during infection, does not function in the host. Previous studies suggested that CueP, a periplasmic copper binding protein, facilitates acquisition of copper by SodCII. CopA and GolT, both inner membrane ATPases that pump copper from the cytoplasm to the periplasm, are a source of copper for CueP. Using in vitro SOD assays, we found that SodCI can also utilize CueP to acquire copper. However, both SodCI and SodCII have a significant fraction of activity independent of CueP and cytoplasmic copper export. We utilized a series of mouse competition assays to address the in vivo role of CueP-mediated SodC activation. A copA golT cueP triple mutant was equally as competitive as the wild type, suggesting that sufficient SodCI is active to defend against phagocytic superoxide independent of CueP and cytoplasmic copper export. We also confirmed that a strain containing a modified SodCII, which is capable of complementing a sodCI deletion, was fully virulent in a copA golT cueP background competed against the wild type. These competitions also address the potential impact of cytoplasmic copper toxicity within the phagosome. Our data suggest that Salmonella does not encounter inhibitory concentrations of copper during systemic infection. IMPORTANCE Salmonella is a leading cause of gastrointestinal disease worldwide. In severe cases, Salmonella can cause life-threatening systemic infections, particularly in very young children, the elderly, or people who are immunocompromised. To cause disease, Salmonella must survive the hostile environment inside host

SOD activity in cam plant kalanchoe daigremontiana exposed to S02

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Zbigniew Miszalski

2014-01-01

Full Text Available The Kalanchoe daigremontiana CAM plants exhibit very low sensitivity to the action of sulphite dioxide. Fumigation for a week with 3 ppm SO2 leads to an increase in the dismutation rate of the oxygen radical expressed in units of SOD activity and an increase in SOD activity itself. This strong increase disappears 100 h after fumigation. A transient increase in SOD activity represents an adaptation mechanism to oxidative stress caused by SO2.

An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis

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Melissa S Rotunno

2013-12-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s of sporadic ALS, which accounts for approximately 90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1 protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a toxic conformation that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.

Preparation and Characterization of Nanoparticles Made from Co-Incubation of SOD and Glucose

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Liping Cai

2017-12-01

Full Text Available The attractive potential of natural superoxide dismutase (SOD in the fields of medicine and functional food is limited by its short half-life in circulation and poor permeability across the cell membrane. The nanoparticle form of SOD might overcome these limitations. However, most preparative methods have disadvantages, such as complicated operation, a variety of reagents—some of them even highly toxic—and low encapsulation efficiency or low release rate. The aim of this study is to present a simple and green approach for the preparation of SOD nanoparticles (NPs by means of co-incubation of Cu/Zn SOD with glucose. This method was designed to prepare nanoscale aggregates based on the possible inhibitory effect of Maillard reaction on heating-induced aggregation during the co-incubation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE results indicated that the Maillard reaction occurred during the co-incubation process. It was found that enzymatically active NPs of Cu/Zn SOD were simultaneously generated during the reaction, with an average particle size of 175.86 ± 0.71 nm, and a Zeta potential of −17.27 ± 0.59 mV, as established by the measurement of enzymatic activity, observations using field emission scanning electron microscope, and analysis of dynamic light scattering, respectively. The preparative conditions for the SOD NPs were optimized by response surface design to increase SOD activity 20.43 fold. These SOD NPs showed storage stability for 25 days and better cell uptake efficacy than natural SOD. Therefore, these NPs of SOD are expected to be a potential drug candidate or functional food factor. To our knowledge, this is the first report on the preparation of nanoparticles possessing the bioactivity of the graft component protein, using the simple and green approach of co-incubation with glucose, which occurs frequently in the food industry during thermal processing.

A single nucleotide change affects fur-dependent regulation of sodB in H. pylori.

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Beth M Carpenter

Full Text Available Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur in the absence of iron (apo-Fur regulation [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter.

A molecular chaperone activity of CCS restores the maturation of SOD1 fALS mutants.

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Luchinat, Enrico; Barbieri, Letizia; Banci, Lucia

2017-12-12

Superoxide dismutase 1 (SOD1) is an important metalloprotein for cellular oxidative stress defence, that is mutated in familiar variants of Amyotrophic Lateral Sclerosis (fALS). Some mutations destabilize the apo protein, leading to the formation of misfolded, toxic species. The Copper Chaperone for SOD1 (CCS) transiently interacts with SOD1 and promotes its correct maturation by transferring copper and catalyzing disulfide bond formation. By in vitro and in-cell NMR, we investigated the role of the SOD-like domain of CCS (CCS-D2). We showed that CCS-D2 forms a stable complex with zinc-bound SOD1 in human cells, that has a twofold stabilizing effect: it both prevents the accumulation of unstructured mutant SOD1 and promotes zinc binding. We further showed that CCS-D2 interacts with apo-SOD1 in vitro, suggesting that in cells CCS stabilizes mutant apo-SOD1 prior to zinc binding. Such molecular chaperone function of CCS-D2 is novel and its implications in SOD-linked fALS deserve further investigation.

Structures of the G85R Variant of SOD1 in Familial Amyotrophic Lateral Sclerosis

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Cao, Xiaohang; Antonyuk, Svetlana V.; Seetharaman, Sai V.; Whitson, Lisa J.; Taylor, Alexander B.; Holloway, Stephen P.; Strange, Richard W.; Doucette, Peter A.; Valentine, Joan Selverstone; Tiwari, Ashutosh; Hayward, Lawrence J.; Padua, Shelby; Cohlberg, Jeffrey A.; Hasnain, S. Samar; Hart, P. John (Texas-HSC); (Cal. State); (UMASS, MED); (UCLA); (Daresbury)

2008-07-21

Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis.

Coal combustion by-product (CCB) utilization in turfgrass sod production

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Schlossberg, M.J.; Miller, W.P. [University of Georgia, Athens, GA (United States). Dept. of Crop & Soil Science

2004-04-01

Coal combustion by-products (CCB) are produced nationwide, generating 101 Mg of waste annually. Though varied, the majority of CCB are crystalline alumino-silicate minerals. Both disposal costs of CCB and interest in alternative horticultural/agricultural production systems have increased recently. Field studies assessed the benefit of CCB and organic waste/product mixtures as supplemental soil/growth media for production of hybrid bermudagrass (Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy) sod. Growth media were applied at depths of 2 to 4 cm (200 to 400 m{sup 3}{center_dot}ha{sup -1}) and vegetatively established by sprigging. Cultural practices typical of commercial methods were employed over 99- or 114-day growth periods. Sod was monitored during these propagation cycles, then harvested, evaluated, and installed offsite in a typical lawn-establishment method. Results showed mixtures of CCB and biosolids as growth media increased yield of biomass, with both media and tissue having greater nutrient content than the control media. Volumetric water content of CCB-containing media significantly exceeded that of control media and soil included with a purchased bermudagrass sod. Once installed, sod grown on CCB-media did not differ in rooting strength from control or purchased sod. When applied as described, physicochemical characteristics of CCB-media are favorable and pose little environmental risk to soil or water resources.

Dietary resveratrol administration increases MnSOD expression and activity in mouse brain

International Nuclear Information System (INIS)

Robb, Ellen L.; Winkelmolen, Lieke; Visanji, Naomi; Brotchie, Jonathan; Stuart, Jeffrey A.

2008-01-01

trans-Resveratrol (3,4',5-trihydroxystilbene; RES) is of interest for its reported protective effects in a variety of pathologies, including neurodegeneration. Many of these protective properties have been attributed to the ability of RES to reduce oxidative stress. In vitro studies have shown an increase in antioxidant enzyme activities following exposure to RES, including upregulation of mitochondrial superoxide dismutase, an enzyme that is capable of reducing both oxidative stress and cell death. We sought to determine if a similar increase in endogenous antioxidant enzymes is observed with RES treatment in vivo. Three separate modes of RES delivery were utilized; in a standard diet, a high fat diet and through a subcutaneous osmotic minipump. RES given in a high fat diet proved to be effective in elevating antioxidant capacity in brain resulting in an increase in both MnSOD protein level (140%) and activity (75%). The increase in MnSOD was not due to a substantial proliferation of mitochondria, as RES treatment induced a 10% increase in mitochondrial abundance (Citrate Synthase activity). The potential neuroprotective properties of MnSOD have been well established, and we demonstrate that a dietary delivery of RES is able to increase the expression and activity of this enzyme in vivo

An ALS-Associated Mutant SOD1 Rapidly Suppresses KCNT1 (Slack) Na+-Activated K+ Channels in Aplysia Neurons.

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Zhang, Yalan; Ni, Weiming; Horwich, Arthur L; Kaczmarek, Leonard K

2017-02-22

Mutations that alter levels of Slack (KCNT1) Na + -activated K + current produce devastating effects on neuronal development and neuronal function. We now find that Slack currents are rapidly suppressed by oligomers of mutant human Cu/Zn superoxide dismutase 1 (SOD1), which are associated with motor neuron toxicity in an inherited form of amyotrophic lateral sclerosis (ALS). We recorded from bag cell neurons of Aplysia californica , a model system to study neuronal excitability. We found that injection of fluorescent wild-type SOD1 (wt SOD1YFP) or monomeric mutant G85R SOD1YFP had no effect on net ionic currents measured under voltage clamp. In contrast, outward potassium currents were significantly reduced by microinjection of mutant G85R SOD1YFP that had been preincubated at 37°C or of cross-linked dimers of G85R SOD1YFP. Reduction of potassium current was also seen with multimeric G85R SOD1YFP of ∼300 kDa or >300 kDa that had been cross-linked. In current clamp recordings, microinjection of cross-linked 300 kDa increased excitability by depolarizing the resting membrane potential, and decreasing the latency of action potentials triggered by depolarization. The effect of cross-linked 300 kDa on potassium current was reduced by removing Na + from the bath solution, or by knocking down levels of Slack using siRNA. It was also prevented by pharmacological inhibition of ASK1 (apoptosis signal-regulating kinase 1) or of c-Jun N-terminal kinase, but not by an inhibitor of p38 mitogen-activated protein kinase. These results suggest that soluble mutant SOD1 oligomers rapidly trigger a kinase pathway that regulates the activity of Na + -activated K + channels in neurons. SIGNIFICANCE STATEMENT Slack Na + -activated K + channels (KCNT1, K Na 1.1) regulate neuronal excitability but are also linked to cytoplasmic signaling pathways that control neuronal protein translation. Mutations that alter the amplitude of these currents have devastating effects on neuronal

Comprehensive analysis to explain reduced or increased SOD1 enzymatic activity in ALS patients and their relatives.

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Keskin, Isil; Birve, Anna; Berdynski, Mariusz; Hjertkvist, Karin; Rofougaran, Reza; Nilsson, Torbjörn K; Glass, Jonathan D; Marklund, Stefan L; Andersen, Peter M

2017-08-01

To characterise stabilities in erythrocytes of mutant SOD1 proteins, compare SOD1 enzymatic activities between patients with different genetic causes of ALS and search for underlying causes of deviant SOD1 activities in individuals lacking SOD1 mutations. Blood samples from 4072 individuals, ALS patients with or without a SOD1 mutation, family members and controls were studied. Erythrocyte SOD1 enzymatic activities normalised to haemoglobin content were determined, and effects of haemoglobin disorders on dismutation assessed. Coding SOD1 sequences were analysed by Sanger sequencing, exon copy number variations by fragment length analysis and by TaqMan Assay. Of the 44 SOD1 mutations found, 75% caused severe destabilisation of the mutant protein but in 25% it was physically stable. Mutations producing structural changes caused halved erythrocyte SOD1 activities. There were no differences in SOD1 activities between patients without a SOD1 mutation and control individuals or carriers of TBK1 mutations and C9orf72 HRE . In the low and high SOD1 activity groups no deviations were found in exon copy numbers and intron gross structures. Thalassemias and iron deficiency were associated with increased SOD1 activity/haemoglobin ratios. Adjunct erythrocyte SOD1 activity analysis reliably signals destabilising SOD1 mutations including intronic mutations that are missed by exon sequencing.

Maximization and handling of sod peat loading. Final report; Palaturpeen kuormituksen maksimointi ja kaesittely. Loppuraportti

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Erkkilae, A.; Nurmi, H.; Paappanen, T.; Frilander, P.

1996-11-01

The objective of this two year (1994-1995) project was to improve especially the efficiency of sod peat production, carried out using spreading wagon method, by increasing the sod peat load set for the field to value 20 kgDgm{sup 2} (original value 10-14 kgDgm{sup 2}), and by studying and developing a collection method for ridging and ridge processing, suitable for high-loads. The research was emphasized to laboratory tests, but some field test were also made. Laboratory test equipment, to be mounted to peat machine simulator, were constructed, and picking-up of sod peat was tested in laboratory. It was possible to increase the sod peat load most accurately to 20 kgDgm{sup 2} by using wave-like sod peat. The picking device of the ridger consisted of a grid, standing the sod up, moving on the field. Above this there is a rotating truncheon coil which transfers the sod along the grid to further processing. The share of the fines by weight, loosened from the field during picking up of the sod was 0.5 % of the sod-mass, and the losses were 11 % of the number of the sod. At the driving speed 2.9 km/h the suitable coil rotation speed was about 20 r/min, hence the rotation speed of the truncheons was twice as high as the driving speed. A picking device, which consisted of two vertical truncheon-coils rotating into opposite directions, was constructed for collection of sod in the ridge. The operation of the device appeared to be good. While picking-up the sod in the ridge on the average 1.3 % of fines was loosened from the field with respect to the sod-mass. 41 % of the fines mixed with the ridge was sieved. The losses were on the average 3.9 % of the sod-mass. The highest measured power demand was 12 kW as the driving speed was 3.0 km/h. Collection method developed within this project, requires more field tests before commercial use

Improving the Delivery of SOD1 Antisense Oligonucleotides to Motor Neurons Using Calcium Phosphate-Lipid Nanoparticles

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Liyu Chen

2017-08-01

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1 in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach. Antisense oligonucleotides (ASOs can efficiently silence proteins with gain-of-function mutations. However, naked ASOs have a short circulation half-life and are unable to cross the blood brain barrier (BBB warranting the use of a drug carrier for effective delivery. In this study, calcium phosphate lipid coated nanoparticles (CaP-lipid NPs were developed for delivery of SOD1 ASO to motor neurons. The most promising nanoparticle formulation (Ca/P ratio of 100:1, had a uniform spherical core–shell morphology with an average size of 30 nm, and surface charge (ζ-potential of −4.86 mV. The encapsulation efficiency of ASO was 48% and stability studies found the particle to be stable over a period of 20 days. In vitro experiments demonstrated that the negatively charged ASO-loaded CaP-lipid NPs could effectively deliver SOD1-targeted ASO into a mouse motor neuron-like cell line (NSC-34 through endocytosis and significantly down-regulated SOD1 expression in HEK293 cells. The CaP-lipid NPs exhibited a pH-dependant dissociation, suggesting that that the acidification of lysosomes is the likely mechanism responsible for facilitating intracellular ASO release. To demonstrate tissue specific delivery and localization of these NPs we performed in vivo microinjections into zebrafish. Successful delivery of these NPs was confirmed for the zebrafish brain, the blood stream, and the spinal cord. These results suggest that Ca

Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration

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Akshay Anand

2013-01-01

Full Text Available Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1 in patients of age-related macular degeneration (AMD and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (χ2=10.516, df=8, P=0.231 indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P=.0001 with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

Manganese superoxide dismutase level in blood cells of patients with breast cancer

International Nuclear Information System (INIS)

Adzic, M.; Niciforovic, A.; Filipovic, D.; Vucic, V.; Neskovic-Konstantinovic, Z.; Radojcic, M.B. . E-mail address of corresponding author: marija@vin.bg.ac.yu; Radojcic, M.B.)

2005-01-01

The intracellular MnSOD levels were determined in peripheral blood cells obtained from two age groups of patients with breast cancer (BC): 30-45 year old patients (premenopausal, n=7, clinical stage 1 to 3) and 46-60 year old patients (peri- and postmenopausal women, n=12, clinical stage 3 or 4), at diagnosis, prior to any clinical treatment. The respective healthy women groups were used as controls. Blood cells were also irradiated in vitro with 2- and 9- Gy of gamma-ray radiation from 60 Co source. The MnSOD levels were determined by the specific immunostaining and quantified by the laser densitometry. The MANOVA analysis and Tukey post-hoc test indicated significantly higher MnSOD levels in both groups of BC patients in relation to the respective controls ( F=25.166, p<0.001). The data indicated that the increased initial MnSOD levels in peripheral blood cells may be related to the presence of BC i.e. they may reflect the system response to the presence of malignant tumour. In addition to that, in vitro radiation challenge of blood cells indicate that MnSOD overexpression may be a good indicator for selection of BC patients that would express increased resistance to oxidative stress imposed by the clinical treatment. (author)

Responses of transgenic Arabidopsis plants and recombinant yeast cells expressing a novel durum wheat manganese superoxide dismutase TdMnSOD to various abiotic stresses.

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Kaouthar, Feki; Ameny, Farhat-Khemakhem; Yosra, Kamoun; Walid, Saibi; Ali, Gargouri; Faiçal, Brini

2016-07-01

In plant cells, the manganese superoxide dismutase (Mn-SOD) plays an elusive role in the response to oxidative stress. In this study, we describe the isolation and functional characterization of a novel Mn-SOD from durum wheat (Triticum turgidum L. subsp. Durum), named TdMnSOD. Molecular phylogeny analysis showed that the durum TdMnSOD exhibited high amino acids sequence identity with other Mn-SOD plants. The three-dimensional structure showed that TdMnSOD forms a homotetramer and each subunit is composed of a predominantly α-helical N-terminal domain and a mixed α/β C-terminal domain. TdMnSOD gene expression analysis showed that this gene was induced by various abiotic stresses in durum wheat. The expression of TdMnSOD enhances tolerance of the transformed yeast cells to salt, osmotic, cold and H2O2-induced oxidative stresses. Moreover, the analysis of TdMnSOD transgenic Arabidopsis plants subjected to different environmental stresses revealed low H2O2 and high proline levels as compared to the wild-type plants. Compared with the non-transformed plants, an increase in the total SOD and two other antioxidant enzyme activities including catalase (CAT) and peroxidases (POD) was observed in the three transgenic lines subjected to abiotic stress. Taken together, these data provide evidence for the involvement of durum wheat TdMnSOD in tolerance to multiple abiotic stresses in crop plants. Copyright © 2016 Elsevier GmbH. All rights reserved.

FDIC Summary of Deposits (SOD) Download File

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Federal Deposit Insurance Corporation — The FDIC's Summary of Deposits (SOD) download file contains deposit data for branches and offices of all FDIC-insured institutions. The Federal Deposit Insurance...

Changes of serum contents of LPO, SOD after treatment with vita. E-C complex in patients with liver spot

International Nuclear Information System (INIS)

Li Qing; Feng Zheng

2005-01-01

Objective: To investigate the changes of serum contents of LPO, SOD and therapeutic efficacy after treatment with Vita. E-C complex in patients with liver spot. Methods: Serum LPO and SOD contents were measured both before and after treatment with Vita E-C complex (Vita. E l00mg, Vita. C 200mg x 3/d for 3 months) in 30 patients with liver spot as well as in 10 controls. Results: Before treatment, the serum LPO contents in the patients were significantly higher than those in controls. After treatment, the LPO contents dropped markedly, being significantly lower than the values before treatment. However, the SOD contents were about the same as those in controls and changes little after treatment. Conclusion: Vita. E-C complex was of definite therapeutic value for the treatment of liver spot. (authors)

ALS mutant SOD1 interacts with G3BP1 and affects stress granule dynamics.

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Gal, Jozsef; Kuang, Lisha; Barnett, Kelly R; Zhu, Brian Z; Shissler, Susannah C; Korotkov, Konstantin V; Hayward, Lawrence J; Kasarskis, Edward J; Zhu, Haining

2016-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Mutations in Cu/Zn superoxide dismutase (SOD1) are responsible for approximately 20 % of the familial ALS cases. ALS-causing SOD1 mutants display a gain-of-toxicity phenotype, but the nature of this toxicity is still not fully understood. The Ras GTPase-activating protein-binding protein G3BP1 plays a critical role in stress granule dynamics. Alterations in the dynamics of stress granules have been reported in several other forms of ALS unrelated to SOD1. To our surprise, the mutant G93A SOD1 transgenic mice exhibited pathological cytoplasmic inclusions that co-localized with G3BP1-positive granules in spinal cord motor neurons. The co-localization was also observed in fibroblast cells derived from familial ALS patient carrying SOD1 mutation L144F. Mutant SOD1, unlike wild-type SOD1, interacted with G3BP1 in an RNA-independent manner. Moreover, the interaction is specific for G3BP1 since mutant SOD1 showed little interaction with four other RNA-binding proteins implicated in ALS. The RNA-binding RRM domain of G3BP1 and two particular phenylalanine residues (F380 and F382) are critical for this interaction. Mutant SOD1 delayed the formation of G3BP1- and TIA1-positive stress granules in response to hyperosmolar shock and arsenite treatment in N2A cells. In summary, the aberrant mutant SOD1-G3BP1 interaction affects stress granule dynamics, suggesting a potential link between pathogenic SOD1 mutations and RNA metabolism alterations in ALS.

Sod1 deficiency reduces incubation time in mouse models of prion disease.

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Shaheen Akhtar

Full Text Available Prion infections, causing neurodegenerative conditions such as Creutzfeldt-Jakob disease and kuru in humans, scrapie in sheep and BSE in cattle are characterised by prolonged and variable incubation periods that are faithfully reproduced in mouse models. Incubation time is partly determined by genetic factors including polymorphisms in the prion protein gene. Quantitative trait loci studies in mice and human genome-wide association studies have confirmed that multiple genes are involved. Candidate gene approaches have also been used and identified App, Il1-r1 and Sod1 as affecting incubation times. In this study we looked for an association between App, Il1-r1 and Sod1 representative SNPs and prion disease incubation time in the Northport heterogeneous stock of mice inoculated with the Chandler/RML prion strain. No association was seen with App, however, significant associations were seen with Il1-r1 (P = 0.02 and Sod1 (P<0.0001 suggesting that polymorphisms at these loci contribute to the natural variation observed in incubation time. Furthermore, following challenge with Chandler/RML, ME7 and MRC2 prion strains, Sod1 deficient mice showed highly significant reductions in incubation time of 20, 13 and 24%, respectively. No differences were detected in Sod1 expression or activity. Our data confirm the protective role of endogenous Sod1 in prion disease.

Anti-apoptotic effects of pan-caspase inhibitor (Z-VAD), SOD or catalase on antimycin A-induced HeLa cell death.

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Han, Yong Hwan; Kim, Suhn Hee; Kim, Sung Zoo; Park, Woo Hyun

2009-01-01

Antimycin A (AMA) is an inhibitor of the electron transport chain in mitochondria. In this study, we investigated the anti-apoptotic effects of pan-caspase inhibitor (Z-VAD), superoxide dismutase (SOD) or catalase on AMA-induced HeLa cell death in relation to the cell cycle. Treatment with Z-VAD, SOD or catalase rescued some HeLa cells from AMA-induced apoptosis, but did not prevent the growth inhibition of HeLa cells by AMA. DNA flow cytometric analysis indicated that treatment with AMA significantly induced an S-phase arrest of the cell cycle at 72 h. Interestingly, Z-VAD, SOD and catalase intensified S-phase arrest in AMA-treated cells. In conclusion, treatment with Z-VAD, SOD or catalase decreased apoptotic levels in AMA-treated cells, which was associated with the enhancement of the S-phase arrest of the cell cycle in these cells.

Prognostic role of ‘prion-like propagation’ in SOD1-linked familial ALS: an alternative view

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Keizo eSugaya

2014-10-01

Full Text Available ‘Prion-like propagation’ has recently been proposed for disease spread in Cu/Zn superoxide dismutase 1 (SOD1-linked familial amyotrophic lateral sclerosis (ALS. Pathological SOD1 conformers are presumed to propagate via cell-to-cell transmission. In this model, the risk-based kinetics of neuronal cell loss over time appears to be represented by a sigmoidal function that reflects the kinetics of intercellular transmission. Here, we describe an alternative view of prion-like propagation in SOD1-linked ALS−its relation to disease prognosis under the protective-aggregation hypothesis. Nucleation-dependent polymerization has been widely accepted as the molecular mechanism of prion propagation. If toxic species of misfolded SOD1, as soluble oligomers, are formed as on-pathway intermediates of nucleation-dependent polymerization, further fibril extension via sequential addition of monomeric mutant SOD1 would be protective against neurodegeneration. This is because the concentration of unfolded mutant SOD1 monomers, which serve as precursor of nucleation and toxic species of mutant SOD1, would decline in proportion to the extent of aggregation. The nucleation process requires that native conformers exist in an unfolded state that may result from escaping the cellular protein quality control machinery. However, prion-like propagation−SOD1 aggregated form self-propagates by imposing its altered conformation on normal SOD1−appears to antagonize the protective role of aggregate growth. The cross-seeding reaction with normal SOD1 would lead to a failure to reduce the concentration of unfolded mutant SOD1 monomers, resulting in continuous nucleation and subsequent generation of toxic species, and influence disease prognosis. In this alternative view, the kinetics of neuronal loss appears to be represented by an exponential function, with decreasing risk reflecting the protective role of aggregate and the potential for cross-seeding reactions between

Genetic biomarkers for ALS disease in transgenic SOD1(G93A mice.

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Ana C Calvo

Full Text Available The pathophysiological mechanisms of both familial and sporadic Amyotrophic Lateral Sclerosis (ALS are unknown, although growing evidence suggests that skeletal muscle tissue is a primary target of ALS toxicity. Skeletal muscle biopsies were performed on transgenic SOD1(G93A mice, a mouse model of ALS, to determine genetic biomarkers of disease longevity. Mice were anesthetized with isoflurane, and three biopsy samples were obtained per animal at the three main stages of the disease. Transcriptional expression levels of seventeen genes, Ankrd1, Calm1, Col19a1, Fbxo32, Gsr, Impa1, Mef2c, Mt2, Myf5, Myod1, Myog, Nnt, Nogo A, Pax7, Rrad, Sln and Snx10, were tested in each muscle biopsy sample. Total RNA was extracted using TRIzol Reagent according to the manufacturer's protocol, and variations in gene expression were assayed by real-time PCR for all of the samples. The Pearson correlation coefficient was used to determine the linear correlation between transcriptional expression levels throughout disease progression and longevity. Consistent with the results obtained from total skeletal muscle of transgenic SOD1(G93A mice and 74-day-old denervated mice, five genes (Mef2c, Gsr, Col19a1, Calm1 and Snx10 could be considered potential genetic biomarkers of longevity in transgenic SOD1(G93A mice. These results are important because they may lead to the exploration of previously unexamined tissues in the search for new disease biomarkers and even to the application of these findings in human studies.

SOD2 Activity Is not Impacted by Hyperoxia in Murine Neonatal Pulmonary Artery Smooth Muscle Cells and Mice

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Anita Gupta

2015-03-01

Full Text Available Pulmonary hypertension (PH complicates bronchopulmonary dysplasia (BPD in 25% of infants. Superoxide dismutase 2 (SOD2 is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice and isogenic SOD2+/+ and SOD2−/+ mice were placed in room air (control or 75% O2 (chronic hyperoxia, CH for 14 days. Right ventricular hypertrophy (RVH was assessed by Fulton’s index. Medial wall thickness (MWT and alveolar area were assessed on formalin fixed lung sections. Pulmonary artery smooth muscle cells (PASMC were placed in 21% or 95% O2 for 24 h. Lung and PASMC protein were analyzed for SOD2 expression and activity. Oxidative stress was measured with a mitochondrially-targeted sensor, mitoRoGFP. CH lungs have increased SOD2 expression, but unchanged activity. SOD2−/+ PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+/+ and SOD2−/+ PASMC. SOD2+/+ and SOD2−/+ CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2−/+ mice develop equivalent disease, this suggests other antioxidant systems may compensate for partial SOD2 expression and activity in the neonatal period during hyperoxia-induced oxidative stress.

Species-specific activation of Cu/Zn SOD by its CCS copper chaperone in the pathogenic yeast Candida albicans.

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Gleason, Julie E; Li, Cissy X; Odeh, Hana M; Culotta, Valeria C

2014-06-01

Candida albicans is a pathogenic yeast of important public health relevance. Virulence of C. albicans requires a copper and zinc containing superoxide dismutase (SOD1), but the biology of C. albicans SOD1 is poorly understood. To this end, C. albicans SOD1 activation was examined in baker's yeast (Saccharomyces cerevisiae), a eukaryotic expression system that has proven fruitful for the study of SOD1 enzymes from invertebrates, plants, and mammals. In spite of the 80% similarity between S. cerevisiae and C. albicans SOD1 molecules, C. albicans SOD1 is not active in S. cerevisiae. The SOD1 appears incapable of productive interactions with the copper chaperone for SOD1 (CCS1) of S. cerevisiae. C. albicans SOD1 contains a proline at position 144 predicted to dictate dependence on CCS1. By mutation of this proline, C. albicans SOD1 gained activity in S. cerevisiae, and this activity was independent of CCS1. We identified a putative CCS1 gene in C. albicans and created heterozygous and homozygous gene deletions at this locus. Loss of CCS1 resulted in loss of SOD1 activity, consistent with its role as a copper chaperone. C. albicans CCS1 also restored activity to C. albicans SOD1 expressed in S. cerevisiae. C. albicans CCS1 is well adapted for activating its partner SOD1 from C. albicans, but not SOD1 from S. cerevisiae. In spite of the high degree of homology between the SOD1 and CCS1 molecules in these two fungal species, there exists a species-specific barrier in CCS-SOD interactions which may reflect the vastly different lifestyles of the pathogenic versus the noninfectious yeast.

Redox susceptibility of SOD1 mutants is associated with the differential response to CCS over-expression in vivo.

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Son, Marjatta; Fu, Qiao; Puttaparthi, Krishna; Matthews, Christina M; Elliott, Jeffrey L

2009-04-01

Over-expression of CCS in G93A SOD1 mice accelerates neurological disease and enhances mitochondrial pathology. We studied the effect of CCS over-expression in transgenic mice expressing G37R, G86R or L126Z SOD1 mutations in order to understand factors which influence mitochondrial dysfunction. Over-expression of CCS markedly decreased survival and produced mitochondrial vacuolation in G37R SOD1 mice but not in G86R or L126Z SOD1 mice. Moreover, CCS/G37R SOD1 spinal cord showed specific reductions in mitochondrial complex IV subunits consistent with an isolated COX deficiency, while no such reductions were detected in CCS/G86R or CCS/L126Z SOD1 mice. CCS over-expression increased the ratio of reduced to oxidized SOD1 monomers in the spinal cords of G37R SOD1 as well as G93A SOD1 mice, but did not influence the redox state of G86R or L126Z SOD1 monomers. The effects of CCS on disease are SOD1 mutation dependent and correlate with SOD1 redox susceptibility.

Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

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Tomoko Kawakami

2012-01-01

although, HO activity was significantly (P<0.05 attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05. CoPP, in EC-SOD(−/− mice, enhanced HO activity (P<0.05 and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/− mice.

Improving enzymatic activities and thermostability of a tri-functional enzyme with SOD, catalase and cell-permeable activities.

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Luangwattananun, Piriya; Eiamphungporn, Warawan; Songtawee, Napat; Bülow, Leif; Isarankura Na Ayudhya, Chartchalerm; Prachayasittikul, Virapong; Yainoy, Sakda

2017-04-10

Synergistic action of major antioxidant enzymes, e.g., superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) is known to be more effective than the action of any single enzyme. Recently, we have engineered a tri-functional enzyme, 6His-MnSOD-TAT/CAT-MnSOD (M-TAT/CM), with SOD, CAT and cell-permeable activities. The protein actively internalized into the cells and showed superior protection against oxidative stress-induced cell death over native enzymes fused with TAT. To improve its molecular size, enzymatic activity and stability, in this study, MnSOD portions of the engineered protein were replaced by CuZnSOD, which is the smallest and the most heat resistant SOD isoform. The newly engineered protein, CAT-CuZnSOD/6His-CuZnSOD-TAT (CS/S-TAT), had a 42% reduction in molecular size and an increase in SOD and CAT activities by 22% and 99%, respectively. After incubation at 70°C for 10min, the CS/S-TAT retained residual SOD activity up to 54% while SOD activity of the M-TAT/CM was completely abolished. Moreover, the protein exhibited a 5-fold improvement in half-life at 70°C. Thus, this work provides insights into the design and synthesis of a smaller but much more stable multifunctional antioxidant enzyme with ability to enter mammalian cells for further application as protective/therapeutic agent against oxidative stress-related conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Overexpression of CCS in G93A-SOD1 mice leads to accelerated neurological deficits with severe mitochondrial pathology.

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Son, Marjatta; Puttaparthi, Krishna; Kawamata, Hibiki; Rajendran, Bhagya; Boyer, Philip J; Manfredi, Giovanni; Elliott, Jeffrey L

2007-04-03

Cu, Zn superoxide dismutase (SOD1) has been detected within spinal cord mitochondria of mutant SOD1 transgenic mice, a model of familial ALS. The copper chaperone for SOD1 (CCS) provides SOD1 with copper, facilitates the conversion of immature apo-SOD1 to a mature holoform, and influences in yeast the cytosolic/mitochondrial partitioning of SOD1. To determine how CCS affects G93A-SOD1-induced disease, we generated transgenic mice overexpressing CCS and crossed them to G93A-SOD1 or wild-type SOD1 transgenic mice. Both CCS transgenic mice and CCS/wild-type-SOD1 dual transgenic mice are neurologically normal. In contrast, CCS/G93A-SOD1 dual transgenic mice develop accelerated neurological deficits, with a mean survival of 36 days, compared with 242 days for G93A-SOD1 mice. Immuno-EM and subcellular fractionation studies on the spinal cord show that G93A-SOD1 is enriched within mitochondria in the presence of CCS overexpression. Our results indicate that CCS overexpression in G93A-SOD1 mice produces severe mitochondrial pathology and accelerates disease course.

Age-Related Hearing Loss in Mn-SOD Heterozygous Knockout Mice

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Makoto Kinoshita

2013-01-01

Full Text Available Age-related hearing loss (AHL reduces the quality of life for many elderly individuals. Manganese superoxide dismutase (Mn-SOD, one of the antioxidant enzymes acting within the mitochondria, plays a crucial role in scavenging reactive oxygen species (ROS. To determine whether reduction in Mn-SOD accelerates AHL, we evaluated auditory function in Mn-SOD heterozygous knockout (HET mice and their littermate wild-type (WT C57BL/6 mice by means of auditory brainstem response (ABR. Mean ABR thresholds were significantly increased at 16 months when compared to those at 4 months in both WT and HET mice, but they did not significantly differ between them at either age. The extent of hair cell loss, spiral ganglion cell density, and thickness of the stria vascularis also did not differ between WT and HET mice at either age. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in the SGC and SV in HET mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. These findings suggest that, although decrease of Mn-SOD by half may increase oxidative stress in the cochlea to some extent, it may not be sufficient to accelerate age-related cochlear damage under physiological aging process.

Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset.

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Christine Vande Velde

Full Text Available Mutations in superoxide dismutase (SOD1 are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS.

Radioimmunoassay of serum SOD-1 in the elderly

International Nuclear Information System (INIS)

Ren Yu'an; Lin Baoyuan

1995-01-01

A RIA for serum SOD-1 was performed in 168 aged subjects including 47 aged healthy subjects and 121 aged patients as well as in 35 healthy young and adult cases serving as control. The measuring results are as follows: serum SOD-1 value of 47 aged healthy subjects are 279.42 +- 89.38 μg/l, 121 aged patients are 405.10 +- 181.29 μg/l, and 35 young and adult cases are 185.80 +- 56.44 μg/l. It shows the obvious difference between the aged group and control group. It also shows the obvious difference between the aged healthy subjects and aged patients. In addition, the clinical evaluation is also discussed

Bermudagrass sod growth and metal uptake in coal combustion by-product-amended media

Energy Technology Data Exchange (ETDEWEB)

Schlossberg, M.J.; Vanags, C.P.; Miller, W.P. [University of Georgia, Athens, GA (USA). Dept. of Crop & Soil Science

2004-04-01

Coal combustion by-products (CCB) include fly ash and bottom ash and are generated nationally at rates of 10{sup 8} Mg yr{sup -1}. Land applications of CCB have improved physicochemical properties of soil, yet inherent bulkiness and trace metal content of CCB often limit their use. Likewise, utilization of biosolids and manure as fertilizer can be problematic due to unfavorable nutrient ratios. A 2-yr field study evaluated environmental and technical parameters associated with CCB-organic waste utilization as growth media in turfgrass sod production. Experimental growth media formulated with CCB and organic waste and a sand-compost control mixture were uniformly spread at rates from 200 to 400 m{sup 3} ha{sup -1} and sprigged with hybrid bermudagrass (Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy). Leaf clippings were collected and analyzed for total elemental content each year. In Year 2, growth media samples were collected during establishment 47 and 84 days after planting (DAP) and viable Escherichia coli organisms were quantified. At harvest (99 or 114 DAP), sod biomass and physicochemical properties of the growth media were measured. During sod propagation, micronutrient and metal content in leaf clippings varied by growth media and time. After 47 d of typical sod field management, viable E. coli pathogens were detected in only one biosolids-amended plot. No viable E. coli were measured at 84 DAP. In both years, sod biomass was greatest in media containing biosolids and fly ash. Following installation of sod, evaluations did not reveal differences by media type or application volume. Using CCB-organic waste mixes at the rates described herein is a rapid and environmentally safe method of bermudagrass sod production.

Higher-level Innovization

DEFF Research Database (Denmark)

Bandaru, Sunith; Tutum, Cem Celal; Deb, Kalyanmoy

2011-01-01

we introduce the higher-level innovization task through an application of a manufacturing process simulation for the Friction Stir Welding (FSW) process where commonalities among two different Pareto-optimal fronts are analyzed. Multiple design rules are simultaneously deciphered from each front...

In yeast redistribution of Sod1 to the mitochondrial intermembrane space provides protection against respiration derived oxidative stress.

Science.gov (United States)

Klöppel, Christine; Michels, Christine; Zimmer, Julia; Herrmann, Johannes M; Riemer, Jan

2010-12-03

The antioxidative enzyme copper-zinc superoxide dismutase (Sod1) is an important cellular defence system against reactive oxygen species (ROS). While the majority of this enzyme is localized to the cytosol, about 1% of the cellular Sod1 is present in the intermembrane space (IMS) of mitochondria. These amounts of mitochondrial Sod1 are increased for certain Sod1 mutants that are linked to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). To date, only little is known about the physiological function of mitochondrial Sod1. Here, we use the model system Saccharomyces cerevisiae to generate cells in which Sod1 is exclusively localized to the IMS. We find that IMS-localized Sod1 can functionally substitute wild type Sod1 and that it even exceeds the protective capacity of wild type Sod1 under conditions of mitochondrial ROS stress. Moreover, we demonstrate that upon expression in yeast cells the common ALS-linked mutant Sod1(G93A) becomes enriched in the mitochondrial fraction and provides an increased protection of cells from mitochondrial oxidative stress. Such an effect cannot be observed for the catalytically inactive mutant Sod1(G85R). Our observations suggest that the targeting of Sod1 to the mitochondrial IMS provides an increased protection against respiration-derived ROS. Copyright © 2010 Elsevier Inc. All rights reserved.

Lethal doses of ionizing radiation versus endogenous level of superoxide dismutase

Energy Technology Data Exchange (ETDEWEB)

Lipecka, K; Domanski, T; Dniaszewska, K; Grabowska, B; Pietrowicz, D; Lindner, P; Cisowska, B; Gorski, H [Military Medical Academy, Lodz (Poland). Inst. of Occupational Medicine

1982-06-22

The stability of superoxide dismutase (SOD) as well as its activity distribution in a human population were investigated. The SOD activity level of the erythrocytes proved to be an index for the endogenous SOD activity in the whole body. In a rat population, having similar SOD frequency distribution as a human population, the mortality due to acute irradiation depended on the SOD level; after a single acute dose approximating the lethal dose (LD/sub 50/30/) the survival depended distinctly on the endogenous SOD activity level.

Wildtype motoneurons, ALS-Linked SOD1 mutation and glutamate profoundly modify astrocyte metabolism and lactate shuttling.

Science.gov (United States)

Madji Hounoum, Blandine; Mavel, Sylvie; Coque, Emmanuelle; Patin, Franck; Vourc'h, Patrick; Marouillat, Sylviane; Nadal-Desbarats, Lydie; Emond, Patrick; Corcia, Philippe; Andres, Christian R; Raoul, Cédric; Blasco, Hélène

2017-04-01

The selective degeneration of motoneuron that typifies amyotrophic lateral sclerosis (ALS) implicates non-cell-autonomous effects of astrocytes. However, mechanisms underlying astrocyte-mediated neurotoxicity remain largely unknown. According to the determinant role of astrocyte metabolism in supporting neuronal function, we propose to explore the metabolic status of astrocytes exposed to ALS-associated conditions. We found a significant metabolic dysregulation including purine, pyrimidine, lysine, and glycerophospholipid metabolism pathways in astrocytes expressing an ALS-causing mutated superoxide dismutase-1 (SOD1) when co-cultured with motoneurons. SOD1 astrocytes exposed to glutamate revealed a significant modification of the astrocyte metabolic fingerprint. More importantly, we observed that SOD1 mutation and glutamate impact the cellular shuttling of lactate between astrocytes and motoneurons with a decreased in extra- and intra-cellular lactate levels in astrocytes. Based on the emergent strategy of metabolomics, this work provides novel insight for understanding metabolic dysfunction of astrocytes in ALS conditions and opens the perspective of therapeutics targets through focusing on these metabolic pathways. GLIA 2017 GLIA 2017;65:592-605. © 2017 Wiley Periodicals, Inc.

Genetic Polymorphisms in SOD (rs2070424, rs7880) and CAT (rs7943316, rs1001179) Enzymes Are Associated with Increased Body Fat Percentage and Visceral Fat in an Obese Population from Central Mexico.

Science.gov (United States)

Hernández-Guerrero, César; Hernández-Chávez, Paulina; Romo-Palafox, Inés; Blanco-Melo, Grecia; Parra-Carriedo, Alicia; Pérez-Lizaur, Ana

2016-07-01

Oxidative disturbance is an important factor involved in the etiology of comorbidities associated with obesity. Genetic polymorphisms such as SOD1 -251A>G, SOD2 47 C>T, CAT -21A>T and CAT -262 C>T have been described to alter the activity of antioxidant enzymes. The aim of the present work was to analyze the association of the mentioned SNPs with obesity and their relationship with anthropometric and clinical variables in this group. The study included 416 Mexican women (208 normal weight, NW and 208 subjects with obesity, OB). Dietary intake, anthropometric, biochemical and clinical features were evaluated and then analyzed in function of the genotypes. The mutated carriers (GA+GG) of SOD -251 were significantly higher in the OB group (0.24) compared to the NW group (0.08). The other SNPs showed no differences compared with control group. When comparing carrier mutated subjects with obesity vs. wild-type obese participants with the SNPs SOD1 -251, SOD2 47 and CAT -262, the carriers showed a significantly (p G is associated with obesity independent of the presence of diabetes or dyslipidemia. Mutated obese carries of SOD1 -251, SOD2 47 and CAT -262 are associated with a higher distribution of fat in comparison with obese wild-type carriers. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

Manganese-superoxide dismutase (MnSOD), a role player in seahorse (Hippocampus abdominalis) antioxidant defense system and adaptive immune system.

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Perera, N C N; Godahewa, G I; Lee, Seongdo; Kim, Myoung-Jin; Hwang, Jee Youn; Kwon, Mun Gyeong; Hwang, Seong Don; Lee, Jehee

2017-09-01

Manganese superoxide dismutase (MnSOD) is a metaloenzyme that catalyzes dismutation of the hazardous superoxide radicals into less hazardous H 2 O 2 and H 2 O. Here, we identified a homolog of MnSOD from big belly seahorse (Hippocampus abdominalis; HaMnSOD) and characterized its structural and functional features. HaMnSOD transcript possessed an open reading frame (ORF) of 672 bp which codes for a peptide of 223 amino acids. Pairwise alignment showed that HaMnSOD shared highest identity with rock bream MnSOD. Results of the phylogenetic analysis of HaMnSOD revealed a close proximity with rock bream MnSOD which was consistent with the result of homology alignment. The intense expression of HaMnSOD was observed in the ovary, followed by the heart and the brain. Further, immune related responses of HaMnSOD towards pathogenic stimulation were observed through bacterial and viral challenges. Highest HaMnSOD expression in response to stimulants Edwardsiella tarda, Streptococcus iniae, lipopolysaccharide (LPS), and polyinosinic-polycytidylic acid (Poly I:C) was observed in the late stage in the blood tissue. Xanthine/xanthine oxidase assay (XOD assay) indicated the ROS-scavenging ability of purified recombinant HaMnSOD (rHaMnSOD). The optimum conditions for the SOD activity of rHaMnSOD were pH 9 and the 25 °C. Collectively, the results obtained through the expressional analysis profiles and the functional assays provide insights into potential immune related and antioxidant roles of HaMnSOD in the big belly seahorse. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential motor neuron impairment and axonal regeneration in sporadic and familiar amyotrophic lateral sclerosis with SOD-1 mutations: lessons from neurophysiology.

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Bocci, Tommaso; Pecori, Chiara; Giorli, Elisa; Briscese, Lucia; Tognazzi, Silvia; Caleo, Matteo; Sartucci, Ferdinando

2011-01-01

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O(-2)) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females) were enrolled in the study and examined basally (T0) and every 4 months (T1, T2, and T3). Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females). We used Macro-EMG and Motor Unit Number Estimation (MUNE) in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS.

Differential Motor Neuron Impairment and Axonal Regeneration in Sporadic and Familiar Amyotrophic Lateral Sclerosis with SOD-1 Mutations: Lessons from Neurophysiology

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Tommaso Bocci

2011-12-01

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1 gene. SOD-1 catalyses the superoxide radical (O−2 into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS patients (34 males; 26 females were enrolled in the study and examined basally (T0 and every 4 months (T1, T2, and T3. Fifteen of these patients are SOD-1 symptomatic mutation carriers (nine males, six females. We used Macro-EMG and Motor Unit Number Estimation (MUNE in order to evaluate the neuronal loss and the re-innervation process at the onset of disease and during follow-up period. Results and Discussion: SOD-1 mutation carriers have a higher number of motor units at the moment of diagnosis when compared with the sporadic form, despite a more dramatic drop in later stages. Moreover, in familiar SOD-1 ALS there is not a specific time interval in which the axonal regeneration can balance the neuronal damage. Taken together, these results strengthen the idea of a different pathogenetic mechanism at the base of sALS and fALS.

Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: A preliminary study of antioxidant defense genes in brain aging.

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Salminen, Lauren E; Schofield, Peter R; Pierce, Kerrie D; Bruce, Steven E; Griffin, Michael G; Tate, David F; Cabeen, Ryan P; Laidlaw, David H; Conturo, Thomas E; Bolzenius, Jacob D; Paul, Robert H

2017-06-30

Oxidative stress is a key mechanism of the aging process that can cause damage to brain white matter and cognitive functions. Polymorphisms in the superoxide dismutase 2 (SOD2) and catalase (CAT) genes have been associated with abnormalities in antioxidant enzyme activity in the aging brain, suggesting a risk for enhanced oxidative damage to white matter and cognition among older individuals with these genetic variants. The present study compared differences in white matter microstructure and cognition among 96 older adults with and without genetic risk factors of SOD2 (rs4880) and CAT (rs1001179). Results revealed higher radial diffusivity in the anterior thalamic radiation among SOD2 CC genotypes compared to CT/TT genotypes. Further, the CC genotype moderated the relationship between the hippocampal cingulum and processing speed, though this did not survive multiple test correction. The CAT polymorphism was not associated with brain outcomes in this cohort. These results suggest that the CC genotype of SOD2 is an important genetic marker of suboptimal brain aging in healthy individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiation damage, treatment of tumor and acute benzene toxicosis effects of superoxide dismutase (SOD)

International Nuclear Information System (INIS)

Jiang Jiagui; Lin Xingcheng; Zhu Yuyu

1987-09-01

The protective effects of SOD on irradiated-mice were studied by white cell counts, determination of taurine in urine, and survival of irradiated-animals. The enzyme was protective against radiation-induced inhibition of lymphocyte blastogenesis. The protective effect of SOD on patients suffered from cancer was also studied by white cell counts. The effect of SOD on white cell counts in mice of benzene toxicosis was also discussed

Import, maturation, and function of SOD1 and its copper chaperone CCS in the mitochondrial intermembrane space.

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Kawamata, Hibiki; Manfredi, Giovanni

2010-11-01

Cu, Zn, superoxide dismutase (SOD1) is a ubiquitous enzyme localized in multiple cellular compartments, including mitochondria, where it concentrates in the intermembrane space (IMS). Similar to other small IMS proteins, the import and retention of SOD1 in the IMS is linked to its folding and maturation, involving the formation of critical intra- and intermolecular disulfide bonds. Therefore, the cysteine residues of SOD1 play a fundamental role in its IMS localization. IMS import of SOD1 involves its copper chaperone, CCS, whose mitochondrial distribution is regulated by the Mia40/Erv1 disulfide relay system in a redox-dependent manner: CCS promotes SOD1 maturation and retention in the IMS. The function of SOD1 in the IMS is still unknown, but it is plausible that it serves to remove superoxide released from the mitochondrial respiratory chain. Mutations in SOD1 cause familial amyotrophic lateral sclerosis (ALS), whose pathologic features include mitochondrial bioenergetic dysfunction. Mutant SOD1 localization in the IMS is not dictated by oxygen concentration and the Mia40/Erv1 system, but is primarily dependent on aberrant protein folding and aggregation. Mutant SOD1 localization and aggregation in the IMS might cause the mitochondrial abnormalities observed in familial ALS and could play a significant role in disease pathogenesis.

Genetic disruption of SOD1 gene causes glucose intolerance and impairs β-cell function.

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Muscogiuri, Giovanna; Salmon, Adam B; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L; Reyna, Sara M; Weir, Gordon; Defronzo, Ralph A; Van Remmen, Holly; Musi, Nicolas

2013-12-01

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction.

Carbohydrate-dependent binding of langerin to SodC, a cell wall glycoprotein of Mycobacterium leprae.

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Kim, Hee Jin; Brennan, Patrick J; Heaslip, Darragh; Udey, Mark C; Modlin, Robert L; Belisle, John T

2015-02-01

Langerhans cells participate in the immune response in leprosy by their ability to activate T cells that recognize the pathogen, Mycobacterium leprae, in a langerin-dependent manner. We hypothesized that langerin, the distinguishing C-type lectin of Langerhans cells, would recognize the highly mannosylated structures in pathogenic Mycobacterium spp. The coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of human langerin (r-langerin). Binding assays performed in microtiter plates, by two-dimensional (2D) Western blotting, and by surface plasmon resonance demonstrated that r-langerin possessed carbohydrate-dependent affinity to glycoproteins in the cell wall of M. leprae. This lectin, however, yielded less binding to mannose-capped lipoarabinomannan (ManLAM) and even lower levels of binding to phosphatidylinositol mannosides. However, the superoxide dismutase C (SodC) protein of the M. leprae cell wall was identified as a langerin-reactive ligand. Tandem mass spectrometry verified the glycosylation of a recombinant form of M. leprae SodC (rSodC) produced in Mycobacterium smegmatis. Analysis of r-langerin affinity by surface plasmon resonance revealed a carbohydrate-dependent affinity of rSodC (equilibrium dissociation constant [KD] = 0.862 μM) that was 20-fold greater than for M. leprae ManLAM (KD = 18.69 μM). These data strongly suggest that a subset of the presumptively mannosylated M. leprae glycoproteins act as ligands for langerin and may facilitate the interaction of M. leprae with Langerhans cells. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

In vitro antioxidant activity, enzyme kinetics, biostability and cellular SOD mimicking ability of 1:1 curcumin-copper (II) complex

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Kunwar, A.; Mishra, B.; Barik, A.; Priyadarsini, K.I.; Narang, H.; Krishna, M.

2008-01-01

In vitro antioxidant activity of 1:1 curcumin copper (II) complex was evaluated by following the inhibition of γ-radiation induced lipid peroxidation and protein oxidation in model systems. The SOD enzyme kinetic parameters K m and V max values and the turn over number of the complex were determined. The complex is stable in bio-fluids and prevents oxidation of lipid and protein solution in presence of H 2 O 2 and showed reduction in MnSOD level in spleen cells without having any effect on cell viability. (author)

In vitro antioxidant activity, enzyme kinetics, biostability and cellular SOD mimicking ability of 1:1 curcumin-copper (II) complex

Energy Technology Data Exchange (ETDEWEB)

Kunwar, A; Mishra, B; Barik, A; Priyadarsini, K I [Radiation and Photochemistry Div., Bhabha Atomic Research Centre, Mumbai (India); Narang, H; Krishna, M [Radiation Biology and Health Sciences Div., Bhabha Atomic Research Centre, Mumbai (India)

2008-01-15

In vitro antioxidant activity of 1:1 curcumin copper (II) complex was evaluated by following the inhibition of {gamma}-radiation induced lipid peroxidation and protein oxidation in model systems. The SOD enzyme kinetic parameters K{sub m} and V{sub max} values and the turn over number of the complex were determined. The complex is stable in bio-fluids and prevents oxidation of lipid and protein solution in presence of H{sub 2}O{sub 2} and showed reduction in MnSOD level in spleen cells without having any effect on cell viability. (author)

Effects of Thermal Stress on the mRNA Expression of SOD, HSP90, and HSP70 in the Spotted Sea Bass ( Lateolabrax maculatus)

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Shin, Moon-Kyeong; Park, Ho-Ra; Yeo, Won-Jun; Han, Kyung-Nam

2018-03-01

The aim of this study was to elucidate the molecular mechanisms underlying the thermal stress response in the spotted sea bass ( Lateolabrax maculatus). Spotted sea basses were exposed to 4 different water temperatures (20, 22, 24, and 28°C) in increasing increments of 2°C/h from 18°C (control) for different time periods (0, 6, 12, 24, 48, 72, and 96 h). Subsequently, 3 tissues (liver, muscle, and gill) were isolated, and the levels of SOD, HSP90, and HSP70 mRNA were assessed. SOD mRNA expression was maintained at baseline levels of control fish at all water temperatures in the liver, while muscle and gill tissue showed an increase followed by a decrease over each certain time with higher water temperature. HSP90 mRNA expression increased in the liver at ≤ 24°C over time, but maintained baseline expression at 28°C. In muscle, HSP90 mRNA expression gradually increased at all water temperatures, but increased and then decreased at ≥ 24°C in gill tissue. HSP70 mRNA expression exhibited an increase and then a decrease in liver tissue at 28°C, but mainly showed similar expression patterns to HSP90 in all tissues. These results suggest the activity of a defense mechanism using SOD, HSP90, and HSP70 in the spotted sea bass upon rapid increases in water temperature, where the expression of these genes indicated differences between tissues in the extent of the defense mechanisms. Also, these results indicate that high water temperature and long-term thermal stress exposure can inhibit physiological defense mechanisms.

Exposure of Mn and FeSODs, but not Cu/ZnSOD, to NO leads to nitrosonium and nitroxyl ions generation which cause enzyme modification and inactivation: an in vitro study.

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Niketíc, V; Stojanović, S; Nikolić, A; Spasić, M; Michelson, A M

1999-11-01

The effect of NO treatment in vitro on structural and functional alterations of Cu/Zn, Mn, and Fe type of SODs was studied. Significant difference in response to NO of Cu/ZnSOD compared to the Mn and Fe types was demonstrated. Cu/ZnSOD was shown to be stable with respect to NO: even on prolonged exposure, NO produced negligible effect on its structure and activity. In contrast, both Mn and Fe types were found to be NO-sensitive: exposure to NO led to their fast and extensive inactivation, which was accompanied by extensive structural alterations, including (in some of the samples tested) the cleavage of enzyme polypeptide chains, presumably at His residues of the enzyme metal binding sites. The generation of nitrosonium (NO+) and nitroxyl (NO-) ions in NO treated Mn and FeSODs, which produce enzyme modifications and inactivation, was demonstrated. The physiological and biomedical significance of described findings is briefly discussed.

The effect of the spaceship carrying on the biological characters and sod activity of eggplant

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Wang Shiheng; Zhang Ya; Zhu Shuijin; Wang Yanfan

2004-01-01

The effects of the space shuttle carrying on the growth and biological characters of eggplant SP 1 population were studied. The results showed that the effect of space shuttle carrying on the growth and development of eggplant SP 1 were very significant on the characters such as the plant height, reproductive development, leaf size, fruit length, fruit quality and fruiting rate etc, especially on the plant development and the fruit size, and it is hopeful to select some good eggplant germplasm or cultivars from the population. The SOD activity showed that the SOD level in the mutant-1 plant was one time more than that in control plant, indicating that the space shuttle carrying may increase the expression of some genes and lead to the great change in morphological characters

AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD

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Josef eBrandauer

2015-03-01

Full Text Available The mitochondrial protein deacetylase sirtuin (SIRT 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS handling. We determined the requirement of AMP-activated protein kinase (AMPK for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p<0.01 and superoxide dismutase 2 (MnSOD; p<0.05 protein abundance in quadriceps muscle of wild-type (WT; n=13-15, but not AMPK α2 kinase dead (KD; n=12-13 mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p=0.051; n=6. To further elucidate a role for AMPK in mediating these effects, we treated WT (n=7-8 and AMPK α2 KD (n=7-9 mice with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR. Four weeks of daily AICAR injections (500 mg/kg resulted in AMPK-dependent increases in SIRT3 (p<0.05 and MnSOD (p<0.01 in WT, but not AMPK α2 KD mice. We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n=9-10. Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p<0.01 and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p<0.05. Finally, the acetylation status of SIRT3 target lysine residues on MnSOD (K122 or oligomycin-sensitivity conferring protein (OSCP; K139 was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling in skeletal muscle in response to exercise training.

Delayed Disease Onset and Extended Survival in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis after Suppression of Mutant SOD1 in the Motor Cortex

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Thomsen, Gretchen M.; Gowing, Genevieve; Latter, Jessica; Chen, Maximus; Vit, Jean-Philippe; Staggenborg, Kevin; Avalos, Pablo; Alkaslasi, Mor; Ferraiuolo, Laura; Likhite, Shibi; Kaspar, Brian K.

2014-01-01

Sporadic amyotrophic lateral sclerosis (ALS) is a fatal disease with unknown etiology, characterized by a progressive loss of motor neurons leading to paralysis and death typically within 3–5 years of onset. Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1G93A rats through targeted delivery of AAV9–SOD1–shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease. PMID:25411487

Transduced human copper chaperone for Cu,Zn-SOD (PEP-1-CCS) protects against neuronal cell death.

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Choi, Soo Hyun; Kim, Dae Won; Kim, So Young; An, Jae Jin; Lee, Sun Hwa; Choi, Hee Soon; Sohn, Eun Jung; Hwang, Seok-Il; Won, Moo Ho; Kang, Tae-Cheon; Kwon, Hyung Joo; Kang, Jung Hoon; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

2005-12-31

Reactive oxygen species (ROS) contribute to the development of various human diseases. Cu,Zn-superoxide dismutase (SOD) is one of the major means by which cells counteract the deleterious effects of ROS. SOD activity is dependent upon bound copper ions supplied by its partner metallochaperone protein, copper chaperone for SOD (CCS). In the present study, we investigated the protective effects of PEP-1-CCS against neuronal cell death and ischemic insults. When PEP-1-CCS was added to the culture medium of neuronal cells, it rapidly entered the cells and protected them against paraquat-induced cell death. Moreover, transduced PEP-1-CCS markedly increased endogenous SOD activity in the cells. Immunohistochemical analysis revealed that it prevented neuronal cell death in the hippocampus in response to transient forebrain ischemia. These results suggest that CCS is essential to activate SOD, and that transduction of PEP-1-CCS provides a potential strategy for therapeutic delivery in various human diseases including stroke related to SOD or ROS.

In-vivo effects of knocking-down metabotropic glutamate receptor 5 in the SOD1G93A mouse model of amyotrophic lateral sclerosis.

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Bonifacino, Tiziana; Cattaneo, Luca; Gallia, Elena; Puliti, Aldamaria; Melone, Marcello; Provenzano, Francesca; Bossi, Simone; Musante, Ilaria; Usai, Cesare; Conti, Fiorenzo; Bonanno, Giambattista; Milanese, Marco

2017-09-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to loss of upper and lower motor neurons (MNs). The mechanisms of neuronal death are largely unknown, thus prejudicing the successful pharmacological treatment. One major cause for MN degeneration in ALS is represented by glutamate(Glu)-mediated excitotoxicity. We have previously reported that activation of Group I metabotropic Glu receptors (mGluR1 and mGluR5) at glutamatergic spinal cord nerve terminals produces abnormal Glu release in the widely studied SOD1 G93A mouse model of ALS. We also demonstrated that halving mGluR1 expression in the SOD1 G93A mouse had a positive impact on survival, disease onset, disease progression, and on a number of cellular and biochemical readouts of ALS. We generated here SOD1 G93A mice with reduced expression of mGluR5 (SOD1 G93A Grm5 -/+ ) by crossing the SOD1 G93A mutant mouse with the mGluR5 heterozigous Grm5 -/+ mouse. SOD1 G93A Grm5 -/+ mice showed prolonged survival probability and delayed pathology onset. These effects were associated to enhanced number of preserved MNs, decreased astrocyte and microglia activation, reduced cytosolic free Ca 2+ concentration, and regularization of abnormal Glu release in the spinal cord of SOD1 G93A Grm5 -/+ mice. Unexpectedly, only male SOD1 G93A Grm5 -/+ mice showed improved motor skills during disease progression vs. SOD1 G93A mice, while SOD1 G93A Grm5 -/+ females did not. These results demonstrate that a lower constitutive level of mGluR5 has a significant positive impact in mice with ALS and support the idea that blocking Group I mGluRs may represent a potentially effective pharmacological approach to the disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Copper-zinc-superoxide dismutase (CuZnSOD), an antioxidant gene from seahorse (Hippocampus abdominalis); molecular cloning, sequence characterization, antioxidant activity and potential peroxidation function of its recombinant protein.

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Perera, N C N; Godahewa, G I; Lee, Jehee

2016-10-01

Copper-zinc-superoxide dismutase (CuZnSOD) from Hippocampus abdominalis (HaCuZnSOD) is a metalloenzyme which belongs to the ubiquitous family of SODs. Here, we determined the characteristic structural features of HaCuZnSOD, analyzed its evolutionary relationships, and identified its potential immune responses and biological functions in relation to antioxidant defense mechanisms in the seahorse. The gene had a 5' untranslated region (UTR) of 67 bp, a coding sequence of 465 bp and a 3' UTR of 313 bp. The putative peptide consists of 154 amino acids. HaCuZnSOD had a predicted molecular mass of 15.94 kDa and a theoretical pI value of 5.73, which is favorable for copper binding activity. In silico analysis revealed that HaCuZnSOD had a prominent Cu-Zn_superoxide_dismutase domain, two Cu/Zn signature sequences, a putative N-glycosylation site, and several active sites including Cu(2+) and Zn(2+) binding sites. The three dimensional structure indicated a β-sheet barrel with 8 β-sheets and two short α-helical regions. Multiple alignment analyses revealed many conserved regions and active sites among its orthologs. The highest amino acid identity to HaCuZnSOD was found in Siniperca chuatsi (87.4%), while Maylandia zebra shared a close relationship in the phylogenetic analysis. Functional assays were performed to assess the antioxidant, biophysical and biochemical properties of overexpressed recombinant (r) HaCuZnSOD. A xanthine/XOD assay gave optimum results at pH 9 and 25 °C indicating these may be the best conditions for its antioxidant action in the seahorse. An MTT assay and flow cytometry confirmed that rHaCuZnSOD showed peroxidase activity in the presence of HCO3(-). In all the functional assays, the level of antioxidant activity of rHaCuZnSOD was concentration dependent; metal ion supplementation also increased its activity. The highest mRNA expressional level of HaCuZnSOD was found in blood. Temporal assessment under pathological stress showed a delay

Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

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Tali Gidalevitz

2009-03-01

Full Text Available Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles.

Resveratrol Derivative-Rich Melinjo Seed Extract Attenuates Skin Atrophy in Sod1-Deficient Mice

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Kenji Watanabe

2015-01-01

Full Text Available The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1 resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (Gnetum gnemon Linn seed extract (MSE contains trans-resveratrol (RSV and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related skin pathologies in mice. Orally MSE and RSV treatment reversed the skin thinning associated with increased oxidative damage in the Sod1−/− mice. Furthermore, MSE and RSV normalized gene expression of Col1a1 and p53 and upregulated gene expression of Sirt1 in skin tissues. In vitro experiments revealed that RSV significantly promoted the viability of Sod1−/− fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generation in vivo and in vitro leading to protecting skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related skin diseases caused by oxidative damages.

Association Between Free Fatty Acid (FFA and Insulin Resistance: The Role of Inflammation (Adiponectin and high sensivity C-reactive Protein/hs-CRP and Stress Oxidative (Superoxide Dismutase/SOD in Obese Non-Diabetic Individual

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Indriyanti Rafi Sukmawati

2009-12-01

Full Text Available BACKGROUND: Obesity is highly related to insulin resistance, therefore, the increased number of obesity is followed by the increased prevalence of type 2 Diabetes Melitus. Obesity is associated with increased of reactive oxygen species (ROS in muscle, liver and endothelial cells. The increase of ROS would lead to insulin resistance (IR and increased pro-inflammatory protein. FFA plays an important role in IR by inhibiting muscle glucose transport and oxidation via effects on serine/threonine phosphorylation of IRS-1. The aim of this study was discover the existence of SOD, hs-CRP and and adiponectin levels towards the occurrence of insulin resistance which was caused by elevated level of FFA and to discover the interaction between SOD, hs-CRP and adiponectin in non diabetic obese adult male. METHODS: This was observational study with cross sectional design. There were 65 obese male non diabetic subjects and 45 non obese male non diabetic subjects who met the criteria. In this study, measurements were done on body mass index (BMI, fasting glucose, insulin, adiponectin, hs-CRP and SOD. Obese was defined as BMI >25 kg/m2, normal weight was defined as BMI 18.5-23 kh/m2 and Insulin Resistance was defined as HOMA-IR >1. RESULTS: This study showed that Hypoadiponectinemia condition, decreased SOD level and high level of hs-CRP is associated with insulin resistance in obese non diabetic subject. Adiponectin and SOD were correlated negatively with insulin resistance in obese non diabetic (Adiponectin, r=-0.455, p<0.001; SOD, r=-0.262, p=0.003, hs-CRP was positively correlated with insulin resistance in obese non diabetic (r=0.592, p<0.001. FFA levels was increased in obese insulin resistance compared with non obese non insulin resistance. The Odds Ratio of Adiponectin, hs-CRP and SOD in this study was analyzed by logistic binary. The OR for SOD 3.6 (p=0.001, hs-CRP 9.1 (p<0.001 and Adiponectin 7.2 (p<0.001. CONCLUSIONS: This study suggested that FFA

Human SOD1 ALS Mutations in a Drosophila Knock-In Model Cause Severe Phenotypes and Reveal Dosage-Sensitive Gain- and Loss-of-Function Components.

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Şahin, Aslı; Held, Aaron; Bredvik, Kirsten; Major, Paxton; Achilli, Toni-Marie; Kerson, Abigail G; Wharton, Kristi; Stilwell, Geoff; Reenan, Robert

2017-02-01

Amyotrophic Lateral Sclerosis (ALS) is the most common adult-onset motor neuron disease and familial forms can be caused by numerous dominant mutations of the copper-zinc superoxide dismutase 1 (SOD1) gene. Substantial efforts have been invested in studying SOD1-ALS transgenic animal models; yet, the molecular mechanisms by which ALS-mutant SOD1 protein acquires toxicity are not well understood. ALS-like phenotypes in animal models are highly dependent on transgene dosage. Thus, issues of whether the ALS-like phenotypes of these models stem from overexpression of mutant alleles or from aspects of the SOD1 mutation itself are not easily deconvolved. To address concerns about levels of mutant SOD1 in disease pathogenesis, we have genetically engineered four human ALS-causing SOD1 point mutations (G37R, H48R, H71Y, and G85R) into the endogenous locus of Drosophila SOD1 (dsod) via ends-out homologous recombination and analyzed the resulting molecular, biochemical, and behavioral phenotypes. Contrary to previous transgenic models, we have recapitulated ALS-like phenotypes without overexpression of the mutant protein. Drosophila carrying homozygous mutations rendering SOD1 protein enzymatically inactive (G85R, H48R, and H71Y) exhibited neurodegeneration, locomotor deficits, and shortened life span. The mutation retaining enzymatic activity (G37R) was phenotypically indistinguishable from controls. While the observed mutant dsod phenotypes were recessive, a gain-of-function component was uncovered through dosage studies and comparisons with age-matched dsod null animals, which failed to show severe locomotor defects or nerve degeneration. We conclude that the Drosophila knock-in model captures important aspects of human SOD1-based ALS and provides a powerful and useful tool for further genetic studies. Copyright © 2017 by the Genetics Society of America.

Altered serum copper homeostasis suggests higher oxidative stress and lower antioxidant capability in patients with chronic hepatitis B.

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Huang, Yansong; Zhang, Yuan; Lin, Zhexuan; Han, Ming; Cheng, Hongqiu

2018-06-01

Copper homeostasis can be altered by inflammation. This study aimed to investigate the alteration of serum copper homeostasis and to explore its clinical significance in patients with chronic hepatitis B (CHB).Thirty-two patients with CHB and 10 aged- and sex-matched healthy controls were recruited. Analyses included serum levels of total copper (TCu), copper ions (Cu), small molecule copper (SMC), ceruloplasmin (CP), Cu/Zn superoxide dismutase 1 (SOD1), urinary copper, and the activities of serum CP and SOD1.The serum TCu and urinary copper levels in patients with CHB were significantly higher than the controls (P = .04 and .003), while the serum Cu was lower than the controls (P = .0002). CP and SOD1 activities in the serum were significantly lower in patients with CHB compared to controls (P = .005) despite higher serum concentrations. In addition, serum alanine aminotransferase inversely correlated with serum CP activity (P = .0318, r = -0.4065).Serum copper homeostasis was altered in this cohort of patients with CHB. The results suggest increased oxidative stress and impaired antioxidant capability in patients with CHB, in addition to necroinflammation. These results may provide novel insights into the diagnosis and treatment of patients with CHB.

EXAFS analysis of a human Cu,Zn SOD isoform focused using non-denaturing gel electrophoresis

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Chevreux, Sylviane; Roudeau, Stephane; Deves, Guillaume; Ortega, Richard [Laboratoire de Chimie Nucleaire Analytique et Bioenvironnementale, CNRS UMR5084, Universite Bordeaux 1, Chemin du Solarium, F-33175 Gradignan cedex (France); Solari, Pier Lorenzo [Synchrotron SOLEIL, L' Orme des Merisiers, BP 48, F-91192 Gif-sur-Yvette cedex, Saint-Aubin (France); Alliot, Isabelle; Testemale, Denis; Hazemann, Jean Louis, E-mail: ortega@cenbg.in2p3.f [FAME, ESRF, 6 rue Jules Horowitz, BP220, F-38043 Grenoble cedex (France)

2009-11-15

Isoelectric point isoforms of a metalloprotein, copper-zinc superoxide dismutase (CuZnSOD), separated on electrophoresis gels were analyzed using X-ray Absorption Spectroscopy. Mutations of this protein are involved in familial cases of amyotrophic lateral sclerosis. The toxicity of mutants could be relied to defects in the metallation state. Our purpose is to establish analytical protocols to study metallation state of protein isoforms such as those from CuZnSOD. We previously highlighted differences in the copper oxidation state between CuZnSOD isoforms using XANES. Here, we present the first results for EXAFS analyses performed at Cu and Zn K-edge on the majoritary expressed isoform of human CuZnSOD separated on electrophoresis gels.

EXAFS analysis of a human Cu,Zn SOD isoform focused using non-denaturing gel electrophoresis

Science.gov (United States)

Chevreux, Sylviane; Solari, Pier Lorenzo; Roudeau, Stéphane; Deves, Guillaume; Alliot, Isabelle; Testemale, Denis; Hazemann, Jean Louis; Ortega, Richard

2009-11-01

Isoelectric point isoforms of a metalloprotein, copper-zinc superoxide dismutase (CuZnSOD), separated on electrophoresis gels were analyzed using X-ray Absorption Spectroscopy. Mutations of this protein are involved in familial cases of amyotrophic lateral sclerosis. The toxicity of mutants could be relied to defects in the metallation state. Our purpose is to establish analytical protocols to study metallation state of protein isoforms such as those from CuZnSOD. We previously highlighted differences in the copper oxidation state between CuZnSOD isoforms using XANES. Here, we present the first results for EXAFS analyses performed at Cu and Zn K-edge on the majoritary expressed isoform of human CuZnSOD separated on electrophoresis gels.

EXAFS analysis of a human Cu,Zn SOD isoform focused using non-denaturing gel electrophoresis

International Nuclear Information System (INIS)

Chevreux, Sylviane; Roudeau, Stephane; Deves, Guillaume; Ortega, Richard; Solari, Pier Lorenzo; Alliot, Isabelle; Testemale, Denis; Hazemann, Jean Louis

2009-01-01

Isoelectric point isoforms of a metalloprotein, copper-zinc superoxide dismutase (CuZnSOD), separated on electrophoresis gels were analyzed using X-ray Absorption Spectroscopy. Mutations of this protein are involved in familial cases of amyotrophic lateral sclerosis. The toxicity of mutants could be relied to defects in the metallation state. Our purpose is to establish analytical protocols to study metallation state of protein isoforms such as those from CuZnSOD. We previously highlighted differences in the copper oxidation state between CuZnSOD isoforms using XANES. Here, we present the first results for EXAFS analyses performed at Cu and Zn K-edge on the majoritary expressed isoform of human CuZnSOD separated on electrophoresis gels.

Stability of Seven Days Sample Storage of Erythrocyte’s SOD and Blood’s GPx

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Miswar Fattah

2012-12-01

Full Text Available The research was about SOD erythrocyte activities at day 0, 1, 3, 5, and 7 which centrifuged at room temperature (22.5 0C and storage temperature (-80 0C, SOD activities at day-0 which centrifuged at 4 0C, SOD whole blood activities with one day incubated at 2-8 0C and GPx activities at day 0, 1, 3, 5, and 7 with 2–8 0C storage temperature. Laboratory analysis were performed by using reagent from Randox Laboratories, and Hitachi 917 analyzer from Boehringer Mannheim. SOD activities were measured at 505 nm absorbance meanwhile 340 nm absorbance is used to measure GPx. Data was analyzed by using t-test method and showed that SOD activities at day 0, 1, 3, 5, and 7 with room temperature centrifuged had no significant differences. Significant differences are found at day-0 with centrifuged at 4 0C and one day incubated whole blood at 2–8 0C. GPx activities at day- 3 had no significant differences. Significant differences are found at day-0,1, 5 and 7 after storage.

Comparative evaluation of serum superoxide dismutase and glutathione levels in periodontally diseased patients: An interventional study

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Thomas Biju

2014-01-01

Full Text Available Background: Periodontal disease is an immune-inflammatory disease characterized by connective tissue breakdown, loss of attachment, and alveolar bone resorption. Under normal physiological conditions, a dynamic equilibrium is maintained between the reactive oxygen species (ROS and antioxidant defense capacity. Oxidative stress occurs when this equilibrium shifts in favor of ROS. Oxidative stress is thought to play a causative role in the pathogenesis of periodontal diseases. Aim: The present study was designed to estimate and compare the superoxide dismutase (SOD and glutathione (GSH levels in the serum of periodontitis, gingivitis, and healthy individuals before and after nonsurgical periodontal therapy. Materials and Methods: The present study was conducted in the Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Deralakatte, Mangalore. The study was designed as a single blinded interventional study comprising 75 subjects, inclusive of both sexes and divided into three groups of 25 patients each. Patients were categorized into chronic periodontitis, gingivitis, and healthy. The severity of inflammation was assessed using gingival index and pocket probing depth. Biochemical analysis was done to estimate the SOD and GSH levels before and after nonsurgical periodontal therapy. Results obtained were then statistically analyzed using ANOVA test and paired t-test. Results: The results showed a higher level of serum SOD and GSH in the healthy group compared to the other groups. The difference was found to be statistically significant (P < 0.0001. The post-treatment levels of SOD were statistically higher than the pre-treatment levels in periodontitis and gingivitis group.

TDP-43 or FUS-induced misfolded human wild-type SOD1 can propagate intercellularly in a prion-like fashion.

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Pokrishevsky, Edward; Grad, Leslie I; Cashman, Neil R

2016-03-01

Amyotrophic lateral sclerosis (ALS), which appears to spread through the neuroaxis in a spatiotemporally restricted manner, is linked to heritable mutations in genes encoding SOD1, TDP-43, FUS, C9ORF72, or can occur sporadically without recognized genetic mutations. Misfolded human wild-type (HuWt) SOD1 has been detected in both familial and sporadic ALS patients, despite mutations in SOD1 accounting for only 2% of total cases. We previously showed that accumulation of pathological TDP-43 or FUS coexist with misfolded HuWtSOD1 in patient motor neurons, and can trigger its misfolding in cultured cells. Here, we used immunocytochemistry and immunoprecipitation to demonstrate that TDP-43 or FUS-induced misfolded HuWtSOD1 can propagate from cell-to-cell via conditioned media, and seed cytotoxic misfolding of endogenous HuWtSOD1 in the recipient cells in a prion-like fashion. Knockdown of SOD1 using siRNA in recipient cells, or incubation of conditioned media with misfolded SOD1-specific antibodies, inhibits intercellular transmission, indicating that HuWtSOD1 is an obligate seed and substrate of propagated misfolding. In this system, intercellular spread of SOD1 misfolding is not accompanied by transmission of TDP-43 or FUS pathology. Our findings argue that pathological TDP-43 and FUS may exert motor neuron pathology in ALS through the initiation of propagated misfolding of SOD1.

PENINGKATAN AKTIVITAS ENZIM SOD SERUM DAN KELUHAN KESEHATAN TERHADAP PAPARAN ASAP PEMBAKARAN KAYU PADA PEKERJA

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Fitri Rokhmalia

2016-04-01

Full Text Available The chronic exposure of nitrogen dioxide and formaldehyde gases effected cellular influence enzymes activity SOD. This study aim to analyze the effect of exposure to nitrogen dioxide and formaldehyde gases against SOD and health complaint of worker in home industry petis. The method of this study was analytical observation with prospective longitudinal study with design study cross-week. Research sites of home industry petis and government Sekardangan office. The population was 2 population that were the workers of home industry petis and the administration worker of government sekardangan office in Desa Sekardangan Kabupaten Sidoarjo with some criteria that worked at male, not getting sickness asma and willing to participate in this study. Sample size had 24 persons that was taken by simple random sampling, 12 persons from each workers home industry petis and administratif worker in government sekardangan office. The analysis result shown that nitrogen dioxide and formaldehyde gases in air effected of enzymes SOD difference before and after exposure working group and not exposed (p<0,05 using paired t-test. The effect of nitrogen dioxide and formaldehyde gases in air effected enzymes activity SOD (p<0,05 using linear regression, but health complaint was effected by enzymes activity SOD (p<0,05 using logistic regression. The conclusion of this study was exposure of nitrogen dioxide and formaldehyde gases effect increasing of enzymes activity SOD of worker at home industry petis. Otherwise, there is effect of exposure of nitrogen dioxide and formaldehyde gases to health complaints. Keywords: nitrogen dioxide, formaldehyde gases, wood burning smoke, SOD, health complaints

Biological effects of CCS in the absence of SOD1 enzyme activation: implications for disease in a mouse model for ALS.

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Proescher, Jody B; Son, Marjatta; Elliott, Jeffrey L; Culotta, Valeria C

2008-06-15

The CCS copper chaperone is critical for maturation of Cu, Zn-superoxide dismutase (SOD1) through insertion of the copper co-factor and oxidization of an intra-subunit disulfide. The disulfide helps stabilize the SOD1 polypeptide, which can be particularly important in cases of amyotrophic lateral sclerosis (ALS) linked to misfolding of mutant SOD1. Surprisingly, however, over-expressed CCS was recently shown to greatly accelerate disease in a G93A SOD1 mouse model for ALS. Herein we show that disease in these G93A/CCS mice correlates with incomplete oxidation of the SOD1 disulfide. In the brain and spinal cord, CCS over-expression failed to enhance oxidation of the G93A SOD1 disulfide and if anything, effected some accumulation of disulfide-reduced SOD1. This effect was mirrored in culture with a C244,246S mutant of CCS that has the capacity to interact with SOD1 but can neither insert copper nor oxidize the disulfide. In spite of disulfide effects, there was no evidence for increased SOD1 aggregation. If anything, CCS over-expression prevented SOD1 misfolding in culture as monitored by detergent insolubility. This protection against SOD1 misfolding does not require SOD1 enzyme activation as the same effect was obtained with the C244,246S allele of CCS. In the G93A SOD1 mouse, CCS over-expression was likewise associated with a lack of obvious SOD1 misfolding marked by detergent insolubility. CCS over-expression accelerates SOD1-linked disease without the hallmarks of misfolding and aggregation seen in other mutant SOD1 models. These studies are the first to indicate biological effects of CCS in the absence of SOD1 enzymatic activation.

Studies on the Effect of 99Tc in colloid on enzyme activity(G.p.x ,G.S.T,SOD) before and after used diadzain

International Nuclear Information System (INIS)

Ahmood, A. M.; Alwan, I. F.; Abd Al-Kream, H. M.

2012-12-01

This study was conducted to determine the effect of Tin -colloid labeled with Technetium -99m on some enzyme activities of treated mice. it was noticed that an increase in the level of Glutathione-S- transferase (GST) glutathione peroxidase (Gpx), super oxide dismutase (SOD) and malonaldehyde (MDA) levels for treated (20) mice compared to the level of control mice Group (20). After That, the use diadzein extracted from soy been and linseed with concentrate of (0.250 mg/Kg), (0.500/Kg) on mice Group (20). It was found decreased activities GST, Gpx , SOD and MDA compared with 9 9mT c Tin-colloid Group without diadzein. (Author)

Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression

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Thanan, Raynoo [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan); Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Ma, Ning [Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 513-0293 (Japan); Iijima, Katsunori; Abe, Yasuhiko; Koike, Tomoyuki; Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Hospital, Sendai, Miyaki 980-8574 (Japan); Pinlaor, Somchai [Department of Parasitology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002 (Thailand); Hiraku, Yusuke; Oikawa, Shinji; Murata, Mariko [Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507 (Japan); Kawanishi, Shosuke, E-mail: kawanisi@suzuka-u.ac.jp [Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670 (Japan)

2012-05-04

Highlights: Black-Right-Pointing-Pointer Inflammation by Barrett's esophagus (BE) is a risk factor of its adenocarcinoma (BEA). Black-Right-Pointing-Pointer 8-Nitroguanine and 8-oxodG are inflammation-related DNA lesions. Black-Right-Pointing-Pointer DNA lesions and iNOS expression were higher in the order, BEA > BE > normal tissues. Black-Right-Pointing-Pointer Proton pump inhibitors suppress DNA damage by increasing Mn-SOD via Nrf2 activation. Black-Right-Pointing-Pointer DNA lesions can be useful biomarkers to predict risk of BEA in BE patients. -- Abstract: Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the risk of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2 Prime -deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-{kappa}B, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA > BE > normal tissues. iNOS expression was significantly higher in the order of BEA > BE > normal tissues, while Mn-SOD expression was significantly lower in the order of BEA < BE < normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6 months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and

Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1.

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Ghadge, Ghanashyam D; Pavlovic, John D; Koduvayur, Sujatha P; Kay, Brian K; Roos, Raymond P

2013-08-01

Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Overexpression of Cu-Zn SOD in Brucella abortus suppresses bacterial intracellular replication via down-regulation of Sar1 activity

Science.gov (United States)

Liu, Xiaofeng; Zhou, Mi; Yang, Yanling; Wu, Jing; Peng, Qisheng

2018-01-01

Brucella Cu-Zn superoxide dismutase (Cu-Zn SOD) is a periplasmic protein, and immunization of mice with recombinant Cu-Zn SOD protein confers protection against Brucella abortus infection. However, the role of Cu-Zn SOD during the process of Brucella infection remains unknown. Here, we report that Cu-Zn SOD is secreted into culture medium and is translocated into host cells independent of type IV secretion systems (T4SS). Furthermore, co-immunoprecipitation and immunofluorescence studies reveal that Brucella abortus Cu-Zn SOD interacts with the small GTPase Sar1. Overexpression of Cu-Zn SOD in Brucella abortus inhibits bacterial intracellular growth by abolishing Sar1 activity in a manner independent of reactive oxygen species (ROS) production. PMID:29515756

Restoration of wet dune slacks on the Dutch Wadden Sea islands : Recolonization after large-scale sod cutting

NARCIS (Netherlands)

Grootjans, AP; Everts, H; Bruin, K; Fresco, L; Grootjans, Ab P.

The effects of sod cutting were studied in a dune area on the Dutch Wadden Sea Island of Texel. Sod cutting was carried out in a range of different dune slacks in order to restore dune slack vegetation with many endangered Red List species. Sod cutting removed approximately 96% of the soil seed

Restoration of Wet Dune Slacks on the Dutch Wadden Sea Islands: Recolonization After Large-Scale Sod Cutting

NARCIS (Netherlands)

Grootjans, A.P.; Everts, H.; Bruin, K.; Fresco, L.

2011-01-01

The effects of sod cutting were studied in a dune area on the Dutch Wadden Sea Island of Texel. Sod cutting was carried out in a range of different dune slacks in order to restore dune slack vegetation with many endangered Red List species. Sod cutting removed approximately 96% of the soil seed

A Model of Oxidative Stress Management: Moderation of Carbohydrate Metabolizing Enzymes in SOD1-Null Drosophila melanogaster

Science.gov (United States)

Bernard, Kristine E.; Parkes, Tony L.; Merritt, Thomas J. S.

2011-01-01

The response to oxidative stress involves numerous genes and mutations in these genes often manifest in pleiotropic ways that presumably reflect perturbations in ROS-mediated physiology. The Drosophila melanogaster SOD1-null allele (cSODn108) is proposed to result in oxidative stress by preventing superoxide breakdown. In SOD1-null flies, oxidative stress management is thought to be reliant on the glutathione-dependent antioxidants that utilize NADPH to cycle between reduced and oxidized form. Previous studies suggest that SOD1-null Drosophila rely on lipid catabolism for energy rather than carbohydrate metabolism. We tested these connections by comparing the activity of carbohydrate metabolizing enzymes, lipid and triglyceride concentration, and steady state NADPH:NADP+ in SOD1-null and control transgenic rescue flies. We find a negative shift in the activity of carbohydrate metabolizing enzymes in SOD1-nulls and the NADP+-reducing enzymes were found to have significantly lower activity than the other enzymes assayed. Little evidence for the catabolism of lipids as preferential energy source was found, as the concentration of lipids and triglycerides were not significantly lower in SOD1-nulls compared with controls. Using a starvation assay to impact lipids and triglycerides, we found that lipids were indeed depleted in both genotypes when under starvation stress, suggesting that oxidative damage was not preventing the catabolism of lipids in SOD1-null flies. Remarkably, SOD1-nulls were also found to be relatively resistant to starvation. Age profiles of enzyme activity, triglyceride and lipid concentration indicates that the trends observed are consistent over the average lifespan of the SOD1-nulls. Based on our results, we propose a model of physiological response in which organisms under oxidative stress limit the production of ROS through the down-regulation of carbohydrate metabolism in order to moderate the products exiting the electron transport chain. PMID

Determining the Effect of Catechins on SOD1 Conformation and Aggregation by Ion Mobility Mass Spectrometry Combined with Optical Spectroscopy

Science.gov (United States)

Zhao, Bing; Zhuang, Xiaoyu; Pi, Zifeng; Liu, Shu; Liu, Zhiqiang; Song, Fengrui

2018-02-01

The aggregation of Cu,Zn-superoxide dismutase (SOD1) plays an important role in the etiology of amyotrophic lateral sclerosis (ALS). For the disruption of ALS progression, discovering new drugs or compounds that can prevent SOD1 aggregation is important. In this study, ESI-MS was used to investigate the interaction of catechins and SOD1. The noncovalent complex of catechins that interact with SOD1 was found and retained in the gas phase under native ESI-MS condition. The conformation changes of SOD1 after binding with catechins were also explored via traveling wave ion mobility (IM) spectrometry. Epigallocatechin gallate (EGCG) can stabilize SOD1 conformation against unfolding in three catechins. To further evaluate the efficacy of EGCG, we monitored the fluorescence changes of dimer E2,E2,-SOD1(apo-SOD1, E:empty) with and without ligands under denaturation conditions, and found that EGCG can inhibit apo-SOD1 aggregation. In addition, the circular dichroism spectra of the samples showed that EGCG can decrease the β-sheet content of SOD1, which can produce aggregates. These results indicated that orthogonal separation dimension in the gas-phase IM coupled with ESI-MS (ESI-IM-MS) can potentially provide insight into the interaction between SOD1 and small molecules. The advantage is that it dramatically decreases the analysis time. Meantime, optical spectroscopy techniques can be used to confirm ESI-IM-MS results. [Figure not available: see fulltext.

Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats

Science.gov (United States)

Satriotomo, Irawan; Grebe, Ashley M.

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model (SOD1G93A), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1G93A rats are not known. Moderate AIH-induced pLTF is normally elicited via cellular mechanisms that require the following: Gq-protein-coupled 5-HT2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that requires the following: Gs-protein-coupled adenosine 2A receptor activation, new TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male SOD1G93A rats and wild-type littermates, we investigated relative Q versus S pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3 kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats, moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although phrenic motor neuron numbers were decreased in end-stage SOD1G93A rats (∼30% survival; p phrenic motor neurons (p phrenic motor plasticity results from amplification of normal cellular mechanisms versus addition/substitution of alternative mechanisms. Greater understanding of mechanisms underlying phrenic motor plasticity in ALS may guide development of new therapies to preserve and/or restore breathing in ALS patients. PMID:28500219

Pengaruh variasi pemberian Snack bar ubi jalar kedelai hitam terhadap Kadar Superoksida Dismutase (SOD darah

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Fitriyono Ayustaningwarno

2014-12-01

Full Text Available Background: Snack bar from sweet potatoes and black soybeans is low GI, fat and calorie snack which haveantioxidant content, such as β-carotene, anthocyanin, isoflavone, and antioxidant activity, so can be an alternativesnack for patients with DM type 2. Antioxidants intake can prevent the oxidative stress that lead micro- and macrovascularcomplications in DM type 2. Antioxidant intake may preserve endogen antioxidant capacity, which is can bedetermined by analyzing SOD concentration.Objective: analyze effect variety of Snack bar from sweet potatoes and black soybeans consume to SOD concentration.Methods: experimental post-pretest research used 3 varieties of sweet potato’s color (red, yellow, and purpleinterventions. SOD concentration was analyzed by colorimetric. Statistic data was analyzed by dependent t-test andOne Way Anova.Results: No different between groups interventions Snack bar from purple, yellow or red sweet potatoes (p=0,122.Group with snack bar from purple sweet potatoes intervention has lowest SOD decreasing percentage among otherintervention groups.Conclusion: Consume snack bar form purple sweet potatoes and black soybeans can preserve SOD concentrationbetter than consume snack bar form yellow or red sweet potatoes and black soybeans

The decreasing effect of exogenous SOD on damage of mice irradiated with 5 Gy 60Co-γ rays

International Nuclear Information System (INIS)

Liu Fenju; Jiang Jiagui; Yi Jian

1999-01-01

The author presents a report on the activity of Superoxide Dismutase (SOD) and the content of LPO measured in tissue of Liver, heart and brain of mice irradiated by 60 Co-γ rays 5 Gy 1, 3, 5 and 8 days after irradiation respectively. After radiation exogenous SOD was immediately i.p. injected into mice. The variation of LPO content in the above mentioned three kinds of tissue has been observed. The result of the measurement shows that after radiation at a dose of 5 Gy 60 Co-γ rays, the LPO content and SOD activity of mice organs varied with radiation time. The LPO content varied earliest in liver, while the variation of LPO content in heart and cerebrum took place 8 days after radiation, meanwhile the activity of SOD in the tissues significantly decreased in comparison with that the control group (P<0.01). After injection with SOD, the LPO content and SOD activity of the organs irradiated for different time significantly decreased and increased in comparison with that in the control group. This shows that the enzyme of SOD is of significant anti-radiation effect

Superior PSZ-SOD Gap-Fill Process Integration Using Ultra-Low Dispensation Amount in STI for 28 nm NAND Flash Memory and Beyond

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Chun Chi Lai

2015-01-01

Full Text Available The gap-fill performance and process of perhydropolysilazane-based inorganic spin-on dielectric (PSZ-SOD film in shallow trench isolation (STI with the ultra-low dispensation amount of PSZ-SOD solution have been investigated in this study. A PSZ-SOD film process includes liner deposition, PSZ-SOD coating, and furnace curing. For liner deposition, hydrophilic property is required to improve the contact angle and gap-fill capability of PSZ-SOD coating. Prior to PSZ-SOD coating, the additional treatment on liner surface is beneficial for the fluidity of PSZ-SOD solution. The superior film thickness uniformity and gap-fill performance of PSZ-SOD film are achieved due to the improved fluidity of PSZ-SOD solution. Following that up, the low dispensation rate of PSZ-SOD solution leads to more PSZ-SOD filling in the trenches. After PSZ-SOD coating, high thermal curing process efficiently promotes PSZ-SOD film conversion into silicon oxide. Adequate conversion from PSZ-SOD into silicon oxide further increases the etching resistance inside the trenches. Integrating the above sequence of optimized factors, void-free gap-fill and well-controlled STI recess uniformity are achieved even when the PSZ-SOD solution dispensation volume is reduced 3 to 6 times compared with conventional condition for the 28 nm node NAND flash and beyond.

[The level of superoxide dismutase expression in primary and metastatic colorectal cancer cells in hypoxia and tissue normoxia].

Science.gov (United States)

Skrzycki, Michał; Czeczot, Hanna; Chrzanowska, Alicja; Otto-Ślusarczyk, Dagmara

2015-11-01

Superoxide oxidase (SOD) is a key antioxidant enzyme protecting cells against oxidative stress, which might induce cancerogenesis. In tumor cells SOD influences the level of the reactive oxygen species (ROS) allowing for survival and proliferation. High rate of cells proliferation in tumor leads to their temporary hypoxia due to lower rate of angiogenesis. Therefore during tumor development, cancer cells function in conditions of hypoxia or tissue normoxia. The aim of study was to evaluate of SOD isoenzymes (SOD1 and SOD2) expression level in cell lines of primary (SW 480) and metastatic (SW 620) colorectal cancer, cultured in hypoxia (1% oxygen), tissue normoxia (10% oxygen), and atmospheric normoxia (21% oxygen). Cells were cultured in MEM medium in different oxygen concentrations (1%, 10%, 21%) in hypoxic chamber with oxygenation regulator. The number of living cells in lines SW 480 and 620 was determined by trypan blue method. Expression of SOD1 and SOD2 at the mRNA level was determined by RT-PCR and PCR. In both studied cell lines (SW 480 and SW 620), the number of living cells (viability) was increased in hypoxia and atmospheric normoxia. The expression level of SOD1 and SOD2 in studied cell lines was different. The lowest level of expression of both SOD isoenzymes was observed in hypoxia. In conditions of atmospheric normoxia the expression level of SOD1 in SW480 cell line was increased, and similar in SW620 cell line comparing to tissue normoxia. Whereas the SOD2 expression level in atmospheric normoxia conditions in both cell lines was significantly increased. Observed differences were statistically significant (p ≤ 0,05). The profile of expression of SOD1 and SOD2 in cell lines SW480 and SW620 indicates differentiated response of tumor cells depending on access to oxygen. Low level of SOD isoenzymes expression in SW480 and SW620 cells in hypoxia indicates decreased production of ROS. Differences of SOD isoenzymes expression level in tissue normoxia

Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation

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Qi Min

2006-01-01

Full Text Available Abstract Detailed study of glial inflammation has been hindered by lack of cell culture systems that spontaneously demonstrate the "neuroinflammatory phenotype". Mice expressing a glycine → alanine substitution in cytosolic Cu, Zn-superoxide dismutase (G93A-SOD1 associated with familial amyotrophic lateral sclerosis (ALS demonstrate age-dependent neuroinflammation associated with broad-spectrum cytokine, eicosanoid and oxidant production. In order to more precisely study the cellular mechanisms underlying glial activation in the G93A-SOD1 mouse, primary astrocytes were cultured from 7 day mouse neonates. At this age, G93A-SOD1 mice demonstrated no in vivo hallmarks of neuroinflammation. Nonetheless astrocytes cultured from G93A-SOD1 (but not wild-type human SOD1-expressing transgenic mouse pups demonstrated a significant elevation in either the basal or the tumor necrosis alpha (TNFα-stimulated levels of proinflammatory eicosanoids prostaglandin E2 (PGE2 and leukotriene B4 (LTB4; inducible nitric oxide synthase (iNOS and •NO (indexed by nitrite release into the culture medium; and protein carbonyl products. Specific cytokine- and TNFα death-receptor-associated components were similarly upregulated in cultured G93A-SOD1 cells as assessed by multiprobe ribonuclease protection assays (RPAs for their mRNA transcripts. Thus, endogenous glial expression of G93A-SOD1 produces a metastable condition in which glia are more prone to enter an activated neuroinflammatory state associated with broad-spectrum increased production of paracrine-acting substances. These findings support a role for active glial involvement in ALS and may provide a useful cell culture tool for the study of glial inflammation.

Reactive oxygen species on bone mineral density and mechanics in Cu,Zn superoxide dismutase (Sod1) knockout mice

International Nuclear Information System (INIS)

Smietana, Michael J.; Arruda, Ellen M.; Faulkner, John A.; Brooks, Susan V.; Larkin, Lisa M.

2010-01-01

Research highlights: → Reactive oxygen species (ROS) are considered to be a factor in the onset of a number of age-associated conditions, including loss of BMD. → Cu,Zn-superoxide dismutase (Sod1) deficient mice have increased ROS, reduced bone mineral density, decreased bending stiffness, and decreased strength compared to WT controls. → Increased ROS caused by the deficiency of Sod1, may be responsible for the changes in BMD and bone mechanics and therefore represent an appropriate model for studying mechanisms of age-associated bone loss. -- Abstract: Reactive oxygen species (ROS) play a role in a number of degenerative conditions including osteoporosis. Mice deficient in Cu,Zn-superoxide dismutase (Sod1) (Sod1 -/- mice) have elevated oxidative stress and decreased muscle mass and strength compared to wild-type mice (WT) and appear to have an accelerated muscular aging phenotype. Thus, Sod1 -/- mice may be a good model for evaluating the effects of free radical generation on diseases associated with aging. In this experiment, we tested the hypothesis that the structural integrity of bone as measured by bending stiffness (EI; N/mm 2 ) and strength (MPa) is diminished in Sod1 -/- compared to WT mice. Femurs were obtained from male and female WT and Sod1 -/- mice at 8 months of age and three-point bending tests were used to determine bending stiffness and strength. Bones were also analyzed for bone mineral density (BMD; mg/cc) using micro-computed tomography. Femurs were approximately equal in length across all groups, and there were no significant differences in BMD or EI with respect to gender in either genotype. Although male and female mice demonstrated similar properties within each genotype, Sod1 -/- mice exhibited lower BMD and EI of femurs from both males and females compared with gender matched WT mice. Strength of femurs was also lower in Sod1 -/- mice compared to WT as well as between genders. These data indicate that increased oxidative stress

Unraveling ALS due to SOD1 mutation through the combination of brain and cervical cord MRI.

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Agosta, Federica; Spinelli, Edoardo Gioele; Marjanovic, Ivan V; Stevic, Zorica; Pagani, Elisabetta; Valsasina, Paola; Salak-Djokic, Biljana; Jankovic, Milena; Lavrnic, Dragana; Kostic, Vladimir S; Filippi, Massimo

2018-02-20

To explore structural and functional changes of the brain and cervical cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the superoxide dismutase ( SOD1 ) gene compared with sporadic ALS. Twenty patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state functional connectivity were performed. Patients with ALS also underwent cervical cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio (MTR). Patients with SOD1 ALS showed longer disease duration and slower rate of functional decline relative to those with sporadic ALS. No cortical thickness abnormalities were found in patients with ALS compared with controls. Fractional anisotropy showed that sporadic ALS patients had significant CST damage relative to both healthy controls ( p = 0.001-0.02) and SOD1-related ALS ( p = 0.05), although the latter showed alterations that were intermediate between controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in the sensorimotor network was observed in patients with sporadic ALS relative to controls. Conversely, patients with SOD1 ALS showed lower cord cross-sectional area along the whole cervical cord relative to those with sporadic ALS ( p ALS showed cervical cord atrophy relative to those with sporadic ALS and a relative preservation of brain motor structural and functional networks. Neurodegeneration in SOD1 ALS is likely to occur primarily in the spinal cord. An objective and accurate estimate of spinal cord damage has potential in the future assessment of preventive SOD1 ALS therapies. © 2018 American Academy of Neurology.

Comparative Analyses of Cu-Zn Superoxide Dismutase (SOD1) and Thioredoxin Reductase (TrxR) at the mRNA Level between Apis mellifera L. and Apis cerana F. (Hymenoptera: Apidae) Under Stress Conditions.

Science.gov (United States)

Koo, Hyun-Na; Lee, Soon-Gyu; Yun, Seung-Hwan; Kim, Hyun Kyung; Choi, Yong Soo; Kim, Gil-Hah

2016-01-01

This study compared stress-induced expression of Cu-Zn superoxide dismutase (SOD1) and thioredoxin reductase (TrxR) genes in the European honeybee Apis mellifera L. and Asian honeybee Apis cerana F. Expression of both SOD1 and TrxR rapidly increased up to 5 h after exposure to cold (4 °C) or heat (37 °C) treatment and then gradually decreased, with a stronger effect induced by cold stress in A. mellifera compared with A. cerana. Injection of stress-inducing substances (methyl viologen, [MV] and H2O2) also increased SOD1 and TrxR expression in both A. mellifera and A. cerana, and this effect was more pronounced with MV than H2O2. Additionally, we heterologously expressed the A. mellifera and A. cerana SOD1 and TrxR proteins in an Escherichia coli expression system, and detection by SDS-PAGE, confirmed by Western blotting using anti-His tag antibodies, revealed bands at 16 and 60 kDa, respectively. Our results show that the expression patterns of SOD1 and TrxR differ between A. mellifera and A. cerana under conditions of low or high temperature as well as oxidative stress. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

Structural and biophysical properties of metal-free pathogenic SOD1 mutants A4V and G93A

Energy Technology Data Exchange (ETDEWEB)

Galaleldeen, Ahmad; Strange, Richard W.; Whitson, Lisa J.; Antonyuk, Svetlana V.; Narayana, Narendra; Taylor, Alexander B.; Schuermann, Jonathan P.; Holloway, Stephen P.; Hasnain, S.Samar; Hart, P. John; (Texas-HSC); (Liverpool)

2010-07-19

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease characterized by the destruction of motor neurons in the spinal cord and brain. A subset of ALS cases are linked to dominant mutations in copper-zinc superoxide dismutase (SOD1). The pathogenic SOD1 variants A4V and G93A have been the foci of multiple studies aimed at understanding the molecular basis for SOD1-linked ALS. The A4V variant is responsible for the majority of familial ALS cases in North America, causing rapidly progressing paralysis once symptoms begin and the G93A SOD1 variant is overexpressed in often studied murine models of the disease. Here we report the three-dimensional structures of metal-free A4V and of metal-bound and metal-free G93A SOD1. In the metal-free structures, the metal-binding loop elements are observed to be severely disordered, suggesting that these variants may share mechanisms of aggregation proposed previously for other pathogenic SOD1 proteins.

REGENERASI DAN PERBANYAKAN RUMPUT LAUT Kappaphycus alvarezii HASIL TRANSFORMASI GEN SUPEROKSIDA DISMUTASE (MaSOD

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Emma Suryati

2017-01-01

Full Text Available Transformasi gen superoxide dismutase (MaSOD pada rumput laut Kappaphycus alvarezii menggunakan Agrobacterium tumefacient telah dilakukan secara in vitro. Transformasi gen MaSOD ke dalam genom rumput laut diharapkan dapat mengurangi cekaman oksidatif terutama yang disebabkan oleh perubahan suhu, salinitas, dan cemaran logam di perairan. Penelitian ini bertujuan untuk regenerasi rumput laut hasil introduksi gen MaSOD dan non-transgenik pada labu kultur. Regenerasi dan perbanyakan rumput laut hasil transformasi gen MaSOD dilakukan di laboratorium pada labu kultur yang diletakkan dalam “culture chamber” yang dilengkapi dengan aerasi menggunakan media kultur yang diperkaya dengan pupuk PES, Grund, Conwy, dan SSW sebagai kontrol, salinitas 20, 25, 30, 35, dan 40 g/L, pH 4, 5, 6, 7, dan 8. Intensitas cahaya antara 500-2.000 lux dengan fotoperiode terang dan gelap 8:16; 12:12; dan 16:8. Untuk merangsang pertumbuhan eksplan dilakukan pemeliharaan dengan penambahan hormon tumbuh IAA dan BAP dengan perbandingan 1:1, 1:2, dan 2:1. Penelitian dilakukan secara bertahap. Evaluasi transgenik dilakukan menggunakan teknik PCR. Hasil penelitian memperlihatkan bahwa sintasan yang paling tinggi diperoleh menggunakan media PES (94%, salinitas 30 g/L (90%, pH 7 (96%, intensitas cahaya pada 1.500 lux (80%, fotoperiode 12:12 (84%, komposisi ZPT dengan campuran IAA dan BAP dengan perbandingan 2:1. Hasil analisis PCR memperlihatkan K. alvarezii transgenik putatif mengandung transgen MaSOD sebanyak 78% dari hasil transformasi. Superoxide dismutase transformation (MaSOD gene of seaweed Kappaphycus alvarezii mediated by Agrobacterium tumefacient has been successfully done in vitro. MaSOD genes introduced into the seaweed genome is expected to reduce oxidative stress caused by environmental conditions such as changes in temperature, salinity and metal contamination of the water. This study aimed to regenerate both the MaSOD transformed seaweed and non-transgenic in a

Knocking down metabotropic glutamate receptor 1 improves survival and disease progression in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis.

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Milanese, Marco; Giribaldi, Francesco; Melone, Marcello; Bonifacino, Tiziana; Musante, Ilaria; Carminati, Enrico; Rossi, Pia I A; Vergani, Laura; Voci, Adriana; Conti, Fiorenzo; Puliti, Aldamaria; Bonanno, Giambattista

2014-04-01

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease reflecting degeneration of upper and lower motoneurons (MNs). The cause of ALS and the mechanisms of neuronal death are still largely obscure, thus impairing the establishment of efficacious therapies. Glutamate (Glu)-mediated excitotoxicity plays a major role in MN degeneration in ALS. We recently demonstrated that the activation of Group I metabotropic Glu autoreceptors, belonging to both type 1 and type 5 receptors (mGluR1 and mGluR5), at glutamatergic spinal cord nerve terminals, produces excessive Glu release in mice over-expressing human superoxide-dismutase carrying the G93A point mutation (SOD1(G93A)), a widely used animal model of human ALS. To establish whether these receptors are implicated in ALS, we generated mice expressing half dosage of mGluR1 in the SOD1(G93A) background (SOD1(G93A)Grm1(crv4/+)), by crossing the SOD1(G93A) mutant mouse with the Grm1(crv4/+) mouse, lacking mGluR1 because of a spontaneous recessive mutation. SOD1(G93A)Grm1(crv4/+) mice showed prolonged survival probability, delayed pathology onset, slower disease progression and improved motor performances compared to SOD1(G93A) mice. These effects were associated to reduction of mGluR5 expression, enhanced number of MNs, decreased astrocyte and microglia activation, normalization of metallothionein and catalase mRNA expression, reduced mitochondrial damage, and decrease of abnormal Glu release in spinal cord of SOD1(G93A)Grm1(crv4/+)compared to SOD1(G93A) mice. These results demonstrate that a lower constitutive level of mGluR1 has a significant positive impact on mice with experimental ALS, thus providing the rationale for future pharmacological approaches to ALS by selectively blocking Group I metabotropic Glu receptors. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Enhanced tethered-flight duration and locomotor activity by overexpression of the human gene SOD1 in Drosophila motorneurons

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Agavni Petrosyan

2015-03-01

Full Text Available Mutation of the human gene superoxide dismutase (hSOD1 is associated with the fatal neurodegenerative disease familial amyotrophic lateral sclerosis (Lou Gehrig’s disease. Selective overexpression of hSOD1 in Drosophila motorneurons increases lifespan to 140% of normal. The current study was designed to determine resistance to lifespan decline and failure of sensorimotor functions by overexpressing hSOD1 in Drosophila‘s motorneurons. First, we measured the ability to maintain continuous flight and wingbeat frequency (WBF as a function of age (5 to 50 days. Flies overexpressing hSOD1 under the D42-GAL4 activator were able to sustain flight significantly longer than controls, with the largest effect observed in the middle stages of life. The hSOD1-expressed line also had, on average, slower wingbeat frequencies in late, but not early life relative to age-matched controls. Second, we examined locomotor (exploratory walking behavior in late life when flies had lost the ability to fly (age ≥ 60 d. hSOD1-expressed flies showed significantly more robust walking activity relative to controls. Findings show patterns of functional decline dissimilar to those reported for other life-extended lines, and suggest that the hSOD1 gene not only delays death but enhances sensorimotor abilities critical to survival even in late life.

Species-specific differences in peroxisome proliferation, catalase, and SOD2 upregulation as well as toxicity in human, mouse, and rat hepatoma cells induced by the explosive and environmental pollutant 2,4,6-trinitrotoluene.

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Naumenko, Ekaterina Anatolevna; Ahlemeyer, Barbara; Baumgart-Vogt, Eveline

2017-03-01

2,4,6-Trinitrotoluene (TNT) has been widely used as an explosive substance and its toxicity is still of interest as it persisted in polluted areas. TNT is metabolized in hepatocytes which are prone to its toxicity. Since analysis of the human liver or hepatocytes is restricted due to ethical reasons, we investigated the effects of TNT on cell viability, reactive oxygen species (ROS) production, peroxisome proliferation, and antioxidative enzymes in human (HepG2), mouse (Hepa 1-6), and rat (H4IIEC3) hepatoma cell lines. Under control conditions, hepatoma cells of all three species were highly comparable exhibiting identical proliferation rates and distribution of their cell cycle phases. However, we found strong differences in TNT toxicity with the lowest IC 50 values (highest cell death rate) for rat cells, whereas human and mouse cells were three to sevenfold less sensitive. Moreover, a strong decrease in cellular dehydrogenase activity (MTT assay) and increased ROS levels were noted. TNT caused peroxisome proliferation with rat hepatoma cells being most responsive followed by those from mouse and human. Under control conditions, rat cells contained fivefold higher peroxisomal catalase and mitochondrial SOD2 activities and a twofold higher capacity to reduce MTT than human and mouse cells. TNT treatment caused an increase in catalase and SOD2 mRNA and protein levels in human and mouse, but not in rat cells. Similarly, human and mouse cells upregulated SOD2 activity, whereas rat cells failed therein. We conclude that TNT induced oxidative stress, peroxisome proliferation and mitochondrial damage which are highest in rat cells rendering them most susceptible toward TNT. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 989-1006, 2017. © 2016 Wiley Periodicals, Inc.

Imidazole-containing phthalazine derivatives inhibit Fe-SOD performance in Leishmania species and are active in vitro against visceral and mucosal leishmaniasis.

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Sánchez-Moreno, M; Gómez-Contreras, F; Navarro, P; Marín, C; Ramírez-Macías, I; Rosales, M J; Campayo, L; Cano, C; Sanz, A M; Yunta, M J R

2015-07-01

The in vitro leishmanicidal activity of a series of imidazole-containing phthalazine derivatives 1-4 was tested on Leishmania infantum, Leishmania braziliensis and Leishmania donovani parasites, and their cytotoxicity on J774·2 macrophage cells was also measured. All compounds tested showed selectivity indexes higher than that of the reference drug glucantime for the three Leishmania species, and the less bulky monoalkylamino substituted derivatives 2 and 4 were clearly more effective than their bisalkylamino substituted counterparts 1 and 3. Both infection rate measures and ultrastructural alterations studies confirmed that 2 and 4 were highly leishmanicidal and induced extensive parasite cell damage. Modifications to the excretion products of parasites treated with 2 and 4 were also consistent with substantial cytoplasmic alterations. On the other hand, the most active compounds 2 and 4 were potent inhibitors of iron superoxide dismutase enzyme (Fe-SOD) in the three species considered, whereas their impact on human CuZn-SOD was low. Molecular modelling suggests that 2 and 4 could deactivate Fe-SOD due to a sterically favoured enhanced ability to interact with the H-bonding net that supports the antioxidant features of the enzyme.

FUS and TARDBP but not SOD1 interact in genetic models of amyotrophic lateral sclerosis.

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Kabashi, Edor; Bercier, Valérie; Lissouba, Alexandra; Liao, Meijiang; Brustein, Edna; Rouleau, Guy A; Drapeau, Pierre

2011-08-01

Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS). Recently, mutations in the Fused in sarcoma gene (FUS) were identified in familial (FALS) ALS cases and sporadic (SALS) patients. Similarly to TDP-43 (coded by TARDBP gene), FUS is an RNA binding protein. Using the zebrafish (Danio rerio), we examined the consequences of expressing human wild-type (WT) FUS and three ALS-related mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALS-related FUS mutations, R521H and R521C, unlike S57Δ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C) and FUS (R521H) or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A). Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1.

FUS and TARDBP but not SOD1 interact in genetic models of amyotrophic lateral sclerosis.

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Edor Kabashi

2011-08-01

Full Text Available Mutations in the SOD1 and TARDBP genes have been commonly identified in Amyotrophic Lateral Sclerosis (ALS. Recently, mutations in the Fused in sarcoma gene (FUS were identified in familial (FALS ALS cases and sporadic (SALS patients. Similarly to TDP-43 (coded by TARDBP gene, FUS is an RNA binding protein. Using the zebrafish (Danio rerio, we examined the consequences of expressing human wild-type (WT FUS and three ALS-related mutations, as well as their interactions with TARDBP and SOD1. Knockdown of zebrafish Fus yielded a motor phenotype that could be rescued upon co-expression of wild-type human FUS. In contrast, the two most frequent ALS-related FUS mutations, R521H and R521C, unlike S57Δ, failed to rescue the knockdown phenotype, indicating loss of function. The R521H mutation caused a toxic gain of function when expressed alone, similar to the phenotype observed upon knockdown of zebrafish Fus. This phenotype was not aggravated by co-expression of both mutant human TARDBP (G348C and FUS (R521H or by knockdown of both zebrafish Tardbp and Fus, consistent with a common pathogenic mechanism. We also observed that WT FUS rescued the Tardbp knockdown phenotype, but not vice versa, suggesting that TARDBP acts upstream of FUS in this pathway. In addition we observed that WT SOD1 failed to rescue the phenotype observed upon overexpression of mutant TARDBP or FUS or upon knockdown of Tardbp or Fus; similarly, WT TARDBP or FUS also failed to rescue the phenotype induced by mutant SOD1 (G93A. Finally, overexpression of mutant SOD1 exacerbated the motor phenotype caused by overexpression of mutant FUS. Together our results indicate that TARDBP and FUS act in a pathogenic pathway that is independent of SOD1.

Peripheral motor axons of SOD1(G127X) mutant mice are susceptible to activity-dependent degeneration

DEFF Research Database (Denmark)

Alvarez Herrero, Susana; Calin, A; Graffmo, K S

2013-01-01

-onset, fast-progression SOD1(G127X) mouse model of amyotrophic lateral sclerosis to long-lasting, high-frequency repetitive activity. Tibial nerves were stimulated at ankle in 7 to 8-month-old SOD1(G127X) mice when they were clinically indistinguishable from wild-type (WT) mice. The evoked compound muscle......-concentrations. It is possible that in SOD1(G127X) there is inadequate energy-dependent Na(+)/K(+) pumping, which may lead to a lethal Na(+) overload....

Structure directing agents induced morphology evolution and phase transition from indium-based rho- to sod-ZMOF

KAUST Repository

Shi, Yanshu; Cairns, Amy; Liu, Yunling; Belmabkhout, Youssef; Cai, Xuechao; Pang, Maolin; Eddaoudi, Mohamed

2017-01-01

In this report, indium-based rho-and sod-ZMOFs with different morphologies and sizes were prepared. Simultaneous morphology evolution and phase transformation from porous rho-to nonporous sod-ZMOFs were reported for the first time by simply varying the concentration of structure directing agents (SDAs).

Structure directing agents induced morphology evolution and phase transition from indium-based rho- to sod-ZMOF

KAUST Repository

Shi, Yanshu

2017-06-23

In this report, indium-based rho-and sod-ZMOFs with different morphologies and sizes were prepared. Simultaneous morphology evolution and phase transformation from porous rho-to nonporous sod-ZMOFs were reported for the first time by simply varying the concentration of structure directing agents (SDAs).

The effect of amyotrophic lateral sclerosis-linked exogenous SOD1-G93A on electrophysiological properties and intracellular calcium in cultured rat astrocytes.

Science.gov (United States)

Milošević, Milena; Bataveljić, Danijela; Nikolić, Ljiljana; Bijelić, Dunja; Andjus, Pavle

2016-01-01

Over 150 mutations in the SOD1 gene that encodes Cu/Zn superoxide dismutase (SOD1) cause 20-25% of familial ALS, albeit without a known gain-of-function mechanism. ALS is also non-cell-autonomous, the interactions between motor neurons and their glial neighbours being implicated in disease progression. The aim here was to investigate the biophysical effects of the exogenous human mutant SOD1-G93A on rat astrocytes in culture. Primary cortical astrocyte cultures were treated with recombinant human apo- mSOD1-G93A vs. wild-type control (wtSOD1) and recorded by patch-clamp and calcium imaging. Results showed that exogenous mSOD1 as well as wtSOD1 induced a decrease of membrane resistance, the effect being persistent (up to 13 min) only for the mutant form. Similarly, whole-cell inward currents in astrocytes were augmented by both wt and mSOD1, but the effect was twice larger and only progressed continuously for the latter. Both forms of SOD1 also induced a rise in intracellular Ca(2+) activity, the effect being dependent on external Ca(2+) and again only persisted with mSOD1, becoming significantly different from wtSOD1 only at longer times (14 min). In conclusion, this study points to membrane permeability and Ca(2+) signalling as processes affected by SOD1-G93A that presents the humoral factor triggering the role of astrocytes in ALS pathophysiology.

Effects of Higher and Lower Level Writing-To-Learn Assignments on Higher and Lower Level Examination Questions

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Nevid, Jeffrey S.; Ambrose, Michael A.; Pyun, Yea Seul

2017-01-01

Our study examined whether brief writing-to-learn assignments linked to lower and higher levels in Bloom's taxonomy affected performance differentially on examination performance in assessing these skill levels. Using a quasi-random design, 91 undergraduate students in an introductory psychology class completed eight lower level and eight higher…

Comparative evaluation of the effect of rock phosphate and monoammonium phosphate on plant P: Nutrition in Sod-podzolic and peat soils

International Nuclear Information System (INIS)

Bogdevitch, I.; Tarasiuk, S.; Putyatin, Yu.; Seraya, T.

2002-01-01

The direct application of finely ground rock phosphate (RP) imported from Russia has been suggested as an alternative to the almost twice more expensive water-soluble monoammonium phosphate (MAP) on acid (moderately limed) Sod-podzolic and peat soils. A pot experiment was conducted in 1997-1998 for a comparative evaluation of P availability from RP and MAP using the 32 P isotope dilution technique. The lupine was grown on Sod-podzolic silty clay loam soil with pH 6.0 and a medium level of available P. Ryegrass plants were grown on peat soil with pH 4.9 and a low level of native soil P fertility. Application of RP and MAP at a rate of 40 mg P/kg soil supplied similar moderate mount of P to lupine plants. The Pdff values, i.e. the fractions of P in the plants derived from the applied RP and MAP, were 7.4 and 8.4%, respectively. The application of the same P fertilizers to the peat soil had different effects on P nutrition of ryegrass plants. The Pdff values were 14.9% for RP and 22.1% for MAP. It may be concluded that for most annual crops water-soluble P forms such as MAP should be preferred. Direct application of RP is recommended for plants with an adequate rhizosphere ability to utilize P, such as lupine on acid Sod-podzolic silty clay loam soils (pH 137 Cs on contaminated, moderately limed Sod-podzolic silty clay loam and peat soils. These soils are widely spread in the radioactive contaminated area of Belarus after the Chernobyl accident. Direct application of RP may be one of the effective countermeasures for the decrease of 137 Cs transfer from the contaminated acid soils to crop production. (author)

Cu,Zn-superoxide dismutase is lower and copper chaperone CCS is higher in erythrocytes of copper-deficient rats and mice.

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West, Elizabeth C; Prohaska, Joseph R

2004-09-01

Discovery of a sensitive blood biochemical marker of copper status would be valuable for assessing marginal copper intakes. Rodent models were used to investigate whether erythrocyte concentrations of copper,zinc-superoxide dismutase (SOD), and the copper metallochaperone for SOD (CCS) were sensitive to dietary copper changes. Several models of copper deficiency were studied in postweanling male Holtzman rats, male Swiss Webster mice offspring, and both rat and mouse dams. Treatment resulted in variable but significantly altered copper status as evaluated by the presence of anemia, and lower liver copper and higher liver iron concentrations in copper-deficient compared with copper-adequate animals. Associated with this copper deficiency were consistent reductions in immunoreactive SOD and robust enhancements in CCS. In most cases, the ratio of CCS:SOD was several-fold higher in red blood cell extracts from copper-deficient compared with copper-adequate rodents. Determination of red cell CCS:SOD may be useful for assessing copper status of humans.

A 50 bp deletion in the SOD1 promoter lowers enzyme expression but is not associated with ALS in Sweden.

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Ingre, Caroline; Wuolikainen, Anna; Marklund, Stefan L; Birve, Anna; Press, Rayomand; Andersen, Peter M

2016-01-01

Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50 bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50 bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50 bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50 bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population.

Screening of a clinically and biochemically diagnosed SOD patient ...

African Journals Online (AJOL)

The disease follows an autosomal recessive pattern of inheritance and causes deficiency in the activity of sulfite oxidase, an enzyme that normally catalyzes conversion of sulfite to sulfate. Aim of the study: SOD is an underdiagnosed disorder and its diagnosis can be difficult in young infants as early clinical features and ...

A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1

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Larmet Yves

2011-04-01

Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. ALS patients, as well as animal models such as mice overexpressing mutant SOD1s, are characterized by increased energy expenditure. In mice, this hypermetabolism leads to energy deficit and precipitates motor neuron degeneration. Recent studies have shown that mutations in the gene encoding the dynein heavy chain protein are able to extend lifespan of mutant SOD1 mice. It remains unknown whether the protection offered by these dynein mutations relies on a compensation of energy metabolism defects. Results SOD1(G93A mice were crossbred with mice harboring the dynein mutant Cramping allele (Cra/+ mice. Dynein mutation increased adipose stores in compound transgenic mice through increasing carbohydrate oxidation and sparing lipids. Metabolic changes that occurred in double transgenic mice were accompanied by the normalization of the expression of key mRNAs in the white adipose tissue and liver. Furthermore, Dynein Cra mutation rescued decreased post-prandial plasma triglycerides and decreased non esterified fatty acids upon fasting. In SOD1(G93A mice, the dynein Cra mutation led to increased expression of IGF-1 in the liver, increased systemic IGF-1 and, most importantly, to increased spinal IGF-1 levels that are potentially neuroprotective. Conclusions These findings suggest that the protection against SOD1(G93A offered by the Cramping mutation in the dynein gene is, at least partially, mediated by a reversal in energy deficit and increased IGF-1 availability to motor neurons.

Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

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Javier Sábado

2014-01-01

Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs. Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1 gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1G93A mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

ApoSOD1 lacking dismutase activity neuroprotects motor neurons exposed to beta-methylamino-L-alanine through the Ca2+/Akt/ERK1/2 prosurvival pathway

Science.gov (United States)

Petrozziello, Tiziana; Secondo, Agnese; Tedeschi, Valentina; Esposito, Alba; Sisalli, MariaJosè; Scorziello, Antonella; Di Renzo, Gianfranco; Annunziato, Lucio

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a severe human adult-onset neurodegenerative disease affecting lower and upper motor neurons. In >20% of cases, the familial form of ALS is caused by mutations in the gene encoding Cu,Zn-superoxide dismutase (SOD1). Interestingly, administration of wild-type SOD1 to SOD1G93A transgenic rats ameliorates motor symptoms through an unknown mechanism. Here we investigated whether the neuroprotective effects of SOD1 are due to the Ca2+-dependent activation of such prosurvival signaling pathway and not to its catalytic activity. To this aim, we also examined the mechanism of neuroprotective action of ApoSOD1, the metal-depleted state of SOD1 that lacks dismutase activity, in differentiated motor neuron-like NSC-34 cells and in primary motor neurons exposed to the cycad neurotoxin beta-methylamino-L-alanine (L-BMAA). Preincubation of ApoSOD1 and SOD1, but not of human recombinant SOD1G93A, prevented cell death in motor neurons exposed to L-BMAA. Moreover, ApoSOD1 elicited ERK1/2 and Akt phosphorylation in motor neurons through an early increase of intracellular Ca2+ concentration ([Ca2+]i). Accordingly, inhibition of ERK1/2 by siMEK1 and PD98059 counteracted ApoSOD1- and SOD1-induced neuroprotection. Similarly, transfection of the dominant-negative form of Akt in NSC-34 motor neurons and treatment with the selective PI3K inhibitor LY294002 prevented ApoSOD1- and SOD1-mediated neuroprotective effects in L-BMAA-treated motor neurons. Furthermore, ApoSOD1 and SOD1 prevented the expression of the two markers of L-BMAA-induced ER stress GRP78 and caspase-12. Collectively, our data indicate that ApoSOD1, which is devoid of any catalytic dismutase activity, exerts a neuroprotective effect through an early activation of Ca2+/Akt/ERK1/2 pro-survival pathway that, in turn, prevents ER stress in a neurotoxic model of ALS. PMID:28085149

APP/SOD1 overexpressing mice present reduced neuropathic pain sensitivity.

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Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Olakowska, Edyta; Lewin-Kowalik, Joanna; London, Jacqueline

2011-07-15

There are controversies regarding pain expression in mentally disabled people, including Down syndrome patients. The aim of this study was to examine neuropathic pain-related behavior and peripheral nerve regeneration in mouse model of Down syndrome. Sciatic nerves of double transgenic mice, overexpressing both amyloid precursor protein (APP) and Cu/Zn superoxide dismutase (SOD1) genes, and FVB/N wild type mice were transected and immediately resutured. Evaluation of autotomy and functional recovery was carried out during 4-week follow-up. We found markedly less severe autotomy in transgenic animals, although the onset of autotomy was significantly delayed in control mice. Interestingly, neuroma formation at the injury site was significantly more prominent in transgenic animals. Sciatic function index outcome was better in transgenic mice than in wild-type group. Histological evaluation revealed no statistically significant differences in the number of GAP-43-positive growth cones and macrophages in the distal stump of the transected nerve between groups. However, in transgenic animals, the regenerating axons were arranged more chaotically. The number of Schwann cells in the distal stump of the transected nerves was significantly lower in transgenic mice. The number of surviving motoneurons was markedly decreased in transgenic group. We measured also the atrophy of denervated muscles and found it decreased in APP/SOD1 overexpressing mice. Taken together, in this model of Down syndrome, we observed increased neuroma formation and decreased autotomy after peripheral nerve injury. Our findings suggest that APP/SOD1 overexpressing mice are less sensitive for neuropathic pain associated with neuroma. Copyright © 2011 Elsevier Inc. All rights reserved.

Radio-sensitivity of the cells from amyotrophic lateral sclerosis model mice transfected with human mutant SOD1

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Wate, Reika; Ito, Hidefumi; Kusaka, Hirofumi; Takahashi, Sentaro; Kubota, Yoshihisa; Suetomi, Katsutoshi; Sato, Hiroshi; Okayasu, Ryuichi

2005-01-01

In order to clarify the possible involvement of oxidative damage induced by ionizing radiation in the onset and/or progression of familial amyotrophic lateral sclerosis (ALS), we studied radio-sensitivity in primary cells derived from ALS model mice expressing human mutant Cu/Zn superoxide dismutase (SOD1). The primary mouse cells expressed both mouse and the mutant human SOD1. The cell survival of the transgenic mice (with mutant SOD1), determined by counting cell numbers at a scheduled time after X-irradiation, is very similar to that of cells from wild type animals. The induction and repair of DNA damage in the transgenic cells, measured by single cell gel electrophoresis and pulsed field gel electrophoresis, are also similar to those of wild type cells. These results indicate that the human mutant SOD1 gene does not seem to contribute to the alteration of radio-sensitivity, at least in the fibroblastic cells used here. Although it is necessary to consider the difference in cell types between fibroblastic and neuronal cells, the present results may suggest that ionizing radiation is not primarily responsible for the onset of familial ALS with the SOD1 mutation, and that the excess risks are probably not a concern for radiation diagnosis and therapy in familial ALS patients. (author)

Short repeats in the heme oxygenase 1 gene promoter is associated with increased levels of inflammation, ferritin and higher risk of type-2 diabetes mellitus.

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Andrews, Mónica; Leiva, Elba; Arredondo-Olguín, Miguel

2016-09-01

We evaluated the relationship between the HO1 genotype, ferritin levels and the risk of type-2 diabetes and inflammation. Eight hundred thirty-five individuals were evaluated and classified according to their nutritional status and the presence of type-2 diabetes: 153 overweight (OW); 62 obese (OB); 55 type-2 diabetes mellitus (DM); 202 OWDM; 239 OBDM and 124 controls (C). We studied biochemical (glycemia, insulin, lipid profile, liver enzyme, creatinine, hsCRP), hematological (hemoglobin, free erythrocyte protoporphyrin, transferrin receptor and serum Fe and ferritin) and oxidative stress (SOD, GHS and TBARS) parameters. We determined heme oxygenase activity and the (GT)n polymorphism in its gene promoter. Individuals with diabetes, independent of nutritional status, showed high levels of ferritin and HO activity compared to control subjects. Allelic frequency was not different between the groups (Chi(2), NS) however, genotypes were different (Chi(2), P1). The SS (short-short) genotype was higher in all DM individuals compared to controls and MM was higher in controls. SM (short-medium) genotype was an independent risk factor for DM in logistic regression analysis. We observed high risk for type-2 diabetes mellitus in the presence of SM genotype and high levels of ferritin (OR adjusted: 2.7; 1.9-3.6; p1; compared to control group). It was also significantly related to inflammation. The SM genotype in HO1 gene promoter and ferritin levels were associated with higher risk for type-2 diabetes and for having a higher marker of inflammation, which is the main risk factor for the development of chronic diseases. Copyright © 2016 Elsevier GmbH. All rights reserved.

Study on the relationship between serum TNF-α, IGF-I levels and lipid peroxidation in patients with fatty liver

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Li Yuqiang; Niu Guoping

2006-01-01

Objective: To assess the relationship between serum TNF-α, IGF-I levels and lipid peroxidation in patients with fatty liver. Methods: Serum TNF-α, IGF-I (with RIA) levels were examined in 44 patients with fatty liver and 30 controls. Ser- um levels of malondialdehyde (MDA), superoxidase (SOD) were measured with chemocolorimetry in these subjects. Results: Serum levels of TNF-α, IGF-I were significantly higher in patients with fatty liver than those in controls P<0.01 ), while the serum levels of MDA, SOD were significantly lower (P<0.01). Serum levels of IGF-I were negatively correlated with MDA levels ( r -0. 4132, P<0.05), TNF-α levels were positive correlated with MDA levels (r=0.4318, P<0.05). Conclusion: Lipid peroxidation was present in patients with fatty liver, with correlated changes of TNF-α and IGF-I levels. (authors)

Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice.

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Kostrominova, Tatiana Y

2010-11-30

In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1(-/-)) mice obtained from The Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1(+/-)) littermates. The results of this study were compared with previously published data on two different strains of Sod1(-/-) mice: one from Dr. Epstein's laboratory (ELSod1(-/-); C57Bl6 background) and the other from Cephalon, Inc. (CSod1(-/-); 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1(-/-) mice from all three strains. The 10-month-old Sod1(-/-)C and JL mice displayed pronounced denervation of the gastrocnemius muscle, whereas the ELSod1(-/-) mice displayed a small degree of denervation at this age, but developed accelerated age-related denervation later on. Denervation markers were up-regulated in skeletal muscle of 10-month-old JLSod1(-/-) mice. This study is the first to show that metallothionein mRNA and protein expression was up-regulated in the skeletal muscle of 10-month-old JLSod1(-/-) mice and was mostly localized to the small atrophic muscle fibers. In conclusion, all three strains of Sod1(-/-) mice develop accelerated age-related muscle denervation, but the genetic background has significant influence on the progress of denervation. Copyright © 2010 Elsevier Inc. All rights reserved.

Astrocyte-neuron co-culture on microchips based on the model of SOD mutation to mimic ALS.

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Kunze, Anja; Lengacher, Sylvain; Dirren, Elisabeth; Aebischer, Patrick; Magistretti, Pierre J; Renaud, Philippe

2013-07-24

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. ALS is believed to be a non-cell autonomous condition, as other cell types, including astrocytes, have been implicated in disease pathogenesis. Hence, to facilitate the development of therapeutics against ALS, it is crucial to better understand the interactions between astrocytes and neural cells. Furthermore, cell culture assays are needed that mimic the complexity of cell to cell communication at the same time as they provide control over the different microenvironmental parameters. Here, we aim to validate a previously developed microfluidic system for an astrocyte-neuron cell culture platform, in which astrocytes have been genetically modified to overexpress either a human wild-type (WT) or a mutated form of the super oxide dismutase enzyme 1 (SOD1). Cortical neural cells were co-cultured with infected astrocytes and studied for up to two weeks. Using our microfluidic device that prevents direct cell to cell contact, we could evaluate neural cell response in the vicinity of astrocytes. We showed that neuronal cell density was reduced by about 45% when neurons were co-cultured with SOD-mutant astrocytes. Moreover, we demonstrated that SOD-WT overexpressing astrocytes reduced oxidative stress on cortical neurons that were in close metabolic contact. In contrast, cortical neurons in metabolic contact with SOD-mutant astrocytes lost their synapsin protein expression after severe glutamate treatment, an indication of the toxicity potentiating effect of the SOD-mutant enzyme.

The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

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Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping; Yang, Hongying

2015-01-01

Highlights: • After co-culture with α-irradiated HaCaT cells, WS1 cells displayed oxidative stress and DNA damage. • Increased miR-21 expression in bystander cells was critical to the occurrence of RIBEs. • SOD2 of bystander cells played an important role in bystander responses. • miR-21 mediated bystander effects through its regulation on SOD2. - Abstract: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30 min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3 h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects

The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes

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Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping [School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123 (China); Yang, Hongying, E-mail: yanghongying@suda.edu.cn [School of Radiation Medicine and Protection, Medical College of Soochow University/Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, 199 Renai Road, Suzhou Industrial Park, Suzhou, Jiangsu Province 215123 (China); Institute of Radiotherapy & Oncology, Soochow University (China)

2015-10-15

Highlights: • After co-culture with α-irradiated HaCaT cells, WS1 cells displayed oxidative stress and DNA damage. • Increased miR-21 expression in bystander cells was critical to the occurrence of RIBEs. • SOD2 of bystander cells played an important role in bystander responses. • miR-21 mediated bystander effects through its regulation on SOD2. - Abstract: Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30 min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3 h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects

Comparing the functional components, SOD-like activities, antimutagenicity, and nutrient compositions of Phellinus igniarius and Phellinus linteus mushrooms

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Nae-Cherng Yang

2016-04-01

Full Text Available Many species of the genus Phellinus possess beneficial properties, including antioxidant, immune-enhancing, and antimutagenic effects. Phenolic compounds and polysaccharides are two kinds of bioactive compounds; however, few studies have compared the differences between Phellinus igniarius and Phellinus linteus in their functional components, functional activities, and nutrient compositions. Herein, the proximate compositions and microelements of the fruiting body of P. igniarius and P. linteus were determined. The fruiting body of P. igniarius and P. linteus were extracted by boiling water [water extract of P. igniarius (WEPI and P. linteus (WEPL]. The contents of total phenolics and polysaccharides, as well as superoxide dismutase (SOD-like and antimutagenic activities of WEPI and WEPL, were compared. We found that WEPI was rich in phenolics and polysaccharides and had higher SOD-like activity than WEPL. Nutrient compositions were mainly different in minerals, whereas anitmutagenicity was similar. All of these results suggested that P. igniarius has greater potential for the development of antioxidant and immunomodulating food products than P. linteus.

Association of Polymorphous Markers Ala(-9Val of SOD2 Gene and C(-262T of CAT Gene in Patients with Hashimotos’ Thyroiditis and Hypothyroidism

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A Mkrtumyan

2008-03-01

Full Text Available A comparative analysis of distribution of alleles and genotypes of polymorphous markers Ala(-9Val of SOD2 gene and C(-262T of CAT gene was performed. Eighty six patients with Hashimotos’ thyroiditis (HT were enrolled in the study. Significant deferens were found by comparison of alleles and genotypes incidence of polymorphous marker Ala(-9Val of SOD2 gene in HT-patients and in control group. Significant increase of incidence of Val/Val genotype (OR = 15,6; p = 0.04 in HT-patients may reflect a higher risk of HT in Val/Val individuals. This hypothesis may be confirmed by increase of malonic dialdehyde and antithyroid antibodies in Val/Val carriers.

Plasma oxidative stress level of IgA nephropathy in children and the effect of early intervention with angiotensin-converting enzyme inhibitors.

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Pei, Yuxin; Xu, Yuanyuan; Ruan, Jingwei; Rong, Liping; Jiang, Mengjie; Mo, Ying; Jiang, Xiaoyun

2016-01-01

The purpose of this study was to investigate the change of the plasma oxidative stress level in children with IgA nephropathy (IgAN) and analyze its relativity to the clinical and pathological classification. To discuss the early effects of angiotensin-converting enzyme inhibitors (ACEIs) on the plasma oxidative stress level in children with IgA nephropathy. Thirty-eight children with IgAN were divided into groups according to their clinical features, pathologic grades, and treatments. Twenty healthy children were included in the control group. The plasma level of advanced oxidation protein products (AOPPs), malonaldehyde (MDA), and superoxide dismutase (SOD) were detected. The plasma level of oxidative stress was significantly increased in the IgAN group, including a higher plasma level of AOPP and MDA and a lower plasma level of SOD. After treatment, the plasma level of oxidative stress was significantly decreased in the ACEI group. The children with IgAN had an increase in the plasma level of oxidative stress, expressed as an increased plasma level of AOPP and MDA and a decreased plasma level of SOD. Oxidative stress was associated with the progression of IgAN in children. Early treatment with ACEI therapy can significantly reduce the plasma level of oxidative stress in children with IgAN. © The Author(s) 2016.

Use of sodC versus ctrA for real-time polymerase chain reaction-based detection of Neisseria meningitidis in sterile body fluids

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Fábio Takenori Higa

2013-04-01

Full Text Available We evaluated the use of a newly described sodC-based real-time-polymerase chain reaction (RT-PCR assay for detecting Neisseria meningitidis in normally sterile sites, such as cerebrospinal fluid and serum. The sodC-based RT-PCR assay has an advantage over ctrA for detecting nongroupable N. meningitidis isolates, which are commonly present in asymptomatic pharyngeal carriage. However, in our study, sodC-based RT-PCR was 7.5% less sensitive than ctrA. Given the public health impact of possible false-negative results due to the use of the sodC target gene alone, sodC-based RT-PCR for the diagnosis of meningococcal meningitis should be used with caution.

Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.

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Hajiani, Maliheh; Razi, Farideh; Golestani, Aboualfazl; Frouzandeh, Mehdi; Owji, Ali Akbar; Khaghani, Shahnaz; Ghannadian, Naghmeh; Shariftabrizi, Ahmad; Pasalar, Parvin

2012-01-01

Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma. Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals. Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group. Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does not dramatically change in response to vitamin E.

The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by α-irradiated keratinocytes.

Science.gov (United States)

Tian, Wenqian; Yin, Xiaoming; Wang, Longxiao; Wang, Jingdong; Zhu, Wei; Cao, Jianping; Yang, Hongying

2015-10-01

Radiation-induced bystander effect (RIBE) is well accepted in the radiation research field by now, but the underlying molecular mechanisms for better understanding this phenomenon caused by intercellular communication and intracellular signal transduction are still incomplete. Although our previous study has demonstrated an important role of miR-21 of unirradiated bystander cells in RIBEs, the direct evidence for the hypothesis that RIBE is epigenetically regulated is still limited and how miR-21 mediates RIBEs is unknown. Reactive oxygen species (ROS) have been demonstrated to be involved in RIBEs, however, the roles of anti-oxidative stress system of cells in RIBEs are unclear. Using transwell insert co-culture system, we investigated medium-mediated bystander responses in WS1 human fibroblasts after co-culture with HaCaT keratinocytes traversed by α-particles. Results showed that the ROS levels in unirradiated bystander WS1 cells were significantly elevated after 30min of co-culture, and 53BP1 foci, a surrogate marker of DNA damage, were obviously induced after 3h of co-culture. This indicates the occurrence of oxidative stress and DNA damage in bystander WS1 cells after co-culture with irradiated keratinocytes. Furthermore, the expression of miR-21 was increased in bystander WS1 cells, downregulation of miR-21 eliminated the bystander responses, overexpression of miR-21 alone could induce bystander-like oxidative stress and DNA damage in WS1 cells. These data indicate an important mediating role of miR-21 in RIBEs. In addition, MnSOD or SOD2 in WS1 cells was involved in the bystander effects, overexpression of SOD2 abolished the bystander oxidative stress and DNA damage, indicating that SOD2 was critical to the induction of RIBEs. Moreover, we found that miR-21 regulated SOD2, suggesting that miR-21 might mediate bystander responses through its regulation on SOD2. In conclusion, this study revealed a profound role of miR-21-regulated SOD2 of unirradiated WS1

Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

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Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2017-06-25

Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in tumor-bearing mice

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Yu Hongsheng; Lu Yanda

2001-01-01

Objective: To study the effect of low dose radiation on tumor growth and changes of erythrocyte immune function and activity of SOD in the tumor-bearing mice. Methods: Kunming strain male mice were implanted with S 180 sarcoma cells in the right inguen subcutaneously as an experimental in situ animal model. Six hours before implantation the mice were given 75 mG whole-body X-ray irradiation and tumor-formation rate was counted 5 days late. From then, every two days the tumor volume was measured to draw a tumor growth curve. Fifteen days later, all mice were killed to measure the tumor weight, observe the necrosis area and the tumor-infiltration lymphoreticular cells (TIL) in the tumor pathologically. At the same time, erythrocyte immune function and activity of SOD were tested. Results: (1) The mice pre-exposed to low dose radiation had a lower tumor formation rate than those without a pre-exposed (P < 0.05). (2) The tumor growth slowed down significantly in mice receiving a low does irradiation; The average tumor weight in mice receiving a low dose irradiation was lighter too (P < 0.05). (3) The tumor necrosis areas were larger and TILs were more in the irradiation group than those of the control group. (4) The erythrocyte immune function and activity of SOD in the irradiation group were all higher significantly than those of the control group ( P < 0.05). Conclusion: Low dose radiation could markedly increase anti-tumor ability of the organism and improve the erythrocyte immune function and activity of SOD in red cells, suggesting it could be useful in clinical cancer treatment

Influence of gross saponins from tribulus terrestris L on SOD activity and MDA content for chronic high intraocular pressure in rabbit

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Nuo Li

2013-05-01

Full Text Available AIM:To observe influence of gross saponins from tribulus terrestris L(GSTTon SOD activity and MDA content for chronic high intraocular pressure in rabbit, and discusses the retina oxidative damage inhibition on chronic high intraocular pressure model of rabbit. METHODS:Totally 24 healthy New Zealand rabbits were randomly divided into 4 groups: normal control group(A group; high intraocular pressure model blank group(B group; high intraocular pressure model with GSTT treated group(C group; high intraocular pressure model with Erigeron brevicapas hand mass(EBHMtreated group(D group. High intraocular pressure model was induced by 20g/L methylcellulose injection into the anterior chamber in B group, C group and D group. D group was injected 5 mg/kg GSTT and C group was injected 4.5mg/kg EBHM and measured intraocular pressure with Schiotz tonometer every day for 4 weeks. The retina tissue superoxide dismutase(SODand maleic dialdehyde(MDAcontent were detected 28 days later. RESULTS: After glaucoma model of rabbit eyes were established, the intraocular pressure during observation period was maintained in 32-39mmHg; High intraocular pressure model blank group and normal control group, EBHM treatment group, GSTT treatment group were compared, the differences of retina MDA, SOD content had statistical significance(P0.05; EBHM treatment group, GSTT treatment group and normal control group were compared, the content of MDA in the retina was still slightly higher(P<0.05, the content of SOD slightly lower(P<0.05 CONCLUSION: GSTT can effectively improve the retina SOD activity of chronic high intraocular pressure in rabbit and reduce the content of MDA, which has a protective effect of persistent high intraocular retinal oxidative stress.

Maternal protein restriction induced-hypertension is associated to oxidative disruption at transcriptional and functional levels in the medulla oblongata.

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de Brito Alves, José L; de Oliveira, Jéssica M D; Ferreira, Diorginis J S; Barros, Monique A de V; Nogueira, Viviane O; Alves, Débora S; Vidal, Hubert; Leandro, Carol G; Lagranha, Cláudia J; Pirola, Luciano; da Costa-Silva, João H

2016-12-01

Maternal protein restriction during pregnancy and lactation predisposes the adult offspring to sympathetic overactivity and arterial hypertension. Although the underlying mechanisms are poorly understood, dysregulation of the oxidative balance has been proposed as a putative trigger of neural-induced hypertension. The aim of the study was to evaluate the association between the oxidative status at transcriptional and functional levels in the medulla oblongata and maternal protein restriction induced-hypertension. Wistar rat dams were fed a control (normal protein; 17% protein) or a low protein ((Lp); 8% protein) diet during pregnancy and lactation, and male offspring was studied at 90 days of age. Direct measurements of baseline arterial blood pressure (ABP) and heart rate (HR) were recorded in awakened offspring. In addition, quantitative RT-PCR was used to assess the mRNA expression of superoxide dismutase 1 (SOD1) and 2 (SOD2), catalase (CAT), glutathione peroxidase (GPx), Glutamatergic receptors (Grin1, Gria1 and Grm1) and GABA(A)-receptor-associated protein like 1 (Gabarapl1). Malondialdehyde (MDA) levels, CAT and SOD activities were examined in ventral and dorsal medulla. Lp rats exhibited higher ABP. The mRNA expression levels of SOD2, GPx and Gabarapl1 were down regulated in medullary tissue of Lp rats (Pmedulla. Taken together, our data suggest that maternal protein restriction induced-hypertension is associated with medullary oxidative dysfunction at transcriptional level and with impaired antioxidant capacity in the ventral medulla. © 2016 John Wiley & Sons Australia, Ltd.

A Cystine-Rich Whey Supplement (Immunocal® Delays Disease Onset and Prevents Spinal Cord Glutathione Depletion in the hSOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

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Erika K. Ross

2014-12-01

Full Text Available Depletion of the endogenous antioxidant, glutathione (GSH, underlies progression of the devastating neurodegenerative disease, amyotrophic lateral sclerosis (ALS. Thus, strategies aimed at elevating GSH may yield new therapeutics for ALS. Here, we investigated the effects of a unique non-denatured whey protein supplement, Immunocal®, in the transgenic Gly position 93 to Ala (G93A mutant hSOD1 (hSOD1G93A mouse model of ALS. Immunocal® is rich in the GSH precursor, cystine, and is therefore capable of bolstering GSH content. Transgenic hSOD1G93A mice receiving Immunocal® displayed a significant delay in disease onset compared to untreated hSOD1G93A controls. Additionally, Immunocal® treatment significantly decreased the rate of decline in grip strength and prevented disease-associated reductions in whole blood and spinal cord tissue GSH levels in end-stage hSOD1G93A mice. However, Immunocal® did not extend survival, likely due to its inability to preserve the mitochondrial GSH pool in spinal cord. Combination treatment with Immunocal® and the anti-glutamatergic compound, riluzole, delayed disease onset and extended survival in hSOD1G93A mice. These findings demonstrate that sustaining tissue GSH with Immunocal® only modestly delays disease onset and slows the loss of skeletal muscle strength in hSOD1G93A mice. Moreover, the inability of Immunocal® to rescue mitochondrial GSH in spinal cord provides a possible mechanism for its lack of effect on survival and is a limiting factor in the potential utility of this supplement as a therapeutic for ALS.

Mechanisms of Enhanced Phrenic Long-Term Facilitation in SOD1G93A Rats.

Science.gov (United States)

Nichols, Nicole L; Satriotomo, Irawan; Allen, Latoya L; Grebe, Ashley M; Mitchell, Gordon S

2017-06-14

Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model ( SOD1 G93A ), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1 G93A rats are not known. Moderate AIH-induced pLTF is normally elicited via cellular mechanisms that require the following: G q -protein-coupled 5-HT 2 receptor activation, new BDNF synthesis, and MEK/ERK signaling (the Q pathway). In contrast, severe AIH elicits pLTF via a distinct mechanism that requires the following: G s -protein-coupled adenosine 2A receptor activation, new TrkB synthesis, and PI3K/Akt signaling (the S pathway). In end-stage male S OD1 G93A rats and wild-type littermates, we investigated relative Q versus S pathway contributions to enhanced pLTF via intrathecal (C4) delivery of small interfering RNAs targeting BDNF or TrkB mRNA, and MEK/ERK (U0126) or PI3 kinase/Akt (PI828) inhibitors. In anesthetized, paralyzed and ventilated rats, moderate AIH-induced pLTF was abolished by siBDNF and UO126, but not siTrkB or PI828, demonstrating that enhanced pLTF occurs via the Q pathway. Although phrenic motor neuron numbers were decreased in end-stage SOD1 G93A rats (∼30% survival; p phrenic motor neurons ( p phrenic motor plasticity results from amplification of normal cellular mechanisms versus addition/substitution of alternative mechanisms. Greater understanding of mechanisms underlying phrenic motor plasticity in ALS may guide development of new therapies to preserve and/or restore breathing in ALS patients. Copyright © 2017 the authors 0270-6474/17/375834-12$15.00/0.

The Effects of Bee Venom Acupuncture on the Central Nervous System and Muscle in an Animal hSOD1G93A Mutant

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MuDan Cai

2015-03-01

Full Text Available Amyotrophic lateral sclerosis (ALS is caused by the degeneration of lower and upper motor neurons, leading to muscle paralysis and respiratory failure. However, there is no effective drug or therapy to treat ALS. Complementary and alternative medicine (CAM, including acupuncture, pharmacopuncture, herbal medicine, and massage is popular due to the significant limitations of conventional therapy. Bee venom acupuncture (BVA, also known as one of pharmacopunctures, has been used in Oriental medicine to treat inflammatory diseases. The purpose of this study is to investigate the effect of BVA on the central nervous system (CNS and muscle in symptomatic hSOD1G93A transgenic mice, an animal model of ALS. Our findings show that BVA at ST36 enhanced motor function and decreased motor neuron death in the spinal cord compared to that observed in hSOD1G93A transgenic mice injected intraperitoneally (i.p. with BV. Furthermore, BV treatment at ST36 eliminated signaling downstream of inflammatory proteins such as TLR4 in the spinal cords of symptomatic hSOD1G93A transgenic mice. However, i.p. treatment with BV reduced the levels of TNF-α and Bcl-2 expression in the muscle hSOD1G93A transgenic mice. Taken together, our findings suggest that BV pharmacopuncture into certain acupoints may act as a chemical stimulant to activate those acupoints and subsequently engage the endogenous immune modulatory system in the CNS in an animal model of ALS.

Combined proteomic and molecular approaches for cloning and characterization of copper-zinc superoxide dismutase (Cu, Zn-SOD2) from garlic (Allium sativum).

Science.gov (United States)

Hadji Sfaxi, Imen; Ezzine, Aymen; Coquet, Laurent; Cosette, Pascal; Jouenne, Thierry; Marzouki, M Nejib

2012-09-01

Superoxide dismutases (SODs; EC 1.15.1.1) are key enzymes in the cells protection against oxidant agents. Thus, SODs play a major role in the protection of aerobic organisms against oxygen-mediated damages. Three SOD isoforms were previously identified by zymogram staining from Allium sativum bulbs. The purified Cu, Zn-SOD2 shows an antagonist effect to an anticancer drug and alleviate cytotoxicity inside tumor cells lines B16F0 (mouse melanoma cells) and PAE (porcine aortic endothelial cells). To extend the characterization of Allium SODs and their corresponding genes, a proteomic approach was applied involving two-dimensional gel electrophoresis and LC-MS/MS analyses. From peptide sequence data obtained by mass spectrometry and sequences homologies, primers were defined and a cDNA fragment of 456 bp was amplified by RT-PCR. The cDNA nucleotide sequence analysis revealed an open reading frame coding for 152 residues. The deduced amino acid sequence showed high identity (82-87%) with sequences of Cu, Zn-SODs from other plant species. Molecular analysis was achieved by a protein 3D structural model.

Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis.

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Parone, Philippe A; Da Cruz, Sandrine; Han, Joo Seok; McAlonis-Downes, Melissa; Vetto, Anne P; Lee, Sandra K; Tseng, Eva; Cleveland, Don W

2013-03-13

Mitochondria have been proposed as targets for toxicity in amyotrophic lateral sclerosis (ALS), a progressive, fatal adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons. A decrease in the capacity of spinal cord mitochondria to buffer calcium (Ca(2+)) has been observed in mice expressing ALS-linked mutants of SOD1 that develop motor neuron disease with many of the key pathological hallmarks seen in ALS patients. In mice expressing three different ALS-causing SOD1 mutants, we now test the contribution of the loss of mitochondrial Ca(2+)-buffering capacity to disease mechanism(s) by eliminating ubiquitous expression of cyclophilin D, a critical regulator of Ca(2+)-mediated opening of the mitochondrial permeability transition pore that determines mitochondrial Ca(2+) content. A chronic increase in mitochondrial buffering of Ca(2+) in the absence of cyclophilin D was maintained throughout disease course and was associated with improved mitochondrial ATP synthesis, reduced mitochondrial swelling, and retention of normal morphology. This was accompanied by an attenuation of glial activation, reduction in levels of misfolded SOD1 aggregates in the spinal cord, and a significant suppression of motor neuron death throughout disease. Despite this, muscle denervation, motor axon degeneration, and disease progression and survival were unaffected, thereby eliminating mutant SOD1-mediated loss of mitochondrial Ca(2+) buffering capacity, altered mitochondrial morphology, motor neuron death, and misfolded SOD1 aggregates, as primary contributors to disease mechanism for fatal paralysis in these models of familial ALS.

Copper exposure induces oxidative injury, disturbs the antioxidant system and changes the Nrf2/ARE (CuZnSOD) signaling in the fish brain: Protective effects of myo-inositol

Energy Technology Data Exchange (ETDEWEB)

Jiang, Wei-Dan; Liu, Yang [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Hu, Kai [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Jiang, Jun [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Li, Shu-Hong [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Feng, Lin, E-mail: fenglin@sicau.edu.cn [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Zhou, Xiao-Qiu, E-mail: xqzhouqq@tom.com [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China)

2014-10-15

Highlights: • Cu exposure increased ROS production, lipid and protein oxidation of fish brain. • Cu exposure caused depletion of some antioxidants in the brain of fish. • Cu exposure up-regulated mRNA levels of brain CuZnSOD, GPx1a and GR genes in fish. • Cu exposure induced Nrf2 nuclear translocation and binding to ARE in fish brain. • Myo-inositol can inhibit Cu-induced toxic effects in the brain of fish. - Abstract: The brain is the center of the nervous system in all vertebrates, and homeostasis of the brain is crucial for fish survival. Copper (Cu) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess. Although Cu is indicated as a potent neurotoxicant, information regarding its threat to fish brain and underlying mechanisms is still scarce. In accordance, the objective of this study was to assess the effects and the potential mechanism of Cu toxicity by evaluating brain oxidative status, the enzymatic and mRNA levels of antioxidant genes, as well as the Nrf2/ARE signaling in the brain of fish after Cu exposure. The protective effects of myo-inositol (MI) against subsequent Cu exposure were also investigated. The results indicate that induction of oxidative stress by Cu is shown by increases in brain ROS production, lipid peroxidation and protein oxidation, which are accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), CuZnSOD, glutathione-S-transferase (GST) and glutathione reductase (GR) activities and glutathione (GSH) content. Cu exposure increased the catalase (CAT) and glutathione peroxidase (GPx) activities. Further molecular results showed that Cu exposure up-regulated CuZnSOD, GPx1a and GR mRNA levels, suggesting an adaptive mechanism against stress. Moreover, Cu exposure increased fish brain Nrf2 nuclear accumulation and increased its ability of binding to ARE (CuZnSOD), which supported the increased CuZnSOD mRNA levels. In addition, Cu exposure caused increases of

Copper exposure induces oxidative injury, disturbs the antioxidant system and changes the Nrf2/ARE (CuZnSOD) signaling in the fish brain: Protective effects of myo-inositol

International Nuclear Information System (INIS)

Jiang, Wei-Dan; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Feng, Lin; Zhou, Xiao-Qiu

2014-01-01

Highlights: • Cu exposure increased ROS production, lipid and protein oxidation of fish brain. • Cu exposure caused depletion of some antioxidants in the brain of fish. • Cu exposure up-regulated mRNA levels of brain CuZnSOD, GPx1a and GR genes in fish. • Cu exposure induced Nrf2 nuclear translocation and binding to ARE in fish brain. • Myo-inositol can inhibit Cu-induced toxic effects in the brain of fish. - Abstract: The brain is the center of the nervous system in all vertebrates, and homeostasis of the brain is crucial for fish survival. Copper (Cu) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess. Although Cu is indicated as a potent neurotoxicant, information regarding its threat to fish brain and underlying mechanisms is still scarce. In accordance, the objective of this study was to assess the effects and the potential mechanism of Cu toxicity by evaluating brain oxidative status, the enzymatic and mRNA levels of antioxidant genes, as well as the Nrf2/ARE signaling in the brain of fish after Cu exposure. The protective effects of myo-inositol (MI) against subsequent Cu exposure were also investigated. The results indicate that induction of oxidative stress by Cu is shown by increases in brain ROS production, lipid peroxidation and protein oxidation, which are accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), CuZnSOD, glutathione-S-transferase (GST) and glutathione reductase (GR) activities and glutathione (GSH) content. Cu exposure increased the catalase (CAT) and glutathione peroxidase (GPx) activities. Further molecular results showed that Cu exposure up-regulated CuZnSOD, GPx1a and GR mRNA levels, suggesting an adaptive mechanism against stress. Moreover, Cu exposure increased fish brain Nrf2 nuclear accumulation and increased its ability of binding to ARE (CuZnSOD), which supported the increased CuZnSOD mRNA levels. In addition, Cu exposure caused increases of

The R213G polymorphism in SOD3 protects against allergic airway inflammation

DEFF Research Database (Denmark)

Gaurav, Rohit; Varasteh, Jason T; Weaver, Michael R

2017-01-01

) in bronchoalveolar lavage fluid and reduced type II innate lymphoid cells (ILC2s) in lungs. SOD mimetic (Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin) attenuated Alternaria-induced expression of IL-33 and IL-8 release in BEAS-2B cells. These results suggest that R213G SNP potentially benefits its carriers...... by resulting in high EC-SOD in airway-lining fluid, which ameliorates allergic airway inflammation by dampening the innate immune response, including IL-33/ST2-mediated changes in ILC2s....

A mouse model of familial ALS has increased CNS levels of endogenous ubiquinol9/10 and does not benefit from exogenous administration of ubiquinol10.

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Jacopo Lucchetti

Full Text Available Oxidative stress and mitochondrial impairment are the main pathogenic mechanisms of Amyotrophic Lateral Sclerosis (ALS, a severe neurodegenerative disease still lacking of effective therapy. Recently, the coenzyme-Q (CoQ complex, a key component of mitochondrial function and redox-state modulator, has raised interest for ALS treatment. However, while the oxidized form ubiquinone10 was ineffective in ALS patients and modestly effective in mouse models of ALS, no evidence was reported on the effect of the reduced form ubiquinol10, which has better bioavailability and antioxidant properties. In this study we compared the effects of ubiquinone10 and a new stabilized formulation of ubiquinol10 on the disease course of SOD1(G93A transgenic mice, an experimental model of fALS. Chronic treatments (800 mg/kg/day orally started from the onset of disease until death, to mimic the clinical trials that only include patients with definite ALS symptoms. Although the plasma levels of CoQ10 were significantly increased by both treatments (from <0.20 to 3.0-3.4 µg/mL, no effect was found on the disease progression and survival of SOD1(G93A mice. The levels of CoQ10 in the brain and spinal cord of ubiquinone10- or ubiquinol10-treated mice were only slightly higher (≤10% than the endogenous levels in vehicle-treated mice, indicating poor CNS availability after oral dosing and possibly explaining the lack of pharmacological effects. To further examine this issue, we measured the oxidized and reduced forms of CoQ9/10 in the plasma, brain and spinal cord of symptomatic SOD1(G93A mice, in comparison with age-matched SOD1(WT. Levels of ubiquinol9/10, but not ubiquinone9/10, were significantly higher in the CNS, but not in plasma, of SOD1(G93A mice, suggesting that CoQ redox system might participate in the mechanisms trying to counteract the pathology progression. Therefore, the very low increases of CoQ10 induced by oral treatments in CNS might be not sufficient to

The effect of nano-TiO2 photocatalysis on the antioxidant activities of Cu, Zn-SOD at physiological pH.

Science.gov (United States)

Zheng, Wen; Zou, Hai-Feng; Lv, Shao-Wu; Lin, Yan-Hong; Wang, Min; Yan, Fei; Sheng, Ye; Song, Yan-Hua; Chen, Jie; Zheng, Ke-Yan

2017-09-01

Security issues of nanoparticles on biological toxicity and potential environmental risk have attracted more and more attention with the rapid development and wide applications of nanotechnology. In this work, we explored the effect and probable mechanism of nano-TiO 2 on antioxidant activity of copper, zinc superoxide dismutase (Cu, Zn-SOD) under natural light and mixed light at physiological pH. Nano-TiO 2 was prepared by sol-hydrothermal method, and then characterized by X-ray Diffraction (XRD) and Transmission electron micrographs (TEM). The Cu, Zn-SOD was purified by sephadex G75 chromatography and qualitatively analyzed by sodium dodecyl sulfate polypropylene amide gel electrophoresis (SDS-PAGE). The effect and mechanism were elucidated base on Fourier Transform Infrared Spectrometer (FT-IR), Circular Dichroism (CD), zeta potential, and electron spin resonance (ESR) methods. Accompanying the results of FT-IR, CD and zeta potential, it could be concluded that nano-TiO 2 had no effect on the antioxidant activity of Cu, Zn-SOD by comparing the relative activity under natural light at physiological pH. But the relative activity of Cu, Zn-SOD significantly decreased along with the increase of nano-TiO 2 concentration under the mixed light. The results of ESR showed the cause of this phenomenon was the Cu(II) in the active site of Cu, Zn-SOD was reduced to Cu(I) by H 2 O 2 and decreased the content of active Cu, Zn-SOD. The reduction can be inhibited by catalase. Excess O 2 ·- produced by nano-TiO 2 photocatalysis under mixed light accumulated a mass of H 2 O 2 through disproportionation reaction in this experimental condition. The results show that nano-TiO 2 cannot affect the antioxidant activity of Cu, Zn-SOD in daily life. The study on the effect of nano-TiO 2 on Cu, Zn-SOD will provide a valid theory support for biological safety and the toxicological effect mechanism of nanomaterials on enzyme. Copyright © 2017 Elsevier B.V. All rights reserved.

Plasma extracellular superoxide dismutase concentration, allelic variations in the SOD3 gene and risk of myocardial infarction and all-cause mortality in people with type 1 and type 2 diabetes.

Science.gov (United States)

Mohammedi, Kamel; Bellili-Muñoz, Naïma; Marklund, Stefan L; Driss, Fathi; Le Nagard, Hervé; Patente, Thiago A; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Marre, Michel; Velho, Gilberto

2015-01-15

Oxidative stress is involved in development of diabetes complications. Extracellular superoxide dismutase (EC-SOD, SOD3) is a major extracellular antioxidant enzyme and is highly expressed in arterial walls. Advanced oxidation protein products (AOPP) and 8-iso-prostaglandin (isoprostane) are markers of oxidative stress. We investigated association of SOD3 gene variants, plasma concentrations of EC-SOD, AOPP and isoprostane with myocardial infarction and mortality in diabetic patients. We studied three cohorts designed to evaluate the vascular complications of diabetes: the GENEDIAB study (469 participants with type 1 diabetes at baseline; follow-up data for 259 participants), the GENESIS study (603 participants with type 1 diabetes at baseline; follow-up data for 525 participants) and the DIABHYCAR study (3137 participants with type 2 diabetes at baseline and follow-up). Duration of follow-up was 9, 5, and 5 years, respectively. Main outcome measures were incidence of myocardial infarction, and cardiovascular and total mortality during follow-up. Six single nucleotide polymorphisms in the SOD3 locus were genotyped in the three cohorts. Plasma concentrations of EC-SOD, AOPP, and isoprostane were measured in baseline samples of GENEDIAB participants. In GENEDIAB/GENESIS pooled cohorts, the minor T-allele of rs2284659 variant was inversely associated with the prevalence at baseline (Odds Ratio 0.48, 95% CI 0.29-0.78, p = 0.004) and the incidence during follow-up of myocardial infarction (Hazard Ratio 0.58, 95% CI 0.40-0.83, p = 0.003) and with cardiovascular (HR 0.33, 95% CI 0.08-0.74, p = 0.004) and all-cause mortality (HR 0.44, 95% CI 0.21-0.73, p = 0.0006). The protective allele was associated with higher plasma EC-SOD and lower plasma AOPP concentrations in GENEDIAB. It was also inversely associated with incidence of myocardial infarction (HR 0.75, 95% CI 0.59-0.94, p = 0.01) and all-cause mortality (HR 0.87, 95% CI 0.79-0.97, p = 0

Effect of nitrogen fertilization, grass species and cultivar on sod production on Valkeasuo peat bog - a case study

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Perttu Virkajärvi

1997-09-01

Full Text Available As part of a research project concerning the agricultural utilization of cut-away peat bogs, a sod production experiment was conducted at Valkeasuo, Tohmajärvi, in 1990-1993. The aim of the experiment was to study the effect of nitrogen and choice of cultivar on sod production and sod quality on peat bogs. The N fertilization rates were 50, 100 and 150kg ha-1. The Poa pratensis cultivars were ‘Conni’, ‘Cynthia’, ‘Haga’ and ‘Julia’, the Festuca rubra cultivars were ‘Center’, ‘Juliska’, ‘Koket’ and ‘Näpsä’ and the Agrostis capillaris cultivar was ‘Rasti’. Two mixtures of P. pratensis/F. rubra and one of A. capillaris/F. rubra imitated commercial sod products. Increasing of N fertilization from 50 kg up to 150 kg ha-1 a had positive effect on general the quality of sod as well as on the green cover before and after transplanting. It increased the thatch formation. The positive effect of N on the number of tillers and green cover in the year following transplanting was dependent on the species and the cultivar. Species and cultivar affected all measured variables excluding thatch formation. Generally, the P. pratensis cultivars tested suited better for sod production than cultivars of F. rubra, but there were clear differences between cultivars within species as well. Although the soil was infertile, the contents of Ca, K, Mg, P, Cu, Fe, Mn, Mo and Zn in the herbage samples were within normal range. The botanical purity was high, which supports the hypothesis that the absence of seed bank of weeds on peat bogs immediately after harvesting the peat can be utilized.

Inhibitors of SOD1 Interaction as an Approach to Slow the Progressive Spread of ALS Symptoms

Science.gov (United States)

2016-07-01

the progression of ALS caused by mutations in this protein . To accomplish this goal, we developed an assay that is based on the observation that the...force. In our assay , this force is the normal interaction that occurs when 2 individual SOD1 proteins come together to form a normal active enzyme...Using recombinant DNA, we create fusion proteins of SOD1 and each half of the luciferase enzyme. In the past year, we have characterized and optimized

Effect of N+ beam exposure on superoxide dismutase and catalase activities and induction of Mn-SOD in Deinococcus radiodurans

International Nuclear Information System (INIS)

Song Daojun; Chen Ruolei; Shao Chunlin; Wu Lijun; Yu Zengliang

2000-01-01

Though bacteria of the radiation-resistant Deinococcus radiodurans have a high resistance to the lethal and mutagenic effects of many DNA-damaging agents, the mechanisms involved in the response of these bacteria to oxidative stress are poorly understood. The superoxide dismutase (SOD) and catalase (CAT) activities produced by these bacteria were measured, and the change of SOD and CAT activities by 20 keV N + beam exposure was examined. Their activities were increased by N + beam exposure from 8 x 10 14 ions/cm 2 to 6 x 10 15 ions/cm 2 . The treatment of H 2 O 2 and [CHCl 3 + CH 3 CH 2 OH] and the measurement of absorption spectrum showed that the increase in SOD activity was resulted from inducible activities of Mn-SOD in D. radiodurans AS1.633 by N + beam exposure. These results suggested that this bacteria possess inducible defense mechanisms against the deleterious effects of oxidisation

Superoxide dismutase (SOD) in boar spermatozoa: purification, biochemical properties and changes in activity during semen storage (16°C) in different extenders.

Science.gov (United States)

Orzołek, Aleksandra; Wysocki, Paweł; Strzeżek, Jerzy; Kordan, Władysław

2013-03-01

The antioxidant system in semen is composed of enzymes, low-molecular weight antioxidants and seminal plasma proteins. Loss of enzymatic activity of superoxide dismutase (SOD) during semen preservation may cause insufficient antioxidant defense of boar spermatozoa. The aim of this study was to isolate and characterize SOD molecular forms from spermatozoa and to describe changes in SOD activity in boar sperm during preservation at 16°C. Sperm extracts were prepared from fresh or diluted semen and used for SOD purification or activity measurement. Ion-exchange chromatography and gel filtration was used to purify SOD molecular forms. BTS, Dilu Cell, M III and Vitasem were used as diluents for 5-day storage of semen at +16°C. The molecular form of SOD released from spermatozoa after cold shock and homogenization had a molecular weight of approximately 67kDa. The activity of the SOD form was the highest at pH 10 within the temperature range between 20 and 45°C. The enzymatic activity of form released after cold shock was inhibited by H2O2 and diethyldithiocarbamate (DDC; by 65 and 40%, respectively). The SOD form released by homogenization was inhibited by H2O2 and DDC (40%). The molecular form released after urea treatment was a 30kDa protein with maximum activity at 20°C and pH 10. Enzymatic activity of this form was inhibited by H2O2 by 35%, DDC by 80% and 2-mercaptoethanol by 15%. The antigenic determinants of SOD isolated from boar seminal plasma and spermatozoa were similar to each other. Susceptibility of spermatozoa to cold shock increased during storage, but the differences between extenders were statistically non-significant. Copyright © 2013 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Detection of novel key residues of MnSOD enzyme and its role in ...

Indian Academy of Sciences (India)

avoidance mechanism and morphological changes (Flowers ... The MnSOD proteins of different species available in salinity condition with their uniprot IDs and domain information ...... relative Lycopersicon pennellii to salt-dependent oxidative.

CuZnSOD gene expression and its relationship with anti-oxidative ...

African Journals Online (AJOL)

... and the minimum in the LY. The proportion of gene expression was positively correlated with the anti-oxidative capacity in muscle. The expression of the CuZnSOD gene was positively correlated with meat colour and tenderness; and negatively correlated with marbling score, drip loss, cooking loss and intramuscular fat.

Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS.

Science.gov (United States)

Nichols, Nicole L; Satriotomo, Irawan; Harrigan, Daniel J; Mitchell, Gordon S

2015-11-01

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600 μM; 12 μL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms

Effect of N+ beam exposure on the activities of Mn-SOD and catalase in deinococcus radiodurans

International Nuclear Information System (INIS)

Song Daojun; Chen Ruolei; Wu Lifang; Li Hong; Yao JIanming; Shao Chunlin; Wu Lijun; Yu Zengliang

2000-01-01

Though the radiation-resistant bacteria Deinococcus radiodurans (D. radiodurans) have a high resistance to the lethal and mutagenic effects of many DNA-damaging agents, the mechanisms involved in the response of these bacteria to oxidative stress are poorly understood. The superoxide dismutase (SOD) and catalase (CAT) activities produced in bacteria (D. radiodurans AS1.633) and their change caused by 20 keV N'+ beam exposure were examined. Results showed that the activities of the enzymes were increased in the case of N + beam exposure from 8 x 10 14 ions/cm 2 to 6 x 10 15 ions/cm 2 . In addition, the treatment of H 2 O 2 and [CHCl 3 + CH 3 CH 2 OH] and the measurement of absorption spectrum showed that the increase of whole SOD activity resulted from inducible activities of Mn-SOD in (a sub-type) D. radiodurans AS1.633. These results suggested that these bacteria possess inducible defense mechanisms against the deleterious effects of oxidization

Safrole oxide induces neuronal apoptosis through inhibition of integrin beta4/SOD activity and elevation of ROS/NADPH oxidase activity.

Science.gov (United States)

Su, Le; Zhao, BaoXiang; Lv, Xin; Wang, Nan; Zhao, Jing; Zhang, ShangLi; Miao, JunYing

2007-02-20

Neuronal apoptosis is a very important event in the development of the central nervous system (CNS), but the underlying mechanisms remain to be elucidated. We have previously shown that safrole oxide, a small molecule, induces integrin beta4 expression and promotes apoptosis in vascular endothelial cells. In this study, the effects of safrole oxide on cell growth and apoptosis have been examined in primary cultures of mouse neurons. Safrole oxide was found to significantly inhibit neuronal cell growth and to induce apoptosis. The inhibitory and apoptotic activities of safrole oxide followed a dose- and time-dependent manner. Interestingly, the expression of integrin beta4 was significantly inhibited with safrole oxide treatment. Furthermore, safrole oxide dramatically increases the level of intracellular reactive oxygen species (ROS) and the activity of NADPH oxidase. Moreover, manganese-dependent superoxide dismutase (MnSOD) activity was decreased significantly with safrole oxide treatment. Our study thus demonstrates that safrole oxide induces neuronal apoptosis through integrin beta4, ROS, NADPH, and MnSOD.

Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta.

Science.gov (United States)

Dobrowolny, Gabriella; Martini, Martina; Scicchitano, Bianca Maria; Romanello, Vanina; Boncompagni, Simona; Nicoletti, Carmine; Pietrangelo, Laura; De Panfilis, Simone; Catizone, Angela; Bouchè, Marina; Sandri, Marco; Rudolf, Rüdiger; Protasi, Feliciano; Musarò, Antonio

2018-04-20

Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1 G93A in transgenic MLC/SOD1 G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1 G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration. The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1 G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity. Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 28, 1105-1119.

Association of the C47T Polymorphism in SOD2 with Amnestic Mild Cognitive Impairment and Alzheimer’s Disease in Carriers of the APOEε4 Allele

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David Gamarra

2015-01-01

Full Text Available Oxidative stress plays an important part in amnestic mild cognitive impairment (aMCI, the prodromal phase of Alzheimer’s disease (AD. Recent evidence shows that polymorphisms in the SOD2 gene affect the elimination of the reactive oxygen species (ROS generated in mitochondria. The aim of this study was to determine whether the functional rs4880 SNP in the SOD2 gene is a risk factor associated with aMCI and sporadic AD. 216 subjects with aMCI, 355 with AD, and 245 controls have been studied. The SNP rs4880 of the SOD2 gene was genotyped by RT-PCR and the APOE genotype was determined by PCR and RFLPs. Different multinomial logistic regression models were used to determine the risk levels for aMCI and AD. Although the T allele of the SOD2 rs4880 SNP gene (rs4880-T is not an independent risk for aMCI or AD, this allele increases the risk to aMCI patients carrying at least one APOEε4 allele. Moreover, rs4880-T allele and APOEε4 allele combination has been found to produce an increased risk for AD compared to aMCI reference patients. These results suggest that APOEε4 and rs4880-T genotype may be a risk for aMCI and a predictor of progression from aMCI to AD.

Data set for phylogenetic tree and RAMPAGE Ramachandran plot analysis of SODs in Gossypium raimondii and G. arboreum.

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Wang, Wei; Xia, Minxuan; Chen, Jie; Deng, Fenni; Yuan, Rui; Zhang, Xiaopei; Shen, Fafu

2016-12-01

The data presented in this paper is supporting the research article "Genome-Wide Analysis of Superoxide Dismutase Gene Family in Gossypium raimondii and G. arboreum" [1]. In this data article, we present phylogenetic tree showing dichotomy with two different clusters of SODs inferred by the Bayesian method of MrBayes (version 3.2.4), "Bayesian phylogenetic inference under mixed models" [2], Ramachandran plots of G. raimondii and G. arboreum SODs, the protein sequence used to generate 3D sructure of proteins and the template accession via SWISS-MODEL server, "SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information." [3] and motif sequences of SODs identified by InterProScan (version 4.8) with the Pfam database, "Pfam: the protein families database" [4].

Effects of Altered Levels of Extracellular Superoxide Dismutase and Irradiation on Hippocampal Neurogenesis in Female Mice

International Nuclear Information System (INIS)

Zou, Yani; Leu, David; Chui, Jennifer; Fike, John R.; Huang, Ting-Ting

2013-01-01

Purpose: Altered levels of extracellular superoxide dismutase (EC-SOD) and cranial irradiation have been shown to affect hippocampal neurogenesis. However, previous studies were only conducted in male mice, and it was not clear if there was a difference between males and females. Therefore, female mice were studied and the results compared with those generated in male mice from an earlier study. Methods and Materials: Female wild-type, EC-SOD-null (KO), and EC-SOD bigenic mice with neuronal-specific expression of EC-SOD (OE) were subjected to a single dose of 5-Gy gamma rays to the head at 8 weeks of age. Progenitor cell proliferation, differentiation, and long-term survival of newborn neurons were determined. Results: Similar to results from male mice, EC-SOD deficiency and irradiation both resulted in significant reductions in mature newborn neurons in female mice. EC-SOD deficiency reduced long-term survival of newborn neurons whereas irradiation reduced progenitor cell proliferation. Overexpression of EC-SOD corrected the negative impacts from EC-SOD deficiency and irradiation and normalized the production of newborn neurons in OE mice. Expression of neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 were significantly reduced by irradiation in wild-type mice, but the levels were not changed in KO and OE mice even though both cohorts started out with a lower baseline level. Conclusion: In terms of hippocampal neurogenesis, EC-SOD deficiency and irradiation have the same overall effects in males and females at the age the studies were conducted

Imbalance in SOD/CAT activities in rat skeletal muscles submitted to treadmill training exercise.

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Pinho, Ricardo A; Andrades, Michael E; Oliveira, Marcos R; Pirola, Aline C; Zago, Morgana S; Silveira, Paulo C L; Dal-Pizzol, Felipe; Moreira, José Cláudio F

2006-10-01

The association between physical exercise and oxidative damage in the skeletal musculature has been the focus of many studies in literature, but the balance between superoxide dismutase and catalase activities and its relation to oxidative damage is not well established. Thus, the aim of the present study was to investigate the association between regular treadmill physical exercise, oxidative damage and antioxidant defenses in skeletal muscle of rats. Fifteen male Wistar rats (8-12 months) were randomly separated into two groups (trained n=9 and untrained n=6). Trained rats were treadmill-trained for 12 weeks in progressive exercise (velocity, time, and inclination). Training program consisted in a progressive exercise (10 m/min without inclination for 10 min/day). After 1 week the speed, time and inclination were gradually increased until 17 m/min at 10% for 50 min/day. After the training period animals were killed, and gastrocnemius and quadriceps were surgically removed to the determination of biochemical parameters. Lipid peroxidation, protein oxidative damage, catalase, superoxide dismutase and citrate synthase activities, and muscular glycogen content were measured in the isolated muscles. We demonstrated that there is a different modulation of CAT and SOD in skeletal muscle in trained rats when compared to untrained rats (increased SOD/CAT ratio). TBARS levels were significantly decreased and, in contrast, a significant increase in protein carbonylation was observed. These results suggest a non-described adaptation of skeletal muscle against exercise-induced oxidative stress.

A botanical containing freeze dried açai pulp promotes healthy aging and reduces oxidative damage in sod1 knockdown flies

OpenAIRE

Laslo, Mara; Sun, Xiaoping; Hsiao, Cheng-Te; Wu, Wells W.; Shen, Rong-Fong; Zou, Sige

2012-01-01

Superoxide dismutase 1 (SOD1), a critical enzyme against oxidative stress, is implicated in aging and degenerative diseases. We previously showed that a nutraceutical containing freeze-dried açai pulp promotes survival of flies fed a high-fat diet or sod1 knockdown flies fed a standard diet. Here, we investigated the effect of açai supplementation initiated at the early or late young adulthood on lifespan, physiological function, and oxidative damage in sod1 knockdown flies. We found that Aça...

Experimental tests on winter cereal: Sod seeding compared to minimum tillage and traditional plowing

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Antoniotto Guidobono Cavalchini

2013-09-01

Full Text Available Compared to traditional plowing and minimum tillage, the sod seeding technique has been tested in order to evaluate the differences in energy consumption, labor and machinery requirement and CO2 emission reduction. The experiments were conducted on winter cereal seeding in a Po valley farm in October 2011. The tests were carried out as follows: wheat variety seeding, over corn and alfalfa crops, in large plots with three repetitions for each thesis. They included: sod seeding anticipated by round up weeding in the case of the plots over alfalfa; traditional plowing at 35 cm followed by rotary tillage and combined seeding (seeder plus rotary tiller; minimum tillage based on ripping at the same depth (35 cm and combined seeder ( seeder plus rotary tiller. The following farm operations - fertilizer, and other agrochemical distributionshave been the same in all the considered theses. The results, statistically significant (P<0.001 in terms of yields, highlighted slight differences: the best data in the case of the traditional plowing both in the case of wheat crop over corn and alfalfa (84.43 and 6.75 t/ha; slightly lower yields for the sod seeding (6.23 and 79.9 t/ha for corn and alfalfa respectively; lower in the case of minimum tillage (5.87; 79.77 t/ha in the two situations. Huge differences in energy and oil consumption have been recorded: in the case of succession to corn 61.47; 35.31; 4.27 kg oil/ha respectively for, traditional plowing, minimum tillage and sod seeding; in the case of alfalfa 61.2; 50.96; 5.14 kg oil/ha respectively for traditional plowing, minimum tillage and sod seeding. The innovative technique, highlighted huge energy saving with an oil consumption equal to 92% and 89% (P<0.001 of what happens in traditional plowing and minimum tillage. Large differences concern labor and machine productivity. These parameters together with oil consumption and machine size [power (kW and weight (t] lead to even greater differences in

The Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells

International Nuclear Information System (INIS)

Secondo, Agnese; De Mizio, Mariarosaria; Zirpoli, Laura; Santillo, Mariarosaria; Mondola, Paolo

2008-01-01

The Cu-Zn superoxide dismutase (SOD1) belongs to a family of isoenzymes that are able to dismutate the oxygen superoxide in hydrogen peroxide and molecular oxygen. This enzyme is secreted by many cellular lines and it is also released trough a calcium-dependent depolarization mechanism involving SNARE protein SNAP 25. Using rat pituitary GH3 cells that express muscarinic receptors we found that SOD1 inhibits P-ERK1/2 pathway trough an interaction with muscarinic M1 receptor. This effect is strengthened by oxotremorine, a muscarinic M agonist and partially reverted by pyrenzepine, an antagonist of M1 receptor; moreover this effect is independent from increased intracellular calcium concentration induced by SOD1. Finally, P-ERK1/2 inhibition was accompanied by the reduction of GH3 cell proliferation. These data indicate that SOD1 beside the well studied antioxidant properties can be considered as a neuromodulator able to affect mitogen-activated protein kinase in rat pituitary cells trough a M1 muscarinic receptor

Efficacy of topotecan treatment on antioxidant enzymes and TBA-RS levels in submandibular glands of rabbits: an experimental study.

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Muluk, Nuray Bayar; Kisa, Uçler; Kaçmaz, Murat; Apan, Alpaslan; Koç, Can

2005-01-01

The aim of this study was to investigate the effects of topotecan (Hycamtin), a topoisomerase I inhibiting anticancer agent, on antioxidant enzymes (SOD, CAT, and GSH-Px) and TBA-RS values of the submandibular glands of the rabbits. The study was conveyed in two groups (Group I, II) and control with a total of 24 rabbits. Eight rabbits in group I received intravenous (i.v.) topotecan (0.25 mg/kg once daily) for 3 days. Eight rabbits in group II received i.v. topotecan (0.5 mg/kg once daily) for 3 days. On the 15th day after administration of topotecan, submandibular glands were removed and levels of the SOD, CAT, and GSH-Px and the TBA-RS in the submandibular glands of the rabbits were examined. SOD, CAT, and GSH-Px values were significantly higher in high-dose topotecan group compared to control group (P TBA-RS values were significantly higher in high-dose topotecan group compared to low-dose topotecan group (P TBA-RS values in group II showed that permanent damage was present because of high-dose topotecan administration in the submandibular glands of the rabbits.

Quest for anionic MOF membranes: Continuous sod -ZMOF membrane with Co2 adsorption-driven selectivity

KAUST Repository

Almaythalony, Bassem

2015-02-11

We report the fabrication of the first continuous zeolite-like metal-organic framework (ZMOF) thin-film membrane. A pure phase sod-ZMOF, sodalite topology, membrane was grown and supported on a porous alumina substrate using a solvothermal crystallization method. The absence of pinhole defects in the film was confirmed and supported by the occurrence of quantifiable time-lags, for all studied gases, during constant volume/variable pressure permeation tests. For both pure and mixed gas feeds, the sod-ZMOF-1 membrane exhibits favorable permeation selectivity toward carbon dioxide over relevant industrial gases such as H2, N2, and CH4, and it is mainly governed by favorable CO2 adsorption.

Inflammation, oxidative stress, and higher expression levels of Nrf2 and NQO1 proteins in the airways of women chronically exposed to biomass fuel smoke.

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Mondal, Nandan Kumar; Saha, Hirak; Mukherjee, Bidisha; Tyagi, Neetu; Ray, Manas Ranjan

2018-01-24

The study was carried out to examine whether chronic exposure to smoke during daily household cooking with biomass fuel (BMF) elicits changes in airway cytology and expressions of Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2]), Keap1 (Kelch-like erythroid-cell-derived protein with CNC homology [ECH]-associated protein 1), and NQO1 (NAD(P)H:quinone oxidoreductase 1) proteins in the airways. For this, 282 BMF-using women (median age 34 year) and 236 age-matched women who cooked with liquefied petroleum gas (LPG) were enrolled. Particulate matter with diameters of LPG. Compared with LPG users, BMF users had 32% more leukocytes in circulation and their sputa were 1.4-times more cellular with significant increase in absolute number of neutrophils, lymphocytes, eosinophils, and alveolar macrophages, suggesting airway inflammation. ROS generation was 1.5-times higher in blood neutrophils and 34% higher in sputum cells of BMF users while erythrocyte SOD was 31% lower and plasma catalase was relatively unchanged, suggesting oxidative stress. In BMF users, Keap1 expression was reduced, the percentage of AEC with nuclear expression of Nrf2 was two- to three-times more, and NQO1 level in sputum cell lysate was two-times higher than that of LPG users. In conclusion, cooking with BMF was associated with Nrf2 activation and elevated NQO1 protein level in the airways. The changes may be adaptive cellular response to counteract biomass smoke-elicited oxidative stress and inflammation-related tissue injury in the airways.

Ruxolitinib synergizes with DMF to kill via BIM+BAD-induced mitochondrial dysfunction and via reduced SOD2/TRX expression and ROS.

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Tavallai, Mehrad; Booth, Laurence; Roberts, Jane L; McGuire, William P; Poklepovic, Andrew; Dent, Paul

2016-04-05

We determined whether the myelofibrosis drug ruxolitinib, an inhibitor of Janus kinases 1/2 (JAK1 and JAK2), could interact with the multiple sclerosis drug dimethyl-fumarate (DMF) to kill tumor cells; studies used the in vivo active form of the drug, mono-methyl fumarate (MMF). Ruxolitinib interacted with MMF to kill brain, breast, lung and ovarian cancer cells, and enhanced the lethality of standard of care therapies such as paclitaxel and temozolomide. MMF also interacted with other FDA approved drugs to kill tumor cells including Celebrex® and Gilenya®. The combination of [ruxolitinib + MMF] inactivated ERK1/2, AKT, STAT3 and STAT5; reduced expression of MCL-1, BCL-XL, SOD2 and TRX; increased BIM expression; decreased BAD S112 S136 phosphorylation; and enhanced pro-caspase 3 cleavage. Expression of activated forms of STAT3, MEK1 or AKT each significantly reduced drug combination lethality; prevented BAD S112 S136 dephosphorylation and decreased BIM expression; and preserved TRX, SOD2, MCL-1 and BCL-XL expression. The drug combination increased the levels of reactive oxygen species in cells, and over-expression of TRX or SOD2 prevented drug combination tumor cell killing. Over-expression of BCL-XL or knock down of BAX, BIM, BAD or apoptosis inducing factor (AIF) protected tumor cells. The drug combination increased AIF : HSP70 co-localization in the cytosol but this event did not prevent AIF : eIF3A association in the nucleus.

Oxidative Stress and Genotoxicity of Long-Term Occupational Exposure to Low Levels of BTEX in Gas Station Workers

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Feng Xiong

2016-12-01

Full Text Available Atmospheric benzene, toluene, ethylbenzene, and xylenes (BTEX can lead to multiple health injuries. However, what remains uncertain is the effect of long-term exposure to low levels of BTEX. Thus, we determined the BTEX levels in the air from the refueling and office areas in gas stations. Then we collected workers’ (200 refueling vs. 52 office workers peripheral blood samples to analyze the serum total-superoxide dismutase (T-SOD, glutathione (GSH, malondialdehyde (MDA, and 8-hydroxydeoxyguanosine (8-OHdG levels. DNA damage was analyzed by the comet assay and micronucleus test in buccal epithelial cells. We found that the levels of BTEX in refueling areas were significantly higher than those in office areas (p < 0.001. The serum T-SOD and GSH of refueling workers were significantly lower than those in office workers (p < 0.001. By contrast, the serum MDA and 8-OHdG of refueling workers were significantly higher than those of office workers (p < 0.001, MDA; p = 0.025, 8-OHdG. Furthermore, tail and Olive tail moments in refueling workers were longer (p = 0.004, tail moment; p = 0.001, Olive tail moment, and the micronucleus rate was higher (p < 0.001 than those in office workers. Taken together, long-term exposure to low levels of BTEX may reduce the antioxidant ability and increase the risk of DNA damage in refueling workers of gas stations.

Protective Effect of Curcumin Supplementation and Light Resistance Exercises on Superoxide Dismutase Enzyme Activity and Malondialdehyde Levels in a Severe Endurance Training Period in Male Wistar Rats

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A Gorzi

2017-07-01

Background and aim: Extreme endurance exercises lead to oxidative stress in athletes. Therefore, the purpose of this study was to investigate the effect of curcumin supplement supplementation and light resistance training on the activity of SOD and MDA levels of male Wistar rats during a 8-week endurance training. Methods: In the present experimental study, 36 male Wistar rats were randomly assigned into one of six control groups, curcumin, endurance training, exercise, after one week of information (age 9 weeks and weight 255.62 ± 19.69 grams. Endurance + resistance, endurance training + curcumin and endurance training + curcumin + resistance. Incremental endurance training (8 weeks, 5 sessions per week was performed on a special treadmill. Speed ​​and running time in the last week reached 35 m / min and 70 minutes. Resistance training (8 weeks, 2 sessions per week was performed on vertical ladder by closing the rat's weight to the tail. Rats received supplemental curcumin by intraperitoneal injection (8 weeks, 3 sessions per week, 30 mg / kg body weight. SOD activity of the muscle was measured using ELISA kits and serum MDA levels using Tobartic acid (TBARS method. Data were analyzed using one-way ANOVA (ANOVA.   Results: The antioxidant enzyme activity of SOD in the endometrial muscle of endurance group (1.08 ± 0.222 μg / ml was significantly lower than control group (22.2 ± 0.481 kg (P = 0.043, and SOD activity in the endurance + resistance group (1.87 ± 0.172, p = 0.44, endurance + curcumin (2.24 ± 0.222; P = 0.039, and endurance + curcumin + resistance (0.202 ± 0.15, p = 0.029 was significantly higher than endurance group. The levels of malondialdehyde in the endurance group (4.27 ± 0.438 nmol / ml protein were significantly higher in comparison with the control group (3.42 ± 0.350 (0.331 and Also, serum MDA levels in endurance + resistance groups (± 3.03 ± 0.342, p = 0.003, endurance + curcumin (p = 0.001, p <0.001, and endurance + curcumin

Influence of genetic variations in the SOD1 gene on the development of ascites and spontaneous bacterial peritonitis in decompensated liver cirrhosis

DEFF Research Database (Denmark)

Schwab, Sebastian; Lehmann, Jennifer; Lutz, Philipp

2017-01-01

BACKGROUND: The balance between generation and elimination of reactive oxygen species by superoxide dismutase (SOD) is crucially involved in the pathophysiology of liver cirrhosis. Reactive oxygen species damage cells and induce inflammation/fibrosis, but also play a critical role in immune defense...... in carriers of rs1041740. In this cohort, rs1041740 was not associated with survival. CONCLUSION: These data suggest a complex role of SOD1 in different processes leading to complications of liver cirrhosis. rs1041740 might be associated with the development of ascites and possibly plays a role in SBP once...... from pathogens. As both processes are involved in the development of liver cirrhosis and its complications, genetic variation of the SOD1 gene was investigated. PATIENTS AND METHODS: Two SOD1 single nucleotide polymorphisms (rs1041740 and rs3844942) were analyzed in 49 cirrhotic patients undergoing...

Seeking homeostasis: Temporal trends in respiration, oxidation, and calcium in SOD1 G93A Amyotrophic Lateral Sclerosis mice

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Cameron W Irvin

2015-07-01

Full Text Available Impairments in mitochondria, oxidative regulation, and calcium homeostasis have been well documented in numerous amyotrophic lateral sclerosis (ALS experimental models, especially in the superoxide dismutase 1 glycine 93 to alanine (SOD1 G93A transgenic mouse. However, the timing of these deficiencies has been debatable. In a systematic review of 45 articles, we examine experimental measurements of cellular respiration, mitochondrial mechanisms, oxidative markers, and calcium regulation. We evaluate the quantitative magnitude and statistical temporal trend of these aggregated assessments in high transgene copy SOD1 G93A mice compared to wild type mice. Analysis of overall trends reveals cellular respiration, intracellular ATP, and corresponding mitochondrial elements (Cox, cytochrome c, complex I, enzyme activity are depressed for the entire lifespan of the SOD1 G93A mouse. Oxidant markers (H2O2, 8OH2’dG, MDA are initially similar to wild type but are double that of wild type by the time of symptom onset despite early post-natal elevation of protective heat shock proteins. All aspects of calcium regulation show early disturbances, although a notable and likely compensatory convergence to near wild type levels appears to occur between 40-80 days (pre-onset, followed by a post-onset elevation in intracellular calcium. The identified temporal trends and compensatory fluctuations provide evidence that the cause of ALS may lay within failed homeostatic regulation, itself, rather than any one particular perturbing event or cellular mechanism. We discuss the vulnerabilities of motoneurons to regulatory instability and possible hypotheses regarding failed regulation and its potential treatment in ALS.

A Novel Iron Chelator-Radical Scavenger Ameliorates Motor Dysfunction and Improves Life Span and Mitochondrial Biogenesis in SOD1G93A ALS Mice.

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Golko-Perez, Sagit; Amit, Tamar; Bar-Am, Orit; Youdim, Moussa B H; Weinreb, Orly

2017-02-01

The aim of the present study was to evaluate the therapeutic effect of the novel neuroprotective multitarget brain permeable monoamine oxidase inhibitor/iron chelating-radical scavenging drug, VAR10303 (VAR), co-administered with high-calorie/energy-supplemented diet (ced) in SOD1 G93A transgenic amyotrophic lateral sclerosis (ALS) mice. Administration of VAR-ced was initiated after the appearance of disease symptoms (at day 88), as this regimen is comparable with the earliest time at which drug therapy could start in ALS patients. Using this rescue protocol, we demonstrated in the current study that VAR-ced treatment provided several beneficial effects in SOD1 G93A mice, including improvement in motor performance, elevation of survival time, and attenuation of iron accumulation and motoneuron loss in the spinal cord. Moreover, VAR-ced treatment attenuated neuromuscular junction denervation and exerted a significant preservation of myofibril regular morphology, associated with a reduction in the expression levels of genes related to denervation and atrophy in the gastrocnemius (GNS) muscle in SOD1 G93A mice. These effects were accompanied by upregulation of mitochondrial DNA and elevated activities of complexes I and II in the GNS muscle. We have also demonstrated that VAR-ced treatment upregulated the mitochondrial biogenesis master regulator, peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) and increased PGC-1α-targeted metabolic genes and proteins, such as, PPARγ, UCP1/3, NRF1/2, Tfam, and ERRα in GNS muscle. These results provide evidence of therapeutic potential of VAR-ced in SOD1 G93A mice with underlying molecular mechanisms, further supporting the importance role of multitarget iron chelators in ALS treatment.

In vitro and in silico cloning of Xenopus laevis SOD2 cDNA and its phylogenetic analysis.

Science.gov (United States)

Purrello, Michele; Di Pietro, Cinzia; Ragusa, Marco; Pulvirenti, Alfredo; Giugno, Rosalba; Di Pietro, Valentina; Emmanuele, Giovanni; Travali, Salvo; Scalia, Marina; Shasha, Dennis; Ferro, Alfredo

2005-02-01

By using the methodology of both wet and dry biology (i.e., RT-PCR and cycle sequencing, and biocomputational technology, respectively) and the data obtained through the Genome Projects, we have cloned Xenopus laevis SOD2 (MnSOD) cDNA and determined its nucleotide sequence. These data and the deduced protein primary structure were compared with all the other SOD2 nucleotide and amino acid sequences from eukaryotes and prokaryotes, published in public databases. The analysis was performed by using both Clustal W, a well known and widely used program for sequence analysis, and AntiClustAl, a new algorithm recently created and implemented by our group. Our results demonstrate a very high conservation of the enzyme amino acid sequence during evolution, which proves a close structure-function relationship. This is to be expected for very ancient molecules endowed with critical biological functions, performed through a specific structural organization. The nucleotide sequence conservation is less pronounced: this too was foreseeable, due to neutral mutations and to the species-specific codon usage. The data obtained by using AntiClustAl are comparable with those produced with Clustal W, which validates this algorithm as an important new tool for biocomputational analysis. Finally, it is noteworthy that evolutionary trees, drawn by using all the available data on SOD2 nucleotide sequences and amino acid and either Clustal W or AntiClustAl, are comparable to those obtained through phylogenetic analysis based on fossil records.

Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.

Science.gov (United States)

Celic, T; Španjol, J; Bobinac, M; Tovmasyan, A; Vukelic, I; Reboucas, J S; Batinic-Haberle, I; Bobinac, D

2014-12-01

Herein we have demonstrated that both superoxide dismutase (SOD) mimic, cationic Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP(3-)), protect against oxidative stress caused by spinal cord ischemia/reperfusion via suppression of nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N-alkylpyridylporphyrins were able to prevent the DNA binding of NF-κB in an aqueous system, whereas MnTBAP(3-) was not. Here, for the first time, in a complex in vivo system-animal model of spinal cord injury-a similar impact of MnTBAP(3-), at a dose identical to that of MnTnHex-2-PyP(5+), was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The downregulation of NF-κB, a major pro-inflammatory signaling protein regulating astrocyte activation, was detected and found to correlate well with the suppression of astrogliosis (as glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP(3-) with reactive nitrogen species (RNS) (.NO/HNO/ONOO(-)) suggests that RNS/MnTBAP(3-)-driven modification of NF-κB protein cysteines may be involved in its therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP(5+) which presumably occurs via reactive

Long-Lived Termite Queens Exhibit High Cu/Zn-Superoxide Dismutase Activity

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Eisuke Tasaki

2018-01-01

Full Text Available In most organisms, superoxide dismutases (SODs are among the most effective antioxidant enzymes that regulate the reactive oxygen species (ROS generated by oxidative energy metabolism. ROS are considered main proximate causes of aging. However, it remains unclear if SOD activities are associated with organismal longevity. The queens of eusocial insects, such as termites, ants, and honeybees, exhibit extraordinary longevity in comparison with the nonreproductive castes, such as workers. Therefore, the queens are promising candidates to study the underlying mechanisms of aging. Here, we found that queens have higher Cu/Zn-SOD activity than nonreproductive individuals of the termite Reticulitermes speratus. We identified three Cu/Zn-SOD sequences and one Mn-SOD sequence by RNA sequencing in R. speratus. Although the queens showed higher Cu/Zn-SOD activity than the nonreproductive individuals, there were no differences in their expression levels of the Cu/Zn-SOD genes RsSOD1 and RsSOD3A. Copper (Cu2+ and Cu+ is an essential cofactor for Cu/Zn-SOD enzyme activity, and the queens had higher concentrations of copper than the workers. These results suggest that the high Cu/Zn-SOD activity of termite queens is related to their high levels of the cofactor rather than gene expression. This study highlights that Cu/Zn-SOD activity contributes to extraordinary longevity in termites.

Local and systemic oxidative stress and glucocorticoid receptor levels in chronic obstructive pulmonary disease patients

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Zeng, Mian; Li, Yue; Jiang, Yujie; Lu, Guifang; Huang, Xiaomei; Guan, Kaipan

2013-01-01

BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To study local and systemic oxidative stress status in COPD patients, and to clarify the relationship between local and systemic oxidative stress. METHODS: Lipid peroxide malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and GSH peroxidase (GSH-PX) levels in induced sputum and plasma, as well as glucocorticoid receptor (GR) levels in peripheral blood leukocytes were examined in 43 acute exacerbation of COPD patients (group A), 35 patients with stable COPD (group B) and 28 healthy controls (14 smokers [group C]; 14 nonsmokers [group D]). RESULTS: MDA levels in induced sputum and plasma decreased progressively in groups A to D, with significant differences between any two groups (P<0.001). GSH, SOD and GSH-PX levels in both induced sputum and plasma increased progressively in groups A to D, with significant differences between any two groups (P<0.001). GR levels in peripheral blood leukocytes decreased progressively in groups D to A (all comparisons P<0.001). Pearson analysis revealed strong correlations between MDA, GSH, SOD and GSH-PX levels in plasma and induced sputum. The activity of SOD in plasma and sputum were both positively correlated with GR levels (partial correlation coefficients 0.522 and 0.574, respectively [P<0.001]). CONCLUSIONS: Oxidative stress levels were elevated in COPD patients. There was a correlation between local and systemic oxidative status in COPD, and between decreased SOD activity and decreased GR levels in COPD patients. PMID:23457673

An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of Caenorhabditis elegans.

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Jiou Wang

2009-01-01

Full Text Available The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level, mutant animals exhibited a reduced number of synaptic vesicles. Neurotoxicity in this system thus appears to be mediated by misfolded SOD1 and is exerted on synaptic vesicle biogenesis and/or trafficking.

Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF

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Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2015-01-01

Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3–5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. PMID:25653590

Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF.

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Alexandre eHenriques

2015-01-01

Full Text Available ABSTRACTBackgroundAmyotrophic lateral sclerosis (ALS is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. ResultsMotoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age, when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age. Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12.ConclusionsOur data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

Gene expression changes in spinal motoneurons of the SOD1(G93A) transgenic model for ALS after treatment with G-CSF.

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Henriques, Alexandre; Kastner, Stefan; Chatzikonstantinou, Eva; Pitzer, Claudia; Plaas, Christian; Kirsch, Friederike; Wafzig, Oliver; Krüger, Carola; Spoelgen, Robert; Gonzalez De Aguilar, Jose-Luis; Gretz, Norbert; Schneider, Armin

2014-01-01

Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1(G93A) mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Motoneurons from SOD1(G93A) mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1(G93A) motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1(G93A) motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS.

Etiology and evidence of systemic acidification in SOD-affected forests of California

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Lee Klinger; Ralph Zingaro

2006-01-01

Pathologists investigating the widespread death of oak trees in the forest ecosystems of northern California concluded, in 2000, that the problem was due to a new plant disease, dubbed sudden oak death (SOD), which is caused by the fungal pathogen Phytophthora ramorum. Since then this one organism has been the focal point of notable efforts to...

Mutagenicity and co-mutagenicity of static magnetic field in SOD-deficient Escherichia coli

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Yoshie, Sachiko; Ikehata, Masateru; Hayakawa, Toshio; Hirota, Noriyuki; Takemura, Taro; Minowa, Takashi; Hanagata, Nobutaka

2008-01-01

The effects of strong static magnetic fields (SMFs) on mutagenesis related to reactive oxygen species were investigated. To estimate mutagenicity of SMFs, superoxide dismutase (SOD)-deficient Escherichia coli QC774 and its parental strain GC4468 were employed. Tester strains were exposed to 5, 10 and 13 T SMFs for 24 hr at 37 C degrees in LB medium. After exposure, mutation frequency on thymine synthesis genes was determined for evaluation of mutagenicity of SMFs exposure. In the result, no statistically significant difference in mutation frequency on thymine synthesis genes was observed between SMF-exposed cells and unexposed cells in all of magnetic flux densities. Furthermore, SMFs up to 13 T did not affect mutagenicity of plumbagine under its presence of 25 μM, respectively. It suggests that SMF did not have either mutagenicity or co-mutagenicity in SOD-deficient and its parental E. coli strains under the condition in this study. (author)

Erythrocytes antioxygant parameters in works occupationally to law levels of ionizing radiation

International Nuclear Information System (INIS)

Klucinski, P.; Martirosian, G.; Wojcik, A.; Grabowska-Bochenek, R.; Gminmski, J.; Mazur, B.; Hrycek, A.; Cieslik, P.

2008-01-01

It has been postulated that ionizing radiation generates reactive oxygen species (ROS). ROS are annihilated by an intracellular enzymatic system composed mainly of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Workers of X-ray departments are occupationally exposed to long-term low levels of ionizing radiation, which may affect their antioxidant status. Erythrocyte activities of SOD, CAT and GPx were measured in 45 workers of X-ray departments and 30 persons who constituted the control group. Subgroups with respect to sex and cigarette smoking were selected. Colorimetric method was used for determination erythrocyte activities of SOD, CAT and GPx. A significant decrease of GPx, SOD and CAT activity in workers as compared to controls was observed. Lower activity of SOD and GPx in female and GPx in male subgroup was found. SOD was significantly more elevated in smoking workers than in the non-smoking staff. Moreover non-smoking employees showed lower SOD and GPx activity in comparison to the non-smoking control. GPx decrease was found in smoking workers in comparison to the smoking control. Additionally, smoking workers showed lower activity of GPx and CAT compared to non-smoking control. (author)

Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS

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De Rose, Francescaelena; Marotta, Roberto; Talani, Giuseppe; Catelani, Tiziano; Solari, Paolo; Poddighe, Simone; Borghero, Giuseppe; Marrosu, Francesco; Sanna, Enrico; Kasture, Sanjay; Acquas, Elio; Liscia, Anna

2017-01-01

The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions. Interestingly, Wse treatment significantly increased lifespan of hSDO1 while Mpe had not effect. Conversely, both Wse and Mpe significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Wse- but not in Mpe-treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Wse and Mpe might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptoms. PMID:28102336

Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression

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Hsieh, Y.-S.; Yang, S.-F.; Chiou, H.-L.; Kuo, D.-Y.

2006-01-01

Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain were performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression

SOD-induced changes in foraging and nesting behavior of insectivorous, cavity-nesting birds

Science.gov (United States)

Kyle Apigian; Barbara Allen-Diaz

2006-01-01

Sudden oak death (SOD) is a tree disease caused by a recently described pathogen, Phytophthora ramorum. The disease affects dozens of plant species, but its effects are particularly pronounced in stands of coast live oak (Quercus agrifolia), often resulting in large stands with dead canopies and many downed trees. Such disease-...

Mitochondrial DNA (mtDNA haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis

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Fernandez-Moreno Mercedes

2011-11-01

Full Text Available Abstract Background Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2 and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers. Methods We analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI, age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes. Results Serum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p Conclusions The increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase

The Effect of Fasting on the Concentration of Enzimatic Antioxidants (Superoxide Dismutase and Glutathione Peroxidase in Rats

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Muliatul Jannah

2016-06-01

Full Text Available Introduction: Consumption of excessive calories can increase the incidence of degenerative diseases mediated by ROS. Caloric restriction, have been shown to increase levels of antioxidants superoxide dismutase (SOD and Gluthatione Peroxidase (GPx. Fasting like Ramadan fasting (FLRF is a form of calorie restriction, but its effect on levels of SOD and GPx remains unclear. Objectives: to investigate the effect of fasting on levels of SOD and GPx. Methods: in a post-test only control group design, sample of 24 rats Sprague Dawley Rats aged 3-month-old, weighing 250-300 grams, were randomly divided into 4 groups. Group 1 (P-70, 2 (P-100, and 3 (P-140 were fasted for 6 hours/day, each group received of 70%, 100% and 140% calories respectively. Group 4 (C-AL received 100% calories, ad libitum. Day 16 blood was taken and levels of SOD and GPx were determined by ELISA. Data were analyzed using one-way ANOVAs, followed by post hoc LSD tests, p<0.05 was considered statistically significant. Results: the results showed that the levels of SOD and GPx occur significant differences between the groups, p = 0.000. The test results post hoc SOD (318.64 and GPx (89.16 group P-70, compared with group C-AL (278.60 and 57.20 was significantly higher (p = 0.00. SOD and GPx P-70 group compared with the group P-140 (92.03 and 48.79, significantly higher (p = 0.00. Compared with group P-100 (296.70 and 75.71 SOD and GPx in group P-70 was significantly higher, p = 0.000. Conclusion: Fasting with calorie intake of 70% and 100% for 15 days can increases levels of SOD and GPx in male rats.

Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice

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Koiram, P.R.; Veerapur, V.P.; Mazhuvancherry, U.K.; Kunwar, A.; Mishra, B.; Barik, A.; Priyadarsini, I.K.

2007-01-01

The effect of mononuclear copper (II) complex of curcumin in 1:1 stoichiometry (hereafter referred to as complex) administered 30 mim before γ-irradiation (4.5 Gy) on alterations in antioxidant and Thiobarbituric acid reactive substances (TBARS) levels in livers was studied in comparison to curcumin at a dose of 50 mg/kg. The different antioxidants like glutathione (GSH), glutathione-S-transferase (GST), catalase, superoxide dismuatase (SOD), TBARS and total thiols were estimated in the liver homogenates excised at different time intervals (1, 2 and 4 h) post irradiation using colorimetric methods. There was a radiation-induced decrease in the levels of all the studied enzymes at 1 h post irradiation, while an increase was observed at later time points. Both curcumin and complex treatment in sham-irradiated mice decreased the levels of GSH and total thiols, whereas there was an increase in the levels of catalase, GST and SOD compared to normal control. Under the influence of irradiation, both curcumin and complex treatment protected the decline in the levels of GSH, GST, SOD, catalase and total thiols, and inhibited radiation-induced lipid peroxidation. Further, the complex was found to be more effective in protecting the enzymes at 1 h post irradiation compared to curcumin treated group. This may be due to the higher rate constants of the complex compared to curcumin for their reactions with various free radicals. (author)

Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice

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Koiram, P R; Veerapur, V P; Mazhuvancherry, U K [Manipal Coll. of Pharmaceutical Sciences, Manipal (India); Kunwar, A; Mishra, B; Barik, A; Priyadarsini, I K [Bhabha Atomic Research Center, Mumbai (India)

2007-05-15

The effect of mononuclear copper (II) complex of curcumin in 1:1 stoichiometry (hereafter referred to as complex) administered 30 mim before {gamma}-irradiation (4.5 Gy) on alterations in antioxidant and Thiobarbituric acid reactive substances (TBARS) levels in livers was studied in comparison to curcumin at a dose of 50 mg/kg. The different antioxidants like glutathione (GSH), glutathione-S-transferase (GST), catalase, superoxide dismuatase (SOD), TBARS and total thiols were estimated in the liver homogenates excised at different time intervals (1, 2 and 4 h) post irradiation using colorimetric methods. There was a radiation-induced decrease in the levels of all the studied enzymes at 1 h post irradiation, while an increase was observed at later time points. Both curcumin and complex treatment in sham-irradiated mice decreased the levels of GSH and total thiols, whereas there was an increase in the levels of catalase, GST and SOD compared to normal control. Under the influence of irradiation, both curcumin and complex treatment protected the decline in the levels of GSH, GST, SOD, catalase and total thiols, and inhibited radiation-induced lipid peroxidation. Further, the complex was found to be more effective in protecting the enzymes at 1 h post irradiation compared to curcumin treated group. This may be due to the higher rate constants of the complex compared to curcumin for their reactions with various free radicals. (author)

Association of manganese superoxide dismutase Ala16Val polymorphism in the incidence of acute myocardial infarction in the Egyptians

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Lobna M. Abdelrauf

2017-12-01

Full Text Available Background: Oxidative stress has been implicated in various diseases including atherosclerosis; the most common pathologic process underlying acute myocardial infarction (AMI. The manganese superoxide dismutase (MnSOD antioxidant enzyme affords the major defense against reactive oxygen species (ROS within the mitochondria. MnSOD Alanine16Valine (A16V single nucleotide polymorphism (SNP has been shown to decrease MnSOD detoxification activity. Aim: A case-control study was conducted to investigate the association between MnSOD A16V polymorphism and the incidence of AMI in the Egyptians, investigate the contribution of oxidative stress represented by hexanoyl lysine adduct (HEL, an oxidative stress biomarker, in the pathogenesis of AMI and finally correlate the MnSOD genotypes with HEL serum levels. Methods: A total of 200 Egyptian subjects were recruited for the study; 100 AMI patients and 100 control subjects. Genotypes of the MnSOD A16V polymorphism were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Serum HEL was measured by ELISA. Results: A significant difference in the distribution of the MnSOD A16V genotypes was observed; VV genotype was significantly higher in AMI than controls (p ≤ 0.0001. Also, studying the allele frequencies revealed that Val allele was significantly higher in AMI than controls (p ≤ 0.0001. Serum analysis showed higher levels of HEL in AMI patients (p = 0.0142. Furthermore, HEL levels were found to be significantly higher in VV genotype in AMI (p = 0.0273. Conclusions: Our study suggests that MnSOD A16V polymorphism is associated with increased risk of developing AMI in the Egyptians. Moreover, the VV genotype is associated with higher HEL levels.

FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis.

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Deng, Han-Xiang; Zhai, Hong; Bigio, Eileen H; Yan, Jianhua; Fecto, Faisal; Ajroud, Kaouther; Mishra, Manjari; Ajroud-Driss, Senda; Heller, Scott; Sufit, Robert; Siddique, Nailah; Mugnaini, Enrico; Siddique, Teepu

2010-06-01

Amyotrophic lateral sclerosis (ALS) is a fatal disorder of motor neuron degeneration. Most cases of ALS are sporadic (SALS), but about 5 to 10% of ALS cases are familial (FALS). Recent studies have shown that mutations in FUS are causal in approximately 4 to 5% of FALS and some apparent SALS cases. The pathogenic mechanism of the mutant FUS-mediated ALS and potential roles of FUS in non-FUS ALS remain to be investigated. Immunostaining was performed on postmortem spinal cords from 78 ALS cases, including SALS (n = 52), ALS with dementia (ALS/dementia, n = 10), and FALS (n = 16). In addition, postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also studied. In total, 100 cases were studied. FUS-immunoreactive inclusions were observed in spinal anterior horn neurons in all SALS and FALS cases, except for those with SOD1 mutations. The FUS-containing inclusions were also immunoreactive with antibodies to TDP43, p62, and ubiquitin. A fraction of tested FUS antibodies recognized FUS inclusions, and specific antigen retrieval protocol appeared to be important for detection of the skein-like FUS inclusions. Although mutations in FUS account for only a small fraction of FALS and SALS, our data suggest that FUS protein may be a common component of the cellular inclusions in non-SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying SALS, non-SOD1 FALS, ALS/dementia, and related disorders. Our data also indicate that SOD1-linked ALS may have a pathogenic pathway distinct from SALS and other types of FALS.

SOD1 Gene +35A/C (exon3/intron3 Polymorphism in Type 2 Diabetes Mellitus among South Indian Population

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K. Nithya

2016-01-01

Full Text Available Superoxide dismutase is an antioxidant enzyme that is involved in defence mechanisms against oxidative stress. Cu/Zn SOD is a variant that is located in exon3/intron3 boundary. The aim of the present study was to investigate whether the Cu/Zn SOD (+35A/C gene polymorphism is associated with the susceptibility to type 2 diabetes mellitus among south Indian population. The study included patients with type 2 diabetes mellitus (n=100 and healthy controls (n=75. DNA was isolated from the blood and genotyping of Cu/Zn SOD gene polymorphism was done by polymerase chain reaction based restriction fragment length polymorphism method. Occurrence of different genotypes and normal (A and mutant (C allele frequencies were determined. The frequency of the three genotypes of the total subjects was as follows: homozygous wild-type A/A (95%, heterozygous genotype A/C (3%, and homozygous mutant C/C (2%. The mutant (C allele and the mutant genotypes (AC/CC were found to be completely absent among the patients with type 2 diabetes mellitus. Absence of mutant genotype (CC shows that the Cu/Zn SOD gene polymorphism may not be associated with the susceptibility to type 2 diabetes mellitus among south Indian population.

Exercise training improves relaxation response and SOD-1 expression in aortic and mesenteric rings from high caloric diet-fed rats

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Antunes Edson

2008-05-01

Full Text Available Abstract Background Obesity has been associated with a variety of disease such as type II diabetes mellitus, arterial hypertension and atherosclerosis. Evidences have shown that exercise training promotes beneficial effects on these disorders, but the underlying mechanisms are not fully understood. The aim of this study was to investigate whether physical preconditioning prevents the deleterious effect of high caloric diet in vascular reactivity of rat aortic and mesenteric rings. Methods Male Wistar rats were divided into sedentary (SD; trained (TR; sedentary diet (SDD and trained diet (TRD groups. Run training (RT was performed in sessions of 60 min, 5 days/week for 12 weeks (70–80% VO2max. Triglycerides, glucose, insulin and nitrite/nitrate concentrations (NOx- were measured. Concentration-response curves to acetylcholine (ACh and sodium nitroprusside (SNP were obtained. Expression of Cu/Zn superoxide dismutase (SOD-1 was assessed by Western blotting. Results High caloric diet increased triglycerides concentration (SDD: 216 ± 25 mg/dl and exercise training restored to the baseline value (TRD: 89 ± 9 mg/dl. Physical preconditioning significantly reduced insulin levels in both groups (TR: 0.54 ± 0.1 and TRD: 1.24 ± 0.3 ng/ml as compared to sedentary animals (SD: 0.87 ± 0.1 and SDD: 2.57 ± 0.3 ng/ml. On the other hand, glucose concentration was slightly increased by high caloric diet, and RT did not modify this parameter (SD: 126 ± 6; TR: 140 ± 8; SDD: 156 ± 8 and TRD 153 ± 9 mg/dl. Neither high caloric diet nor RT modified NOx- levels (SD: 27 ± 4; TR: 28 ± 6; SDD: 27 ± 3 and TRD: 30 ± 2 μM. Functional assays showed that high caloric diet impaired the relaxing response to ACh in mesenteric (about 13%, but not in aortic rings. RT improved the relaxing responses to ACh either in aortic (28%, for TR and 16%, to TRD groups or mesenteric rings (10%, for TR and 17%, to TRD groups that was accompanied by up-regulation of SOD-1

Quest for anionic MOF membranes: Continuous sod -ZMOF membrane with Co2 adsorption-driven selectivity

KAUST Repository

Almaythalony, Bassem; Shekhah, Osama; Swaidan, Raja; Belmabkhout, Youssef; Pinnau, Ingo; Eddaoudi, Mohamed

2015-01-01

We report the fabrication of the first continuous zeolite-like metal-organic framework (ZMOF) thin-film membrane. A pure phase sod-ZMOF, sodalite topology, membrane was grown and supported on a porous alumina substrate using a solvothermal

Serum Antioxidative Enzymes Levels and Oxidative Stress Products in Age-Related Cataract Patients

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Dong Chang

2013-01-01

Full Text Available Purpose. To investigate the activity of antioxidative enzymes and the products of oxidative stress in patients with age-related cataracts and compare the findings with those in healthy control subjects. Method. Sixty patients with age-related cataract and sixty healthy controls of matched age and gender were included in this study. Serum samples were obtained to detect the antioxidative enzymes of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px, and oxidation degradation products of malondialdehyde (MDA, 4-hydroxynonenal (4-HNE, conjugated diene (CD, advanced oxidation protein products (AOPP, protein carbonyl (PC, and 8-hydroxydeoxyguanosine (8-OHdG. Results. Serum SOD, GSH-Px, and CAT activities in cataract group were significantly decreased as compared to the control subjects (P<0.05. The levels of MDA, 4-HNE, and CD in cataract patients were significantly higher than those in the control subjects (P<0.05, P<0.01. Cataract patients had higher levels of 8-OHdG, AOPP, and PC with respect to the comparative group of normal subjects (P<0.01. And there was no statistical significance in concentration of antioxidative enzymes and oxidative stress products in patients with different subtype cataract. Conclusions. Oxidative stress is an important risk factor in the development of age-related cataract, and augmentation of the antioxidant defence systems may be of benefit to prevent or delay cataractogenesis.

MnSOD and catalase transgenes demonstrate that protection of islets from oxidative stress does not alter cytokine toxicity.

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Chen, Hainan; Li, Xiaoyan; Epstein, Paul N

2005-05-01

Reactive oxygen species (ROS) and nitric oxide (NO) are proposed mediators of cytokine-induced beta-cell destruction in type 1 diabetes. We produced transgenic mice with increased beta-cell expression of manganese superoxide dismutase (MnSOD) and catalase. Expression of these antioxidants increased beta-cell ROS scavenging and improved beta-cell survival after treatment with different sources of ROS. MnSOD or catalase conferred protection against streptozotocin (STZ)-induced beta-cell injury. Coexpression of MnSOD and catalase provided synergistic protection against peroxynitrite and STZ. To determine the potential effect of these antioxidants on cytokine-induced toxicity, we exposed isolated islets to a cytokine mixture, including interleukin-1beta and interferon-gamma. Cytokine toxicity was measured as reduced metabolic activity after 6 days and reduced insulin secretion after 1 day. Cytokines increased ROS production, and both antioxidants were effective in reducing cytokine-induced ROS. However, MnSOD and/or catalase provided no protection against cytokine-induced injury. To understand this, the nuclear factor-kappaB (NF-kappaB) signaling cascade was investigated. Antioxidants reduced NF-kappaB activation by ROS, but none of the antioxidants altered activation by cytokines, as measured by inhibitor of kappaB phosphorylation, NF-kappaB translocation, inducible NO synthase activation, and NO production. Our data agree with previous reports that antioxidants benefit beta-cell survival against ROS damage, but they are not consistent with reports that antioxidants reduce cytokine toxicity. ROS appear to have no role in cytokine toxicity in primary beta-cells.

Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

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Ramos, Geovana Brotto; Salomão, Heloisa; Francio, Angela Schneider; Fava, Vinícius Medeiros; Werneck, Renata Iani; Mira, Marcelo Távora

2016-08-01

Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy. © 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.

Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up

International Nuclear Information System (INIS)

Grundmark, Birgitta; Zethelius, Björn; Garmo, Hans; Holmberg, Lars

2011-01-01

Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se. ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms. In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (≤80 μg/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa. S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue

Measuring Neuromuscular Junction Functionality in the SOD1(G93A) Animal Model of Amyotrophic Lateral Sclerosis.

Science.gov (United States)

Rizzuto, Emanuele; Pisu, Simona; Musarò, Antonio; Del Prete, Zaccaria

2015-09-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that leads to motor neuron degeneration, alteration in neuromuscular junctions (NMJs), muscle atrophy, and paralysis. To investigate the NMJ functionality in ALS we tested, in vitro, two innervated muscle types excised from SOD1(G93A) transgenic mice at the end-stage of the disease: the Soleus, a postural muscle almost completely paralyzed at that stage, and the diaphragm, which, on the contrary, is functional until death. To this aim we employed an experimental protocol that combined two types of electrical stimulation: the direct stimulation and the stimulation through the nerve. The technique we applied allowed us to determine the relevance of NMJ functionality separately from muscle contractile properties in SOD1(G93A) animal model. Functional measurements revealed that the muscle contractility of transgenic diaphragms is almost unaltered in comparison to control muscles, while transgenic Soleus muscles were severely compromised. In contrast, when stimulated via the nerve, both transgenic muscle types showed a strong decrease of the contraction force, a slowing down of the kinetic parameters, as well as alterations in the neurotransmission failure parameter. All together, these results confirm a severely impaired functionality in the SOD1(G93A) neuromuscular junctions.

The Effects of Long-Term Feeding of Rodent Food Bars on Lipid Peroxidation And Antioxidant Enzyme Levels In Fisher Rats

Science.gov (United States)

Ramirez, Joel; Zirkle-Yoshida, M.; Piert, S.; Barrett, J.; Yul, D.; Dalton, B.; Girten, B.

2001-01-01

A specialized rodent food bar diet has been developed and utilized successfully for short-duration shuttle missions. Recent tests conducted in preparation for experiments aboard the International Space Station (ISS) indicated that long-term food bar feeding for three months induced hyperlipidemia in rats. This study examined oxidative stress status in livers of these same animals. Spectrophotometric analysis of 79 Fischer rat livers (40 female and 39 male) for lipid peroxidation (LPO) and superoxide dismutase (SOD) was conducted using Bioxytech LPO-587(TM) assay kit and SOD-525(Tm) assay kit, respectively. The treatment groups consisted of 20 male CHOW and 19 male FOOD BAR rats and 20 female CHOW and 20 female FOOD BAR rats. Statistical analysis to compare differences between groups was performed by standard analysis of variance procedures. The male FOOD BAR group LPO mean (3.6 +/- 0.2 mmol/g) was significantly (p less than or equal to 0.05) greater than that of the male CHOW group (2.1 +/-0.1 mmol/g). Moreover the female FOOD BAR group LPO mean (2.9 +/-0.1 mmol/g) was also significantly greater than the female CHOW group mean (2.2 +/-0.1 mmol/g). The mean values for SOD in both male and female groups showed no significant differences between CHOW and FOOD BAR groups. These results show that LPO levels were significantly higher in both the male and female FOOD BAR groups compared to CHOW groups and that there was no concomitant increase in SOD levels across the group. In addition, males showed a greater difference than females in terms of LPO levels. These findings suggest a need for further investigation into the use of the current food bar formulation for long-term experiments such as those planned for the ISS.

Basic study on low dose radiation effect: SOD activity of immune organs and hemogram in rats

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Kaneko, Ichiro; Mizutani, Takeo; Nakano, Kazushiro; Edamatsu, Rei; Mori, Akitane.

1989-01-01

We examined the effect of low dose radiation on SOD activities of immune organs such as thymus, spleen, bone marrow in rats and hematological findings changes. Animals were exposed to radiation in a wholebody fashion, 4 hours before sacrifice. SOD activities in thymus and bone marrow cells from the rats X-ray irradiated at doses of 0.25∼0.50 Gy/10 min were enhanced in comparison with those of non-irradiated rats. The enhancement was also observed in spleen cells obtained from group of rats irradiated at 0.05 Gy/10 min. Radiation exposure with over 0.50 Gy/10 min gave rats inhibitory responses in those immune organs. The changes in homogram were not observed with γ-ray exposure of less than 0.10 Gy/10 min. (author)

Radio frequency plasma nitriding of aluminium at higher power levels

International Nuclear Information System (INIS)

Gredelj, Sabina; Kumar, Sunil; Gerson, Andrea R.; Cavallaro, Giuseppe P.

2006-01-01

Nitriding of aluminium 2011 using a radio frequency plasma at higher power levels (500 and 700 W) and lower substrate temperature (500 deg. C) resulted in higher AlN/Al 2 O 3 ratios than obtained at 100 W and 575 deg. C. AlN/Al 2 O 3 ratios derived from X-ray photoelectron spectroscopic analysis (and corroborated by heavy ion elastic recoil time of flight spectrometry) for treatments preformed at 100 (575 deg. C), 500 (500 deg. C) and 700 W (500 deg. C) were 1.0, 1.5 and 3.3, respectively. Scanning electron microscopy revealed that plasma nitrided surfaces obtained at higher power levels exhibited much finer nodular morphology than obtained at 100 W

Assessing the Need for Higher Levels of Care Among Problem Gambling Outpatients.

Science.gov (United States)

Ledgerwood, David M; Arfken, Cynthia L

2017-12-01

Most treatment for gambling disorder is provided on an outpatient basis. Only a small number of jurisdictions in North America provide higher levels of gambling treatment, such as residential or intensive outpatient (IOP) care, despite the potential need for these services. Further, there appear to be few guidelines for determining appropriate level of gambling treatment. The aim of the present study was to assess the appropriateness of higher levels of problem gambling care among clients receiving outpatient treatment. Problem gamblers and their therapists independently completed questionnaires that assessed the need and desire for residential and IOP treatment. About 42% of problem gambling outpatients noted that they would be "probably" or "definitely" willing to attend residential treatment, and about half indicated they would be equally likely to attend IOP. Therapists recommended about a third of their clients as appropriate for higher levels of care. For both client and therapist assessments, there was a significant association between desire or recommendation for level of treatment and severity of gambling and co-occurring problems. Further, therapist recommendations for level of care were significantly associated with client willingness to attend higher levels of treatment. Our data reveal the potential need for higher levels of care for problem gambling, as evaluated by clients and their therapists. Policy implications for the funding of residential and IOP treatment are discussed.

Bee Venom Acupuncture Augments Anti-Inflammation in the Peripheral Organs of hSOD1G93A Transgenic Mice.

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Lee, Sun-Hwa; Choi, Sun-Mi; Yang, Eun Jin

2015-07-29

Amyotrophic lateral sclerosis (ALS) includes progressively degenerated motor neurons in the brainstem, motor cortex, and spinal cord. Recent reports demonstrate the dysfunction of multiple organs, including the lungs, spleen, and liver, in ALS animals and patients. Bee venom acupuncture (BVA) has been used for treating inflammatory diseases in Oriental Medicine. In a previous study, we demonstrated that BV prevented motor neuron death and increased anti-inflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. In this study, we examined whether BVA's effects depend on acupuncture point (ST36) in the organs, including the liver, spleen and kidney, of hSOD1G93A transgenic mice. We found that BV treatment at ST36 reduces inflammation in the liver, spleen, and kidney compared with saline-treatment at ST36 and BV injected intraperitoneally in symptomatic hSOD1G93A transgenic mice. Those findings suggest that BV treatment combined with acupuncture stimulation is more effective at reducing inflammation and increasing immune responses compared with only BV treatment, at least in an ALS animal model.

Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARγ/CuZn-SOD axis expression in diet-induced obesity mice.

Science.gov (United States)

Araújo, Tiago Gomes; Oliveira, Alexandre Gabarra; Vecina, Juliana Falcato; Marin, Rodrigo Miguel; Franco, Eryvelton Souza; Abdalla Saad, Mario J; de Sousa Maia, Maria Bernadete

2016-08-01

Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-α and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor γ (PPARγ) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARγ/Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARγ/CuZn-SOD axis expression.

Role of nitric oxide and antioxidant enzymes in the pathogenesis of oral cancer.

Science.gov (United States)

Patel, Jayendrakumar B; Shah, Franky D; Shukla, Shilin N; Shah, Pankaj M; Patel, Prabhudas S

2009-01-01

Oral cancer is the leading malignancy in India. Nitric oxide and antioxidant enzymes play an important role in etiology of oral cancer. Therefore, the present study evaluates nitric oxide and antioxidant enzyme levels in healthy individual without tobacco habits (NHT, N=30) and healthy individuals with tobacco habits (WHT, n=90), patients with oral precancers (OPC, n=15) and oral cancer patients (n=126). Blood samples were collected from the subjects. NO2 + NO3 (nitrite+nitrate), superoxide dismutase (SOD) and catalase levels were estimated using highly specific spectrophotometeric methods. Statistical analysis was done by SPSS statistical software version 10. Mean plasma NO2 + NO3 levels were elevated in patients with OPC and oral cancer patients as compared to the controls. Mean activities of erythrocyte SOD and catalase were higher in WHT than NHT. Erythrocyte SOD and catalase levels were higher in WHT and patients with OPC as compared to NHT. The erythrocyte SOD and catalase activities were lower in oral cancer patients than patients with OPC. The erythrocyte SOD activity was higher in advanced oral cancer than the early disease. Erythrocyte catalase activity was lower in poorly differentiated tumors than well and moderately differentiated tumors. Pearson's correlation analysis revealed that alterations in plasma NO2 + NO3 levels were negatively associated with changes in erythrocyte SOD activities. The data revealed that the alterations in antioxidant activities were associated with production of nitric oxide in oral cancer, which may have significant role in oral carcinogenesis.

miR-140-5p regulates hypoxia-mediated human pulmonary artery smooth muscle cell proliferation, apoptosis and differentiation by targeting Dnmt1 and promoting SOD2 expression

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yanwei; Xu, Jing, E-mail: xujingdoc@163.com

2016-04-22

miR-140-5p is down-regulated in patients with pulmonary arterial hypertension (PAH) and experimental models of PAH, and inhibits hypoxia-mediated pulmonary artery smooth muscle cell (PASMC) proliferation in vitro. Delivery of synthetic miR-140-5p prevents and treats established, experimental PAH. DNA methyltransferase 1 (Dnmt1) is up-regulated in PAH associated human PASMCs (HPASMCs), which promotes the development of PAH by hypermethylation of CpG islands within the promoter for superoxide dismutase 2 (SOD2) and down-regulating SOD2 expression. We searched for miR-140-5p targets using TargetScan, PicTar and MiRanda tools, and found that Dnmt1 is a potential target of miR-140-5p. Based on these findings, we speculated that miR-140-5p might target Dnmt1 and regulate SOD2 expression to regulate hypoxia-mediated HPASMC proliferation, apoptosis and differentiation. We detected the expression of miR-140-5p, Dnmt1 and SOD2 by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assays, respectively, and found down-regulation of miR-140-5p and SOD2 and up-regulation of Dnmt1 exist in PAH tissues and hypoxia-mediated HPASMCs. Cell proliferation, apoptosis and differentiation detection showed that miR-140-5p inhibits proliferation and promotes apoptosis and differentiation of HPASMCs in hypoxia, while the effect of Dnmt1 on hypoxia-mediated HPASMCs is reversed. Luciferase assay confirmed that miR-140-5p targets Dnmt1 directly. An inverse correlation is also found between miR-140-5p and Dnmt1 in HPASMCs. In addition, we further investigated whether miR-140-5p and Dnmt1 regulate HPASMC proliferation, apoptosis and differentiation by regulating SOD2 expression, and the results confirmed our speculation. Taken together, these results indicated that miR-140-5p at least partly targets Dnmt1 and regulates SOD2 expression to inhibit proliferation and promote apoptosis and differentiation of HPASMCs in hypoxia. - Highlights: • miR-140-5p and SOD2 are down

The effect of SOD1 mutation on cellular bioenergetic profile and viability in response to oxidative stress and influence of mutation-type.

Directory of Open Access Journals (Sweden)

Katie Richardson

Full Text Available Amyotrophic Lateral Sclerosis (ALS is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. Substantial evidence implicates oxidative stress and mitochondrial dysfunction as early events in disease progression. Our aim was to ascertain whether mutation of the SOD1 protein increases metabolic functional susceptibility to oxidative stress. Here we used a motor neuron-like cell line (NSC34 stably transfected with various human mutant SOD1 transgenes (G93A, G37R, H48Q to investigate the impact of oxidative stress on cell viability and metabolic function within intact cells. NSC34 cells expressing mutant SOD1 showed a dose dependent reduction in cell viability when exposed to oxidative stress induced by hydrogen peroxide, with variation between mutations. The G93A transfectants showed greater cell death and LDH release compared to cells transfected with the other SOD1 mutations, and H48Q showed an accelerated decline at later time points. Differences in mitochondrial bioenergetics, including mitochondrial respiration, coupling efficiency and proton leak, were identified between the mutations, consistent with the differences observed in viability. NSC34 cells expressing G93A SOD1 displayed reduced coupled respiration and mitochondrial membrane potential compared to controls. Furthermore, the G93A mutation had significantly increased metabolic susceptibility to oxidative stress, with hydrogen peroxide increasing ROS production, reducing both cellular oxygen consumption and glycolytic flux in the cell. This study highlights bioenergetic defects within a cellular model of ALS and suggests that oxidative stress is not only detrimental to oxygen consumption but also glycolytic flux, which could lead to an energy deficit in the cell.

Differential Motor Neuron Impairment and Axonal Regeneration in Sporadic and Familiar Amyotrophic Lateral Sclerosis with SOD-1 Mutations: Lessons from Neurophysiology

OpenAIRE

Bocci, Tommaso; Pecori, Chiara; Giorli, Elisa; Briscese, Lucia; Tognazzi, Silvia; Caleo, Matteo; Sartucci, Ferdinando

2011-01-01

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disorder of the motor system. About 10% of cases are familial and 20% of these families have point mutations in the Cu/Zn superoxide dismutase 1 (SOD-1) gene. SOD-1 catalyses the superoxide radical (O−2) into hydrogen peroxide and molecular oxygen. The clinical neurophysiology in ALS plays a fundamental role in differential diagnosis between the familial and sporadic forms and in the assessment of its severity and progression. Sixty ALS pa...

Polymorphism variant of MnSOD A16V and risk of female infertility in northern Iran

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Mostafa Pournourali

2016-12-01

Conclusion: It is suggested that the MnSOD A16V polymorphism may be associated with a risk of female infertility in northern Iran. More studies should be considered with a larger number of patients and controls to confirm our results.

Modification of booming level for higher correlation with booming sensation; Booming level no koseidoka

Energy Technology Data Exchange (ETDEWEB)

Hatano, S; Hashimoto, T [Seikei University, Tokyo (Japan)

1997-10-01

In our previous study, we proposed a objective measure, i.e., Booming Level for quantifying booming sensation caused by car interior noise. In this paper, Booming Level was modified with its weighting function and within the process of calculation 1/3 octave band level was modified for the best match with subjective result. These modifications were conducted through a subjective experiment rating booming sensation with sounds having much lower frequency contents below 63Hz. With this modified Booming Level, we have obtained higher correlation for rating booming sensation with sounds having prominent low frequency components. 1 ref., 10 figs.

Tolerance of spermatogonia to oxidative stress is due to high levels of Zn and Cu/Zn superoxide dismutase.

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Fritzie T Celino

Full Text Available BACKGROUND: Spermatogonia are highly tolerant to reactive oxygen species (ROS attack while advanced-stage germ cells such as spermatozoa are much more susceptible, but the precise reason for this variation in ROS tolerance remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using the Japanese eel testicular culture system that enables a complete spermatogenesis in vitro, we report that advanced-stage germ cells undergo intense apoptosis and exhibit strong signal for 8-hydroxy-2'-deoxyguanosine, an oxidative DNA damage marker, upon exposure to hypoxanthine-generated ROS while spermatogonia remain unaltered. Activity assay of antioxidant enzyme, superoxide dismutase (SOD and Western blot analysis using an anti-Copper/Zinc (Cu/Zn SOD antibody showed a high SOD activity and Cu/Zn SOD protein concentration during early spermatogenesis. Immunohistochemistry showed a strong expression for Cu/Zn SOD in spermatogonia but weak expression in advanced-stage germ cells. Zn deficiency reduced activity of the recombinant eel Cu/Zn SOD protein. Cu/Zn SOD siRNA decreased Cu/Zn SOD expression in spermatogonia and led to increased oxidative damage. CONCLUSIONS/SIGNIFICANCE: These data indicate that the presence of high levels of Cu/Zn SOD and Zn render spermatogonia resistant to ROS, and consequently protected from oxidative stress. These findings provide the biochemical basis for the high tolerance of spermatogonia to oxidative stress.

Evaluating Superoxide Dismutase (SOD, Glutathione (GSH, Malondialdehyde (MDA and the Histological Changes of the Lung Tissue after γ-Irradiation in Rats

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Abolhasan Rezaeyan

2016-09-01

Full Text Available Background & Objective: The lung is a radiosensitive organ and its damage is a dose-limiting factor in radiotherapy. Different side effects such as pneumonia and lung fibrosis are found in patients with thorax irradiation. The objective of the present study is to evaluate the effects of γ-irradiation on acute and chronic injuries of lung tissue in rats. Materials & Methods: 32 rats were divided into two groups. Control group consisted of 14 rats that underwent shame irradiation. In radiation group, 18 rats underwent γ-irradiation. The rats were exposed to γ-irradiation 18 Gy using a single fraction cobalt-60 unit. Eight rats in each group were sacrificed 24 hours after radiotherapy for determining Superoxide Dismutase (SOD, Glutathione (GSH, Malondialdehyde (MDA, and histopathological evaluations. Remained animals were sacrificed eight weeks after radiotherapy for histopathological evaluation. Results: Compared to control group, the level of SOD and GSH significantly decreased and MDA level significantly increased in radiation group 24 hours following irradiation, (p=0.001, p<0.001, p=0.001 respectively. Early histopathological results after 24 hours showed that radiation increases neutrophil, macrophage, and inflammation incidence compared to control group (p<0.05. Late histopathological evaluation after eight weeks revealed significant increase in factors including mast cells, pulmonary edema, vascular thickness, vascular damage, and also inflammation and fibrosis incidence in case group compared to radiation group  (p<0.05. Conclusion: Localized chest radiation with dose of 18 Gy induces changes in oxidative stress indices and histopathological lung tissue damage in short and long term.

Electron-positron annihilation into hadrons at the higher-loop levels

Energy Technology Data Exchange (ETDEWEB)

Nesterenko, A.V. [Joint Institute for Nuclear Research, Bogoliubov Laboratory of Theoretical Physics, Dubna (Russian Federation)

2017-12-15

The strong corrections to the R-ratio of electron-positron annihilation into hadrons are studied at the higher-loop levels. Specifically, the derivation of a general form of the commonly employed approximate expression for the R-ratio (which constitutes its truncated re-expansion at high energies) is delineated, the appearance of the pertinent π{sup 2}-terms is expounded, and their basic features are examined. It is demonstrated that the validity range of such approximation is strictly limited to √(s)/Λ > exp(π/2) ≅ 4.81 and that it converges rather slowly when the energy scale approaches this value. The spectral function required for the proper calculation of the R-ratio is explicitly derived and its properties at the higher-loop levels are studied. The developed method of calculation of the spectral function enables one to obtain the explicit expression for the latter at an arbitrary loop level. By making use of the derived spectral function the proper expression for the R-ratio is calculated up to the five-loop level and its properties are examined. It is shown that the loop convergence of the proper expression for the R-ratio is better than that of its commonly employed approximation. The impact of the omitted higher-order π{sup 2}-terms on the latter is also discussed. (orig.)

Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

Science.gov (United States)

Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

2016-03-16

Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. © 2016 The Authors.

Higher-level gait disorders: an open frontier.

Science.gov (United States)

Nutt, John G

2013-09-15

The term higher-level gait disorders (HLGD) defines a category of balance and gait disorders that are not explained by deficits in strength, tone, sensation, or coordination. HLGD are characterized by various combinations of disequilibrium and impaired locomotion. A plethora of new imaging techniques are beginning to determine the neural circuits that are the basis of these disorders. Although a variety of neurodegenerative and other pathologies can produce HLGD, the most common cause appears to be microvascular disease that causes white-matter lesions and thereby disrupts balance/locomotor circuits. © 2013 Movement Disorder Society.

Do Superoxide Dismutase (SOD) and Catalase (CAT) protect Cells from DNA Damage Induced by Active Arsenicals?

Science.gov (United States)

Superoxide dismutase (SOD) catalyzes the conversion of superoxide to hydrogen peroxide, which can be converted to water and oxygen through the action of catalase. Heterozygous mice of strain B6: 129S7-SodltmlLeb/J were obtained from Jackson Laboratories and bred to produce offspr...

Antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients

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Taysa Ribeiro Schalcher

2013-09-01

Full Text Available Introduction The immune response caused by Mycobacterium leprae is a risk factor for the development of oxidative stress (OS in leprosy patients. This study aimed to assess OS in leprosy patients before the use of a multidrug therapy. Methods We evaluated the nitric oxide (NO concentration; antioxidant capacity; levels of malondialdehyde, methemoglobin and reduced glutathione; and the activity of catalase and superoxide dismutase (SOD in leprosy patients. Results We observed lower SOD activity in these leprosy patients; however, the NO levels and antioxidant capacity were increased. Conclusions The infectious process in response to M. leprae could primarily be responsible for the OS observed in these patients.

Detection of Sequence-Specific Tyrosine Nitration of Manganese SOD and SERCA in Cardiovascular Disease and Aging

Energy Technology Data Exchange (ETDEWEB)

Xu, Shanqin; Ying, Jia; Jiang, Bingbing; Guo, Wei; Adachi, Takeshi; Sharov, Victor; Lazar, Harold; Menzoian, James; Knyushko, Tanya V.; Bigelow, Diana J.; Schoneich, Christian; Cohen, Richard

2006-06-01

Nitration of protein tyrosine residues (nY) is a marker of oxidative stress and may alter the biological activity of the modified proteins. The aim of this study was to develop antibodies towards site-specific nY-modified proteins and to use histochemical and immunoblotting to demonstrate protein nitration in tissues. Affinity-purified polyclonal antibodies towards peptides with known nY sites in MnSOD nY-34 and of two adjacent nY in the sarcoplasmic endoplasmic reticulum calcium ATPase (SERCA2 di-nY-294,295) were developed. Kidneys from rats infused with angiotensin II with known MnSOD nY and aorta from atherosclerotic rabbits and aging rat skeletal and cardiac sarcoplasmic reticulum with known SERCA di-nY were used for positive controls. Staining for MnSOD nY-34 was most intense in distal renal tubules and collecting ducts. Staining of atherosclerotic aorta for SERCA2 di-nY was most intense in atherosclerotic plaques. Aging rat skeletal muscle and atherosclerotic aorta and cardiac atrium from human diabetic patients also stained positively. Staining was decreased by sodium dithionite that chemically reduces nitrotyrosine to aminotyrosine, and the antigenic nY-peptide blocked staining for each respective nY site, but not for the other. As previously demonstrated, immunoblotting failed to detect these modified proteins in whole tissue lysates, but did when the proteins were concentrated. Immunohistochemical staining for specific nY-modified tyrosine residues offers the ability to assess the effects of oxidant stress associated with pathological conditions on individual proteins whose function may be affected in specific tissue sites.

Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model.

Science.gov (United States)

Rapti, Kleopatra; Diokmetzidou, Antigoni; Kloukina, Ismini; Milner, Derek J; Varela, Aimilia; Davos, Constantinos H; Capetanaki, Yassemi

2017-09-01

Oxidative stress has been linked strongly to cell death and cardiac remodeling processes, all hallmarks of heart failure. Mice deficient for desmin (des-/-), the major muscle specific intermediate filament protein, develop dilated cardiomyopathy and heart failure characterized by mitochondrial defects and cardiomyocyte death. The cellular and biochemical alterations in the hearts of these mice strongly suggest that oxidative stress is one of the mechanisms contributing to the pathogenesis of the phenotype. Recently, we showed that indeed the desmin deficient cardiomyocytes are under increased oxidative stress. In order to verify these findings in vivo, we generated transgenic animals overexpressing SOD2 (MnSOD) and/or catalase in the heart and crossed them with des-/- mice, thus allowing us to evaluate the contribution of oxidative injury in inherited cardiomyopathies, as well as the therapeutic potential of antioxidant strategies. Moderate MnSOD and/or catalase overexpression in des-/- hearts leads to a marked decrease in intracellular reactive oxygen species (ROS), ameliorates mitochondrial and other ultrastructural defects, minimizes myocardial degeneration and leads to a significant improvement of cardiac function. Importantly, catalase overexpression increased the 50% survival rate of des-/- mice in an obligatory exercise to 100%. In contrast, MnSOD overexpression enhanced the lethality of des-/- mice, underscoring the importance of a fine balanced cellular redox status. Overall, the present study supports the contribution of oxidative stress in the development of des-/- cardiomyopathy and points to a well-considered antioxidant treatment as therapeutic for cardiomyopathies. Copyright © 2017 Elsevier Inc. All rights reserved.

Optimised and rapid pre-clinical screening in the SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS).

Science.gov (United States)

Mead, Richard J; Bennett, Ellen J; Kennerley, Aneurin J; Sharp, Paul; Sunyach, Claire; Kasher, Paul; Berwick, Jason; Pettmann, Brigitte; Battaglia, Guiseppe; Azzouz, Mimoun; Grierson, Andrew; Shaw, Pamela J

2011-01-01

The human SOD1(G93A) transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS). In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease. These models have two major drawbacks. Firstly the generation of robust preclinical data in these models has been highlighted as an area for concern. Secondly, the amount of time required for a single preclinical experiment in these models (3-4 months) is a hurdle to the development of new therapies. We have developed an inbred C57BL/6 mouse line from the original mixed background (SJLxC57BL/6) SOD1(G93A) transgenic line and show here that the disease course is remarkably consistent and much less prone to background noise, enabling reduced numbers of mice for testing of therapeutics. Secondly we have identified very early readouts showing a large decline in motor function compared to normal mice. This loss of motor function has allowed us to develop an early, sensitive and rapid screening protocol for the initial phases of denervation of muscle fibers, observed in this model. We describe multiple, quantitative readouts of motor function that can be used to interrogate this early mechanism. Such an approach will increase throughput for reduced costs, whilst reducing the severity of the experimental procedures involved.

Cerebrospinal fluid cortisol levels are higher in patients with delirium versus controls

Directory of Open Access Journals (Sweden)

White Timothy O

2010-02-01

Full Text Available Abstract Background High plasma cortisol levels can cause acute cognitive and neuropsychiatric dysfunction, and have been linked with delirium. CSF cortisol levels more closely reflect brain exposure to cortisol, but there are no studies of CSF cortisol levels in delirium. In this pilot study we acquired CSF specimens at the onset of spinal anaesthesia in patients undergoing hip fracture surgery, and compared CSF and plasma cortisol levels in delirium cases versus controls. Findings Delirium assessments were performed the evening before or on the morning of operation with a standard battery comprising cognitive tests, mental status assessments and the Confusion Assessment Method. CSF and plasma samples were obtained at the onset of the operation and cortisol levels measured. Twenty patients (15 female, 5 male aged 62 - 93 years were studied. Seven patients were diagnosed with delirium. The mean ages of cases (81.4 (SD 7.2 and controls (80.5 (SD 8.7 were not significantly different (p = 0.88. The median (interquartile range CSF cortisol levels were significantly higher in cases (63.9 (40.4-102.1 nmol/L than controls (31.4 (21.7-43.3 nmol/L; Mann-Whitney U, p = 0.029. The median (interquartile range of plasma cortisol was also significantly higher in cases (968.8 (886.2-1394.4 nmol/L, than controls (809.4 (544.0-986.4 nmol/L; Mann Whitney U, p = 0.036. Conclusions These findings support an association between higher CSF cortisol levels and delirium. This extends previous findings linking higher plasma cortisol and delirium, and suggests that more definitive studies of the relationship between cortisol levels and delirium are now required.

Storytelling in the digital world: achieving higher-level learning objectives.

Science.gov (United States)

Schwartz, Melissa R

2012-01-01

Nursing students are not passive media consumers but instead live in a technology ecosystem where digital is the language they speak. To prepare the next generation of nurses, educators must incorporate multiple technologies to improve higher-order learning. The author discusses the evolution and use of storytelling as part of the digital world and how digital stories can be aligned with Bloom's Taxonomy so that students achieve higher-level learning objectives.

Egyptian greenhouse cultivation at a higher level with Dutch Technology ; Annual Report 2013

NARCIS (Netherlands)

Elings, A.; Helm, van der F.P.M.; Blok, C.; Meijer, R.J.M.; Lahiani, Y.; Janmaat, A.; Zaki, M.; Hassan, H.

2014-01-01

The project ‘Egyptian greenhouse cultivation at a higher level with Dutch technology’ is co-funded under the Top Sector Programme Horticulture and Starting Materials. The project wants to realizes through the use of Dutch technology a higher level of sustainability of Egyptian protected cultivation,

Higher transcription levels in ascorbic acid biosynthetic and recycling genes were associated with higher ascorbic acid accumulation in blueberry.

Science.gov (United States)

Liu, Fenghong; Wang, Lei; Gu, Liang; Zhao, Wei; Su, Hongyan; Cheng, Xianhao

2015-12-01

In our preliminary study, the ripe fruits of two highbush blueberry (Vaccinium corymbosum L.) cultivars, cv 'Berkeley' and cv 'Bluecrop', were found to contain different levels of ascorbic acid. However, factors responsible for these differences are still unknown. In the present study, ascorbic acid content in fruits was compared with expression profiles of ascorbic acid biosynthetic and recycling genes between 'Bluecrop' and 'Berkeley' cultivars. The results indicated that the l-galactose pathway was the predominant route of ascorbic acid biosynthesis in blueberry fruits. Moreover, higher expression levels of the ascorbic acid biosynthetic genes GME, GGP, and GLDH, as well as the recycling genes MDHAR and DHAR, were associated with higher ascorbic acid content in 'Bluecrop' compared with 'Berkeley', which indicated that a higher efficiency ascorbic acid biosynthesis and regeneration was likely to be responsible for the higher ascorbic acid accumulation in 'Bluecrop'. Copyright © 2015 Elsevier Ltd. All rights reserved.

PENGARUH DAUN UBI JALAR UNGU TERHADAP KADAR SUPEROKSID DISMUTASE TIKUS YANG DIPAPAR ASAP ROKOK (EFFECT OF PURPLE SWEET POTATO LEAVES ON SUPEROXIDE DISMUTASE LEVEL ON RATS EXPOSED TO CIGARETTE SMOKE

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Inggita Kusumastuty

2014-12-01

Superoxide Dismutase (SOD is an enzymatic antioxidant that protects cells from oxidative stress by catalyzing dismutase from superoxide into O2 and H2O2. The purple sweet potato leave (Ipomoea batatas L. Lam is a kind of vegetable plant that contains  high polyphenol which is about 1805 mgGAE on 100-gram edible portions. This research was aimed to determine the effect of purple sweet potato leaves powder in SOD levels that had been given to an animal model with cigarette smoke exposure. 6-8 week- male Rattus novergicus-wistar’s strain was used in this experiment that weighed about 140-250 gram and the entire rats were in healthy condition and were never exposed to another treatment before. Firstly, the rats were prepared in one week which was then divided into 5 treatment groups, a group that had not been exposed to cigarette smoke (P0, cigarette smoke exposed (P1, and exposed to cigarette smoke with the addition PSPL flour treatment in varying doses: 0.07g (P2, 0.14g (P3, and 0.28g (P4 for 30 days. After that, SOD levels were measured with spectrophotometry method. The result shows that there was obviously a significant difference between the treatment groups (ANOVA, p=0.000. In short, it was found that the given PSPL dosages resulted in higher SOD’s level. Keywords :, purple sweet potato leaves, Superoxide Dismutase level, cigarette smoking

Optimised and rapid pre-clinical screening in the SOD1(G93A transgenic mouse model of amyotrophic lateral sclerosis (ALS.

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Richard J Mead

Full Text Available The human SOD1(G93A transgenic mouse has been used extensively since its development in 1994 as a model for amyotrophic lateral sclerosis (ALS. In that time, a great many insights into the toxicity of mutant SOD1 have been gained using this and other mutant SOD transgenic mouse models. They all demonstrate a selective toxicity towards motor neurons and in some cases features of the pathology seen in the human disease. These models have two major drawbacks. Firstly the generation of robust preclinical data in these models has been highlighted as an area for concern. Secondly, the amount of time required for a single preclinical experiment in these models (3-4 months is a hurdle to the development of new therapies. We have developed an inbred C57BL/6 mouse line from the original mixed background (SJLxC57BL/6 SOD1(G93A transgenic line and show here that the disease course is remarkably consistent and much less prone to background noise, enabling reduced numbers of mice for testing of therapeutics. Secondly we have identified very early readouts showing a large decline in motor function compared to normal mice. This loss of motor function has allowed us to develop an early, sensitive and rapid screening protocol for the initial phases of denervation of muscle fibers, observed in this model. We describe multiple, quantitative readouts of motor function that can be used to interrogate this early mechanism. Such an approach will increase throughput for reduced costs, whilst reducing the severity of the experimental procedures involved.

The protective effect of propolis on damage to lung and blood in rats by inhaled radioactive radon and its progeny

International Nuclear Information System (INIS)

Ding Jiansong; Nie Jihua; Tong Jian

2006-01-01

Twenty-eight male wistar rats were randomly divided into seven groups, i.e. the radon groups (3), the propolis+radon groups (3) and the control (1). The propolis+radon groups were fed intragastrically with propolis 0.2 g/kg, before exposing them, together with the radon groups, to radon and its progeny with the cumulative dose up to 30, 67 and 111 working level month (WLM), respectively. The levels of SOD (superoxide dismutase) and MDA (Malonic dialdehyde) in blood and lung tissue were determined. The SOD level of in blood and lung tissues of the radon groups decreased significantly and the MDA level increased. The MDA level in lung tissue of the 30 WLM propolis+radon group was significantly higher than the 30 WLM radon group. The SOD level in lung tissue of the 67 WLM propolis+radon group was significantly higher, but the MDA level was significantly lower, than the 67 WLM radon group. Both the SOD and MDA levels in blood and lung tissue of the 111 WLM propolis+radon group were significantly higher than the 111 WLM radon group. In conclusion, the inhalation of radon and its progeny can lead to persistent disturbance of the redox state in rats. Propolis show some protective effects on the redox damage under the experimental conditions. (authors)

A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS.

Science.gov (United States)

Hatzipetros, Theo; Kidd, Joshua D; Moreno, Andy J; Thompson, Kenneth; Gill, Alan; Vieira, Fernando G

2015-10-06

The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.

Activation of immunity, immune response, antioxidant ability, and resistance against Vibrio alginolyticus in white shrimp Litopenaeus vannamei decrease under long-term culture at low pH.

Science.gov (United States)

Chen, Yu-Yuan; Chen, Jiann-Chu; Tseng, Kuei-Chi; Lin, Yong-Chin; Huang, Chien-Lun

2015-10-01

The growth, activation of immunity, immune parameters, and transcript levels of cytMnSOD, mtMnSOD, ecCuZnSOD, glutathione peroxidase (GPx), catalase, lysozyme, and penaeidin 3a were examined in white shrimp Litopenaeus vannamei reared at pH 6.8 and 8.1 after 24 weeks. No significant difference in growth was observed between the two groups. An in vitro study indicated that phenoloxidase activity and respiratory bursts (RB, release of the superoxide anion) were significantly higher in the haemocytes of pH 8.1 shrimp (shrimp reared at pH 8.1) than in pH 6.8 shrimp (shrimp reared at pH 6.8). An in vivo study indicated that the levels of immune parameters of pH 8.1 shrimp were significantly higher than in pH 6.8 shrimp, and the transcript levels of cytMnSOD, ecCuZnSOD, glutathione peroxidase, lysozyme, and penaeidin 3a were down-regulated in pH 6.8 shrimp. In another experiment, shrimp reared at pH 6.8 and 8.1 for 24 weeks were challenged with Vibrio alginolyticus. The mortality rate of pH 6.8 shrimp was significantly higher than in pH 8.1 shrimp over 12-168 h. Phagocytic activity, phagocytic index, and clearance efficiency to V. alginolyticus were significantly lower in pH 6.8 shrimp. We concluded that shrimp under long-term culture at pH 6.8 exhibited decreased resistance against V. alginolyticus as evidenced by reductions in the activation of immunity and immune parameters together with decreased transcript levels of cytMnSOD, ecCuZnSOD, GPx, lysozyme, and penaeidin 3a. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential survival among sSOD-1* genotypes in Chinook Salmon

Science.gov (United States)

Hayes, Michael C.; Reisenbichler, Reginald R.; Rubin, Stephen P.; Wetzel, Lisa A.; Marshall , Anne R.

2011-01-01

Differential survival and growth were tested in Chinook salmon Oncorhynchus tshawytscha expressing two common alleles, *–100 and *–260, at the superoxide dismutase locus (sSOD-1*). These tests were necessary to support separate studies in which the two alleles were used as genetic marks under the assumption of mark neutrality. Heterozygous adults were used to produce progeny with –100/–100, –100/–260, and –260/–260 genotypes that were reared in two natural streams and two hatcheries in the states of Washington and Oregon. The latter also were evaluated as returning adults. In general, the genotype ratios of juveniles reared at hatcheries were consistent with high survival and little or no differential survival in the hatchery. Adult returns at one hatchery were significantly different from the expected proportions, and the survival of the –260/–260 genotype was 0.56–0.89 times that of the –100/–100 genotype over four year-classes. Adult returns at a second hatchery (one year-class) were similar but not statistically significant: survival of the –260/–260genotype relative to the –100/–100 genotype was 0.76. The performance of the heterozygote group was intermediate at both hatcheries. Significant differences in growth were rarely observed among hatchery fish (one year-class of juveniles and one age-class of adult males) but were consistent with greater performance for the –100/–100 genotype. Results from two groups of juveniles reared in streams (one year-class from each stream) suggested few differences in growth, but the observed genotype ratios were significantly different from the expected ratios in one stream. Those differences were consistent with the adult data; survival for the –260/–260 genotype was 76% of that of the –100/–100 genotype. These results, which indicate nonneutrality among sSOD-1* genotypes, caused us to modify our related studies and suggest caution in the interpretation of results and analyses in

Higher fuel prices are associated with lower air pollution levels.

Science.gov (United States)

Barnett, Adrian G; Knibbs, Luke D

2014-05-01

Air pollution is a persistent problem in urban areas, and traffic emissions are a major cause of poor air quality. Policies to curb pollution levels often involve raising the price of using private vehicles, for example, congestion charges. We were interested in whether higher fuel prices were associated with decreased air pollution levels. We examined an association between diesel and petrol prices and four traffic-related pollutants in Brisbane from 2010 to 2013. We used a regression model and examined pollution levels up to 16 days after the price change. Higher diesel prices were associated with statistically significant short-term reductions in carbon monoxide and nitrogen oxides. Changes in petrol prices had no impact on air pollution. Raising diesel taxes in Australia could be justified as a public health measure. As raising taxes is politically unpopular, an alternative political approach would be to remove schemes that put a downward pressure on fuel prices, such as industry subsidies and shopping vouchers that give fuel discounts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic polymorphisms of antioxidant enzymes CAT and SOD affect the outcome of clinical, biochemical, and anthropometric variables in people with obesity under a dietary intervention.

Science.gov (United States)

Hernández-Guerrero, César; Parra-Carriedo, Alicia; Ruiz-de-Santiago, Diana; Galicia-Castillo, Oscar; Buenrostro-Jáuregui, Mario; Díaz-Gutiérrez, Carmen

2018-01-01

Genetic polymorphisms of antioxidant enzymes CAT, GPX, and SOD are involved in the etiology of obesity and its principal comorbidities. The aim of the present study was to analyze the effect of aforementioned SNPs over the output of several variables in people with obesity after a nutritional intervention. The study included 92 Mexican women, which received a dietary intervention by 3 months. Participants were genotyped and stratified into two groups: (1) carriers; mutated homozygous plus heterozygous (CR) and (2) homozygous wild type (WT). A comparison between CR and WT was done in clinical (CV), biochemical (BV), and anthropometric variables (AV), at the beginning and at the end of the intervention. Participants ( n  = 92) showed statistically significant differences ( p  T GPX1 (rs1050450), - 251A>G SOD1 (rs2070424), and - 262C>T CAT (rs1001179). (B) Only CR showed statistically changes ( p  T CAT (rs7943316) and 47C>T SOD2 (rs4880). The dietary intervention effect was statistically significantly between the polymorphisms of 47C>T SOD2 and BMI, SBP, TBARS, total cholesterol, and C-LCL ( p  T CAT (rs7943316) and SBP, DBP, total cholesterol, and atherogenic index ( p  CAT enzymes.

Mitochondrial oxidative stress and nitrate tolerance – comparison of nitroglycerin and pentaerithrityl tetranitrate in Mn-SOD+/- mice

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Stalleicken Dirk

2006-11-01

Full Text Available Abstract Background Chronic therapy with nitroglycerin (GTN results in a rapid development of nitrate tolerance which is associated with an increased production of reactive oxygen species (ROS. According to recent studies, mitochondrial ROS formation and oxidative inactivation of the organic nitrate bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2 play an important role for the development of nitrate and cross-tolerance. Methods Tolerance was induced by infusion of wild type (WT and heterozygous manganese superoxide dismutase mice (Mn-SOD+/- with ethanolic solution of GTN (12.5 μg/min/kg for 4 d. For comparison, the tolerance-free pentaerithrityl tetranitrate (PETN, 17.5 μg/min/kg for 4 d was infused in DMSO. Vascular reactivity was measured by isometric tension studies of isolated aortic rings. ROS formation and aldehyde dehydrogenase (ALDH-2 activity was measured in isolated heart mitochondria. Results Chronic GTN infusion lead to impaired vascular responses to GTN and acetylcholine (ACh, increased the ROS formation in mitochondria and decreased ALDH-2 activity in Mn-SOD+/- mice. In contrast, PETN infusion did not increase mitochondrial ROS formation, did not decrease ALDH-2 activity and accordingly did not lead to tolerance and cross-tolerance in Mn-SOD+/- mice. PETN but not GTN increased heme oxygenase-1 mRNA in EA.hy 926 cells and bilirubin efficiently scavenged GTN-derived ROS. Conclusion Chronic GTN infusion stimulates mitochondrial ROS production which is an important mechanism leading to tolerance and cross-tolerance. The tetranitrate PETN is devoid of mitochondrial oxidative stress induction and according to the present animal study as well as numerous previous clinical studies can be used without limitations due to tolerance and cross-tolerance.

Neuroprotective Effect of Bexarotene in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

Science.gov (United States)

Riancho, Javier; Ruiz-Soto, María; Berciano, María T.; Berciano, José; Lafarga, Miguel

2015-01-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper and lower motor neurons (MNs) without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favorable safety profile whose effects have been recently investigated in other neurodegenerative diseases. In this study, we analyze the potential therapeutic effect of Bxt in the SOD1G93A mouse model of ALS. Mice were treated with Bxt or vehicle five times per week from day 60 onward. Survival, weight, and neuromuscular function studies together with histological and biochemical analyses were performed. Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight, and extended mice survival up to 30% of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic stages in ALS-transgenic mice. Bxt treatment contributed to preserve the MN homeostasis in the SOD1G93A mice. Particularly, it reduced the neuronal loss and the chromatolytic response, induced nucleolar hypertrophy, decreased the formation of ubiquitylated inclusions, and modulated the lysosomal response. As an agonist of the retinoic-X receptor (RXR) pathway, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. Bxt also contributed to protect the MN environment by reducing reactive astrogliosis and preserving perisomatic synapsis. Overall, these neuroprotective effects suggest that treatment with Bxt could be useful in ALS, particularly in those cases related to SOD1 mutations. PMID:26190974

Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus.

Science.gov (United States)

Hamed, Saher; Brenner, Benjamin; Aharon, Anat; Daoud, Deeb; Roguin, Ariel

2009-10-30

The function of endothelial progenitor cells (EPCs), which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO) and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD), the enzyme that neutralizes superoxide anion (O2-). Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. EPCs from diabetic patients generated more O2-, had higher NAD(P)H oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

CCS and SOD1 mRNA are reduced after copper supplementation in peripheral mononuclear cells of individuals with high serum ceruloplasmin concentration.

Science.gov (United States)

Suazo, Miriam; Olivares, Felipe; Mendez, Marco A; Pulgar, Rodrigo; Prohaska, Joseph R; Arredondo, Miguel; Pizarro, Fernando; Olivares, Manuel; Araya, Magdalena; González, Mauricio

2008-04-01

The limits of copper homeostatic regulation in humans are not known, making it difficult to define the milder effects of early copper excess. Furthermore, a robust assay to facilitate the detection of early stages of copper excess is needed. To address these issues, we assessed changes in relative mRNA abundance of methallothionein 2A (MT2A), prion (PrP), amyloid precursor-like protein 2 (APLP2), Cu/Zn superoxide dismutase (SOD1) and its copper chaperone (CCS) in peripheral mononuclear cells (PMNCs) from healthy adults representing the 5% highest and lowest extremes in the distribution curve of serum ceruloplasmin (Cp) concentrations of 800 individuals. The intracellular Cu content was also determined. PMNCs were isolated from individuals before and after exposure to a single daily dose of 10 mg Cu (as CuSO(4)) for 2 months. Results showed that although there were fluctuations in serum Cp values of the samples assessed before copper exposure, no significant differences were observed in cell copper content or in the relative abundance of MT2A, PrP and APLP2 transcripts in PMNCs. Also, these values were not modified after copper supplementation. However, CCS and SOD1 mRNA levels were reduced in PMNCs after copper supplementation in the individuals with the high Cp values, suggesting that they should be further explored as biomarkers of moderate copper overload in humans.

Neuronal glucose metabolism is impaired while astrocytic TCA cycling is unaffected at symptomatic stages in the hSOD1G93A mouse model of amyotrophic lateral sclerosis.

Science.gov (United States)

Tefera, Tesfaye W; Borges, Karin

2018-01-01

Although alterations in energy metabolism are known in ALS, the specific mechanisms leading to energy deficit are not understood. We measured metabolite levels derived from injected [1- 13 C]glucose and [1,2- 13 C]acetate (i.p.) in cerebral cortex and spinal cord extracts of wild type and hSOD1 G93A mice at onset and mid disease stages using high-pressure liquid chromatography, 1 H and 13 C nuclear magnetic resonance spectroscopy. Levels of spinal and cortical CNS total lactate, [3- 13 C]lactate, total alanine and [3- 13 C]alanine, but not cortical glucose and [1- 13 C]glucose, were reduced mostly at mid stage indicating impaired glycolysis. The [1- 13 C]glucose-derived [4- 13 C]glutamate, [4- 13 C]glutamine and [2- 13 C]GABA amounts were diminished at mid stage in cortex and both time points in spinal cord, suggesting decreased [3- 13 C]pyruvate entry into the TCA cycle. Lack of changes in [1,2- 13 C]acetate-derived [4,5- 13 C]glutamate, [4,5- 13 C]glutamine and [1,2- 13 C]GABA levels indicate unchanged astrocytic 13 C-acetate metabolism. Reduced levels of leucine, isoleucine and valine in CNS suggest compensatory breakdown to refill TCA cycle intermediate levels. Unlabelled, [2- 13 C] and [4- 13 C]GABA concentrations were decreased in spinal cord indicating that impaired glucose metabolism contributes to hyperexcitability and supporting the use of treatments which increase GABA amounts. In conclusion, CNS glucose metabolism is compromised, while astrocytic TCA cycling appears to be normal in the hSOD1 G93A mouse model at symptomatic disease stages.

Functional and crystallographic characterization of Salmonella typhimurium Cu,Zn superoxide dismutase coded by the sodCI virulence gene

NARCIS (Netherlands)

Pesce, A; Battistoni, A; Stroppolo, ME; Polizio, F; Nardini, M; Kroll, JS; Langford, PR; O'Neill, P; Sette, M; Desideri, A; Bolognesi, M

2000-01-01

The functional and three-dimensional structural features of Cu,Zn superoxide dismutase coded by the Salmonella typhimurium sodCI gene, have been characterized. Measurements of the catalytic rate indicate that this enzyme is the most efficient superoxide dismutase analyzed so far, a feature that may

An empirical study on educational investment for all levels of higher education in China

OpenAIRE

YANG Juan; David MAYSTON

2009-01-01

With the expanding of higher education in China from 1999, more and more youngsters are able to invest in higher education, resulting a high unemployment rate for higher education graduates and more and more graduates employed in non-graduate position, while the analysis upon risk and return to each level of high education is absent due to the limitation of dataset. The paper employs college students sample survey to research the determinants of all levels of higher education beginning wages,...

Acute Pre-/Post-Treatment with 8th Day SOD-Like Supreme (a Free Radical Scavenging Health Product Protects against Oxidant-Induced Injury in Cultured Cardiomyocytes and Hepatocytes In Vitro as Well as in Mouse Myocardium and Liver In Vivo

Directory of Open Access Journals (Sweden)

Pou Kuan Leong

2017-04-01

Full Text Available 8th Day superoxide dismutase (SOD-Like Supreme (SOD-Like Supreme, a free radical scavenging health product is an antioxidant-enriched fermentation preparation with free radical scavenging properties. In the present study, the cellular/tissue protective actions of SOD-Like Supreme against menadione toxicity in cultured H9c2 cardiomyocytes and in AML12 hepatocytes as well as oxidant-induced injury in the mouse myocardium and liver were investigated. SOD-Like Supreme was found to possess potent free radical scavenging activity in vitro as assessed by an oxygen radical absorbance capacity assay. Incubation with SOD-Like Supreme (0.5–3% (v/v was shown to protect against menadione-induced toxicity in H9c2 and AML12 cells, as evidenced by increases in cell viability. The ability of SOD-Like Supreme to protect against menadione cytotoxicity was associated with an elevation in the cellular reduced glutathione (GSH/oxidized glutathione (GSSG ratio in menadione-challenged cells. Consistent with the cell-based studies, pre-/post-treatment with SOD-Like Supreme (0.69 and 2.06 mL/kg, three intermittent doses per day for two consecutive days was found to protect against isoproterenol-induced myocardial injury and carbon tetrachloride hepatotoxicity in mice. The cardio/hepatoprotection afforded by SOD-Like Supreme was also paralleled by increases in myocardial/hepatic mitochondrial GSH/GSSG ratios in the SOD-Like Supreme-treated/oxidant-challenged mice. In conclusion, incubation/treatment with SOD-Like Supreme was found to protect against oxidant-induced injury in vitro and in vivo, presumably by virtue of its free radical scavenging activity.

A higher-level MRP supertree of placental mammals

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Bininda-Emonds Olaf RP

2006-11-01

Full Text Available Abstract Background The higher-level phylogeny of placental mammals has long been a phylogenetic Gordian knot, with disagreement about both the precise contents of, and relationships between, the extant orders. A recent MRP supertree that favoured 'outdated' hypotheses (notably, monophyly of both Artiodactyla and Lipotyphla has been heavily criticised for including low-quality and redundant data. We apply a stringent data selection protocol designed to minimise these problems to a much-expanded data set of morphological, molecular and combined source trees, to produce a supertree that includes every family of extant placental mammals. Results The supertree is well-resolved and supports both polyphyly of Lipotyphla and paraphyly of Artiodactyla with respect to Cetacea. The existence of four 'superorders' – Afrotheria, Xenarthra, Laurasiatheria and Euarchontoglires – is also supported. The topology is highly congruent with recent (molecular phylogenetic analyses of placental mammals, but is considerably more comprehensive, being the first phylogeny to include all 113 extant families without making a priori assumptions of suprafamilial monophyly. Subsidiary analyses reveal that the data selection protocol played a key role in the major changes relative to a previously published higher-level supertree of placentals. Conclusion The supertree should provide a useful framework for hypothesis testing in phylogenetic comparative biology, and supports the idea that biogeography has played a crucial role in the evolution of placental mammals. Our results demonstrate the importance of minimising poor and redundant data when constructing supertrees.

Effect of 5-week moderate intensity endurance training on the oxidative stress, muscle specific uncoupling protein (UCP3) and superoxide dismutase (SOD2) contents in vastus lateralis of young, healthy men.

Science.gov (United States)

Majerczak, J; Rychlik, B; Grzelak, A; Grzmil, P; Karasinski, J; Pierzchalski, P; Pulaski, L; Bartosz, G; Zoladz, J A

2010-12-01

In the present study fifteen male subjects (age: 22.7 ± 0.5 years; BMI: 23.5 ± 0.6 kg x m⁻²; VO₂(max) 46.0 ± 1.0 mL x kg⁻¹ x min⁻¹) performed 5 week moderate intensity endurance training. The training resulted in a significant increase in maximal oxygen uptake (VO₂(max)) (P=0.048) and power output reached at VO₂(max) (P=0.0001). No effect of training on the uncoupling protein 3 (UCP3) content in the vastus lateralis was found (P>0.05). The improvement of physical capacity was accompanied by no changes in cytochrome-c and cytochrome-c oxidase contents in the vastus lateralis (P>0.05). However, the training resulted in an increase (P=0.02) in mitochondrial manganese superoxide dismutase (SOD2) content in this muscle. Moreover, a significant decrease (P=0.028) in plasma basal isoprostanes concentration [F₂isoprostanes](pl) accompanied by a clear tendency to lower (P=0.08) gluthatione disulfide concentration [GSSG](pl) and tendency to higher (P=0.08) total antioxidant capacity (TAC) was observed after the training. We have concluded that as little as 5 weeks of moderate intensity endurance training is potent to improve physical capacity and antioxidant protection in humans. Surprisingly, these effects occur before any measurable changes in UCP3 protein content. We postulate that the training-induced improvement in the antioxidant protection at the muscle level is due to an increase in SOD2 content and that therefore, the role of UCP3 in the enhancement of physical capacity and antioxidant protection, at least in the early stage of training, is rather questionable.

Regression analysis of γ-ray effect on sod activity and MDA content in four vegetable leaves

International Nuclear Information System (INIS)

Wang Zegang; Feng Min; Hu Jianwei; Gao Yue; Lv Haiyan; Luo Shishi; Zheng Haoxian; Ma Fei; Ge Cailin

2005-01-01

Dynamic effects of γ-ray on SOD, POD activities and MDA content in leaves of four vegetable varieties were studied. The results were quantitatively described by the method of curve fitting and establishing mathematical model. The parameters of the formula suggested that the four vegetable varieties' sensitivity to radiation appeared as following order: Basella rubra>Lactuca sativa>Lactuca sativa spp>Brassica Chinensis. (authors)

Does dietary iodine regulate oxidative stress and adiponectin levels in human breast milk?

Science.gov (United States)

Gutiérrez-Repiso, Carolina; Velasco, Inés; Garcia-Escobar, Eva; Garcia-Serrano, Sara; Rodríguez-Pacheco, Francisca; Linares, Francisca; Ruiz de Adana, Maria Soledad; Rubio-Martin, Elehazara; Garrido-Sanchez, Lourdes; Cobos-Bravo, Juan Francisco; Priego-Puga, Tatiana; Rojo-Martinez, Gemma; Soriguer, Federico; García-Fuentes, Eduardo

2014-02-10

Little is known about the association between iodine and human milk composition. In this study, we investigated the association between iodine and different markers of oxidative stress and obesity-related hormones in human breast milk. This work is composed of two cross-sectional studies (in lactating women and in the general population), one prospective and one in vitro. In the cross-sectional study in lactating women, the breast milk iodine correlated negatively with superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) activities, and with adiponectin levels. An in vitro culture of human adipocytes with 1 μM potassium iodide (KI, dose similar to the human breast milk iodine concentration) produced a significant decrease in adiponectin, GSH-Px, SOD1, and SOD2 mRNA expression. However, after 2 months of treatment with KI in the prospective study, a positive correlation was found between 24-h urinary iodine and serum adiponectin. Our observations lead to the hypothesis that iodine may be a factor directly involved in the regulation of oxidative stress and adiponectin levels in human breast milk.

Senescence marker protein-30/superoxide dismutase 1 double knockout mice exhibit increased oxidative stress and hepatic steatosis

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Yoshitaka Kondo

2014-01-01

Full Text Available Superoxide dismutase 1 (SOD1 is an antioxidant enzyme that converts superoxide anion radicals into hydrogen peroxide and molecular oxygen. The senescence marker protein-30 (SMP30 is a gluconolactonase that functions as an antioxidant protein in mammals due to its involvement in ascorbic acid (AA biosynthesis. SMP30 also participates in Ca2+ efflux by activating the calmodulin-dependent Ca2+-pump. To reveal the role of oxidative stress in lipid metabolism defects occurring in non-alcoholic fatty liver disease pathogenesis, we generated SMP30/SOD1-double knockout (SMP30/SOD1-DKO mice and investigated their survival curves, plasma and hepatic lipid profiles, amounts of hepatic oxidative stress, and hepatic protein levels expressed by genes related to lipid metabolism. While SMP30/SOD1-DKO pups had no growth retardation by 14 days of age, they did have low plasma and hepatic AA levels. Thereafter, 39% and 53% of male and female pups died by 15–24 and 89 days of age, respectively. Compared to wild type, SMP30-KO and SOD1-KO mice, by 14 days SMP30/SOD1-DKO mice exhibited: (1 higher plasma levels of triglyceride and aspartate aminotransferase; (2 severe accumulation of hepatic triglyceride and total cholesterol; (3 higher levels of superoxide anion radicals and thiobarbituric acid reactive substances in livers; and (4 decreased mRNA and protein levels of Apolipoprotein B (ApoB in livers – ApoB is an essential component of VLDL secretion. These results suggest that high levels of oxidative stress due to concomitant deficiency of SMP30 and/or AA, and SOD1 cause abnormal plasma lipid metabolism, hepatic lipid accumulation and premature death resulting from impaired VLDL secretion.

Acrolein-Induced Oxidative Stress and Cell Death Exhibiting Features of Apoptosis in the Yeast Saccharomyces cerevisiae Deficient in SOD1.

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Kwolek-Mirek, Magdalena; Zadrąg-Tęcza, Renata; Bednarska, Sabina; Bartosz, Grzegorz

2015-04-01

The yeast Saccharomyces cerevisiae is a useful eukaryotic model to study the toxicity of acrolein, an important environmental toxin and endogenous product of lipid peroxidation. The study was aimed at elucidation of the cytotoxic effect of acrolein on the yeast deficient in SOD1, Cu, Zn-superoxide dismutase which is hypersensitive to aldehydes. Acrolein generated within the cell from its precursor allyl alcohol caused growth arrest and cell death of the yeast cells. The growth inhibition involved an increase in production of reactive oxygen species and high level of protein carbonylation. DNA condensation and fragmentation, exposition of phosphatidylserine at the cell surface as well as decreased dynamic of actin microfilaments and mitochondria disintegration point to the induction of apoptotic-type cell death besides necrotic cell death.

Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models.

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Marcelo R Vargas

Full Text Available The nuclear factor erythroid 2-related factor 2 (Nrf2 governs the expression of antioxidant and phase II detoxifying enzymes. Nrf2 activation can prevent or reduce cellular damage associated with several types of injury in many different tissues and organs. Dominant mutations in Cu/Zn-superoxide dismutase (SOD1 cause familial forms of amyotrophic lateral sclerosis (ALS, a fatal disorder characterized by the progressive loss of motor neurons and subsequent muscular atrophy. We have previously shown that Nrf2 activation in astrocytes delays neurodegeneration in ALS mouse models. To further investigate the role of Nrf2 in ALS we determined the effect of absence of Nrf2 or its restricted overexpression in neurons or type II skeletal muscle fibers on symptoms onset and survival in mutant hSOD1 expressing mice. We did not observe any detrimental effect associated with the lack of Nrf2 in two different mutant hSOD1 animal models of ALS. However, restricted Nrf2 overexpression in neurons or type II skeletal muscle fibers delayed disease onset but failed to extend survival in hSOD1(G93A mice. These results highlight the concept that not only the pharmacological target but also the cell type targeted may be relevant when considering a Nrf2-mediated therapeutic approach for ALS.

Impairment of mitochondrial calcium handling in a mtSOD1 cell culture model of motoneuron disease

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Zippelius Annette

2009-06-01

Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage – dependent cytosolic Ca2+ elevations and mitochondria – controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT and G93A (SH-SY5YG93A expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. Conclusion In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations

Lack of TNF-alpha receptor type 2 protects motor neurons in a cellular model of amyotrophic lateral sclerosis and in mutant SOD1 mice but does not affect disease progression.

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Tortarolo, Massimo; Vallarola, Antonio; Lidonnici, Dario; Battaglia, Elisa; Gensano, Francesco; Spaltro, Gabriella; Fiordaliso, Fabio; Corbelli, Alessandro; Garetto, Stefano; Martini, Elisa; Pasetto, Laura; Kallikourdis, Marinos; Bonetto, Valentina; Bendotti, Caterina

2015-10-01

Changes in the homeostasis of tumor necrosis factor α (TNFα) have been demonstrated in patients and experimental models of amyotrophic lateral sclerosis (ALS). However, the contribution of TNFα to the development of ALS is still debated. TNFα is expressed by glia and neurons and acts through the membrane receptors TNFR1 and TNFR2, which may have opposite effects in neurodegeneration. We investigated the role of TNFα and its receptors in the selective motor neuron death in ALS in vitro and in vivo. TNFR2 expressed by astrocytes and neurons, but not TNFR1, was implicated in motor neuron loss in primary SOD1-G93A co-cultures. Deleting TNFR2 from SOD1-G93A mice, there was partial but significant protection of spinal motor neurons, sciatic nerves, and tibialis muscles. However, no improvement of motor impairment or survival was observed. Since the sciatic nerves of SOD1-G93A/TNFR2-/- mice showed high phospho-TAR DNA-binding protein 43 (TDP-43) accumulation and low levels of acetyl-tubulin, two indices of axonal dysfunction, the lack of symptom improvement in these mice might be due to impaired function of rescued motor neurons. These results indicate the interaction between TNFR2 and membrane-bound TNFα as an innovative pathway involved in motor neuron death. Nevertheless, its inhibition is not sufficient to stop disease progression in ALS mice, underlining the complexity of this pathology. We show evidence of the involvement of neuronal and astroglial TNFR2 in the motor neuron degeneration in ALS. Both concur to cause motor neuron death in primary astrocyte/spinal neuron co-cultures. TNFR2 deletion partially protects motor neurons and sciatic nerves in SOD1-G93A mice but does not improve their symptoms and survival. However, TNFR2 could be a new target for multi-intervention therapies. © 2015 International Society for Neurochemistry.

Evolutive and structural characterization of Nostoc commune iron-superoxide dismutase that is fit for modification.

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Ma, Y; Lu, M; Li, J-Y; Qin, Y; Gong, X-G

2012-10-04

Superoxide dismutase (SOD) has extensive clinical applications for protecting organisms from toxic oxidation. In this study, the integrated iron-superoxide dismutase gene (fe-sod) coding sequence of Nostoc commune stain CHEN was cloned from genomic DNA and compared to sods from other reported algae. These analyses of immunology and phylogenetics indicated that this Fe-SOD is considerably homologous with SODs from lower prokaryotes (Fe-SOD or Mn-SOD) but not those from higher animals (Cu/Zn-SOD). In addition, the N. commune Fe-SOD shows 67 to 93% protein sequence identity to 10 other algal Fe-SODs (or Mn-SODs) and 69 to 93% gene sequence identity. Rare nonsynonymous substitutions imply that algal SODs are being subjected to strong natural selection. Interestingly, the N. commune Fe-SOD enzyme molecule has a compact active center that is highly conserved (38.1% of residues are absolutely conserved), and 2 loose ends localized outside the molecule and inclined to mutate (only 11.5% of residues are absolutely conserved). Based on associative analyses of evolution, structure, and function, this special phenomenon is attributed to function-dependent evolution through negative natural selection. Under strong natural selection, although the mutation is random on the gene level, the exterior region is inclined to mutate on the protein level owing to more nonsynonymous substitutions in the exterior region, which demonstrates the theoretical feasibility of modifying Fe-SOD on its ends to overcome its disadvantages in clinical applications.

Visual Acuity does not Moderate Effect Sizes of Higher-Level Cognitive Tasks

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Houston, James R.; Bennett, Ilana J.; Allen, Philip A.; Madden, David J.

2016-01-01

Background Declining visual capacities in older adults have been posited as a driving force behind adult age differences in higher-order cognitive functions (e.g., the “common cause” hypothesis of Lindenberger & Baltes, 1994). McGowan, Patterson and Jordan (2013) also found that a surprisingly large number of published cognitive aging studies failed to include adequate measures of visual acuity. However, a recent meta-analysis of three studies (LaFleur & Salthouse, 2014) failed to find evidence that visual acuity moderated or mediated age differences in higher-level cognitive processes. In order to provide a more extensive test of whether visual acuity moderates age differences in higher-level cognitive processes, we conducted a more extensive meta-analysis of topic. Methods Using results from 456 studies, we calculated effect sizes for the main effect of age across four cognitive domains (attention, executive function, memory, and perception/language) separately for five levels of visual acuity criteria (no criteria, undisclosed criteria, self-reported acuity, 20/80-20/31, and 20/30 or better). Results As expected, age had a significant effect on each cognitive domain. However, these age effects did not further differ as a function of visual acuity criteria. Conclusion The current meta-analytic, cross-sectional results suggest that visual acuity is not significantly related to age group differences in higher-level cognitive performance—thereby replicating LaFleur and Salthouse (2014). Further efforts are needed to determine whether other measures of visual functioning (e.g. contrast sensitivity, luminance) affect age differences in cognitive functioning. PMID:27070044

Comparison of dendritic calcium transients in juvenile wild type and SOD1G93A mouse lumbar motoneurons

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Katharina Ann Quinlan

2015-04-01

Full Text Available Previous studies of spinal motoneurons in the SOD1 mouse model of amyotrophic lateral sclerosis have shown alterations long before disease onset, including increased dendritic branching, increased persistent Na+ and Ca2+ currents, and impaired axonal transport. In this study dendritic Ca2+ entry was investigated using 2 photon excitation fluorescence microscopy and whole-cell patch-clamp of juvenile (P4-11 motoneurons. Neurons were filled with both Ca2+ Green-1 and Texas Red dextrans, and line scans performed throughout. Steps were taken to account for different sources of variability, including 1 dye filling and laser penetration, 2 dendritic anatomy, and 3 the time elapsed from the start of recording. First, Ca2+ Green-1 fluorescence was normalized by Texas Red; next, neurons were reconstructed so anatomy could be evaluated; finally, time was recorded. Customized software detected the largest Ca2+ transients (area under the curve from each line scan and matched it with parameters above. Overall, larger dendritic diameter and shorter path distance from the soma were significant predictors of larger transients, while time was not significant up to 2 hours (data thereafter was dropped. However, Ca2+ transients showed additional variability. Controlling for previous factors, significant variation was found between Ca2+ signals from different processes of the same neuron in 3/7 neurons. This could reflect differential expression of Ca2+ channels, local neuromodulation or other variations. Finally, Ca2+ transients in SOD1G93A motoneurons were significantly smaller than in non-transgenic motoneurons. In conclusion, motoneuron processes show highly variable Ca2+ transients, but these transients are smaller overall SOD1G93A motoneurons.

Nitric oxide and superoxide dismutase modulate endothelial progenitor cell function in type 2 diabetes mellitus

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Brenner Benjamin

2009-10-01

Full Text Available Abstract Background The function of endothelial progenitor cells (EPCs, which are key cells in vascular repair, is impaired in diabetes mellitus. Nitric oxide (NO and reactive oxygen species can regulate EPC functions. EPCs tolerate oxidative stress by upregulating superoxide dismutase (SOD, the enzyme that neutralizes superoxide anion (O2-. Therefore, we investigated the roles of NO and SOD in glucose-stressed EPCs. Methods The functions of circulating EPCs from patients with type 2 diabetes were compared to those from healthy individuals. Healthy EPCs were glucose-stressed, and then treated with insulin and/or SOD. We assessed O2- generation, NO production, SOD activity, and their ability to form colonies. Results EPCs from diabetic patients generated more O2-, had higher NAD(PH oxidase and SOD activity, but lower NO bioavailability, and expressed higher mRNA and protein levels of p22-phox, and manganese SOD and copper/zinc SOD than those from the healthy individuals. Plasma glucose and HbA1c levels in the diabetic patients were correlated negatively with the NO production from their EPCs. SOD treatment of glucose-stressed EPCs attenuated O2- generation, restored NO production, and partially restored their ability to form colonies. Insulin treatment of glucose-stressed EPCs increased NO production, but did not change O2- generation and their ability to form colonies. However, their ability to produce NO and to form colonies was fully restored after combined SOD and insulin treatment. Conclusion Our data provide evidence that SOD may play an essential role in EPCs, and emphasize the important role of antioxidant therapy in type 2 diabetic patients.

Franck--Hertz experiment with higher excitation level measurements

International Nuclear Information System (INIS)

Liu, F.H.

1987-01-01

The measurement of the higher levels of 6 3 P 2 and 6 1 P 1 of the mercury atom in the Franck--Hertz experiment has been introduced into the junior and senior laboratory course by using a homemade tetrode Franck--Hertz tube. The main structure of the tube is described. The optimum operating conditions are in the temperature range between 130 and 150 0 C and the collector currents are of the order of 10 -9 A. The additional observations of the famous Franck--Hertz experiment in the laboratory course will give the students more familiarity with the quantum behavior of atoms

The dependence of the content of Cs137 forms in sod-podzolic sabulous soil of different degree of humidification on the basic soil tillage

International Nuclear Information System (INIS)

Tsybulko, N.N.; Ermolenko, A.V.; Lazarevich, S.S.

2011-01-01

The dependence of the content of 137 Cs-forms in sod-podzolic sabulous soils of different degree of humidification on the basic soil tillage is presented. Structure (in %) of plant available 137Cs in automorphic and semi-hydromorphic soils is shown. The influence of soil tillage type on 137Cs content is analyzed per 2007-2008. Content (in %) of plant available 137Cs in automorphic and semi-hydromorphic soils during moldboard plowing, beardless plowing, surface disc plowing and minimum tillage is evaluated. In sod-podzolic sabulous soils with 137 Cs pollution density which equals to 13-15 Cu/km2 the content of the accessible for plants forms (water-soluble, exchangeable, mobile forms) makes in average 9-11%; of those inaccessible (not exchangeable, fixed) 89-91%. It is established, that the degree of the hydromorphic feature in sod-podzolic sabolous soil influence the content of accessible forms of 1376cs in its top layer. The chisel tillage and the minimum tillage make it possible to decrease the accessible 137Cs connections by 2-4%

Perceived Effectiveness of Professional Development Programs of Teachers at Higher Education Level

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Malik, Sufiana Khatoon; Nasim, Uzma; Tabassum, Farkhanda

2015-01-01

The major purpose of the study was to assess the perceived effectiveness of professional development programs of teachers at higher educational level. The objectives of the study were: "to assess university level teachers'" opinion about effectiveness of professional development training with reference to quality teaching, to measure…

Reactive oxygen species and fatigue-induced prolonged low-frequency force depression in skeletal muscle fibres of rats, mice and SOD2 overexpressing mice.

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Bruton, Joseph D; Place, Nicolas; Yamada, Takashi; Silva, José P; Andrade, Francisco H; Dahlstedt, Anders J; Zhang, Shi-Jin; Katz, Abram; Larsson, Nils-Göran; Westerblad, Håkan

2008-01-01

Skeletal muscle often shows a delayed force recovery after fatiguing stimulation, especially at low stimulation frequencies. In this study we focus on the role of reactive oxygen species (ROS) in this fatigue-induced prolonged low-frequency force depression. Intact, single muscle fibres were dissected from flexor digitorum brevis (FDB) muscles of rats and wild-type and superoxide dismutase 2 (SOD2) overexpressing mice. Force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)) were measured. Fibres were stimulated at different frequencies before and 30 min after fatigue induced by repeated tetani. The results show a marked force decrease at low stimulation frequencies 30 min after fatiguing stimulation in all fibres. This decrease was associated with reduced tetanic [Ca(2+)](i) in wild-type mouse fibres, whereas rat fibres and mouse SOD2 overexpressing fibres instead displayed a decreased myofibrillar Ca(2+) sensitivity. The SOD activity was approximately 50% lower in wild-type mouse than in rat FDB muscles. Myoplasmic ROS increased during repeated tetanic stimulation in rat fibres but not in wild-type mouse fibres. The decreased Ca(2+) sensitivity in rat fibres could be partially reversed by application of the reducing agent dithiothreitol, whereas the decrease in tetanic [Ca(2+)](i) in wild-type mouse fibres was not affected by dithiothreitol or the antioxidant N-acetylcysteine. In conclusion, we describe two different causes of fatigue-induced prolonged low-frequency force depression, which correlate to differences in SOD activity and ROS metabolism. These findings may have clinical implications since ROS-mediated impairments in myofibrillar function can be counteracted by reductants and antioxidants, whereas changes in SR Ca(2+) handling appear more resistant to interventions.

Seeking a Higher Level of Arts Integration across the Curriculum

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Sotiropoulou-Zormpala, Marina

2016-01-01

To seek a higher level of arts integration across the education curriculum, I investigated designs of teaching through arts activities that would motivate educators to adopt the spirit of "aesthetic teaching." Two different designs were tested, with the second as a continuation of the first. Each ascribes a different educational role to…

Effects of Edaravone on Hippocampal Antioxidants in EL Mice.

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Baba, Asami; Kawakami, Yasuhiko; Saito, Kenichi; Murashima, Yoshiya L; Itoh, Yasuhiko

2016-01-01

The role of oxidative stress in susceptibility to seizures has been the focus of several recent studies. The aim of the present study was to evaluate the antiepileptic effects of the free radical scavenger edaravone on EL mice, a strain that is highly susceptible to convulsive seizures. EL mice were treated intraperitoneally with edaravone or saline for 1 week. The levels of reduced glutathione (GSH), oxidized glutathione (GSSG) and 3 isozymes of superoxide dismutase (SOD) (cytoplasmic copper- and zinc-containing SOD, extracellular SOD, and mitochondrial manganese-containing SOD) were measured in the hippocampus, and electroencephalograms (EEGs) were used to evaluate seizure sensitivity. Hippocampal levels of GSSG were lower in the edaravone group than in the untreated control group, and the GSH/GSSG ratio, Cu/Zn-SOD, and EC-SOD activities were higher in the edaravone group. Edaravone shortened the duration of interictal spike discharges and clinically suppressed epileptic seizures. Edaravone increases antioxidant potency and reduces seizure susceptibility in EL mice, making it a promising novel antiepileptic agent.

Purification of a Fe-SOD excreted by Leishmania braziliensis for specific antibodies detection in Mexican human sera: Cutting-edge the knowledge

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Silvia Stefania Longoni

2016-06-01

Full Text Available Clinical diagnosis of leishmaniasis is highly complex, presenting a wide range of clinical manifestations, sometimes non-specific, and thus the epidemiological study and diagnostic need specific molecular markers for each Leishmania species. Leishmania spp. posses different Fe-SOD isoforms, one of which is excreted into the external milieu and, presenting immunogenic characteristics, is a very reliable molecular marker. Superoxide dismutases (SODs are antioxidant metal-enzymes responsible for the dismutation of superoxide ion into hydrogen peroxide and molecular oxygen, and it is considered an important virulence factor. In this manuscript we have purified the iron(Fe-SOD excreted by Leishmania braziliensis using ion-exchange and molecular-sieve chromatography and we have studied it as an antigen in serodiagnostic analyses in ELISA and Western blot techniques, testing 213 human sera from Mexico. Indeed, L. braziliensis Fe-SODe has been purified 123.26 times with a specific activity of about 893.66 U/mg of protein. Applying the purified enzymes in serological tests we found 17.84% sera positive. We have demonstrated that the purified enzyme is more sensitive than the non-purified ones and we also demonstrated, for the first time, the presence of antibodies against L. braziliensis, not the main species in the country, in human population from Hidalgo and Nuevo Leon States.

PRE-SERVICE MATHEMATICS TEACHERS’ CONCEPTION OF HIGHER-ORDER THINKING LEVEL IN BLOOM'S TAXONOMY

OpenAIRE

Damianus D Samo

2017-01-01

The purpose of this study is to explore pre-service mathematics teachers' conception of higher-order thinking in Bloom's Taxonomy, to explore pre-service mathematics teachers' ability in categorizing six cognitive levels of Bloom's Taxonomy as lower-order thinking and higher-order thinking, and pre-service mathematics teachers' ability in identifying some questionable items as lower-order and higher-order thinking. The higher-order thinking is the type of non-algorithm thinking which include ...

Factorizable S-matrix for SO(D)/SO(2) circle times SO(D - 2) non-linear σ models with fermions

International Nuclear Information System (INIS)

Abdalla, E.; Lima-Santos, A.

1988-01-01

The authors compute the exact S matrix for the non-linear sigma model with symmetry SO(D)/SO(2) circle times SO(D-2) coupled to fermions in a minimal or supersymmetric way. The model has some relevance in string theory with non-zero external curvature

Variations in gene expression levels in four European zebra mussel, Dreissena polymorpha, populations in relation to metal bioaccumulation: A field study.

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Kerambrun, E; Rioult, D; Delahaut, L; Evariste, L; Pain-Devin, S; Auffret, M; Geffard, A; David, E

2016-12-01

The present study was performed to validate the suitability of using gene expression in zebra mussels, Dreissena polymorpha, for biomonitoring of freshwater environment. Mussels were collected in four French rivers (Meuse, Moselle, Oise and Vilaine) in spring and autumn. Relative gene expression of 9 candidate genes involved in cellular metabolic activities (Cytochrome-c-oxidase - cox, and ATP synthase - atp), detoxification process (Metallothionein - mt and Glutathion-S-Transferase - gst), oxidative stress (Catalase - cat, Superoxyde Dismutase - sod and Glutathion peroxidase - gpx) and digestive functions (Amylase - amy and Cellulase - ghf) were measured in digestive gland. Metal bioaccumulation in tissues and morphometric parameters were also analyzed to interpret molecular responses. All our results are consistent with different physiological reactions to environmental condition between zebra mussel populations. In spring, the levels of mt, sod, gpx, cat, atp, amy and ghf relative expression were significantly higher in mussels with the lowest metal bioaccumulation (the Meuse) compared to at least one of the other sites. In autumn, this higher expression levels in Meuse River were still observed for gpx, cat, atp and amy. This study has also pointed out different sources of variability in gene expression (individual size, season, trophic resources and origin of mussels) which are inevitable in natural fluctuant environment. This underlines the importance to take them into account in field study to propose a correct interpretation of biomarker responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Late Holocene higher sea level and its radiocarbon dates in Okierabu-jima, Ryukyus

International Nuclear Information System (INIS)

Koba, Motoharu; Omoto, Kunio; Takahashi, Tatsuo.

1980-01-01

Okierabu-jima of the Ryukyu Islands, which is a poly-terraced Pleistocene raised coral reef island, doesn't have a Holocene raised coral reef, but coastal erosional features showing higher sea levels in Holocene. The authors obtained some data indicating the period of one of the Holocene higher sea levels. All radiocarbon dates concerning Okierabu-jima's Holocene sea-level changes are plotted on the date-height coordinates. The paleo sea level between 5000 and 2000 y. B. P. lies above the broken line drawn from 6 m below to 2.18 m above the present sea level. The period of the highest sea level in Holocene seems to be about 3000 to 2000 y. B. P. in this island. Its height is presumably 2.4 m a. s. l. derived on an average from heights of stacks and coastal benches in the almost all coasts of the island (Koba, 1974). Beach rocks were already formed at the landward extremity of the reef flat corresponding to the almost present sea level about 1300 y. B. P. (author)

Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant.

Science.gov (United States)

Bruijn, L I; Beal, M F; Becher, M W; Schulz, J B; Wong, P C; Price, D L; Cleveland, D W

1997-07-08

Mutations in superoxide dismutase 1 (SOD1; EC 1.15.1.1) are responsible for a proportion of familial amyotrophic lateral sclerosis (ALS) through acquisition of an as-yet-unidentified toxic property or properties. Two proposed possibilities are that toxicity may arise from imperfectly folded mutant SOD1 catalyzing the nitration of tyrosines [Beckman, J. S., Carson, M., Smith, C. D. & Koppenol, W. H. (1993) Nature (London) 364, 584] through use of peroxynitrite or from peroxidation arising from elevated production of hydroxyl radicals through use of hydrogen peroxide as a substrate [Wiedau-Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. D., Roe, J. A., Valentine, J. S. & Bredesen, D. E. (1996) Science 271, 515-518]. To test these possibilities, levels of nitrotyrosine and markers for hydroxyl radical formation were measured in two lines of transgenic mice that develop progressive motor neuron disease from expressing human familial ALS-linked SOD1 mutation G37R. Relative to normal mice or mice expressing high levels of wild-type human SOD1, 3-nitrotyrosine levels were elevated by 2- to 3-fold in spinal cords coincident with the earliest pathological abnormalities and remained elevated in spinal cord throughout progression of disease. However, no increases in protein-bound nitrotyrosine were found during any stage of SOD1-mutant-mediated disease in mice or at end stage of sporadic or SOD1-mediated familial human ALS. When salicylate trapping of hydroxyl radicals and measurement of levels of malondialdehyde were used, there was no evidence throughout disease progression in mice for enhanced production of hydroxyl radicals or lipid peroxidation, respectively. The presence of elevated nitrotyrosine levels beginning at the earliest stages of cellular pathology and continuing throughout progression of disease demonstrates that tyrosine nitration is one in vivo aberrant property of this ALS-linked SOD1 mutant.

Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

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Kerti, Lucia; Witte, A Veronica; Winkler, Angela; Grittner, Ulrike; Rujescu, Dan; Flöel, Agnes

2013-11-12

For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.

MnSOD and CAT polymorphisms modulate the effect of the Mediterranean diet on breast cancer risk among Greek-Cypriot women.

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Kakkoura, Maria G; Demetriou, Christiana A; Loizidou, Maria A; Loucaides, Giorgos; Neophytou, Ioanna; Malas, Simon; Kyriacou, Kyriacos; Hadjisavvas, Andreas

2016-06-01

Oxidative stress arises due to a cellular imbalance in oxidants and antioxidants and/or due to an altered activity of antioxidant enzymes, caused by SNPs. Oxidative stress increases susceptibility to breast cancer (BC) risk, and we previously showed that the Mediterranean diet (MD), which is rich in antioxidants, reduces BC risk in Greek-Cypriot women. Here, we investigated the effect of MnSOD (p.Val16Ala, rs4880) and CAT (-262C>T, rs1001179) SNPs on the association between the MD and BC risk in the case-control study of BC MASTOS in Cyprus. Dietary intake data were obtained using a 32-item food frequency questionnaire, from which a dietary pattern was previously derived, using principal component analysis. This pattern included high loadings of vegetables, fruit, legumes and fish, a combination that closely resembles the MD and was used as our dietary variable. High vegetable intake lowered BC risk in women with at least one MnSOD Val allele (ORHigh vs. Low for Val/Val = 0.56, 95 % CI 0.35-0.88, for Val/Ala = 0.57, 95 % CI 0.39-0.82), or one CAT -262C allele (ORHigh vs. Low for -262CC = 0.66, 95 % CI 0.47-0.92, for -262CT = 0.53, 95 % CI 0.35-0.81). High fish intake conferred a decreased BC risk of CAT -262CC women (ORQ4 vs. Q1 0.66, 95 % CI 0.47-0.92) compared with the CAT -262TT women and low fish intake (ORQ2 vs. Q1 2.79, 95 % CI 1.08-7.17). Additionally, high fish intake reduced BC risk in MnSOD Val/Val women (ORQ4 vs. Q1 0.63, 95 % CI 0.40-0.98). p interaction values were, however, not statistically significant. Our results demonstrate that the antioxidative effects of the MD against BC risk may be enhanced by the wild-type alleles of the MnSOD or CAT SNPs among Greek-Cypriot women.

Factors identified with higher levels of career satisfaction of physicians in Andalusia, Spain

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Juan Nicolás Peña-Sánchez

2014-09-01

Full Text Available The satisfaction of physicians is a world-wide issue linked with the quality of health services; their satisfaction needs to be studied from a multi-dimensional perspective, considering lower- and higher-order needs. The objectives of this study were to: i measure the career satisfaction of physicians; ii identify differences in the dimensions of career satisfaction; and iii test factors that affect higher- and lower-order needs of satisfaction among physicians working in Andalusian hospitals (Spain. Forty-one percent of 299 eligible physicians participated in a study conducted in six selected hospitals. Physicians reported higher professional, inherent, and performance satisfaction than personal satisfaction. Foreign physicians reported higher levels of personal and performance satisfaction than local physicians, and those who received non-monetary incentives had higher professional and performance satisfaction. In conclusion, physicians in the selected Andalusian hospitals reported low levels of personal satisfaction. Non-monetary incentives were more relevant to influence their career satisfaction. Further investigations are recommended to study differences in the career satisfaction between foreign and local physicians.

Protein Oxidation Levels After Different Corneal Collagen Cross-Linking Methods.

Science.gov (United States)

Turkcu, Ummuhani Ozel; Yuksel, Nilay; Novruzlu, Sahin; Yalinbas, Duygu; Bilgihan, Ayse; Bilgihan, Kamil

2016-03-01

To evaluate advanced oxidation protein products (AOPP) levels, superoxide dismutase (SOD) enzyme activity, and total sulfhydryl (TSH) levels in rabbit corneas after different corneal collagen cross-linking (CXL) methods. Eighteen eyes of 9 adult New Zealand rabbits were divided into 3 groups of 6 eyes. The standard CXL group was continuously exposed to UV-A at a power setting of 3 mW/cm for 30 minutes. The accelerated CXL (A-CXL) group was continuously exposed to UV-A at a power setting of 30 mW/cm for 3 minutes. The pulse light-accelerated CXL (PLA-CXL) group received UV-A at a power setting of 30 mW/cm for 6 minutes of pulsed exposure (1 second on, 1 second off). Corneas were obtained after 1 hour of UV-A exposure, and 360-degree keratotomy was performed. SOD enzyme activity, AOPP, and TSH levels were measured in the corneal tissues. Compared with the standard CXL and A-CXL groups (133.2 ± 8.5 and 140.2 ± 6.2 μmol/mg, respectively), AOPP levels were found to be significantly increased in the PLA-CXL group (230.7 ± 30.2 μmol/mg) (P = 0.005 and 0.009, respectively). SOD enzyme activities and TSH levels did not differ between the groups (P = 0.167 and 0.187, respectively). CXL creates covalent bonds between collagen fibers because of reactive oxygen species. This means that more oxygen concentration during the CXL method will produce more reactive oxygen species and, thereby, AOPP. This means that in which CXL method occurs in more oxygen concentration that will produce more reactive oxygen species and thereby AOPP. This study demonstrated that PLA-CXL results in more AOPP formation than did standard CXL and A-CXL.

Intake of Lutein-Rich Vegetables Is Associated with Higher Levels of Physical Activity

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Georgina Crichton

2015-09-01

Full Text Available Levels of physical inactivity, a major contributor to burden of disease, are high in many countries. Some preliminary research suggests that circulating lutein concentrations are associated with high levels of physical activity (PA. We aimed to assess whether the intake of lutein-containing foods, including vegetables and eggs, is associated with levels of PA in two studies conducted in different countries. Dietary data and PA data collected from participants in two cross-sectional studies: the Maine-Syracuse Longitudinal Study (MSLS, conducted in Central New York, USA (n = 972, and the Observation of Cardiovascular Risk Factors in Luxembourg Study (ORISCAV-LUX (n = 1331 were analyzed. Higher intakes of lutein containing foods, including green leafy vegetables, were associated with higher levels of PA in both study sites. Increasing the consumption of lutein-rich foods may have the potential to impact positively on levels of PA. This needs to be further explored in randomized controlled trials.

Teaching at higher levels

Science.gov (United States)

1998-11-01

Undergraduate physics programmes for the 21st century were under discussion at a recent event held in Arlington, USA, open to two or three members of the physics faculties of universities from across the whole country. The conference was organized by the American Association of Physics Teachers with co-sponsorship from the American Institute of Physics, the American Physical Society and Project Kaleidoscope. Among the various aims were to learn about physics departments that have successfully revitalized their undergraduate physics programmes with innovative introductory physics courses and multi-track majors programmes. Engineers and life scientists were to be asked directly how physics programmes can better serve their students, and business leaders would be speaking on how physics departments can help to prepare their students for the diverse careers that they will eventually follow. It was planned to highlight ways that departments could fulfil their responsibilities towards trainee teachers, to identify the resources needed for revitalizing a department's programme, and to develop guidelines and recommendations for a funding programme to support collaborative efforts among physics departments for carrying out the enhancements required. More details about the conference can be found on the AAPT website (see http://www.aapt.org/programs/rupc.html). Meanwhile the UK's Higher Education Funding Council has proposed a two-pronged approach to the promotion of high quality teaching and learning, as well as widening participation in higher education from 1999-2000. A total of £60m should be available to support these initiatives by the year 2001-2002. As part of this scheme the Council will invite bids from institutions to support individual academics in enhancing learning and teaching, as well as in recognition of individual excellence. As with research grants, such awards would enable staff to pursue activities such as the development of teaching materials

Process-oriented guided inquiry learning strategy enhances students' higher level thinking skills in a pharmaceutical sciences course.

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Soltis, Robert; Verlinden, Nathan; Kruger, Nicholas; Carroll, Ailey; Trumbo, Tiffany

2015-02-17

To determine if the process-oriented guided inquiry learning (POGIL) teaching strategy improves student performance and engages higher-level thinking skills of first-year pharmacy students in an Introduction to Pharmaceutical Sciences course. Overall examination scores and scores on questions categorized as requiring either higher-level or lower-level thinking skills were compared in the same course taught over 3 years using traditional lecture methods vs the POGIL strategy. Student perceptions of the latter teaching strategy were also evaluated. Overall mean examination scores increased significantly when POGIL was implemented. Performance on questions requiring higher-level thinking skills was significantly higher, whereas performance on questions requiring lower-level thinking skills was unchanged when the POGIL strategy was used. Student feedback on use of this teaching strategy was positive. The use of the POGIL strategy increased student overall performance on examinations, improved higher-level thinking skills, and provided an interactive class setting.

Extension of TFTR operations to higher toroidal field levels

International Nuclear Information System (INIS)

Woolley, R.D.

1995-01-01

For the past year, TFTR has sometimes operated at extended toroidal field (TF) levels. The extension to 5.6 Tesla (79 kA) was crucial for TFTR's November 1994 10.7 MW DT fusion power record. The extension to 6.0 Tesla (85 kA) was commissioned on 9 September 1995. There are several reasons that one could expect the TF coils to survive the higher stresses that develop at higher fields. They were designed to operate at 5.2 Tesla with a vertical field of 0.5 Tesla, whereas the actual vertical field needed for the plasma does not exceed 0.35 Tesla. Their design specification explicitly required they survive some pulses at 6.0 Tesla. TF coil mechanical analysis computer models available during coil design were crude, leading to conservative design. And design analyses also had to consider worst-case misoperations that TFTR's real time Coil Protection Calculators (CPCs) now positively prevent from occurring

Factors associated with higher levels of depressive symptoms among international university students in the Philippines.

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Lee, Romeo B; Maria, Madelene Sta; Estanislao, Susana; Rodriguez, Cristina

2013-11-01

Over the years, the number of international university students has been increasing in the Philippines. Depression tends to be common among this demographic sector, because of the varying challenges and expectations associated with studying abroad. Depression can be prevented if its symptoms, particularly those at higher levels, are identified and addressed early and effectively. This survey examined the social and demographic factors that are significantly associated with higher levels of depressive symptoms. One hundred twenty-six international university students were interviewed using the University Students Depression Inventory. Of the 13 factors analyzed, 3 were found with statistically significant associations with more intense levels of depressive symptoms. These factors were: level of satisfaction with one's financial condition, level of closeness with parents, and level of closeness with peers. In identifying international students with greater risk for depression, characteristics related to their financial condition and primary group relationships can be considered. There is a need to carry out more studies to confirm this initial evidence. The findings can help guide further discourse, research and program to benefit international students with higher levels of depressive symptoms.

Process-Oriented Guided Inquiry Learning Strategy Enhances Students’ Higher Level Thinking Skills in a Pharmaceutical Sciences Course

Science.gov (United States)

Verlinden, Nathan; Kruger, Nicholas; Carroll, Ailey; Trumbo, Tiffany

2015-01-01

Objective. To determine if the process-oriented guided inquiry learning (POGIL) teaching strategy improves student performance and engages higher-level thinking skills of first-year pharmacy students in an Introduction to Pharmaceutical Sciences course. Design. Overall examination scores and scores on questions categorized as requiring either higher-level or lower-level thinking skills were compared in the same course taught over 3 years using traditional lecture methods vs the POGIL strategy. Student perceptions of the latter teaching strategy were also evaluated. Assessment. Overall mean examination scores increased significantly when POGIL was implemented. Performance on questions requiring higher-level thinking skills was significantly higher, whereas performance on questions requiring lower-level thinking skills was unchanged when the POGIL strategy was used. Student feedback on use of this teaching strategy was positive. Conclusion. The use of the POGIL strategy increased student overall performance on examinations, improved higher-level thinking skills, and provided an interactive class setting. PMID:25741027

Quercetin Protects Primary Human Osteoblasts Exposed to Cigarette Smoke through Activation of the Antioxidative Enzymes HO-1 and SOD-1

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Karl F. Braun

2011-01-01

Full Text Available Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS. The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO- 1 and superoxide-dismutase- (SOD- 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.

Sediment oxygen demand of wetlands in the oil sands region of northeastern Alberta

International Nuclear Information System (INIS)

Slama, C.; Gardner Costa, J.; Ciborowski, J.

2010-01-01

Sediment oxygen demand (SOD) can significantly influence the dissolved oxygen concentrations in shallow water bodies. This study discussed the types of sediments used to reclaim wetlands and their influence on SOD, successional processes, and ecosystem trajectories. The study hypothesized that oil sands process material (OSPM) affected wetlands would support cyanobacterial biofilms as opposed to submergent macrophytes as a result of insufficient phosphorus levels. SOD was assessed by monitoring dissolved oxygen concentrations within domes placed on the sediment surface for a 3-hour period. Gas flux and composition analyses were used to quantify the biological SOD components. Chemical SOD components were then determined by subtraction. Concentrations of phosphorus bioavailable to the macrophytes were estimated using plant root simulator probes. The study showed that OSPM wetlands exhibited higher chemical SOD and SOD than reference wetlands, and supported benthic biofilms as opposed to the submergent macrophyte communities typically found in northeastern Alberta wetlands.

Sediment oxygen demand of wetlands in the oil sands region of northeastern Alberta

Energy Technology Data Exchange (ETDEWEB)

Slama, C.; Gardner Costa, J.; Ciborowski, J. [Windsor Univ., ON (Canada)

2010-07-01

Sediment oxygen demand (SOD) can significantly influence the dissolved oxygen concentrations in shallow water bodies. This study discussed the types of sediments used to reclaim wetlands and their influence on SOD, successional processes, and ecosystem trajectories. The study hypothesized that oil sands process material (OSPM) affected wetlands would support cyanobacterial biofilms as opposed to submergent macrophytes as a result of insufficient phosphorus levels. SOD was assessed by monitoring dissolved oxygen concentrations within domes placed on the sediment surface for a 3-hour period. Gas flux and composition analyses were used to quantify the biological SOD components. Chemical SOD components were then determined by subtraction. Concentrations of phosphorus bioavailable to the macrophytes were estimated using plant root simulator probes. The study showed that OSPM wetlands exhibited higher chemical SOD and SOD than reference wetlands, and supported benthic biofilms as opposed to the submergent macrophyte communities typically found in northeastern Alberta wetlands.

Higher Levels of Psychopathy Predict Poorer Motor Control: Implications for Understanding the Psychopathy Construct

OpenAIRE

Robinson, Michael D.; Bresin, Konrad

2014-01-01

A review of the literature suggests that higher levels of psychopathy may be linked to less effective behavioral control. However, several commentators have urged caution in making statements of this type in the absence of direct evidence. In two studies (total N = 142), moment-to-moment accuracy in a motor control task was examined as a function of dimensional variations in psychopathy in an undergraduate population. As hypothesized, motor control was distinctively worse at higher levels of ...

Presymptomatic Treatment with Acetylcholinesterase Antisense Oligonucleotides Prolongs Survival in ALS (G93A-SOD1 Mice

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Gotkine Marc

2013-01-01

Full Text Available Objective. Previous research suggests that acetylcholinesterase (AChE may be involved in ALS pathogenesis. AChE enzyme inhibitors can upregulate AChE transcription which in certain contexts can have deleterious (noncatalytic effects, making them theoretically harmful in ALS, whilst AChE antisense-oligonucleotides (mEN101, which downregulate AChE may be beneficial. Our aim was to investigate whether downregulation of AChE using mEN101 is beneficial in an ALS mouse model. Methods. ALS (G93A-SOD1 mice received saline, mEN101, inverse-EN101, or neostigmine. Treatments were administered from 5 weeks. Disease-onset and survival were recorded. Additional mice were sacrificed for pathological analysis at 15 weeks of age. In a follow-up experiment treatment was started at the symptomatic stage at a higher dose. Results. mEN101 given at the presymptomatic (but not symptomatic stage prolonged survival and attenuated motor-neuron loss in ALS mice. In contrast, neostigmine exacerbated the clinical parameters. Conclusions. These results suggest that AChE may be involved in ALS pathogenesis. The accelerated disease course with neostigmine suggests that any beneficial effects of mEN101 occur through a non-catalytic rather than cholinergic mechanism.

Influence of percutaneous stimulation of hepatic region with mid-frequency pulse current on the activity of serum GSH-PX, SOD, T-AOC and the content of malondialdehyde in exercise-induced fatigued soldiers

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Peng-yi DAI

2014-03-01

Full Text Available Objective 　To explore the influence of percutaneous stimulation of the hepatic region with mid-frequency pulsed current on the serum activity of glutathione peroxidase (GSH-PX, superoxide dismutase (SOD and total antioxidant capacity and content of malondialdehyde (MDA in exercise-induced fatigued soldiers. Methods 　Sixty healthy male recruits without training history were randomly divided into control group and stimulation group (n=30. Subjects in both groups received intensive training for 5 weeks (trained from Monday to Saturday, and rest on Sunday to establish an exercise-induced fatigue model. The recruits in stimulation group received rehabilitation therapy of percutaneous stimulation of the hepatic region with mid-frequency pulse current (frequency was 1024Hz, dynamic cycle 1s, stimulation time 20min, output intensity ≤80mA after the training immediately. In every Sunday morning of the 1st, 3rd and 5th week, venous blood samples were obtained from recruits of both groups for determination of the serum activity of GSH-PX, SOD and T-AOC and content of MDA. Results 　In both groups, the serum activity of GSH-PX and T-AOC on 5th weekend was lower than that of 1st and 3rd weekends, and the serum activity of GSH-PX and T-AOC on 3rd weekend was lower than that of 1st weekend (P0.05; the serum MDA content on 5th weekend was higher than that of 3rd and 1st weekends, and the content on 3rd weekend was higher than that of 1st weekend (P<0.01. The activity of GSH-PX, SOD and T-AOC increased and the MDA content decreased on 1st, 3rd and 5th weekends in stimulation group when compared with control group (P<0.05, P<0.01. Conclusions 　The percutaneous stimulation of the hepatic region by mid-frequency pulsed current in exercise-induced fatigued soldiers may improve the activity of antioxidant enzymes in the liver, enhance the function of antioxidant system, promote free radical scavenging, delay the occurrence of and promote the recovery from

Higher Level Visual Cortex Represents Retinotopic, Not Spatiotopic, Object Location

Science.gov (United States)

Kanwisher, Nancy

2012-01-01

The crux of vision is to identify objects and determine their locations in the environment. Although initial visual representations are necessarily retinotopic (eye centered), interaction with the real world requires spatiotopic (absolute) location information. We asked whether higher level human visual cortex—important for stable object recognition and action—contains information about retinotopic and/or spatiotopic object position. Using functional magnetic resonance imaging multivariate pattern analysis techniques, we found information about both object category and object location in each of the ventral, dorsal, and early visual regions tested, replicating previous reports. By manipulating fixation position and stimulus position, we then tested whether these location representations were retinotopic or spatiotopic. Crucially, all location information was purely retinotopic. This pattern persisted when location information was irrelevant to the task, and even when spatiotopic (not retinotopic) stimulus position was explicitly emphasized. We also conducted a “searchlight” analysis across our entire scanned volume to explore additional cortex but again found predominantly retinotopic representations. The lack of explicit spatiotopic representations suggests that spatiotopic object position may instead be computed indirectly and continually reconstructed with each eye movement. Thus, despite our subjective impression that visual information is spatiotopic, even in higher level visual cortex, object location continues to be represented in retinotopic coordinates. PMID:22190434

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms in dilutional pseudoanemia (sports anemia).

Science.gov (United States)

Miranda-Vilela, Ana L; Akimoto, Arthur K; Alves, Penha C Z; Pereira, Luiz C S; Klautau-Guimarães, Maria N; Grisolia, Cesar K

2010-04-01

Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb.) is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala), CAT (21A/T) and GPX1 (Pro198Leu) gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration) and RDW (red cell distribution width), the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

Consequences of moral Kohlberg´s moral development levels in higher education

OpenAIRE

Bordignon, Nelso Antonio

2011-01-01

Abstract Introduction. This article presents the results of a research work about the implications of Kohlberg´s moral development level in higher education. Objective. To identify the state of moral development among higher education teachers, departing from the orientation they give to their lives and to those of their students, and from what they think and say they do for their students´ moral education.With the results, an analysis is done in order to establish the impli...

Parasitization by Scleroderma guani influences expression of superoxide dismutase genes in Tenebrio molitor.

Science.gov (United States)

Zhu, Jia-Ying; Ze, Sang-Zi; Stanley, David W; Yang, Bin

2014-09-01

Superoxide dismutase (SOD) is an antioxidant enzyme involved in detoxifying reactive oxygen species. In this study, we identified genes encoding the extracellular and intracellular copper-zinc SODs (ecCuZnSOD and icCuZnSOD) and a manganese SOD (MnSOD) in the yellow mealworm beetle, Tenebrio molitor. The cDNAs for ecCuZnSOD, icCuZnSOD, and MnSOD, respectively, encode 24.55, 15.81, and 23.14 kDa polypeptides, which possess structural features typical of other insect SODs. They showed 20-94% identity to other known SOD sequences from Bombyx mori, Musca domestica, Nasonia vitripennis, Pediculus humanus corporis, and Tribolium castaneum. Expression of these genes was analyzed in selected tissues and developmental stages, and following exposure to Escherichia coli and parasitization by Scleroderma guani. We recorded expression of all three SODs in cuticle, fat body, and hemocytes and in the major developmental stages. Relatively higher expressions were detected in late-instar larvae and pupae, compared to other developmental stages. Transcriptional levels were upregulated following bacterial infection. Analysis of pupae parasitized by S. guani revealed that expression of T. molitor SOD genes was significantly induced following parasitization. We infer that these genes act in immune response and in host-parasitoid interactions. © 2014 Wiley Periodicals, Inc.

A Different Approach to Assess Oxidative Stress in Dengue Hemorrhagic Fever Patients Through The Calculation of Oxidative Stress Index

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Edi Hartoyo

2017-09-01

Full Text Available The objectives of this study were to determine the involvement of Oxidative Stress (OS in the pathogenesis of dengue hemorrhagic fever (DHF through the analysis of oxidative stress Index (OSI. The levels of malondialdehyde (MDA, superoxide dismutase (SOD and catalase (CAT activity, and OSI were measured in 61 child dengue patients and (aged 6 months–18 years with three different stages of DHF, i.e stage I, II, and III. The results show that the levels of MDA, SOD and CAT activity, and OSI significantly different between the group. The all parameters that investigated in this present study seems higher MDA level and OSI in the higher grade of DHF, except for SOD and CAT activity. From this result, it can be concluded that oxidative stress pathways might be involved in the pathomechanism of DHF and OSI might be used as a biomarker for OS and the severity in DHF patients.

Superoxide Dismutase: A Predicting Factor for Boar Semen Characteristics for Short-Term Preservation

Science.gov (United States)

Nemec Svete, Alenka

2014-01-01

Superoxide dismutase (SOD), total antioxidant capacity (TAC), and thiobarbituric acid reactive substances (TBARS) in seminal plasma were evaluated on the basis of receiver operating characteristics (ROC) analysis as predictors for distinguishing satisfactory from unsatisfactory boar semen samples after storage. SOD on day 0 correlated significantly with progressive motility (r = −0.686; P Semen samples that, after 3 days of storage, fulfilled all criteria for semen characteristics (viability > 85%, motility > 70%, progressive motility > 25%, and normal morphology > 50%) had significantly lower SOD levels on the day 0 than those with at least one criterion not fulfilled (P semen will suit the requirements for satisfactory semen characteristics after storage, while semen with SOD levels higher than 1.05 U/mL will not fulfill with 100% accuracy at least one semen characteristic after storage. These results support the proposal that SOD in fresh boar semen can be used as a predictor of semen quality after storage. PMID:24729963

Radiation hormesis in plant - Analysis and utilization of plant antioxidative mechanism by radiation

Energy Technology Data Exchange (ETDEWEB)

Lee, Haeng Soon; Kwon, Seok Yoon; Shin, Seung Yung [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea)

2000-04-01

In the tobacco transgenic plants simultaneously expressing SOD and APX in chloroplast, the specific activities of SOD and APX (CA, AM, C/A, A/C) were much higher than in the transgenic plants expressing SOD (CuZnSOD, MnSOD) or APX alone, respectively. Plant growth was severely inhibited showing a well correlation with the dose of gamma-irradiation. In 70 Gy-irradiation, C/A plants showed a slight resistance to gamma radiation. The stAPX gene in tobacco was not as strongly affected by gamma irradiation. After irradiation, the stAPX transcript level decreased at 2 h, then slightly increased at 6 h and the level was maintained until 48 h. Catalase transcripts level decreased at the early time point but at the late time points the level slightly increased. The gamma radiation-induced changes of proteins in tobacco suspension cells were investigated by two-dimensional gel electrophoresis. In the gamma-irradiated cells, a few polypeptides of were newly synthesized, increased, and decreased by comparing total proteins from gamma-irradiated and non-irradiated tobacco suspension cells. With the isolation and analysis of these polypeptides, irradiation-induced proteins could be developed. 35 refs., 5 figs. (Author)

Investigating Student Choices in Performing Higher-Level Comprehension Tasks Using TED

Science.gov (United States)

Bianchi, Francesca; Marenzi, Ivana

2016-01-01

The current paper describes a first experiment in the use of TED talks and open tagging exercises to train higher-level comprehension skills, and of automatic logging of the student's actions to investigate the student choices while performing analytical tasks. The experiment took advantage of an interactive learning platform--LearnWeb--that…

Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk.

Science.gov (United States)

Bonfante, Ivan Luiz Padilha; Chacon-Mikahil, Mara Patricia Traina; Brunelli, Diego Trevisan; Gáspari, Arthur Fernandes; Duft, Renata Garbellini; Oliveira, Alexandre Gabarra; Araujo, Tiago Gomes; Saad, Mario Jose Abdalla; Cavaglieri, Cláudia Regina

2017-12-01

Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r -0.46, p = 0.04), neck circumference (r -0.51, p = 0.02), free fat mass (r -0.49, p = 0.02), triglycerides (r -0.43, p = 0.05) and risk of developing T2DM (r -0.61, p = 0.04) were observed. These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance.

Digital Immigrants and Digital Natives: Learning Business Informatics at Higher Educational Level

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Suša Dalia

2014-09-01

Full Text Available Background: The term digital natives refer to those born since the 1980s and have been growing up surrounded by technology. On the other hand, digital immigrants are born before 1980s and learned how to use technology later in life. Objectives: Goal of the paper is to explore attitudes of digital native students on the course of Business Informatics at higher educational institutions (HEIs, and to compare them with attitudes of digital immigrants. Methods/Approach: The survey was conducted in 2014 using the sample of first-year Business Informatics students from the Faculty of Economics and Business in Zagreb, Croatia. Results were compared with a research conducted in 1998. Results: In comparison to an earlier research, digital natives perceive their level of competency in the subject of Business Informatics before teaching practices much higher compared to digital immigrants. However, there is still an increase in digital native students’ level of competency in the subject before and after teaching practices. Conclusions: The research confirms a shift from digital immigrants to digital natives who show high level of interest for Business Informatics course topics and find its utility very high. However, constant improvement of delivering knowledge is needed in order to keep these high levels.

Genes with stable DNA methylation levels show higher evolutionary conservation than genes with fluctuant DNA methylation levels.

Science.gov (United States)

Zhang, Ruijie; Lv, Wenhua; Luan, Meiwei; Zheng, Jiajia; Shi, Miao; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Shang, Zhenwei; Duan, Lian; Jiang, Yongshuai

2015-11-24

Different human genes often exhibit different degrees of stability in their DNA methylation levels between tissues, samples or cell types. This may be related to the evolution of human genome. Thus, we compared the evolutionary conservation between two types of genes: genes with stable DNA methylation levels (SM genes) and genes with fluctuant DNA methylation levels (FM genes). For long-term evolutionary characteristics between species, we compared the percentage of the orthologous genes, evolutionary rate dn/ds and protein sequence identity. We found that the SM genes had greater percentages of the orthologous genes, lower dn/ds, and higher protein sequence identities in all the 21 species. These results indicated that the SM genes were more evolutionarily conserved than the FM genes. For short-term evolutionary characteristics among human populations, we compared the single nucleotide polymorphism (SNP) density, and the linkage disequilibrium (LD) degree in HapMap populations and 1000 genomes project populations. We observed that the SM genes had lower SNP densities, and higher degrees of LD in all the 11 HapMap populations and 13 1000 genomes project populations. These results mean that the SM genes had more stable chromosome genetic structures, and were more conserved than the FM genes.

Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility.

Science.gov (United States)

Orouji Jokar, Tahereh; Fourman, Lindsay T; Lee, Hang; Mentzinger, Katherine; Fazeli, Pouneh K

2018-02-01

Unexplained infertility (UI), defined as the inability to conceive after 12 months of unprotected intercourse with no diagnosed cause, affects 10% to 30% of infertile couples. An improved understanding of the mechanisms underlying UI could lead to less invasive and less costly treatment strategies. Abnormalities in thyroid function and hyperprolactinemia are well-known causes of infertility, but whether thyrotropin (TSH) and prolactin levels within the normal range are associated with UI is unknown. To compare TSH and prolactin levels in women with UI and women with a normal fertility evaluation except for an azoospermic or severely oligospermic male partner. Cross-sectional study including women evaluated at a large academic health system between 1 January 2000 and 31 December 2012 with normal TSH (levels within the normal range of the assay and ≤5 mIU/L) and normal prolactin levels (≤20 ng/mL) and either UI (n = 187) or no other cause of infertility other than an azoospermic or severely oligospermic partner (n = 52). TSH and prolactin. Women with UI had significantly higher TSH levels than controls [UI: TSH 1.95 mIU/L, interquartile range: (1.54, 2.61); severe male factor: TSH 1.66 mIU/L, interquartile range: (1.25, 2.17); P = 0.003]. This finding remained significant after we controlled for age, body mass index, and smoking status. Nearly twice as many women with UI (26.9%) had a TSH ≥2.5 mIU/L compared with controls (13.5%; P < 0.05). Prolactin levels did not differ between the groups. Women with UI have higher TSH levels compared with a control population. More studies are necessary to determine whether treatment of high-normal TSH levels decreases time to conception in couples with UI. Copyright © 2017 Endocrine Society

Effects of Shenlong Decoction on Learning and Memory Abilities as well as SOD and MDA in Brain-aging Model Mice Induced by D-Galactose

Institute of Scientific and Technical Information of China (English)

Liu Yi; Wang Fawei; Yang Minghui; Zheng Qingping; Wang Youjing

2006-01-01

@@ Brain aging (dementia) model mice were made by cervical subcutaneous injection of D-galactose solution.Learning and memory abilities were detected with water maze test and superoxide dismulase(SOD)activities and malondiadehyde (MDA) contents in the liver and brain were determined after intragastrical administration of Shenlong Decoction (参龙汤) for 6 weeks. The results indicated that the swimming time was shortened and the correct swimming times increased, SOD activity raised and MDA content decreased in the three Shenlong Decoction groups with different doses as compared with the model group. It is concluded that Shenlong Decoction has the effects of anti-free radical injuries and improving the learning and memory abilities of the brain-aging mice induced by D-galactose.

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease.

Science.gov (United States)

Ju, Chun-Rong; Chen, Miao; Zhang, Jian-Heng; Lin, Zhi-Ya; Chen, Rong-Chang

2016-01-01

To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV) function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD). The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE) less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP) levels were analyzed as a comparison of myostatin. The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL) were significantly higher in patients with cor pulmonale (16.68 ± 2.95) than in those without (13.56 ± 3.09), and much higher than in controls (8.79±2.79), with each pmyostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each pmyostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.

β-endorphins Plasma Level is Higher in Lean Polycystic Ovary Syndrome (PCOS) Women.

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Kiałka, M; Milewicz, T; Spałkowska, M; Krzyczkowska-Sendrakowska, M; Wasyl, B; Pełka, A; Krzysiek, J

2016-01-01

The evaluation the β-endorphin plasma levels in lean women with polycystic ovary syndrome as well as in women without this disorder. The associations between β-endorphins and other laboratory parameters were also investigated. 31 women lean, defined as women with normal range body mass index, 15 with polycystic ovary syndrome and 16 without this disorder were included to the study. In all the patients the level of β-endorphins was measured. Also the diagnostic laboratory profile including hormone assessment was made in all patients. There were significant differences in β-endorphin levels between the 2 groups. The β-endorphin level was higher in the polycystic ovary syndrome group compared to the healthy controls (15.5±4.37 pg/ml vs. 6.9±2.47 pg/ml, ppolycystic ovary syndrome group. Increase in β-endorphin level of 1 pg/ml was associated with an increase of cortisol at 8 am level of 1.134 µg/dl and decrease of sex hormone binding globuline of 0.948 nmol/l in polycystic ovary syndrome group. Our study showed that the levels of β-endorphins were significantly higher in lean patients with polycystic ovary syndrome than in lean controls. Moreover, β-endorphins levels were found to be correlated with other hormonal parameters. In this respect, β-endorphins may play a role in polycystic ovary syndrome pathophysiology. © Georg Thieme Verlag KG Stuttgart · New York.

Change of direction ability test differentiates higher level and lower level soccer referees

Science.gov (United States)

Los, Arcos A; Grande, I; Casajús, JA

2016-01-01

This report examines the agility and level of acceleration capacity of Spanish soccer referees and investigates the possible differences between field referees of different categories. The speed test consisted of 3 maximum acceleration stretches of 15 metres. The change of direction ability (CODA) test used in this study was a modification of the Modified Agility Test (MAT). The study included a sample of 41 Spanish soccer field referees from the Navarre Committee of Soccer Referees divided into two groups: i) the higher level group (G1, n = 20): 2ndA, 2ndB and 3rd division referees from the Spanish National Soccer League (28.43 ± 1.39 years); and ii) the lower level group (G2, n = 21): Navarre Provincial League soccer referees (29.54 ± 1.87 years). Significant differences were found with respect to the CODA between G1 (5.72 ± 0.13 s) and G2 (6.06 ± 0.30 s), while no differences were encountered between groups in acceleration ability. No significant correlations were obtained in G1 between agility and the capacity to accelerate. Significant correlations were found between sprint and agility times in the G2 and in the total group. The results of this study showed that agility can be used as a discriminating factor for differentiating between national and regional field referees; however, no observable differences were found over the 5 and 15 m sprint tests. PMID:27274111

Does peer learning or higher levels of e-learning improve learning abilities?

DEFF Research Database (Denmark)

Worm, Bjarne Skjødt; Jensen, Kenneth

2013-01-01

The fast development of e-learning and social forums demands us to update our understanding of e-learning and peer learning. We aimed to investigate if higher, pre-defined levels of e-learning or social interaction in web forums improved students' learning ability....

The antioxidant level of Alaska's wild berries: high, higher and highest

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Roxie Rodgers Dinstel

2013-08-01

Full Text Available Background . In the last few years, antioxidants have become the stars of the nutritional world. Antioxidants are important in terms of their ability to protect against oxidative cell damage that can lead to conditions, such as Alzheimer's disease, cancer and heart disease – conditions also linked with chronic inflammation. The antioxidant and anti-inflammatory effects of Alaska's wild berries may have the potential to help prevent these diseases. Objective . To discover the antioxidant levels of Alaska wild berries and the ways these antioxidant levels translate when preservation methods are applied to the berry. Design . This research centred on both the raw berries and products made from the berries. In the first year, a variety of wild berries were tested to discover their oxygen radical absorption capacity (ORAC in the raw berries. The second level of the research project processed 4 different berries – blueberries, lingonberries, salmonberries, highbush cranberries – into 8 or 9 products made from these berries. The products were tested for both ORAC as well as specific antioxidants. Results . The Alaska wild berries collected and tested in the first experiment ranged from 3 to 5 times higher in ORAC value than cultivated berries from the lower 48 states. For instance, cultivated blueberries have an ORAC scale of 30. Alaska wild dwarf blueberries measure 85. This is also higher than lower 48 wild blueberries, which had a score of 61. All of the Alaskan berries tested have a level of antioxidant considered nutritionally valuable, ranging from 19 for watermelon berries to 206 for lingonberries on the ORAC scale. With the processed products made from 4 Alaska wild berries, one of the unexpected outcomes of the research was that the berries continued to have levels of antioxidants considered high, despite the effects of commonly used heat-processing techniques. When berries were dehydrated, per gram ORAC values increased. Conclusion

Significant in vivo anti-inflammatory activity of Pytren4Q-Mn a superoxide dismutase 2 (SOD2 mimetic scorpiand-like Mn (II complex.

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Carolina Serena

Full Text Available The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight.We have recently reported that two SOD mimetic compounds, the Mn(II complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q Mn(II complexes, in cultured macrophages and in a murine model of inflammation, by measuring the degree of protection they could provide against the cellular injury produced by lipopolisacharide, a bacterial endotoxin.In this report we show that the Mn(II complex of Pytren4Q but not that of Pytren2Q effectively protected human cultured THP-1 macrophages and whole mice from the inflammatory effects produced by LPS. These results obtained with two molecules that are isomers highlight the importance of gathering experimental data from animal models of disease in assessing the potential of candidate molecules.The effective anti-inflammatory activity of the Mn(II complex of Pytren4Q in addition to its low toxicity, water solubility and ease of production would suggest it is worth taking into consideration for future pharmacological studies.

Multisensory Stimulation to Improve Low- and Higher-Level Sensory Deficits after Stroke: A Systematic Review.

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Tinga, Angelica Maria; Visser-Meily, Johanna Maria Augusta; van der Smagt, Maarten Jeroen; Van der Stigchel, Stefan; van Ee, Raymond; Nijboer, Tanja Cornelia Wilhelmina

2016-03-01

The aim of this systematic review was to integrate and assess evidence for the effectiveness of multisensory stimulation (i.e., stimulating at least two of the following sensory systems: visual, auditory, and somatosensory) as a possible rehabilitation method after stroke. Evidence was considered with a focus on low-level, perceptual (visual, auditory and somatosensory deficits), as well as higher-level, cognitive, sensory deficits. We referred to the electronic databases Scopus and PubMed to search for articles that were published before May 2015. Studies were included which evaluated the effects of multisensory stimulation on patients with low- or higher-level sensory deficits caused by stroke. Twenty-one studies were included in this review and the quality of these studies was assessed (based on eight elements: randomization, inclusion of control patient group, blinding of participants, blinding of researchers, follow-up, group size, reporting effect sizes, and reporting time post-stroke). Twenty of the twenty-one included studies demonstrate beneficial effects on low- and/or higher-level sensory deficits after stroke. Notwithstanding these beneficial effects, the quality of the studies is insufficient for valid conclusion that multisensory stimulation can be successfully applied as an effective intervention. A valuable and necessary next step would be to set up well-designed randomized controlled trials to examine the effectiveness of multisensory stimulation as an intervention for low- and/or higher-level sensory deficits after stroke. Finally, we consider the potential mechanisms of multisensory stimulation for rehabilitation to guide this future research.

Antioxidant enzyme level response to prooxidant allelochemicals in larvae of the southern armyworm moth, Spodoptera eridania.

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Pritsos, C A; Ahmad, S; Elliott, A J; Pardini, R S

1990-01-01

Larvae of the southern armyworm, Spodoptera eridania, are highly polyphagous feeders which frequently encounter and feed upon plants containing high levels of prooxidant allelochemicals. While ingestion of moderate quantities of prooxidants can be tolerated by these larvae, ingestion of larger quantities can result in toxicity. Studies were conducted to assess the role of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in the protection of S. eridania against redox active prooxidant plant allelochemicals. Dietary exposure of mid-fifth-instar larvae to either quercetin (a flavonoid) or xanthotoxin (a photoactive furanocoumarin), which generate superoxide radical, and singlet oxygen, respectively, resulted in an increase in SOD levels. CAT levels increased in all groups of S. eridania including control insects. This may have been due to the sudden exposure to food following an extended fast of 18 h (to insure that larvae would not reject the diet because of the prooxidants' bitter taste) with an eventual lowering of CAT values with time. GR activities did not significantly change except for a slight inhibition at the highest prooxidant concentrations used at 12-h post-ingestion. The data from these studies suggest that SOD responds to prooxidant challenges in these insects and together with CAT and GR contributes to the insect's defense against potentially toxic prooxidant compounds.

The V16A polymorphism in SOD2 is associated with increased risk of diabetic nephropathy and cardiovascular disease in type 1 diabetes

DEFF Research Database (Denmark)

Möllsten, A; Jorsal, Anders; Lajer, Maria Stenkil

2009-01-01

on the development of cardiovascular disease. METHODS: Type 1 diabetes patients attending the Steno Diabetes Center, Gentofte, Denmark, between 1993 and 2001 were enrolled in this study. A total of 441 cases with diabetic nephropathy (albumin excretion > or =300 mg/24 h) and 314 controls with persistent....... The hazard ratio was 1.6 (95% CI 1.0-2.5). CONCLUSIONS/INTERPRETATION: The MnSOD V16A polymorphism is involved in the development of nephropathy caused by type 1 diabetes and seems to predict cardiovascular disease during follow-up....... affects the localisation of MnSOD and therefore its ability to scavenge superoxide radicals. In a Danish cohort of type 1 diabetes patients, we sought to confirm previous findings of association between the V allele and the risk of diabetic nephropathy and to investigate the influence of this polymorphism...

Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz).

Science.gov (United States)

Xu, Jia; Yang, Jun; Duan, Xiaoguang; Jiang, Yueming; Zhang, Peng

2014-08-05

Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis. Transgenic cassava plants that co-express cytosolic superoxide dismutase (SOD), MeCu/ZnSOD, and ascorbate peroxidase (APX), MeAPX2, were produced and tested for tolerance against oxidative and chilling stresses. The up-regulation of MeCu/ZnSOD and MeAPX2 expression was confirmed by the quantitative reverse transcriptase-polymerase chain reaction, and enzymatic activity analyses in the leaves of transgenic cassava plant lines with a single-transgene integration site. Upon exposure to ROS-generating agents, 100 μM ROS-generating reagent methyl viologen and 0.5 M H₂O₂, higher levels of enzymatic activities of SOD and APX were detected in transgenic plants than the wild type. Consequently, the oxidative stress parameters, such as lipid peroxidation, chlorophyll degradation and H₂O₂ synthesis, were lower in the transgenic lines than the wild type. Tolerance to chilling stress at 4°C for 2 d was greater in transgenic cassava, as observed by the higher levels of SOD, catalase, and ascorbate-glutathione cycle enzymes (e.g., APX, monodehydroascorbate reductase, dehydroascorbate reducatase and glutathione reductase) and lower levels of malondialdehyde content. These results suggest that the expression of native cytosolic SOD and APX simultaneously activated the antioxidative defense mechanisms via cyclic ROS scavenging, thereby improving its tolerance to cold stress.

Wellbeing in the Welfare State: level not higher, distribution not more equitable

NARCIS (Netherlands)

R. Veenhoven (Ruut)

2000-01-01

textabstract'Wellbeing' and 'welfare' are often bracketed together, in particular wellbeing and state-welfare. The level of wellbeing is believed to be higher in welfare states, and its distribution more equitable. This theory is tested in a comparative study of 40 nations 1980-1990. The size of

Higher Plasma Myostatin Levels in Cor Pulmonale Secondary to Chronic Obstructive Pulmonary Disease.

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Chun-Rong Ju

Full Text Available To analyze plasma myostatin levels and investigate their relationship with right ventricular (RV function in patients with cor pulmonale secondary to chronic obstructive pulmonary disease (COPD.The study recruited 81 patients with advanced COPD and 40 age-matched controls. The patients were divided into two groups: those with cor pulmonale and those without. Echocardiography was used to evaluate RV function and morphology, and the value of tricuspid annular plane systolic excursion (TAPSE less than 16 mm was considered RV dysfunction. Plasma myostatin levels were analyzed by enzyme-linked immunosorbent assay, and B-type natriuretic peptide (BNP levels were analyzed as a comparison of myostatin.The data detected cor pulmonale in 39/81 patients, with the mean value of TAPSE of 14.3 mm. Plasma myostatin levels (ng/mL were significantly higher in patients with cor pulmonale (16.68 ± 2.95 than in those without (13.56 ± 3.09, and much higher than in controls (8.79±2.79, with each p<0.01. Significant differences were also found in plasma BNP levels among the three groups (p<0.05. Multivariate regression analysis suggested that myostatin levels were significantly correlated with the values of TAPSE and RV myocardium performance index among the COPD patients, and that BNP levels were significantly correlated only with systolic pulmonary arterial pressure, with each p<0.05.Plasma myostatin levels are increased in COPD patients who have cor pulmonale. Stronger correlations of plasma myostatin levels with echocardiographic indexes of the right heart suggest that myostatin might be superior to BNP in the early diagnosis of cor pulmonale in COPD.

The effects of 3% diquafosol sodium eye drop application on meibomian gland and ocular surface alterations in the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

Science.gov (United States)

Ikeda, Keisuke; Simsek, Cem; Kojima, Takashi; Higa, Kazunari; Kawashima, Motoko; Dogru, Murat; Shimizu, Takahiko; Tsubota, Kazuo; Shimazaki, Jun

2018-04-01

The purpose of the study is to investigate the effect of 3% diquafosol sodium eye drops on meibomian gland and ocular surface alterations in the superoxide dismutase-1 (Sod1 -/- ) mice in comparison to the wild-type mouse. Three percent diquafosol sodium eye drop was instilled to 20 eyes of 10 50-week-old male Sod1 -/- mice and 22 eyes of 11 C57BL/6 strain 50-week-old wild-type (WT) male mice six times a day for 2 weeks. Aqueous tear secretion quantity was measured with phenol red-impregnated cotton threads without anesthesia. Tear film stability and corneal epithelial damage were assessed by fluorescein and lissamine green staining. We also performed oil red O (ORO) lipid staining to evaluate the lipid changes in the meibomian glands. Meibomian gland specimens underwent hematoxylin and eosin staining to examine histopathological changes and meibomian gland acinar unit density after sacrifice. Immunohistochemistry staining was performed using cytokeratin 4, cytokeratin 13, and transglutaminase-1 antibodies. Quantitative real-time polymerase chain reaction for cytokeratin 4, cytokeratin 13, and transglutaminase-1 mRNA expression was also performed. The aqueous tear quantity, the mean tear film breakup time, and the number of lipid droplets significantly improved in the Sod1 -/- mice with treatment. The mean meibomian acinar unit density did not change in the Sod1 -/- mice and WT mice after treatment. Application of 3% diquafosol sodium eye drop significantly decreased the corneal fluorescein and lissamine green staining scores in the Sod1 -/- mice after 2 weeks. We showed a notable increase in cytokeratin 4, cytokeratin 13 immunohistochemistry staining, and cytokeratin 4, cytokeratin 13 mRNA expressions with a marked decrease in immunohistochemistry staining and significant decline in mRNA expression of transglutaminase-1 after 3% diquafosol sodium treatment. Topical application of 3% diquafosol sodium eye drop improved the number of lipid droplets, tear stability

The effects of different levels of catalase and superoxide dismutase in modified Beltsville extender on rooster post-thawed sperm quality.

Science.gov (United States)

Amini, Mahmood Reza; Kohram, Hamid; Zare-Shahaneh, Ahmad; Zhandi, Mahdi; Sharideh, Hossein; Nabi, Mohammad Mehdi

2015-06-01

Oxidative damage of sperm by means of reactive oxygen species generated by the cellular components of semen is one of the main reasons for decreased sperm motility and fertility during the freeze-thawing process. This study was conducted to determine the influence of catalase (CAT) and superoxide dismutase (SOD) on rooster sperm motility, viability and MDA level after freezing and thawing. Semen samples from 10 sexually-mature Ross 308 breeder roosters were collected and pooled, divided into nine equal parts and diluted with modified Beltsville extender containing no antioxidants (control), or supplemented with 50, 100, 200 and 300 μg/mL CAT, or 50, 100, 200 and 300 U/mL SOD. After thawing, sperm motility and motion parameters were assessed using a CASA system. Sperm viability and MDA level were assessed by eosin-nigrosin and MDA test, respectively. The results of this experiment showed that the extender supplemented with 100 and 200 μg CAT, and 50 U SOD had the highest sperm motility (Prooster semen. Copyright © 2015 Elsevier Inc. All rights reserved.

Dietary carotenoid-rich oil supplementation improves exercise-induced anisocytosis in runners: influences of haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms in dilutional pseudoanemia ("sports anemia"

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Ana L. Miranda-Vilela

2010-01-01

Full Text Available Physical training induces beneficial adaptation, whereas exhaustive exercises increase reactive oxygen-species generation, thereby causing oxidative damage in plasma and erythrocytes, fractions susceptible to lipid peroxidation. Pequi (Caryocar brasiliense Camb. is a Brazilian Cerrado fruit containing a carotenoid-rich oil. The aim was to investigate the effects of pequi-oil on exercise-induced oxidative damage in plasma and erythrocytes, after running in the same environment and undergoing weekly training under the same conditions as to type, intensity and length. Evaluations were accomplished after outdoor running on flat land before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after running and submitted to TBARS assay and erythrogram analysis. Haptoglobin, MnSOD (Val9Ala, CAT (21A/T and GPX1 (Pro198Leu gene polymorphisms were priorly investigated, so as to estimate genetic influence The reduction in erythrocytes, hemoglobin and hematocrit after pequi-oil treatment was notably associated with higher plasma expansion. Except for MCHC (mean corpuscular hemoglobin concentration and RDW (red cell distribution width, the results were influenced by the polymorphisms studied. The best response to pequi-oil was presented by MnSOD Val/Val, CAT AA or AT genotypes and the GPX1 Pro allele. The significantly lower RDW and higher MHCH values were related to pequi-oil protective effects. Pequi oil, besides possessing other nutritional properties, showed protective blood effects.

Medicinal Mushroom Cracked-Cap Polypore, Phellinus rimosus (Higher Basidiomycetes) Attenuates Acute Ethanol-Induced Lipid Peroxidation in Mice.

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Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K

2015-01-01

Alcohol abuse and alcoholism remain one of the major health issues worldwide, especially in developing countries. The protective effect of Phellinus rimosus against acute alcohol-induced lipid peroxidation in the liver, kidney, and brain as well as its effect against antioxidant enzyme activity such as superoxide (SOD) and catalase (CAT) in the liver was evaluated in mice. Ethyl acetate extract of Ph. Rimosus (50 mg/kg body wt, p.o.) 1 h before each administration of alcohol (3 mL/kg, p.o.; total 2 doses at 24-h intervals) protected against lipid peroxidation in all organs and attenuated the decline of SOD and CAT activity in the liver. The fold increase in lipid peroxidation, including conjugated diene and thiobarbituric acid reactive substance (TBARS) levels, was highest in the liver. There were 2.6- and 1.5- fold increases in TBARS levels in the liver of the alcohol alone- and alcohol+Ph. Rimosus-treated groups, compared with that of the normal group. Activity of SOD and CAT in the liver of alcohol- and alcohol+Ph. Rimosus- treated animals was 9.05±1.38, 18.76±1.71, and 11.26±1.02, 31.58±3.35 IU/mg protein, respectively. Extract at 1 mg/mL inhibited 50.6% activity of aniline hydroxylase (CYP2E1) in liver homogenate. From these results, we concluded that the extract significantly protected against the lipid peroxidation. Protection in the liver may be due to the inhibitory effect on CYP2E1 as well as the direct radical scavenging effect of Ph. Rimosus, which warrants further research.

Higher Dialysate Matrix Metalloproteinase-2 Levels Are Associated with Peritoneal Membrane Dysfunction

Science.gov (United States)

Cho, Yeoungjee; Johnson, David W.; Vesey, David A.; Hawley, Carmel M.; Pascoe, Elaine M.; Clarke, Margaret; Topley, Nicholas

2016-01-01

♦ Background: Peritoneal dialysis (PD) patients develop progressive and cumulative peritoneal injury with longer time spent on PD. The present study aimed to a) describe the trend of peritoneal injury biomarkers, matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), in incident PD patients, b) to explore the capacity of dialysate MMP-2 to predict peritoneal solute transport rate (PSTR) and peritonitis, and c) to evaluate the influence of neutral pH, low glucose degradation product (GDP) PD solution on these outcomes. ♦ Methods: The study included 178 participants from the balANZ trial who had at least 1 stored dialysate sample. Changes in PSTR and peritonitis were primary outcome measures, and the utility of MMP-2 in predicting these outcomes was analyzed using multilevel linear regression and multilevel Poisson regression, respectively. ♦ Results: Significant linear increases in dialysate MMP-2 and TIMP-1 concentrations were observed (p < 0.001), but neither was affected by the type of PD solutions received (MMP-2: p = 0.07; TIMP-1: p = 0.63). An increase in PSTR from baseline was associated with higher levels of MMP-2 (p = 0.02), and the use of standard solutions over longer PD duration (p = 0.001). The risk of peritonitis was independently predicted by higher dialysate MMP-2 levels (incidence rate ratio [IRR] per ng/mL 1.01, 95% confidence interval [CI] 1.005 – 1.02, p = 0.002) and use of standard solutions (Biocompatible solution: IRR 0.45, 95% CI 0.24 – 0.85, p = 0.01). ♦ Conclusion: Dialysate MMP-2 and TIMP-1 concentrations increased with longer PD duration. Higher MMP-2 levels were associated with faster PSTR and future peritonitis risk. Administration of biocompatible solutions exerted no significant effect on dialysate levels of MMP-2 or TIMP-1, but did counteract the increase in PSTR and the risk of peritonitis associated with the use of standard PD solutions. This is the first longitudinal study to examine

Induction of antioxidant enzyme activity and lipid peroxidation level in ion-beam-bombarded rice seeds

Science.gov (United States)

Semsang, Nuananong; Yu, LiangDeng

2013-07-01

Low-energy ion beam bombardment has been used to mutate a wide variety of plant species. To explore the indirect effects of low-energy ion beam on biological damage due to the free radical production in plant cells, the increase in antioxidant enzyme activities and lipid peroxidation level was investigated in ion-bombarded rice seeds. Local rice seeds were bombarded with nitrogen or argon ion beams at energies of 29-60 keV and ion fluences of 1 × 1016 ions cm-2. The activities of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione S-transferase (GST) and lipid peroxidation level were assayed in the germinated rice seeds after ion bombardment. The results showed most of the enzyme activities and lipid peroxidation levels in both the argon and nitrogen bombarded samples were higher than those in the natural control. N-ion bombardment could induce higher levels of antioxidant enzyme activities in the rice samples than the Ar-ion bombardment. Additional effects due to the vacuum condition were found to affect activities of some antioxidant enzymes and lipid peroxidation level. This study demonstrates that ion beam bombardment and vacuum condition could induce the antioxidant enzyme activity and lipid peroxidation level which might be due to free radical production in the bombarded rice seeds.

The TrkAIII oncoprotein inhibits mitochondrial free radical ROS-induced death of SH-SY5Y neuroblastoma cells by augmenting SOD2 expression and activity at the mitochondria, within the context of a tumour stem cell-like phenotype.

Directory of Open Access Journals (Sweden)

Pierdomenico Ruggeri

Full Text Available The developmental and stress-regulated alternative TrkAIII splice variant of the NGF receptor TrkA is expressed by advanced stage human neuroblastomas (NBs, correlates with worse outcome in high TrkA expressing unfavourable tumours and exhibits oncogenic activity in NB models. In the present study, we report that constitutive TrkAIII expression in human SH-SY5Y NB cells inhibits Rotenone, Paraquat and LY83583-induced mitochondrial free radical reactive oxygen species (ROS-mediated death by stimulating SOD2 expression, increasing mitochondrial SOD2 activity and attenuating mitochondrial free radical ROS production, in association with increased mitochondrial capacity to produce H2O2, within the context of a more tumour stem cell-like phenotype. This effect can be reversed by the specific TrkA tyrosine kinase inhibitor GW441756, by the multi-kinase TrkA inhibitors K252a, CEP-701 and Gö6976, which inhibit SOD2 expression, and by siRNA knockdown of SOD2 expression, which restores the sensitivity of TrkAIII expressing SH-SY5Y cells to Rotenone, Paraquat and LY83583-induced mitochondrial free radical ROS production and ROS-mediated death. The data implicate the novel TrkAIII/SOD2 axis in promoting NB resistance to mitochondrial free radical-mediated death and staminality, and suggest that the combined use of TrkAIII and/or SOD2 inhibitors together with agents that induce mitochondrial free radical ROS-mediated death could provide a therapeutic advantage that may also target the stem cell niche in high TrkA expressing unfavourable NB.

Higher Levels of Albuminuria within the Normal Range Predict Incident Hypertension

OpenAIRE

Forman, John P.; Fisher, Naomi D.L.; Schopick, Emily L.; Curhan, Gary C.

2008-01-01

Higher levels of albumin excretion within the normal range are associated with cardiovascular disease in high-risk individuals. Whether incremental increases in urinary albumin excretion, even within the normal range, are associated with the development of hypertension in low-risk individuals is unknown. This study included 1065 postmenopausal women from the first Nurses’ Health Study and 1114 premenopausal women from the second Nurses’ Health Study who had an albumin/creatinine ratio

Histamine Regulates the Inflammatory Profile of SOD1-G93A Microglia and the Histaminergic System Is Dysregulated in Amyotrophic Lateral Sclerosis

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Savina Apolloni

2017-11-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a late-onset motor neuron disease where activated glia release pro-inflammatory cytokines that trigger a vicious cycle of neurodegeneration in the absence of resolution of inflammation. Given the well-established role of histamine as a neuron-to-glia alarm signal implicated in brain disorders, the aim of this study was to investigate the expression and regulation of the histaminergic pathway in microglial activation in ALS mouse model and in humans. By examining the contribution of the histaminergic system to ALS, we found that particularly via H1 and H4 receptors, histamine promoted an anti-inflammatory profile in microglia from SOD1-G93A mice by modulating their activation state. A decrease in NF-κB and NADPH oxidase 2 with an increase in arginase 1 and P2Y12 receptor was induced by histamine only in the ALS inflammatory environment, but not in the healthy microglia, together with an increase in IL-6, IL-10, CD163, and CD206 phenotypic markers in SOD1-G93A cells. Moreover, histaminergic H1, H2, H3, and H4 receptors, and histamine metabolizing enzymes histidine decarboxylase, histamine N-methyltransferase, and diamine oxidase were found deregulated in spinal cord, cortex, and hypothalamus of SOD1-G93A mice during disease progression. Finally, by performing a meta-analysis study, we found a modulated expression of histamine-related genes in cortex and spinal cord from sporadic ALS patients. Our findings disclose that histamine acts as anti-inflammatory agent in ALS microglia and suggest a dysregulation of the histaminergic signaling in ALS.

Genetic Correction of SOD1 Mutant iPSCs Reveals ERK and JNK Activated AP1 as a Driver of Neurodegeneration in Amyotrophic Lateral Sclerosis

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Akshay Bhinge

2017-04-01

Full Text Available Summary: Although mutations in several genes with diverse functions have been known to cause amyotrophic lateral sclerosis (ALS, it is unknown to what extent causal mutations impinge on common pathways that drive motor neuron (MN-specific neurodegeneration. In this study, we combined induced pluripotent stem cells-based disease modeling with genome engineering and deep RNA sequencing to identify pathways dysregulated by mutant SOD1 in human MNs. Gene expression profiling and pathway analysis followed by pharmacological screening identified activated ERK and JNK signaling as key drivers of neurodegeneration in mutant SOD1 MNs. The AP1 complex member JUN, an ERK/JNK downstream target, was observed to be highly expressed in MNs compared with non-MNs, providing a mechanistic insight into the specific degeneration of MNs. Importantly, investigations of mutant FUS MNs identified activated p38 and ERK, indicating that network perturbations induced by ALS-causing mutations converge partly on a few specific pathways that are drug responsive and provide immense therapeutic potential. : In this article, Bhinge, Stanton, and colleagues use genome editing of patient-derived iPSCs to model ALS phenotypic defects in vitro. Transcriptomic analysis of disease MNs reveals activation of MAPK, AP1, WNT, cell-cycle, and p53 signaling in ALS MNs. Pharmacological screening uncovers activated ERK and JNK signaling as therapeutic targets in ALS. Keywords: ALS, SOD1, FUS, CRISPR-Cas9, p38, ERK, JNK, WNT, TP53, JUN

Tamarix hispida zinc finger protein ThZFP1 participates in salt and osmotic stress tolerance by increasing proline content and SOD and POD activities.

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Zang, Dandan; Wang, Chao; Ji, Xiaoyu; Wang, Yucheng

2015-06-01

Zinc finger proteins (ZFPs) are a large family that play important roles in various biological processes, such as signal transduction, RNA binding, morphogenesis, transcriptional regulation, abiotic or biotic stress response. However, the functions of ZFPs involved in abiotic stress are largely not known. In the present study, we cloned and functionally characterized a ZFP gene, ThZFP1, from Tamarix hispida. The expression of ThZFP1 is highly induced by NaCl, mannitol or ABA treatment. To study the function of ThZFP1 involved in abiotic stress response, transgenic T. hispida plants with overexpression or knockdown of ThZFP1 were generated using a transient transformation system. Gain- and loss-of-function studies of ThZFP1 suggested that ThZFP1 can induce the expression of a series of genes, including delta-pyrroline-5-carboxylate synthetase (P5CS), peroxidase (POD) and superoxide dismutase (SOD), leading to accumulation of proline and enhanced activities of SOD and POD. These physiological changes enhanced proline content and reactive oxygen species (ROS) scavenging capability when exposed to salt or osmotic stress. All the results obtained from T. hispida plants were further confirmed by analyses of the transgenic Arabidopsis plants overexpressing ThZFP1. These data together suggested that ThZFP1 positively regulates proline accumulation and activities of SOD and POD under salt and osmotic stress conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Degenerative myelopathy in German Shepherd Dog: comparison of two molecular assays for the identification of the SOD1:c.118G>A mutation.

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Capucchio, Maria Teresa; Spalenza, Veronica; Biasibetti, Elena; Bottero, Maria Teresa; Rasero, Roberto; Dalmasso, Alessandra; Sacchi, Paola

2014-02-01

Degenerative myelopathy (DM) is a late-onset, slowly progressive degeneration of spinal cord white matter which is reported primarily in large breed dogs. The missense mutation SOD1:c.118G>A is associated with this pathology in several dog breeds, including the German Shepherd Dog (GSD). The aims of the present study were to develop a tool for the rapid screening of the SOD1 mutation site in dogs and to evaluate the association of the polymorphism with DM in the German Shepherd breed. Two different techniques were compared: a minisequencing test and a real-time pcr allelic discrimination assay. Both approaches resulted effective and efficient. A sample of 47 dogs were examined. Ten subjects presented the symptoms of the illness; for one of them the diagnosis was confirmed by postmortem investigations and it resulted to be an A/A homozygote. In another clinically suspected dog, heterozygote A/G, the histopathological examination of the medulla showed moderate axon and myelin degenerative changes. GSD shows a frequency of the mutant allele equal to 0.17, quite high being a high-risk allele. Because canine DM has a late onset in adulthood and homozygous mutant dogs are likely as fertile as other genotypes, the natural selection is mild and the mutant allele may reach high frequencies. A diagnostic test, easy to implement, may contribute to control the gene diffusion in populations. The SOD1:c.118G>A mutation could be a useful marker for breeding strategies intending to reduce the incidence of DM.

Gender in higher level education and professional training in water supply and sanitation.

Science.gov (United States)

Borba, M

1997-01-01

While more women are participating in training and decision-making in the local-level drinking water and sanitation sectors, this is not occurring at higher levels because of the gender imbalance that remains in higher-level sector education and professional training programs. This imbalance is characterized by gender-biased science curricula and by a lack of female role models. Even in developing countries where female enrollment outstrips that of men in higher education, women commonly prepare for careers in areas that are less valued than sanitary engineering. This imbalance ignores the fact that women can perform technical and managerial skills as competently as men. A similar male-dominated pattern emerges in professional training courses offered by development agencies, especially courses that focus on management issues. Low female school attendance begins when girls must forego primary school attendance to help their mothers in domestic chores, such as fetching water. Inadequate sanitation facilities for girls at schools also pose impediments. Efforts to improve this situation include 1) a promotional brochure developed by the Botswana Ministry of Education to raise awareness of the importance of men's and women's work as technicians and engineers in the water and sanitation sector among secondary school students; 2) creation of free schools and universities in Oman, where the numbers of women in previously male-dominated jobs are increasing; and 3) promotion of female education at the Asian Institute of Technology.

An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

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Olmo, Francisco; Urbanová, Kristína; Rosales, Maria Jose; Martín-Escolano, Ruben; Sánchez-Moreno, Manuel; Marín, Clotilde

2015-12-01

In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.

Changes of serum inflammatory factors, adipokines and oxidative stress in patients with diabetic retinopathy

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Nurong Guri Maimaiti

2017-08-01

Full Text Available Objective: To investigate the changes of serum inflammatory factors, adipokines and oxidative stress in patients with diabetic retinopathy. Methods: A total of 130 patients with type 2 diabetes mellitus admitted in our hospital from January 2015 to June 2016 were selected and divided into 41 cases with diabetic retinopathy (NDR, 44 cases with nonproliferative retinopathy (NPDR and 45 cases with proliferative retinopathy group (PDR, another 40 healthy volunteers in our hospital were selected as control group (NC, and the serum levels of IL-6, TNF-α, hs-CRP, leptin, adiponectin, MDA and SOD were detected. Results: There were significant differences in the levels of IL-6, TNF-α and hs-CRP in groups, PDR group was the highest, which were respectively (18.19 ± 3.84 pg/mL, (197.48 ± 13.78 ng/L and (8.13 ± 0.74 mg/L, significantly higher than that of NC group, NDR group and NPDR group, NPDR group followed, respectively (14.07 ± 3.62 pg/mL, (115.29 ± 20.08 ng/L and (5.62 ± 0.83 mg/L, which were significantly higher than that of NC and NDR groups. NDR group were (12.67 ± 3.93 pg/mL, (89.49 ± 10.49 ng/L and (3.91 ± 0.49 mg/L respectively, significantly higher than the NC group, the difference was statistically significant. There were significant differences among groups of leptin and adiponectin, the leptin level in PDR group was the highest, (23.19 ± 6.48 μg/mL, which was significantly higher than NC group, NDR group and NPDR group, adiponectin was the lowest (3.70 ± 1.02 g/mL, lower than that in NC group, NDR group and NPDR group, the levels of leptin in NPDR group were higher than NC group and NDR group while adiponectin were lower than the two groups. Leptin levels in NDR group were significantly higher than those in NC group while adiponectin were lower than those in NC group, the differences were statistically significant. The levels of MDA and SOD in each group were significantly different. MDA in PDR group was the highest, (17.77 �

Changes of serum inflammatory factors, adipokines and oxidative stress in patients with diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

Nurong Guri Maimaiti; Akomatine Tuhuti

2017-01-01

Objective: To investigate the changes of serum inflammatory factors, adipokines and oxidative stress in patients with diabetic retinopathy. Methods: A total of 130 patients with type 2 diabetes mellitus admitted in our hospital from January 2015 to June 2016 were selected and divided into 41 cases with diabetic retinopathy (NDR), 44 cases with nonproliferative retinopathy (NPDR) and 45 cases with proliferative retinopathy group (PDR), another 40 healthy volunteers in our hospital were selected as control group (NC), and the serum levels of IL-6, TNF-α, hs-CRP, leptin, adiponectin, MDA and SOD were detected. Results: There were significant differences in the levels of IL-6, TNF-α and hs-CRP in groups, PDR group was the highest, which were respectively (18.19 ± 3.84) pg/mL, (197.48 ± 13.78) ng/L and (8.13 ± 0.74) mg/L, significantly higher than that of NC group, NDR group and NPDR group, NPDR group followed, respectively (14.07 ± 3.62) pg/mL, (115.29 ± 20.08) ng/L and (5.62 ± 0.83) mg/L, which were significantly higher than that of NC and NDR groups. NDR group were (12.67 ± 3.93) pg/mL, (89.49 ± 10.49) ng/L and (3.91 ± 0.49) mg/L respectively, significantly higher than the NC group, the difference was statistically significant. There were significant differences among groups of leptin and adiponectin, the leptin level in PDR group was the highest, (23.19 ± 6.48) μg/mL, which was significantly higher than NC group, NDR group and NPDR group, adiponectin was the lowest (3.70 ± 1.02) g/mL, lower than that in NC group, NDR group and NPDR group, the levels of leptin in NPDR group were higher than NC group and NDR group while adiponectin were lower than the two groups. Leptin levels in NDR group were significantly higher than those in NC group while adiponectin were lower than those in NC group, the differences were statistically significant. The levels of MDA and SOD in each group were significantly different. MDA in PDR group was the highest, (17.77 ± 4

Aberrant association of misfolded SOD1 with Na(+)/K(+)ATPase-α3 impairs its activity and contributes to motor neuron vulnerability in ALS

NARCIS (Netherlands)

Ruegsegger, Céline; Maharjan, Niran; Goswami, Anand; Filézac de L'Etang, Audrey; Weis, Joachim; Troost, Dirk; Heller, Manfred; Gut, Heinz; Saxena, Smita

2016-01-01

Amyotrophic lateral sclerosis (ALS) is an adult onset progressive motor neuron disease with no cure. Transgenic mice overexpressing familial ALS associated human mutant SOD1 are a commonly used model for examining disease mechanisms. Presently, it is well accepted that alterations in motor neuron

PPARγ activation abolishes LDL-induced proliferation of human aortic smooth muscle cells via SOD-mediated down-regulation of superoxide

International Nuclear Information System (INIS)

Heo, Kyung-Sun; Kim, Dong-Uk; Ryoo, Sungwoo; Nam, Miyoung; Baek, Seung Tae; Kim, Lila; Park, Song-Kyu; Myung, Chang-Seon; Hoe, Kwang-Lae

2007-01-01

Native LDL would be a mitogenic and chemotactic stimulus of VSMC proliferation and differentiation in the atherosclerotic lesion where endothelial disruption occurred. In previous studies, our group investigated the molecular mechanisms by which LDL induces IL-8 production and by which PPARα activation abolishes LDL effects in human aortic SMCs (hAoSMCs). Herein is the first report of PPARγ activation by troglitazone (TG) exerting its inhibitory effects on LDL-induced cell proliferation via generation not of H 2 O 2 , but of O2?-, and the subsequent activation of Erk1/2 in hAoSMCs. Moreover, in this study TG abolished the LDL-accelerated G 1 -S progression to control levels via down-regulation of active cyclinD1/CDK4 and cyclinE/CDK2 complexes and up-regulation of p21 Cip1 expression. TG exerted its anti-proliferative effects through the up-regulation of basal superoxide dismutase (SOD) expression. This data suggests that the regulation of O2?- is located at the crossroads between LDL signaling and cell proliferation

Higher-level fusion for military operations based on abductive inference: proof of principle

Science.gov (United States)

Pantaleev, Aleksandar V.; Josephson, John

2006-04-01

The ability of contemporary military commanders to estimate and understand complicated situations already suffers from information overload, and the situation can only grow worse. We describe a prototype application that uses abductive inferencing to fuse information from multiple sensors to evaluate the evidence for higher-level hypotheses that are close to the levels of abstraction needed for decision making (approximately JDL levels 2 and 3). Abductive inference (abduction, inference to the best explanation) is a pattern of reasoning that occurs naturally in diverse settings such as medical diagnosis, criminal investigations, scientific theory formation, and military intelligence analysis. Because abduction is part of common-sense reasoning, implementations of it can produce reasoning traces that are very human understandable. Automated abductive inferencing can be deployed to augment human reasoning, taking advantage of computation to process large amounts of information, and to bypass limits to human attention and short-term memory. We illustrate the workings of the prototype system by describing an example of its use for small-unit military operations in an urban setting. Knowledge was encoded as it might be captured prior to engagement from a standard military decision making process (MDMP) and analysis of commander's priority intelligence requirements (PIR). The system is able to reasonably estimate the evidence for higher-level hypotheses based on information from multiple sensors. Its inference processes can be examined closely to verify correctness. Decision makers can override conclusions at any level and changes will propagate appropriately.

Actividad antiinflamatoria de la enzima superóxido dismutasa (SOD), purificada de la especie Allium sativum (ajo)

OpenAIRE

Soberón, Mercedes; Suárez, Silvia; Arnao, Inés; Guija, Emilio; Troncoso, Luzmila; Rojas, Luis; Saldaña, Ítalo; Cordero, Adriana

2013-01-01

Objetivos: Demostrar la actividad antiinflamatoria de la enzima superóxido dismutasa (SOD) purificada de Allium sativum (ajo). Diseño: Experimental. Institución: Centro de Investigación de Bioquímica y Nutrición, Facultad de Medicina, UNMSM Material biológico: Ratas y Allium sativum. Principales medidas de resultados: Muestra de ajo triturada con tampón fosfato 50 mM pH 7,4, incubada 40 minutos y filtrada; fue sometida a extracción con cloroformo:etanol 1:1 (v/v). Se descartó la fase acuosa. ...

The effect of modifiable healthy practices on higher-level functional capacity decline among Japanese community dwellers

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Rei Otsuka

2017-03-01

Full Text Available This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living, and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997–2000 who participated in a follow-up postal survey (2013. Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role. The odds ratio (OR and 95% confidence interval (CI for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0–4, 5–6, 7–8 groups were 1.00 (reference, 0.63 (0.44–0.92, and 0.54 (0.31–0.94. For the score of social role decline, multivariate adjusted ORs (95% CIs were 1.00 (reference, 0.62 (0.40–0.97, and 0.46 (0.23–0.90, respectively (P for trend = 0.04. Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan.

The effect of modifiable healthy practices on higher-level functional capacity decline among Japanese community dwellers.

Science.gov (United States)

Otsuka, Rei; Nishita, Yukiko; Tange, Chikako; Tomida, Makiko; Kato, Yuki; Nakamoto, Mariko; Ando, Fujiko; Shimokata, Hiroshi; Suzuki, Takao

2017-03-01

This study aimed to clarify the effects of the accumulation of 8 modifiable practices related to health, including smoking, alcohol drinking, physical activity, sleeping hours, body mass index, dietary diversity, ikigai (life worth living), and health checkup status, on higher-level functional capacity decline among Japanese community dwellers. Data were derived from the National Institute for Longevity Sciences - Longitudinal Study of Aging. Subjects comprised 1269 men and women aged 40 to 79 years at baseline (1997-2000) who participated in a follow-up postal survey (2013). Higher-level functional capacity was measured using the Tokyo Metropolitan Institute of Gerontology Index of Competence (total score and 3 subscales: instrumental self-maintenance, intellectual activity, and social role). The odds ratio (OR) and 95% confidence interval (CI) for a decline in higher-level functional capacity in the follow-up study according to the total number of healthy practices were analyzed using the lowest category as a reference. Multivariate adjusted ORs (95% CIs) for the total score of higher-level functional capacity, which declined according to the total number of healthy practices (0-4, 5-6, 7-8 groups) were 1.00 (reference), 0.63 (0.44-0.92), and 0.54 (0.31-0.94). For the score of social role decline, multivariate adjusted ORs (95% CIs) were 1.00 (reference), 0.62 (0.40-0.97), and 0.46 (0.23-0.90), respectively (P for trend = 0.04). Having more modifiable healthy practices, especially in social roles, may protect against a decline in higher-level functional capacity among middle-aged and elderly community dwellers in Japan.

Effects of Resveratrol on Methotrexate-Induced Testicular Damage in Rats

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Esin Yuluğ

2013-01-01

Full Text Available This study investigated the probable protective effects of resveratrol (RES, an antioxidant, against methotrexate- (MTX- induced testis damage. Twenty-four male Sprague Dawley rats were randomly divided into four groups: control, RES, MTX, and MTX + RES groups. Rats were sacrificed at the end of the experiment. Plasma and tissue malondialdehyde (MDA levels, superoxide dismutase (SOD and catalase (CAT activity in tissue, testicular histopathological damage scores, and testicular and epididymal epithelial apoptotic index (AI were evaluated. The MTX group had significantly higher plasma and tissue MDA levels and significantly lower SOD and CAT activity than those of the control group. In the MTX + RES group, plasma and tissue MDA levels decreased significantly and SOD activity rose significantly compared to the MTX group. The MTX group had significantly lower Johnsen’s testicular biopsy score (JTBS values than those of the control group. JTBS was significantly higher in the MTX + RES group than in the MTX group. AI increased in the testis and epididymis in the MTX group and significantly decreased in the MTX + RES group. Our results indicate that RES has protective effects against MTX-induced testis damage at the biochemical, histopathological, and apoptotic levels.

The Sequence Characteristics and Expression Models Reveal Superoxide Dismutase Involved in Cold Response and Fruiting Body Development in Volvariella volvacea

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Jun-Jie Yan

2016-01-01

Full Text Available As the first defence for cells to counteract the toxicity of active oxygen, superoxide dismutase (SOD plays an important role in the response of living organisms to stress and cell differentiation. One extracellular Cu-ZnSOD (ecCu-ZnSOD, and two MnSODs, were identified based on the Volvariella volvacea genome sequence. All three genes have complicated alternative splicing modes during transcription; only when the fourth intron is retained can the Vv_Cu-Znsod1 gene be translated into a protein sequence with SOD functional domains. The expression levels of the three sod genes in the pilei are higher than in the stipe. The Vv_Cu-Znsod1 and the Vv_Mnsod2 are co-expressed in different developmental stages of the fruiting body, with the highest level of expression in the pilei of the egg stage, and they show a significant, positive correlation with the efficiency of karyogamy, indicating the potential role of these two genes during karyogamy. The expression of the ecCu-Znsod and two Vv_Mnsod genes showed a significant up-regulated when treated by cold stress for one hour; however, the lack of the intracellular Cu-ZnSOD encoding gene (icCu-Znsod and the special locus of the ecCu-Znsod gene initiation codon suggested a possible reason for the autolysis phenomenon of V. volvacea in cold conditions.

Associations between Depressive State and Impaired Higher-Level Functional Capacity in the Elderly with Long-Term Care Requirements.

Science.gov (United States)

Ogata, Soshiro; Hayashi, Chisato; Sugiura, Keiko; Hayakawa, Kazuo

2015-01-01

Depressive state has been reported to be significantly associated with higher-level functional capacity among community-dwelling elderly. However, few studies have investigated the associations among people with long-term care requirements. We aimed to investigate the associations between depressive state and higher-level functional capacity and obtain marginal odds ratios using propensity score analyses in people with long-term care requirements. We conducted a cross-sectional study based on participants aged ≥ 65 years (n = 545) who were community dwelling and used outpatient care services for long-term preventive care. We measured higher-level functional capacity, depressive state, and possible confounders. Then, we estimated the marginal odds ratios (i.e., the change in odds of impaired higher-level functional capacity if all versus no participants were exposed to depressive state) by logistic models using generalized linear models with the inverse probability of treatment weighting (IPTW) for propensity score and design-based standard errors. Depressive state was used as the exposure variable and higher-level functional capacity as the outcome variable. The all absolute standardized differences after the IPTW using the propensity scores were functional capacity.

Excess boron responsive regulations of antioxidative mechanism at physio-biochemical and molecular levels in Arabidopsis thaliana.

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Kayıhan, Doğa Selin; Kayıhan, Ceyhun; Çiftçi, Yelda Özden

2016-12-01

This work was aimed to evaluate the effect of boron (B) toxicity on oxidative damage level, non-enzymatic antioxidant accumulation such as anthocyanin, flavonoid and proline and expression levels of antioxidant enzymes including superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and glutathione reductase (GR) and their respective activities as well as expression levels of miR398 and miR408 in Arabidopsis thaliana. Plants were germinated and grown on MS medium containing 1 mM B (1B) and 3 mM B (3B) for 14 d. Toxic B led to a decrease of photosynthetic pigments and an increase in accumulation of total soluble and insoluble sugars in accordance with phenotypically viewed chlorosis of seedlings through increasing level of B concentration. Along with these inhibitions, a corresponding increase in contents of flavonoid, anthocyanin and proline occurred that provoked oxidative stress tolerance. 3B caused a remarkable increase in total SOD activity whereas the activities of APX, GR and CAT remained unchanged as verified by expected increase in H 2 O 2 content. In contrast to GR, the coincidence was found between the expressions of SOD and APX genes and their respective activities. 1B induced mir398 expression, whereas 3B did not cause any significant change in expression of mir408 and mir398. Expression levels of GR genes were coordinately regulated with DHAR2 expression. Moreover, the changes in expression level of MDAR2 was in accordance with changes in APX6 expression and total APX activity, indicating fine-tuned regulation of ascorbate-glutathione cycle which might trigger antioxidative responses against B toxicity in Arabidopsis thaliana. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Higher plasma level of STIM1, OPG are correlated with stent restenosis after PCI.

Science.gov (United States)

Li, Haibin; Jiang, Zhian; Liu, Xiangdong; Yang, Zhihui

2015-01-01

Percutaneous Coronary Intervention (PCI) is one of the most effective treatments for Coronary Heart Disease (CHD), but the high rate of In Stent Restenosis (ISR) has plagued clinicians after PCI. We aim to investigate the correlation of plasma Stromal Interaction Molecular 1 (STIM1) and Osteoprotegerin (OPG) level with stent restenosis after PCI. A total of 100 consecutive patients with Coronary Heart Disease (CHD) received PCI procedure were recruited. Coronary angiography was performed 8 months after their PCI. Then patients were divided into 2 groups: observation group was composed by patients who existing postoperative stenosis after intervention; Control group was composed by patients with no postoperative stenosis. The plasma levels of STIM, OPG in all patients were tested before and after intervention. Pearson correlation and multiple linear regression analysis were performed to analysis the correlation between STIM, OPG level and postoperative stenosis. 35 cases were divided into observation group and other 65 were divided into control group. The plasma levels of STIM, OPG have no statistical difference before their PCI procedure, but we observed higher level of High-sensitivity C-reactive protein (Hs-CRP) existed in observation group. We observed higher level of plasma STIM, OPG in observation group when compared with control group after PCI procedure (P PCI, which could provide useful information for the restenosis control after PCI.

Multi-domain, higher order level set scheme for 3D image segmentation on the GPU