WorldWideScience

Sample records for protein oxidative stress

  1. Chaperones, but not oxidized proteins, are ubiquitinated after oxidative stress

    DEFF Research Database (Denmark)

    Kästle, Marc; Reeg, Sandra; Rogowska-Wrzesinska, Adelina

    2012-01-01

    of these proteins by MALDI tandem mass spectrometry (MALDI MS/MS). As a result we obtained 24 different proteins which can be categorized into the following groups: chaperones, energy metabolism, cytoskeleton/intermediate filaments, and protein translation/ribosome biogenesis. The special set of identified......, ubiquitinated proteins confirm the thesis that ubiquitination upon oxidative stress is no random process to degrade the mass of oxidized proteins, but concerns a special group of functional proteins....

  2. A Nucleocytoplasmic Shuttling Protein in Oxidative Stress Tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Ow, David W.; Song, Wen

    2003-03-26

    Plants for effective extraction of toxic metals and radionuclides must tolerate oxidative stress. To identify genes that enhance oxidative stress tolerance, an S. pombe cDNA expression plasmid library was screened for the ability to yield hypertolerant colonies. Here, we report on the properties of one gene that confers hypertolerance to cadmium and oxidizing chemicals. This gene appears to be conserved in other organisms as homologous genes are found in human, mouse, fruitfly and Arabidopsis. The fruitfly and Arabidopsis genes likewise enhance oxidative stress tolerance in fission yeast. During oxidative stress, the amount of mRNA does not change, but protein fusions to GFP relocate from the cytoplasm to the nucleus. The same pattern is observed with the Arabidopsis homologue-GFP fusion protein. This behavior suggests a signaling role in oxidative stress tolerance and these conserved proteins may be targets for engineering stress tolerant plants for phytoremediation.

  3. Effect of oxidative stress on homer scaffolding proteins.

    Directory of Open Access Journals (Sweden)

    Igor Nepliouev

    Full Text Available Homer proteins are a family of multifaceted scaffolding proteins that participate in the organization of signaling complexes at the post-synaptic density and in a variety of tissues including striated muscle. Homer isoforms form multimers via their C-terminal coiled coil domains, which allows for the formation of a polymeric network in combination with other scaffolding proteins. We hypothesized that the ability of Homer isoforms to serve as scaffolds would be influenced by oxidative stress. We have found by standard SDS-PAGE of lysates from adult mouse skeletal muscle exposed to air oxidation that Homer migrates as both a dimer and monomer in the absence of reducing agents and solely as a monomer in the presence of a reducing agent, suggesting that Homer dimers exposed to oxidation could be modified by the presence of an inter-molecular disulfide bond. Analysis of the peptide sequence of Homer 1b revealed the presence of only two cysteine residues located adjacent to the C-terminal coiled-coil domain. HEK 293 cells were transfected with wild-type and cysteine mutant forms of Homer 1b and exposed to oxidative stress by addition of menadione, which resulted in the formation of disulfide bonds except in the double mutant (C246G, C365G. Exposure of myofibers from adult mice to oxidative stress resulted in decreased solubility of endogenous Homer isoforms. This change in solubility was dependent on disulfide bond formation. In vitro binding assays revealed that cross-linking of Homer dimers enhanced the ability of Homer 1b to bind Drebrin, a known interacting partner. Our results show that oxidative stress results in disulfide cross-linking of Homer isoforms and loss of solubility of Homer scaffolds. This suggests that disulfide cross-linking of a Homer polymeric network may contribute to the pathophysiology seen in neurodegenerative diseases and myopathies characterized by oxidative stress.

  4. Protein Thiols as an Indication of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yousef Rezaei Chianeh

    2014-06-01

    Full Text Available Thiol is an organic compound that contain sulphhydryl group that have a critical role in preventing any involvement of oxidative stress in the cell. These defensive functions are generally considered to be carried out by the low molecular weight thiol glutathione and by cysteine residues in the active sites of proteins such as thioredoxin and peroxiredoxin. In addition, there are thiols exposed on protein surfaces that are not directly involved with protein function, although they can interact with the intracellular environment.The process of protection of the cell against an oxidative damage occur by thiol and cystein residue that has a low molecular weight. These residue are present in the active sites of a protein like, peroxiredoxin and thioredoxin. Apart from intracellular antioxidant defense mechanism by protein thiol, there are presence of thiol in outer surface of protein that are not involved with the function of protein, even though they can interact with intracellular part of the cell. [Archives Medical Review Journal 2014; 23(3.000: 443-456

  5. Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

    Science.gov (United States)

    Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

    2013-09-01

    The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

  6. Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress

    Science.gov (United States)

    Oxidative stress is a commonly cited mechanism of toxicity of environmental agents. Ubiquitous environmental chemicals such as the diesel exhaust component 1,2-naphthoquinone (1,2-NQ)induce oxidative stress by redox cycling, which generates hydrogen peroxide (H202). Cysteinylthio...

  7. Protein oxidation in plant mitochondria as a stress indicator

    DEFF Research Database (Denmark)

    Møller, I.M.; Kristensen, B.K.

    2004-01-01

    oxidation of cysteine and methionine side chains is an important mechanism for regulating enzyme activity. Mitochondria from both mammalian and plant tissues contain a number of oxidised proteins, but the relative abundance of these post-translationally modified forms is as yet unknown......, as are the consequences of the modification for the properties and turnover time of the proteins. Specific proteins appear to be particularly vulnerable to oxidative carbonylation in the matrix of plant mitochondria; these include several enzymes of the Krebs cycle, glycine decarboxylase, superoxide dismutase and heat...... shock proteins. Plant mitochondria contain a number of different proteases, but their role in removing oxidatively damaged proteins is, as yet, unclear....

  8. Oxidative stress impairs the heat stress response and delays unfolded protein recovery.

    Directory of Open Access Journals (Sweden)

    Masaaki Adachi

    2009-11-01

    Full Text Available Environmental changes, air pollution and ozone depletion are increasing oxidative stress, and global warming threatens health by heat stress. We now face a high risk of simultaneous exposure to heat and oxidative stress. However, there have been few studies investigating their combined adverse effects on cell viability.Pretreatment of hydrogen peroxide (H(2O(2 specifically and highly sensitized cells to heat stress, and enhanced loss of mitochondrial membrane potential. H(2O(2 exposure impaired the HSP40/HSP70 induction as heat shock response (HSR and the unfolded protein recovery, and enhanced eIF2alpha phosphorylation and/or XBP1 splicing, land marks of ER stress. These H(2O(2-mediated effects mimicked enhanced heat sensitivity in HSF1 knockdown or knockout cells. Importantly, thermal preconditioning blocked H(2O(2-mediated inhibitory effects on refolding activity and rescued HSF1 +/+ MEFs, but neither blocked the effects nor rescued HSF1 -/- MEFs. These data strongly suggest that inhibition of HSR and refolding activity is crucial for H(2O(2-mediated enhanced heat sensitivity.H(2O(2 blocks HSR and refolding activity under heat stress, thereby leading to insufficient quality control and enhancing ER stress. These uncontrolled stress responses may enhance cell death. Our data thus highlight oxidative stress as a crucial factor affecting heat tolerance.

  9. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2012-01-01

    Full Text Available The unceasing need for oxygen is in contradiction to the fact that it is in fact toxic to mammals. Namely, its monovalent reduction can have as a consequence the production of short-living, chemically very active free radicals and certain non-radical agents (nitrogen-oxide, superoxide-anion-radicals, hydroxyl radicals, peroxyl radicals, singlet oxygen, peroxynitrite, hydrogen peroxide, hypochlorous acid, and others. There is no doubt that they have numerous positive roles, but when their production is stepped up to such an extent that the organism cannot eliminate them with its antioxidants (superoxide-dismutase, glutathione-peroxidase, catalase, transferrin, ceruloplasmin, reduced glutathion, and others, a series of disorders is developed that are jointly called „oxidative stress.“ The reactive oxygen species which characterize oxidative stress are capable of attacking all main classes of biological macromolecules, actually proteins, DNA and RNA molecules, and in particular lipids. The free radicals influence lipid peroxidation in cellular membranes, oxidative damage to DNA and RNA molecules, the development of genetic mutations, fragmentation, and the altered function of various protein molecules. All of this results in the following consequences: disrupted permeability of cellular membranes, disrupted cellular signalization and ion homeostasis, reduced or loss of function of damaged proteins, and similar. That is why the free radicals that are released during oxidative stress are considered pathogenic agents of numerous diseases and ageing. The type of damage that will occur, and when it will take place, depends on the nature of the free radicals, their site of action and their source. [Projekat Ministarstva nauke Republike Srbije, br. 173034, br. 175061 i br. 31085

  10. Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases

    Directory of Open Access Journals (Sweden)

    Bogna Gryszczyńska

    2017-01-01

    Full Text Available Objectives. The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP and carbonylated proteins, expressed as protein carbonyl content (C=O in abdominal aortic aneurysms (AAA, aortoiliac occlusive disease (AIOD, and chronic kidney disease (CKD. Design and Methods. The study was carried out in a group of 35 AAA patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE included 50 patients or hemodialysis (HD consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP. Results. The concentration of AOPP in both AAA and AIOD groups was higher than in PRE and HD groups according to descending order: AAA~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and AAA according to the descending order: PRE~HD > AAA~AIOD. Conclusions. AAA, AIOD, and CKD-related atherosclerosis (PRE and HD contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.

  11. Oxidative stress and CCN1 protein in human skin connective tissue aging

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    2016-06-01

    Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

  12. Investigation on oxidative stress of nitric oxide synthase interacting protein from Clonorchis sinensis.

    Science.gov (United States)

    Bian, Meng; Xu, Qingxia; Xu, Yanquan; Li, Shan; Wang, Xiaoyun; Sheng, Jiahe; Wu, Zhongdao; Huang, Yan; Yu, Xinbing

    2016-01-01

    Numerous evidences indicate that excretory-secretory products (ESPs) from liver flukes trigger the generation of free radicals that are associated with the initial pathophysiological responses in host cells. In this study, we first constructed a Clonorchis sinensis (C. sinensis, Cs)-infected BALB/c mouse model and examined relative results respectively at 3, 5, 7, and 9 weeks postinfection (p.i.). Quantitative reverse transcription (RT)-PCR indicated that the transcriptional level of both endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) gradually decreased with lastingness of infection, while the transcriptional level of inducible NOS (iNOS) significantly increased. The level of malondialdehyde (MDA) in sera of infected mouse significantly increased versus the healthy control group. These results showed that the liver of C. sinensis-infected mouse was in a state with elevated levels of oxidation stress. Previously, C. sinensis NOS interacting protein coding gene (named CsNOSIP) has been isolated and recombinant CsNOSIP (rCsNOSIP) has been expressed in Escherichia coli, which has been confirmed to be a component present in CsESPs and confirmed to play important roles in immune regulation of the host. In the present paper, we investigated the effects of rCsNOSIP on the lipopolysaccharide (LPS)-induced activated RAW264.7, a murine macrophage cell line. We found that endotoxin-free rCsNOSIP significantly promoted the levels of nitric oxide (NO) and reactive oxygen species (ROS) after pretreated with rCsNOSIP, while the level of SOD decreased. Furthermore, rCsNOSIP could also increase the level of lipid peroxidation MDA. Taken together, these results suggested that CsNOSIP was a key molecule which was involved in the production of nitric oxide (NO) and its reactive intermediates, and played an important role in oxidative stress during C. sinensis infection.

  13. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Osredkar Joško

    2012-05-01

    Full Text Available The human organism is exposed to the influence of various forms of stress, either physical, psychological or chemical, which all have in common that they may adversely affect our body. A certain amount of stress is always present and somehow directs, promotes or inhibits the functioning of the human body. Unfortunately, we are now too many and too often exposed to excessive stress, which certainly has adverse consequences. This is especially true for a particular type of stress, called oxidative stress. All aerobic organisms are exposed to this type of stress because they produce energy by using oxygen. For this type of stress you could say that it is rather imperceptibly involved in our lives, as it becomes apparent only at the outbreak of certain diseases. Today we are well aware of the adverse impact of radicals, whose surplus is the main cause of oxidative stress. However, the key problem remains the detection of oxidative stress, which would allow us to undertake timely action and prevent outbreak of many diseases of our time. There are many factors that promote oxidative stress, among them are certainly a fast lifestyle and environmental pollution. The increase in oxidative stress can also trigger intense physical activity that is directly associated with an increased oxygen consumption and the resulting formation of free radicals. Considering generally positive attitude to physical activity, this fact may seem at first glance contradictory, but the finding has been confimed by several studies in active athletes. Training of a top athlete daily demands great physical effort, which is also reflected in the oxidative state of the organism. However, it should be noted that the top athletes in comparison with normal individuals have a different defense system, which can counteract the negative effects of oxidative stress. Quite the opposite is true for irregular or excessive physical activity to which the body is not adapted.

  14. Characterization of the Bat proteins in the oxidative stress response of Leptospira biflexa.

    Science.gov (United States)

    Stewart, Philip E; Carroll, James A; Dorward, David W; Stone, Hunter H; Sarkar, Amit; Picardeau, Mathieu; Rosa, Patricia A

    2012-12-13

    Leptospires lack many of the homologs for oxidative defense present in other bacteria, but do encode homologs of the Bacteriodes aerotolerance (Bat) proteins, which have been proposed to fulfill this function. Bat homologs have been identified in all families of the phylum Spirochaetes, yet a specific function for these proteins has not been experimentally demonstrated. We investigated the contribution of the Bat proteins in the model organism Leptospira biflexa for their potential contributions to growth rate, morphology and protection against oxidative challenges. A genetically engineered mutant strain in which all bat ORFs were deleted did not exhibit altered growth rate or morphology, relative to the wild-type strain. Nor could we demonstrate a protective role for the Bat proteins in coping with various oxidative stresses. Further, pre-exposing L. biflexa to sublethal levels of reactive oxygen species did not appear to induce a general oxidative stress response, in contrast to what has been shown in other bacterial species. Differential proteomic analysis of the wild-type and mutant strains detected changes in the abundance of a single protein only - HtpG, which is encoded by the gene immediately downstream of the bat loci. The data presented here do not support a protective role for the Leptospira Bat proteins in directly coping with oxidative stress as previously proposed. L. biflexa is relatively sensitive to reactive oxygen species such as superoxide and H2O2, suggesting that this spirochete lacks a strong, protective defense against oxidative damage despite being a strict aerobe.

  15. The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress.

    Science.gov (United States)

    Ren, Jiayi; Liu, Chunpeng; Zhao, Dan; Fu, Jing

    2018-05-15

    The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1 °C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p stress groups. Malondialdehyde (MDA) content was significantly increased (p stress except the 0.5 h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

  16. The p66(Shc adaptor protein controls oxidative stress response in early bovine embryos.

    Directory of Open Access Journals (Sweden)

    Dean H Betts

    Full Text Available The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

  17. Methionine sulfoxides in serum proteins as potential clinical biomarkers of oxidative stress

    OpenAIRE

    Satoko Suzuki; Yoshio Kodera; Tatsuya Saito; Kazumi Fujimoto; Akari Momozono; Akinori Hayashi; Yuji Kamata; Masayoshi Shichiri

    2016-01-01

    Oxidative stress contributes to the pathophysiology of a variety of diseases, and circulating biomarkers of its severity remains a topic of great interest for researchers. Our peptidomic strategy enables accurate and reproducible analysis of circulating proteins/peptides with or without post-translational modifications. Conventional wisdom holds that hydrophobic methionines exposed to an aqueous environment or experimental handling procedures are vulnerable to oxidation. However, we show that...

  18. Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

    Science.gov (United States)

    Pergolizzi, Barbara; Carriero, Vitina; Abbadessa, Giuliana; Penna, Claudia; Berchialla, Paola; De Francia, Silvia; Bracco, Enrico; Racca, Silvia

    2017-10-01

    Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

  19. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    International Nuclear Information System (INIS)

    Curtis, Carol D; Thorngren, Daniel L; Nardulli, Ann M

    2010-01-01

    During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

  20. Metformin induces oxidative stress in white adipocytes and raises uncoupling protein 2 levels.

    Science.gov (United States)

    Anedda, Andrea; Rial, Eduardo; González-Barroso, M Mar

    2008-10-01

    Metformin is a drug widely used to treat type 2 diabetes. It enhances insulin sensitivity by improving glucose utilization in tissues like liver or muscle. Metformin inhibits respiration, and the decrease in cellular energy activates the AMP-activated protein kinase that in turn switches on catabolic pathways. Moreover, metformin increases lipolysis and beta-oxidation in white adipose tissue, thereby reducing the triglyceride stores. The uncoupling proteins (UCPs) are transporters that lower the efficiency of mitochondrial oxidative phosphorylation. UCP2 is thought to protect against oxidative stress although, alternatively, it could play an energy dissipation role. The aim of this work was to analyse the involvement of UCP2 on the effects of metformin in white adipocytes. We studied the effect of this drug in differentiating 3T3-L1 adipocytes and found that metformin causes oxidative stress since it increases the levels of reactive oxygen species (ROS) and lowers the aconitase activity. Variations in UCP2 protein levels parallel those of ROS. Metformin also increases lipolysis in these cells although only when the levels of ROS and UCP2 have decreased. Hence, UCP2 does not appear to be needed to facilitate fatty acid oxidation. Furthermore, treatment of C57BL/6 mice with metformin also augmented the levels of UCP2 in epididymal white adipose tissue. We conclude that metformin treatment leads to the overexpression of UCP2 in adipocytes to minimize the oxidative stress that is probably due to the inhibition of respiration caused by the drug.

  1. Attenuation of iron-binding proteins in ARPE-19 cells reduces their resistance to oxidative stress.

    Science.gov (United States)

    Karlsson, Markus; Kurz, Tino

    2016-09-01

    Oxidative stress-related damage to retinal pigment epithelial (RPE) cells is an important feature in the development of age-related macular degeneration. Iron-catalysed intralysosomal production of hydroxyl radicals is considered a major pathogenic factor, leading to lipofuscin formation with ensuing depressed cellular autophagic capacity, lysosomal membrane permeabilization and apoptosis. Previously, we have shown that cultured immortalized human RPE (ARPE-19) cells are extremely resistant to exposure to bolus doses of hydrogen peroxide and contain considerable amounts of the iron-binding proteins metallothionein (MT), heat-shock protein 70 (HSP70) and ferritin (FT). According to previous findings, autophagy of these proteins depresses lysosomal redox-active iron. The aim of this study was to investigate whether up- or downregulation of these proteins would affect the resistance of ARPE-19 cells to oxidative stress. The sensitivity of ARPE-19 cells to H2 O2 exposure was tested following upregulation of MT, HSP70 and/or FT by pretreatment with ZnSO4 , heat shock or FeCl3 , as well as siRNA-mediated downregulation of the same proteins. Upregulation of MT, HSP70 and FT did not improve survival following exposure to H2 O2 . This was interpreted as existence of an already maximal protection. Combined siRNA-mediated attenuation of both FT chains (H and L), or simultaneous downregulation of all three proteins, made the cells significantly more susceptible to oxidative stress confirming the importance of iron-binding proteins. The findings support our hypothesis that the oxidative stress resistance exhibited by RPE cells may be explained by a high autophagic influx of iron-binding proteins that would keep levels of redox-active lysosomal iron low. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  2. Fluorescent proteins such as eGFP lead to catalytic oxidative stress in cells.

    Science.gov (United States)

    Ganini, Douglas; Leinisch, Fabian; Kumar, Ashutosh; Jiang, JinJie; Tokar, Erik J; Malone, Christine C; Petrovich, Robert M; Mason, Ronald P

    2017-08-01

    Fluorescent proteins are an important tool that has become omnipresent in life sciences research. They are frequently used for localization of proteins and monitoring of cells [1,2]. Green fluorescent protein (GFP) was the first and has been the most used fluorescent protein. Enhanced GFP (eGFP) was optimized from wild-type GFP for increased fluorescence yield and improved expression in mammalian systems [3]. Many GFP-like fluorescent proteins have been discovered, optimized or created, such as the red fluorescent protein TagRFP [4]. Fluorescent proteins are expressed colorless and immature and, for eGFP, the conversion to the fluorescent form, mature, is known to produce one equivalent of hydrogen peroxide (H 2 O 2 ) per molecule of chromophore [5,6]. Even though it has been proposed that this process is non-catalytic and generates nontoxic levels of H 2 O 2 [6], this study investigates the role of fluorescent proteins in generating free radicals and inducing oxidative stress in biological systems. Immature eGFP and TagRFP catalytically generate the free radical superoxide anion (O 2 •- ) and H 2 O 2 in the presence of NADH. Generation of the free radical O 2 •- and H 2 O 2 by eGFP in the presence of NADH affects the gene expression of cells. Many biological pathways are altered, such as a decrease in HIF1α stabilization and activity. The biological pathways altered by eGFP are known to be implicated in the pathophysiology of many diseases associated with oxidative stress; therefore, it is critical that such experiments using fluorescent proteins are validated with alternative methodologies and the results are carefully interpreted. Since cells inevitably experience oxidative stress when fluorescent proteins are expressed, the use of this tool for cell labeling and in vivo cell tracing also requires validation using alternative methodologies. Published by Elsevier B.V.

  3. Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress and heat shock protein response.

    Science.gov (United States)

    Zhao, Panpan; Guo, Ying; Zhang, Wen; Chai, Hongliang; Xing, Houjuan; Xing, Mingwei

    2017-01-01

    Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning risk factors for neurological toxicity in humans. However, little is known about the effects of arsenic on the nervous system of Gallus Gallus. To investigate whether arsenic induce neurotoxicity and influence the oxidative stress and heat shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line chickens were treated with different doses of arsenic trioxide (As 2 O 3 ). The histological changes, antioxidant enzyme activity, and the expressions of Hsps were detected. Results showed slightly histology changes were obvious in the brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH-Px) and catalase (CAT) were decreased compared to the control, whereas the malondialdehyde (MDA) content was increased gradually along with increase in diet-arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were up-regulated. These results suggested that sub-chronic exposure to arsenic induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of oxidants and antioxidants. Increased heat shock response tried to protect chicken brain tissues from tissues damage caused by oxidative stress. The mechanisms of neurotoxicity induced by arsenic include oxidative stress and heat shock protein response in chicken brain tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    Science.gov (United States)

    Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

    2015-01-01

    Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

  5. Imbalance of heterologous protein folding and disulfide bond formation rates yields runaway oxidative stress

    Directory of Open Access Journals (Sweden)

    Tyo Keith EJ

    2012-03-01

    Full Text Available Abstract Background The protein secretory pathway must process a wide assortment of native proteins for eukaryotic cells to function. As well, recombinant protein secretion is used extensively to produce many biologics and industrial enzymes. Therefore, secretory pathway dysfunction can be highly detrimental to the cell and can drastically inhibit product titers in biochemical production. Because the secretory pathway is a highly-integrated, multi-organelle system, dysfunction can happen at many levels and dissecting the root cause can be challenging. In this study, we apply a systems biology approach to analyze secretory pathway dysfunctions resulting from heterologous production of a small protein (insulin precursor or a larger protein (α-amylase. Results HAC1-dependent and independent dysfunctions and cellular responses were apparent across multiple datasets. In particular, processes involving (a degradation of protein/recycling amino acids, (b overall transcription/translation repression, and (c oxidative stress were broadly associated with secretory stress. Conclusions Apparent runaway oxidative stress due to radical production observed here and elsewhere can be explained by a futile cycle of disulfide formation and breaking that consumes reduced glutathione and produces reactive oxygen species. The futile cycle is dominating when protein folding rates are low relative to disulfide bond formation rates. While not strictly conclusive with the present data, this insight does provide a molecular interpretation to an, until now, largely empirical understanding of optimizing heterologous protein secretion. This molecular insight has direct implications on engineering a broad range of recombinant proteins for secretion and provides potential hypotheses for the root causes of several secretory-associated diseases.

  6. Protein oxidative stress markers in peritoneal fluids of women with deep infiltrating endometriosis are increased.

    Science.gov (United States)

    Santulli, Pietro; Chouzenoux, Sandrine; Fiorese, Mauro; Marcellin, Louis; Lemarechal, Herve; Millischer, Anne-Elodie; Batteux, Frédéric; Borderie, Didier; Chapron, Charles

    2015-01-01

    Are protein oxidative stress markers [thiols, advanced oxidation protein products (AOPP), protein carbonyls and nitrates/nitrites] in perioperative peritoneal fluid higher in women with histologically proven endometriosis when compared with endometriosis-free controls? Protein oxidative stress markers are significantly increased in peritoneal fluids from women with deep infiltrating endometriosis with intestinal involvement when compared with endometriosis-free controls. Endometriosis is a common gynaecologic condition characterized by an important inflammatory process. Various source of evidence support the role of oxidative stress in the development of endometriosis. We conducted a prospective laboratory study in a tertiary-care university hospital between January 2011 and December 2012, and included 235 non-pregnant women, younger than 42 year old, undergoing surgery for a benign gynaecological condition. After complete surgical exploration of the abdomino-pelvic cavity, 150 women with histologically proven endometriosis and 85 endometriosis-free controls women were enrolled. Women with endometriosis were staged according to a surgical classification in three different phenotypes of endometriosis: superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA) and deeply infiltrating endometriosis (DIE). Perioperative peritoneal fluids samples were obtained from all study participants. Thiols, AOPP, protein carbonyls and nitrates/nitrites were assayed in all peritoneal samples. Concentrations of peritoneal AOPP were significantly higher in endometriosis patients than in the control group (median, 128.9 µmol/l; range, 0.3-1180.1 versus median, 77.8 µmol/l; range, 0.8-616.1; P peritoneal nitrates/nitrites were higher in endometriosis patients than in the control group (median, 24.8 µmol/l; range, 1.6-681.6 versus median, 18.5 µmol/l; range, 1.6-184.5; P peritoneal fluids protein AOPP and nitrates/nitrites were significantly increased only in DIE samples

  7. Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

    International Nuclear Information System (INIS)

    Song Jun; Li Jing; Mourot, Joshua M.; Mark Evers, B.; Chung, Dai H.

    2008-01-01

    We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)ζ, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKζ siRNA transfection decreased H 2 O 2 -induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKζ also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKζ rapidly translocated to the cytoplasm following H 2 O 2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKζ, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells

  8. Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster.

    Science.gov (United States)

    Ahamed, Maqusood; Posgai, Ryan; Gorey, Timothy J; Nielsen, Mark; Hussain, Saber M; Rowe, John J

    2010-02-01

    Due to the intensive commercial application of silver nanoparticles (Ag NPs), risk assessment of this nanoparticle is of great importance. Our previous in vitro study demonstrated that Ag NPs caused DNA damage and apoptosis in mouse embryonic stem cells and fibroblasts. However, toxicity of Ag NPs in vivo is largely lacking. This study was undertaken to examine the toxic effects of well-characterized polysaccharide coated 10 nm Ag NPs on heat shock stress, oxidative stress, DNA damage and apoptosis in Drosophila melanogaster. Third instar larvae of D. melanogaster were fed a diet of standard cornmeal media mixed with Ag NPs at the concentrations of 50 and 100 microg/ml for 24 and 48 h. Ag NPs up-regulated the expression of heat shock protein 70 and induced oxidative stress in D. melanogaster. Malondialdehyde level, an end product of lipid peroxidation was significantly higher while antioxidant glutathione content was significantly lower in Ag NPs exposed organisms. Activities of antioxidant enzyme superoxide dismutase and catalase were also significantly higher in the organisms exposed to Ag NPs. Furthermore, Ag NPs up-regulated the cell cycle checkpoint p53 and cell signaling protein p38 that are involved in the DNA damage repair pathway. Moreover, activities of caspase-3 and caspase-9, markers of apoptosis were significantly higher in Ag NPs exposed organisms. The results indicate that Ag NPs in D. melanogaster induce heat shock stress, oxidative stress, DNA damage and apoptosis. This study suggests that the organism is stressed and thus warrants more careful assessment of Ag NPs using in vivo models to determine if chronic exposure presents developmental and reproductive toxicity. Copyright 2009 Elsevier Inc. All rights reserved.

  9. Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Ahamed, Maqusood; Posgai, Ryan; Gorey, Timothy J.; Nielsen, Mark; Hussain, Saber M.; Rowe, John J.

    2010-01-01

    Due to the intensive commercial application of silver nanoparticles (Ag NPs), risk assessment of this nanoparticle is of great importance. Our previous in vitro study demonstrated that Ag NPs caused DNA damage and apoptosis in mouse embryonic stem cells and fibroblasts. However, toxicity of Ag NPs in vivo is largely lacking. This study was undertaken to examine the toxic effects of well-characterized polysaccharide coated 10 nm Ag NPs on heat shock stress, oxidative stress, DNA damage and apoptosis in Drosophila melanogaster. Third instar larvae of D. melanogaster were fed a diet of standard cornmeal media mixed with Ag NPs at the concentrations of 50 and 100 μg/ml for 24 and 48 h. Ag NPs up-regulated the expression of heat shock protein 70 and induced oxidative stress in D. melanogaster. Malondialdehyde level, an end product of lipid peroxidation was significantly higher while antioxidant glutathione content was significantly lower in Ag NPs exposed organisms. Activities of antioxidant enzyme superoxide dismutase and catalase were also significantly higher in the organisms exposed to Ag NPs. Furthermore, Ag NPs up-regulated the cell cycle checkpoint p53 and cell signaling protein p38 that are involved in the DNA damage repair pathway. Moreover, activities of caspase-3 and caspase-9, markers of apoptosis were significantly higher in Ag NPs exposed organisms. The results indicate that Ag NPs in D. melanogaster induce heat shock stress, oxidative stress, DNA damage and apoptosis. This study suggests that the organism is stressed and thus warrants more careful assessment of Ag NPs using in vivo models to determine if chronic exposure presents developmental and reproductive toxicity.

  10. Moonlight-like proteins of the cell wall protect sessile cells of Candida from oxidative stress.

    Science.gov (United States)

    Serrano-Fujarte, Isela; López-Romero, Everardo; Cuéllar-Cruz, Mayra

    2016-01-01

    Biofilms of Candida species are associated with high morbidity and hospital mortality. Candida forms biofilms by adhering to human host epithelium through cell wall proteins (CWP) and simultaneously neutralizing the reactive oxygen species (ROS) produced during the respiratory burst by phagocytic cells. The purpose of this paper is to identify the CWP of Candida albicans, Candida glabrata, Candida krusei and Candida parapsilosis expressed after exposure to different concentrations of H2O2 using a proteomic approach. CWP obtained from sessile cells, both treated and untreated with the oxidizing agent, were resolved by one and two-dimensional (2D-PAGE) gels and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Some of these proteins were identified and found to correspond to moonlighting CWP such as: (i) glycolytic enzymes, (ii) heat shock, (iii) OSR proteins, (iv) general metabolic enzymes and (v) highly conserved proteins, which are up- or down-regulated in the presence or absence of ROS. We also found that the expression of these CWP is different for each Candida species. Moreover, RT-PCR assays allowed us to demonstrate that transcription of the gene coding for Eno1, one of the moonlight-like CWP identified in response to the oxidant agent, is differentially regulated. To our knowledge this is the first demonstration that, in response to oxidative stress, each species of Candida, differentially regulates the expression of moonlighting CWP, which may protect the organism from the ROS generated during phagocytosis. Presumptively, these proteins allow the pathogen to adhere and form a biofilm, and eventually cause invasive candidiasis in the human host. We propose that, in addition to the antioxidant mechanisms present in Candida, the moonlighting CWP also confer protection to these pathogens from oxidative stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Cth2 Protein Mediates Early Adaptation of Yeast Cells to Oxidative Stress Conditions.

    Directory of Open Access Journals (Sweden)

    Laia Castells-Roca

    Full Text Available Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon. In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.

  12. Seasonal variability of oxidative stress markers in city bus drivers. Part II. Oxidative damage to lipids and proteins.

    Science.gov (United States)

    Rossner, Pavel; Svecova, Vlasta; Milcova, Alena; Lnenickova, Zdena; Solansky, Ivo; Sram, Radim J

    2008-07-03

    The aim of the present study was to investigate the seasonal variability of markers of oxidative damage to lipids (15-F2t-isoprostane, 15-F2t-IsoP) and proteins (protein carbonyl levels) in 50 bus drivers and 50 controls from Prague, Czech Republic, and to identify factors affecting oxidative stress markers. The samples were collected in three seasons with different levels of air pollution. The exposure to environmental pollutants (carcinogenic polycyclic aromatic hydrocarbons, c-PAHs, particulate matter, PM2.5 and PM10, and volatile organic compounds, VOC) was monitored by personal and/or stationary monitors. For the analysis of both markers, ELISA techniques were used. The median levels of individual markers in bus drivers versus controls were as follows: 15-F2t-IsoP (nmol/mmol creatinine): winter 2005, 0.81 versus 0.68 (pbus drivers in winter seasons, but not in summer. Lipid peroxidation was positively correlated with c-PAHs and PM exposure; protein oxidation correlated negatively and was highest in summer suggesting another factor(s) affecting protein carbonyl levels.

  13. Role of oxidative stress in methamphetamine-induced dopaminergic toxicity mediated by protein kinase Cδ.

    Science.gov (United States)

    Shin, Eun-Joo; Duong, Chu Xuan; Nguyen, Xuan-Khanh Thi; Li, Zhengyi; Bing, Guoying; Bach, Jae-Hyung; Park, Dae Hun; Nakayama, Keiichi; Ali, Syed F; Kanthasamy, Anumantha G; Cadet, Jean Lud; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2012-06-15

    This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (-/-) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (-/-) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (-/-) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Assessment of acute phase proteins and oxidative stress status of Nigerians using bleaching agents

    International Nuclear Information System (INIS)

    Akibinu, M.O.; Arinola, O.G.; Afolabi, K.A.

    2010-01-01

    The disruption of primary innate immune function of the epidermal layer of the skin accounts for the susceptibility of individuals using bleaching agents to localized or systemic infections. This subverted innate immunity in these people may lead to other pathological conditions. The resultant effects of skin bleaching and phagocytes activation in response to infections have not been studied in Nigerians using bleaching agents. The present study therefore assessed the levels of C-reactive protein (CRP), albumin, total antioxidant potential (TAP), total plasma peroxides (TPP), oxidative stress index (OSI) and malonaldehyde (MDA) in the users bleaching agents. Thirty (30) people who had used bleaching agents for average of 4.9 + 1.2 years participated in this study. They were recruited from various schools and markets within the city of Ibadan, Oyo State, Nigeria. Thirty apparently healthy staffs of University College Hospital Ibadan, Ibaadan, Nigeria, who had never used bleaching agents served as controls. All the subjects used for this study had no metabolic abnormality and tested negative to both HIV and hepatitis B infections. The mean value of TAP (p 0.20) when compared with the controls. Oxidative stress and chronic inflammation are possible consequences of skin bleaching. The users of skin bleaching agents may need antioxidant therapies to avert the risks of oxidative stress. (author)

  15. Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress.

    Directory of Open Access Journals (Sweden)

    Des Raj Kashyap

    2014-07-01

    Full Text Available Mammalian Peptidoglycan Recognition Proteins (PGRPs are a family of evolutionary conserved bactericidal innate immunity proteins, but the mechanism through which they kill bacteria is unclear. We previously proposed that PGRPs are bactericidal due to induction of reactive oxygen species (ROS, a mechanism of killing that was also postulated, and later refuted, for several bactericidal antibiotics. Here, using whole genome expression arrays, qRT-PCR, and biochemical tests we show that in both Escherichia coli and Bacillus subtilis PGRPs induce a transcriptomic signature characteristic of oxidative stress, as well as correlated biochemical changes. However, induction of ROS was required, but not sufficient for PGRP killing. PGRPs also induced depletion of intracellular thiols and increased cytosolic concentrations of zinc and copper, as evidenced by transcriptome changes and supported by direct measurements. Depletion of thiols and elevated concentrations of metals were also required, but by themselves not sufficient, for bacterial killing. Chemical treatment studies demonstrated that efficient bacterial killing can be recapitulated only by the simultaneous addition of agents leading to production of ROS, depletion of thiols, and elevation of intracellular metal concentrations. These results identify a novel mechanism of bacterial killing by innate immunity proteins, which depends on synergistic effect of oxidative, thiol, and metal stress and differs from bacterial killing by antibiotics. These results offer potential targets for developing new antibacterial agents that would kill antibiotic-resistant bacteria.

  16. Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

  17. Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.

    Science.gov (United States)

    Park, Su-Jung; Ciccone, Samantha L M; Beck, Brian D; Hwang, Byounghoon; Freie, Brian; Clapp, D Wade; Lee, Suk-Hee

    2004-07-16

    Fanconi anemia (FANC) is a heterogeneous genetic disorder characterized by a hypersensitivity to DNA-damaging agents, chromosomal instability, and defective DNA repair. Eight FANC genes have been identified so far, and five of them (FANCA, -C, -E, -F, and -G) assemble in a multinuclear complex and function at least in part in a complex to activate FANCD2 by monoubiquitination. Here we show that FANCA and FANCG are redox-sensitive proteins that are multimerized and/or form a nuclear complex in response to oxidative stress/damage. Both FANCA and FANCG proteins exist as monomers under non-oxidizing conditions, whereas they become multimers following H2O2 treatment. Treatment of cells with oxidizing agent not only triggers the multimeric complex of FANCA and FANCG in vivo but also induces the interaction between FANCA and FANCG. N-Ethylmaleimide treatment abolishes multimerization and interaction of FANCA and FANCG in vitro. Taken together, our results lead us to conclude that FANCA and FANCG uniquely respond to oxidative damage by forming complex(es) via intermolecular disulfide linkage(s), which may be crucial in forming such complexes and in determining their function.

  18. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    International Nuclear Information System (INIS)

    Srisuttee, Ratakorn; Koh, Sang Seok; Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae; Jhun, Byung Hak; Horio, Yoshiyuki; Chung, Young-Hwa

    2012-01-01

    Highlights: ► Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. ► Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. ► Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. ► Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of β-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  19. Oxidative stress and S-100B protein in children with bacterial meningitis

    Directory of Open Access Journals (Sweden)

    Hamed Enas A

    2009-10-01

    Full Text Available Abstract Background Bacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO and reactive oxygen species in the complex pathophysiology of bacterial meningitis. Methods In the present study, serum and CSF levels of NO, lipid peroxide (LPO (mediators for oxidative stress and lipid peroxidation; total thiol, superoxide dismutase (SOD (antioxidant mediators and S-100B protein (mediator of astrocytes activation and injury, were investigated in children with bacterial meningitis (n = 40. Albumin ratio (CSF/serum is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio is indicative of intrathecal synthesis. Results Compared to normal children (n = 20, patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p Conclusion This study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.

  20. Whey protein concentrate supplementation protects rat brain against aging-induced oxidative stress and neurodegeneration.

    Science.gov (United States)

    Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

    2018-05-01

    Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids and is consumed as a functional food, incorporating a wide range of nutritional attributes. The purpose of this study is to evaluate the neuroprotective effect of WPC on rat brain during aging. Young (4 months) and old (24 months) male Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days. Biomarkers of oxidative stress and antioxidant capacity in terms of ferric reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T-SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and acetylcholinesterase (AChE) activity were measured in brain of control and experimental (WPC supplemented) groups. In addition, gene expression and histopathological studies were also performed. The results indicate that WPC augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old control. Furthermore, WPC-treated groups exhibited significant reduction in LHP, PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)-1β, IL-6), and upregulated the expression of marker genes associated with autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase, Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional nutritional food supplement that prevents the progression of age-related oxidative damage in Wistar rats.

  1. The involvement of wheat F-box protein gene TaFBA1 in the oxidative stress tolerance of plants.

    Directory of Open Access Journals (Sweden)

    Shu-Mei Zhou

    Full Text Available As one of the largest gene families, F-box domain proteins have been found to play important roles in abiotic stress responses via the ubiquitin pathway. TaFBA1 encodes a homologous F-box protein contained in E3 ubiquitin ligases. In our previous study, we found that the overexpression of TaFBA1 enhanced drought tolerance in transgenic plants. To investigate the mechanisms involved, in this study, we investigated the tolerance of the transgenic plants to oxidative stress. Methyl viologen was used to induce oxidative stress conditions. Real-time PCR and western blot analysis revealed that TaFBA1 expression was up-regulated by oxidative stress treatments. Under oxidative stress conditions, the transgenic tobacco plants showed a higher germination rate, higher root length and less growth inhibition than wild type (WT. The enhanced oxidative stress tolerance of the transgenic plants was also indicated by lower reactive oxygen species (ROS accumulation, malondialdehyde (MDA content and cell membrane damage under oxidative stress compared with WT. Higher activities of antioxidant enzymes, including superoxide dismutase (SOD, catalase (CAT, ascorbate peroxidase (APX and peroxidase (POD, were observed in the transgenic plants than those in WT, which may be related to the upregulated expression of some antioxidant genes via the overexpression of TaFBA1. In others, some stress responsive elements were found in the promoter region of TaFBA1, and TaFBA1 was located in the nucleus, cytoplasm and plasma membrane. These results suggest that TaFBA1 plays an important role in the oxidative stress tolerance of plants. This is important for understanding the functions of F-box proteins in plants' tolerance to multiple stress conditions.

  2. Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury

    Directory of Open Access Journals (Sweden)

    Jian-Ying Chuang

    2017-04-01

    Full Text Available After sudden traumatic brain injuries, secondary injuries may occur during the following days or weeks, which leads to the accumulation of reactive oxygen species (ROS. Since ROS exacerbate brain damage, it is important to protect neurons against their activity. Zinc finger protein 179 (Znf179 was shown to act as a neuroprotective factor, but the regulation of gene expression under oxidative stress remains unknown. In this study, we demonstrated an increase in Znf179 protein levels in both in vitro model of hydrogen peroxide (H2O2-induced ROS accumulation and animal models of traumatic brain injury. Additionally, we examined the sub-cellular localization of Znf179, and demonstrated that oxidative stress increases Znf179 nuclear shuttling and its interaction with specificity protein 1 (Sp1. Subsequently, the positive autoregulation of Znf179 expression, which is Sp1-dependent, was further demonstrated using luciferase reporter assay and green fluorescent protein (GFP-Znf179-expressing cells and transgenic mice. The upregulation of Sp1 transcriptional activity induced by the treatment with nerve growth factor (NGF led to an increase in Znf179 levels, which further protected cells against H2O2-induced damage. However, Sp1 inhibitor, mithramycin A, was shown to inhibit NGF effects, leading to a decrease in Znf179 expression and lower cellular protection. In conclusion, the results obtained in this study show that Znf179 autoregulation through Sp1-dependent mechanism plays an important role in neuroprotection, and NGF-induced Sp1 signaling may help attenuate more extensive (ROS-induced damage following brain injury.

  3. A Novel Peptide from Soybean Protein Isolate Significantly Enhances Resistance of the Organism under Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Heran Ma

    Full Text Available Recent studies have indicated that protein hydrolysates have broad biological effects. In the current study we describe a novel antioxidative peptide, FDPAL, from soybean protein isolate (SPI. The aim of this study was to purify and characterize an antioxidative peptide from SPI and determine its antioxidative mechanism. LC-MS/MS was used to isolate and identify the peptide from SPI. The sequence of the peptide was determined to be Phe-Asp-Pro-Ala-Leu (FDPAL, 561 Da. FDPAL can cause significant enhancement of resistance to oxidative stress both in cells as well as simple organisms. In Caenorhabditis elegans (C. elegans, FDPAL can up-regulate the expression of certain genes associated with resistance. The antioxidant activity of this peptide can be attributed to the presence of a specific amino acid sequence. Results from our work suggest that FDPAL can facilitate potential applications of proteins carrying this sequence in the nutraceutical, bioactive material and clinical medicine areas, as well as in cosmetics and health care products.

  4. Identification of Oxidative Stress Related Proteins as Biomarkers for Lung Cancer and Chronic Obstructive Pulmonary Disease in Bronchoalveolar Lavage

    Directory of Open Access Journals (Sweden)

    Amancio Carnero

    2013-02-01

    Full Text Available Lung cancer (LC and chronic obstructive pulmonary disease (COPD commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC. Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF. A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

  5. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Srisuttee, Ratakorn [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Koh, Sang Seok [Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Department of Functional Genomics, University of Science and Technology, Daejeon 305-333 (Korea, Republic of); Malilas, Waraporn; Moon, Jeong; Cho, Il-Rae [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Jhun, Byung Hak [Department of Applied Nanoscience, Pusan National University, Busan 609-735 (Korea, Republic of); Horio, Yoshiyuki [Department of Pharmacology, Sapporo Medical University, Sapporo 060-8556 (Japan); Chung, Young-Hwa, E-mail: younghc@pusan.ac.kr [WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735 (Korea, Republic of)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. Black-Right-Pointing-Pointer Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. Black-Right-Pointing-Pointer Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. Black-Right-Pointing-Pointer Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of {beta}-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  6. Aerobic lineage of the oxidative stress response protein rubrerythrin emerged in an ancient microaerobic, (hyperthermophilic environment

    Directory of Open Access Journals (Sweden)

    Juan Pablo Cardenas

    2016-11-01

    Full Text Available Rubrerythrins (RBRs are non-heme di-iron proteins belonging to the ferritin-like superfamily (FLSF. They are involved in oxidative stress defense as peroxide scavengers in a wide range of organisms. The vast majority of RBRs, including classical forms of this protein, contain a C-terminal rubredoxin-like domain involved in electron transport that is used during catalysis in anaerobic conditions. Rubredoxin is an ancient and large protein family of short length (<100 residues that contains a Fe-S center involved in electron transfer. However, functional forms of the enzyme lacking the rubredoxin-like domain have been reported (e.g., sulerythrin and ferriperoxin. In this study, phylogenomic evidence is presented that suggests that a complete lineage of rubrerythrins, lacking the rubredoxin-like domain, arose in an ancient microaerobic and (hyperthermophilic environments in the ancestors of the Archaea Thermoproteales and Sulfolobales. This lineage (termed the aerobic-type lineage subsequently evolved to become adapted to environments with progressively lower temperatures and higher oxygen concentrations via the acquisition of two co-localized genes, termed DUF3501 and RFO, encoding a conserved protein of unknown function and a predicted Fe-S oxidoreductase respectively. Proposed Horizontal Gene Transfer (HGT events from these archaeal ancestors to Bacteria expanded the opportunities for further evolution of this RBR including adaption to lower temperatures. The second lineage (termed the cyanobacterial lineage is proposed to have evolved in cyanobacterial ancestors, maybe in direct response to the production of oxygen via oxygenic photosynthesis during the Great Oxygen Event (GOE. It is hypothesized that both lineages of RBR emerged in a largely anaerobic world with whiffs of oxygen and that their subsequent independent evolutionary trajectories allowed microorganisms to transition from this anaerobic world to an aerobic one.

  7. THE ROLE OF PROTEIN OXIDATIVE MODIFICATION IN REDOX-REGULATION OF CASPASE-3 ACTIVITY IN BLOOD LYMPHOCYTES DURING OXIDATIVE STRESS IN VITRO

    Directory of Open Access Journals (Sweden)

    O. L. Nosareva

    2015-01-01

    Full Text Available The formation of oxidative stress lies at the heart of many frequent and socially-important diseases. Blood lymphocytes are the cells which provide immunological control of our organism. As a result of their function implementation blood lymphocytes contact with different endogenic and exogenic factors, which can lead to active oxygen species production activation, macromolecules oxidative modification and to cell survival alteration. At the present time it is essential to expand and deepen the fundamental knowledge of blood lymphocytes apoptosis regulation peculiarities. The research objective was to establish the interaction among alterations of glutathione system condition, carbonylation level, protein glutathionylation and caspase-3 activity in blood lymphocytes during oxidative stress in vitro.Material and Methods. The material for research was blood lymphocytes cultivated with addition of hydrogen peroxide in final concentration of 0,5 mmol and/or protein SH-group inhibitor N-ethylmaleimide – 5 mmol, protector – 5 mmol – 1,4-dithioerythritol. Reduced, oxidized and protein-bound glutathione concentration was measured by method of spectropho-tometry, additionally, the ratio size of reduced to oxidized thiol fraction was estimated. With help of enzymoimmunoassay the level of protein carbonyl derivatives was evaluated; caspase-3 activity was registered by spectrofluorometric method.Results. Protein SH-group blocking in blood lymphocytes during oxidative stress in vitro was accompanied by protein-bound glutathione concentration rapid decrease in connection with increase of protein carbonyl derivatives content and caspase-3 activity. Protein SH-group protection in blood lymphocytes during oxidative stress in vitro was accompanied by concentration increase of protein-bound glutathione and protein carbonyl derivatives under comparable values of enzyme activity under study.Conclusion. The carried out research shows that caspase-3 and protein

  8. The Neuron-Specific Protein TMEM59L Mediates Oxidative Stress-Induced Cell Death.

    Science.gov (United States)

    Zheng, Qiuyang; Zheng, Xiaoyuan; Zhang, Lishan; Luo, Hong; Qian, Lingzhi; Fu, Xing; Liu, Yiqian; Gao, Yuehong; Niu, Mengxi; Meng, Jian; Zhang, Muxian; Bu, Guojun; Xu, Huaxi; Zhang, Yun-Wu

    2017-08-01

    TMEM59L is a newly identified brain-specific membrane-anchored protein with unknown functions. Herein we found that both TMEM59L and its homolog, TMEM59, are localized in Golgi and endosomes. However, in contrast to a ubiquitous and relatively stable temporal expression of TMEM59, TMEM59L expression was limited in neurons and increased during development. We also found that both TMEM59L and TMEM59 interacted with ATG5 and ATG16L1, and that overexpression of them triggered cell autophagy. However, overexpression of TMEM59L induced intrinsic caspase-dependent apoptosis more dramatically than TMEM59. In addition, downregulation of TMEM59L prevented neuronal cell death and caspase-3 activation caused by hydrogen peroxide insults and reduced the lipidation of LC3B. Finally, we found that AAV-mediated knockdown of TMEM59L in mice significantly ameliorated caspase-3 activation, increased mouse duration in the open arm during elevated plus maze test, reduced mouse immobility time during forced swim test, and enhanced mouse memory during Y-maze and Morris water maze tests. Together, our study indicates that TMEM59L is a pro-apoptotic neuronal protein involved in animal behaviors such as anxiety, depression, and memory, and that TMEM59L downregulation protects neurons against oxidative stress.

  9. Controlled formation of emulsion gels stabilized by salted myofibrillar protein under malondialdehyde (MDA)-induced oxidative stress.

    Science.gov (United States)

    Zhou, Feibai; Sun, Weizheng; Zhao, Mouming

    2015-04-15

    This study presented the cold-set gelation of emulsions stabilized by salted myofibrillar protein (MP) under oxidative stress originated from malondialdehyde (MDA). Gel properties were compared over a range of MDA/NaCl concentrations including gel viscoelastic properties, strength, water-holding capacity (WHC), amount of protein entrapped, and microstructure. The oxidative stability of emulsion gels as indicated by lipid hydroperoxide was further determined and compared. Results indicated that emulsion stabilized by MP at swollen state under certain ionic strengths (0.2-0.6 M) was the premise of gel formation under MDA. In the presence of intermediate MDA concentrations (2.5-10 mM), the emulsion gels showed an improved elasticity, strength, WHC, and oxidative stability. This improvement should be mainly attributed to the enhanced protein-protein cross-linkings via MDA, which were homogeneously formed among absorbed and/or unabsorbed proteins, entrapping a greater amount and fractions of protein within network. Therefore, the oil droplets were better adherent to the gel matrix. Nevertheless, addition of high MDA concentrations (25-50 mM) led to the formation of excessive covalent bonds, which might break protein-protein bonds and trigger the desorption of protein from the interface. This ultimately caused "oil leak" phenomena as well as the collapse of gel structure and, thus, overall decreased gel properties and oxidative stability.

  10. Formoterol attenuates increased oxidative stress and myosin protein loss in respiratory and limb muscles of cancer cachectic rats

    Directory of Open Access Journals (Sweden)

    Anna Salazar-Degracia

    2017-12-01

    Full Text Available Muscle mass loss and wasting are characteristic features of patients with chronic conditions including cancer. Therapeutic options are still scarce. We hypothesized that cachexia-induced muscle oxidative stress may be attenuated in response to treatment with beta2-adrenoceptor-selective agonist formoterol in rats. In diaphragm and gastrocnemius of tumor-bearing rats (108 AH-130 Yoshida ascites hepatoma cells inoculated intraperitoneally with and without treatment with formoterol (0.3 mg/kg body weight/day for seven days, daily subcutaneous injection, redox balance (protein oxidation and nitration and antioxidants and muscle proteins (1-dimensional immunoblots, carbonylated proteins (2-dimensional immunoblots, inflammatory cells (immunohistochemistry, and mitochondrial respiratory chain (MRC complex activities were explored. In the gastrocnemius, but not the diaphragm, of cancer cachectic rats compared to the controls, protein oxidation and nitration levels were increased, several functional and structural proteins were carbonylated, and in both study muscles, myosin content was reduced, inflammatory cell counts were greater, while no significant differences were seen in MRC complex activities (I, II, and IV. Treatment of cachectic rats with formoterol attenuated all the events in both respiratory and limb muscles. In this in vivo model of cancer-cachectic rats, the diaphragm is more resistant to oxidative stress. Formoterol treatment attenuated the rise in oxidative stress in the limb muscles, inflammatory cell infiltration, and the loss of myosin content seen in both study muscles, whereas no effects were observed in the MRC complex activities. These findings have therapeutic implications as they demonstrate beneficial effects of the beta2 agonist through decreased protein oxidation and inflammation in cachectic muscles, especially the gastrocnemius.

  11. Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead

    International Nuclear Information System (INIS)

    Stacchiotti, Alessandra; Morandini, Fausta; Bettoni, Francesca; Schena, Ilaria; Lavazza, Antonio; Grigolato, Pier Giovanni; Apostoli, Pietro; Rezzani, Rita; Aleo, Maria Francesca

    2009-01-01

    A close link between stress protein up-regulation and oxidative damage may provide a novel therapeutic tool to counteract nephrotoxicity induced by toxic metals in the human population, mainly in children, of industrialized countries. Here we analysed the time course of the expression of several heat shock proteins, glucose-regulated proteins and metallothioneins in a rat proximal tubular cell line (NRK-52E) exposed to subcytotoxic doses of inorganic mercury and lead. Concomitantly, we used morphological and biochemical methods to evaluate metal-induced cytotoxicity and oxidative damage. In particular, as biochemical indicators of oxidative stress we detected reactive oxygen species (ROS) and nitrogen species (RNS), total glutathione (GSH) and glutathione-S-transferase (GST) activity. Our results clearly demonstrated that mercury increases ROS and RNS levels and the expressions of Hsp25 and inducible Hsp72. These findings are corroborated by evident mitochondrial damage, apoptosis or necrosis. By contrast, lead is unable to up-regulate Hsp72 but enhances Grp78 and activates nuclear Hsp25 translocation. Furthermore, lead causes endoplasmic reticulum (ER) stress, vacuolation and nucleolar segregation. Lastly, both metals stimulate the over-expression of MTs, but with a different time course. In conclusion, in NRK-52E cell line the stress response is an early and metal-induced event that correlates well with the direct oxidative damage induced by mercury. Indeed, different chaperones are involved in the specific nephrotoxic mechanism of these environmental pollutants and work together for cell survival.

  12. Advanced oxidation protein products — biological marker of oxidative stress = Zaawansowane produkty utleniania białek – biologiczne markery stresu oksydacyjnego

    Directory of Open Access Journals (Sweden)

    Anna Cwynar

    2016-09-01

      ABSTRACT Advanced oxidation protein products (AOPPs are mostly derivatives of oxidatively modified albumin. The results of many experimental studies confirm intensification of oxidative modifications of proteins and an increase in concentration of advanced oxidation protein products (AOPPs in different pathological conditions, particularly those with well documented involvement of oxidative stress in their etiopathogenesis, but also those where its role is not yet well understood. Currently intensive research is carried out on the possibility of using AOPPs as useful indicators for diagnosing, prognosis and monitoring of diseases.   Keywords: advanced oxidation protein products, autoimmune disease, oxidative stress   STRESZCZENIE Zaawansowane produkty utleniania białek (AOPPs, to najczęściej pochodne zmodyfikowanej oksydacyjnie albuminy. Wyniki licznych badań doświadczalnych potwierdzają nasilenie oksydacyjnych modyfikacji białek i wzrost stężenia zaawansowanych produktów utleniania białek (AOPPs w różnych stanach patologicznych, szczególnie tych o dobrze udokumentowanym udziale stresu oksydacyjnego w ich etiopatogenezie, ale także takich, w których jego rola nie jest jeszcze dobrze poznana.. Obecnie trwają intensywne badania nad możliwością wykorzystania AOPPs, jako użytecznych wskaźników do diagnozowania, prognozowania oraz monitorowania chorób.   Słowa kluczowe: zaawansowane produkty utleniania białek, choroby autoimmunologiczne, stres oksydacyjny

  13. Oxidative Stress in BPH

    Directory of Open Access Journals (Sweden)

    Murat Savas

    2009-01-01

    The present study has shown that there were not relationship between potency of oxidative stress and BPH. Further well designed studies should be planned to find out whether the oxidative stress-related parameters play role in BPH as an interesting pathology in regard of the etiopathogenesis. Keywords: benign prostatic hyperplasia, oxidative stress, prostate

  14. Oxidative Stress in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Varsha Shukla

    2011-01-01

    Full Text Available It has been demonstrated that oxidative stress has a ubiquitous role in neurodegenerative diseases. Major source of oxidative stress due to reactive oxygen species (ROS is related to mitochondria as an endogenous source. Although there is ample evidence from tissues of patients with neurodegenerative disorders of morphological, biochemical, and molecular abnormalities in mitochondria, it is still not very clear whether the oxidative stress itself contributes to the onset of neurodegeneration or it is part of the neurodegenerative process as secondary manifestation. This paper begins with an overview of how oxidative stress occurs, discussing various oxidants and antioxidants, and role of oxidative stress in diseases in general. It highlights the role of oxidative stress in neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's diseases and amyotrophic lateral sclerosis. The last part of the paper describes the role of oxidative stress causing deregulation of cyclin-dependent kinase 5 (Cdk5 hyperactivity associated with neurodegeneration.

  15. Heavy metals induce oxidative stress and trigger oxidative stress-mediated heat shock protein (hsp) modulation in the intertidal copepod Tigriopus japonicus.

    Science.gov (United States)

    Kim, Bo-Mi; Rhee, Jae-Sung; Jeong, Chang-Bum; Seo, Jung Soo; Park, Gyung Soo; Lee, Young-Mi; Lee, Jae-Seong

    2014-11-01

    Heat shock proteins (hsps) are induced by a wide range of environmental stressors including heavy metals in aquatic organisms. However, the effect of heavy metals on zooplankton at the molecular level remains still unclear. In this study, we measured the intracellular reactive oxygen species (ROS) level and the antioxidant enzyme activities for 96 h after exposure to five heavy metals: arsenic (As), cadmium (Cd), copper (Cu), silver (Ag), and zinc (Zn) in the intertidal copepod Tigriopus japonicus. Activities of the antioxidant enzymes were highly elevated in metal-exposed copepods, indicating that heavy metals can induce oxidative stress by generating ROS, and stimulate the involvement of antioxidant enzymes as cellular defense mechanisms. Subsequently, transcriptional changes in hsp gene families were further investigated in the metal-exposed groups for 96 h. The ROS level and glutathione (GSH) content were significantly increased in Ag-, As-, and Cu-exposed copepods, while they were only slightly elevated in Cd- and Zn-exposed groups. Based on the numbers of significantly modulated hsp genes and their expression levels for 96 h, we measured the effect of heavy metals to stress genes of T. japonicus in the following order: Cu > Zn > Ag > As > Cd, implying that Cu acts as a stronger oxidative stress inducer than other heavy metals. Of them, the expression of hsp20 and hsp70 genes was substantially modulated by exposure to heavy metals, indicating that these genes would provide a sensitive molecular biomarker for aquatic monitoring of heavy metal pollution. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Oxidative stress induces macroautophagy of amyloid beta-protein and ensuing apoptosis

    DEFF Research Database (Denmark)

    Zheng, Lin; Kågedal, Katarina; Dehvari, Nodi

    2009-01-01

    to intralysosomal accumulation of Abeta in cultured neuroblastoma cells. We hypothesized that oxidative stress promotes AD by stimulating macroautophagy of Abeta that further may induce cell death by destabilizing lysosomal membranes. To investigate such possibility, we compared the effects of hyperoxia (40...

  17. Seasonal variability of oxidative stress markers in city bus drivers – Part II: Oxidative damage to lipids and proteins

    Czech Academy of Sciences Publication Activity Database

    Rössner ml., Pavel; Švecová, Vlasta; Milcová, Alena; Lněničková, Zdena; Solanský, I.; Šrám, Radim

    2008-01-01

    Roč. 642, 1-2 (2008), s. 21-27 ISSN 0027-5107 R&D Projects: GA MŽP SL/5/160/05 Institutional research plan: CEZ:AV0Z50390512 Keywords : Air pollution * Oxidative stress * Bus drivers Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.198, year: 2008

  18. Transcript and protein analysis reveals better survival skills of monocyte-derived dendritic cells compared to monocytes during oxidative stress.

    Directory of Open Access Journals (Sweden)

    Ilse Van Brussel

    Full Text Available BACKGROUND: Dendritic cells (DCs, professional antigen-presenting cells with the unique ability to initiate primary T-cell responses, are present in atherosclerotic lesions where they are exposed to oxidative stress that generates cytotoxic reactive oxygen species (ROS. A large body of evidence indicates that cell death is a major modulating factor of atherogenesis. We examined antioxidant defence systems of human monocyte-derived (moDCs and monocytes in response to oxidative stress. METHODS: Oxidative stress was induced by addition of tertiary-butylhydroperoxide (tert-BHP, 30 min. Cellular responses were evaluated using flow cytometry and confocal live cell imaging (both using 5-(and-6-chloromethyl-2,7-dichlorodihydrofluorescein diacetate, CM-H(2DCFDA. Viability was assessed by the neutral red assay. Total RNA was extracted for a PCR profiler array. Five genes were selected for confirmation by Taqman gene expression assays, and by immunoblotting or immunohistochemistry for protein levels. RESULTS: Tert-BHP increased CM-H(2DCFDA fluorescence and caused cell death. Interestingly, all processes occurred more slowly in moDCs than in monocytes. The mRNA profiler array showed more than 2-fold differential expression of 32 oxidative stress-related genes in unstimulated moDCs, including peroxiredoxin-2 (PRDX2, an enzyme reducing hydrogen peroxide and lipid peroxides. PRDX2 upregulation was confirmed by Taqman assays, immunoblotting and immunohistochemistry. Silencing PRDX2 in moDCs by means of siRNA significantly increased CM-DCF fluorescence and cell death upon tert-BHP-stimulation. CONCLUSIONS: Our results indicate that moDCs exhibit higher intracellular antioxidant capacities, making them better equipped to resist oxidative stress than monocytes. Upregulation of PRDX2 is involved in the neutralization of ROS in moDCs. Taken together, this points to better survival skills of DCs in oxidative stress environments, such as atherosclerotic plaques.

  19. Nitrosative/oxidative stress conditions regulate thioredoxin-interacting protein (TXNIP) expression and thioredoxin-1 (TRX-1) nuclear localization.

    Science.gov (United States)

    Ogata, Fernando Toshio; Batista, Wagner Luiz; Sartori, Adriano; Gesteira, Tarsis Ferreira; Masutani, Hiroshi; Arai, Roberto Jun; Yodoi, Junji; Stern, Arnold; Monteiro, Hugo Pequeno

    2013-01-01

    Thioredoxin (TRX-1) is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras-ERK1/2 MAP Kinases signaling pathway. In situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through down-regulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXNIP). Once activated by the oxidants, SNAP and H₂O₂, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXNIP. In the presence of the MEK inhibitors (PD98059 or UO126), or in cells transfected with the Protein Enriched in Astrocytes (PEA-15), a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. In conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases.

  20. Nitrosative/oxidative stress conditions regulate thioredoxin-interacting protein (TXNIP expression and thioredoxin-1 (TRX-1 nuclear localization.

    Directory of Open Access Journals (Sweden)

    Fernando Toshio Ogata

    Full Text Available Thioredoxin (TRX-1 is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras-ERK1/2 MAP Kinases signaling pathway. In situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP, TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through down-regulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXNIP. Once activated by the oxidants, SNAP and H₂O₂, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXNIP. In the presence of the MEK inhibitors (PD98059 or UO126, or in cells transfected with the Protein Enriched in Astrocytes (PEA-15, a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. In conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases.

  1. Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress

    International Nuclear Information System (INIS)

    Hayakawa, Hiroshi; Fujikane, Aya; Ito, Riyoko; Matsumoto, Masaki; Nakayama, Keiichi I.; Sekiguchi, Mutsuo

    2010-01-01

    Research highlights: → We performed comprehensive survey for proteins that bind to oxidized RNA. → HNRNPD and HNRNPC proteins were identified as oxidized RNA binding proteins. → Knockdown of HNRNPD/C expression caused increased sensitivity to H 2 O 2 . → Amounts of HNRNPD protein rapidly decreased when cells were exposed to H 2 O 2 . -- Abstract: Exposure of cells to oxygen radicals damage various biologically important molecules. Among the oxidized bases produced in nucleic acids, 8-oxo-7,8-dihydroguanine (8-oxoguanine) is particularly important since it causes base mispairing. To ensure accurate gene expression, organisms must have a mechanism to discriminate 8-oxoguanine-containing RNA from normal transcripts. We searched for proteins that specifically bind to 8-oxoguanine-containing RNA from human HeLa cell extracts, and the candidate proteins were identified using mass spectrometry. Among the identified candidates, splicing isoform 1 of heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) and splicing isoform C1 of heterogeneous nuclear ribonucleoprotein C1/C2 (HNRNPC) exhibited strong abilities to bind to oxidized RNA. The amount of HNRNPD protein rapidly decreased when cells were exposed to hydrogen peroxide, an agent that enhances oxidative stress. Moreover, the suppression of HNRNPD expression by siRNA caused cells to exhibit an increased sensitivity to hydrogen peroxide. The application of siRNA against HNRNPC also caused an increase in sensitivity to hydrogen peroxide. Since no additive effect was observed with a combined addition of siRNAs for HNRNPD and HNRNPC, we concluded that the two proteins may function in the same mechanism for the accurate gene expression.

  2. Proteomics of the oxidative stress response induced by hydrogen peroxide and paraquat reveals a novel AhpC-like protein in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Hare, Nathan J; Scott, Nichollas E; Shin, Eun Hye H

    2011-01-01

    hypothetical antioxidant protein (PA3450) that shares sequence similarity with 1-Cys peroxiredoxins. Other induced proteins included known oxidative stress proteins (superoxide dismutase and catalase), as well as those involved in iron acquisition (siderophore biosynthesis and receptor proteins FpvA and Fpt...

  3. Advanced oxidation protein products and malondialdehyde - the new biological markers of oxidative stress - are elevated in postmenopausal women.

    Science.gov (United States)

    Cakir, Tansel; Goktas, Bulent; Mutlu, Mehmet F; Mutlu, Ilknur; Bilgihan, Ayse; Erdem, Mehmet; Erdem, Ahmet

    2016-01-01

    The aim of the study was to measure advanced oxidation protein products (AOPPs) as markers for oxidative stress to evaluate cardiovascular risk in pre- and postmenopausal women and to compare the results with malondialde-hyde (MDA) levels. Twenty premenopausal women and 84 naturally postmenopausal patients were enrolled in the study. AOPP and MDA plasma levels were measured. The postmenopausal group was further subdivided into two groups: postmenopausal age of 40-49 and of 50-59 years. AOPP and MDA levels were compared between premenopausal, 40-49 and 50-59 year old menopausal women. Plasma AOPP and MDA levels in postmenopausal women were increased when compared with their premeno-pausal peers (123.83 ± 55.51 μmol/L vs. 61.59 ± 16.42 μmol/L and 6.50 ± 1.05 μmol/L vs. 5.98 ± 0.77 μmol/L; respectively). Mean plasma AOPP levels in the two menopausal age groups were both significantly higher from the premenopausal group (118.64 ± 59.1 μmol/L vs. 61.59 ± 16.42 μmol/L and 132.31 ± 48.97 μmol/L vs. 61.59 ± 16.42 μmol/L; respectively). No significant difference was found in mean AOPP levels between postmenopausal subjects of 40-49 and 50-59 years age (118.64 ± 59.12 μmol/L vs. 132.31 ± 48.97 μmol/L). Mean plasma MDA levels of each of two postmenopausal age groups were both significantly higher from the premenopausal group (6.50 ± 1.04 μmol/L vs. 5.98 ± 0.77 μmol/L and 6.50 ± 1.10 μmol/L vs. 5.98 ± 0.77 μmol/L; respectively). However, no statistically significant difference between the two postmenopausal age groups (6.50 ± 1.04 μmol/L vs. 6.50 ± 1.10 μmol/L) was found. AOPP and MDA levels are elevated in postmenopausal women as compared to their premenopausal peers, suggesting they can be used as markers for cardiovascular risk in postmenopausal women.

  4. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein.

    Directory of Open Access Journals (Sweden)

    Hana Malínská

    Full Text Available Inflammation and oxidative and dicarbonyl stress play important roles in the pathogenesis of type 2 diabetes. Metformin is the first-line drug of choice for the treatment of type 2 diabetes because it effectively suppresses gluconeogenesis in the liver. However, its "pleiotropic" effects remain controversial. In the current study, we tested the effects of metformin on inflammation, oxidative and dicarbonyl stress in an animal model of inflammation and metabolic syndrome, using spontaneously hypertensive rats that transgenically express human C-reactive protein (SHR-CRP. We treated 8-month-old male transgenic SHR-CRP rats with metformin (5 mg/kg/day mixed as part of a standard diet for 4 weeks. A corresponding untreated control group of male transgenic SHR-CRP rats were fed a standard diet without metformin. In a similar fashion, we studied a group of nontransgenic SHR treated with metformin and an untreated group of nontransgenic SHR controls. In each group, we studied 6 animals. Parameters of glucose and lipid metabolism and oxidative and dicarbonyl stress were measured using standard methods. Gene expression profiles were determined using Affymetrix GeneChip Arrays. Statistical significance was evaluated by two-way ANOVA. In the SHR-CRP transgenic strain, we found that metformin treatment decreased circulating levels of inflammatory response marker IL-6, TNFα and MCP-1 while levels of human CRP remained unchanged. Metformin significantly reduced oxidative stress (levels of conjugated dienes and TBARS and dicarbonyl stress (levels of methylglyoxal in left ventricles, but not in kidneys. No significant effects of metformin on oxidative and dicarbonyl stress were observed in SHR controls. In addition, metformin treatment reduced adipose tissue lipolysis associated with human CRP. Possible molecular mechanisms of metformin action-studied by gene expression profiling in the liver-revealed deregulated genes from inflammatory and insulin signaling

  5. Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Preeti Shahi

    2016-01-01

    Full Text Available Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious disease which targets the intestine and/or liver, is the second most common cause of human death due to a protozoan after malaria. Although amebiasis is usually asymptomatic, E. histolytica has potent pathogenic potential. During host infection, the parasite is exposed to reactive oxygen species that are produced and released by cells of the innate immune system at the site of infection. The ability of the parasite to survive oxidative stress (OS is essential for a successful invasion of the host. Although the effects of OS on the regulation of gene expression in E. histolytica and the characterization of some proteins whose function in the parasite's defense against OS have been previously studied, our knowledge of oxidized proteins in E. histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale identification and quantification of the oxidized proteins in oxidatively stressed E. histolytica trophozoites using resin-assisted capture coupled to mass spectrometry. We detected 154 oxidized proteins (OXs and the functions of some of these proteins were associated with antioxidant activity, maintaining the parasite's cytoskeleton, translation, catalysis, and transport. We also found that oxidation of the Gal/GalNAc impairs its function and contributes to the inhibition of E. histolytica adherence to host cells. We also provide evidence that arginase, an enzyme which converts L-arginine into L-ornithine and urea, is involved in the protection of the parasite against OS. Collectively, these results emphasize the importance of OS as a critical regulator of E. histolytica's functions and indicate a new role for arginase in E. histolytica's resistance to OS.

  6. Melatonin ameliorates oxidative stress, modulates death receptor pathway proteins, and protects the rat cerebrum against bisphenol-A-induced apoptosis.

    Science.gov (United States)

    El-Missiry, Mohamed A; Othman, Azza I; Al-Abdan, Monera A; El-Sayed, Aml A

    2014-12-15

    Epidemiological reports have indicated a correlation between the increasing of bisphenol-A (BPA) levels in the environment and the incidence of neurodegenerative diseases. In the present study, the protective effect of melatonin on oxidative stress and the death receptor apoptotic proteins in the cerebrum of the bisphenol-A-treated rats were examined. Adult male rats were orally administered melatonin (10mg/kg bw) concurrently with BPA (50mg/kg bw) 3 days a week for 6 weeks. BPA exposure resulted in significant elevations of oxidative stress, as evidenced by the increased malondialdehyde level and the decreased glutathione level and superoxide dismutase activity in the cerebrum. BPA caused an upregulation of p53 and CD95-Fas and activation of capsases-3 and 8, resulting in cerebral cell apoptosis. Melatonin significantly attenuated the BPA-evoked brain oxidative stress, modulated apoptotic-regulating proteins and protected against apoptosis. These data suggest that melatonin modulated important steps in the death receptor apoptotic pathway which likely related to its redox control properties. Melatonin is a promising pharmacological agent for preventing the potential neurotoxicity of BPA following occupational or environmental exposures. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Effects of heat shock protein 90 expression on pectoralis major oxidation in broilers exposed to acute heat stress.

    Science.gov (United States)

    Hao, Y; Gu, X H

    2014-11-01

    This study was conducted to determine the effects of heat shock protein 90 (HSP90) expression on pH, lipid peroxidation, heat shock protein 70 (HSP70), and glucocorticoid receptor (GR) expression of pectoralis major in broilers exposed to acute heat stress. In total, 90 male broilers were randomly allocated to 3 groups: control (CON), heat stress (HS), or geldanamycin treatment (GA). On d 41, the broilers in the GA group were injected intraperitoneally with GA (5 μg/kg of BW), and the broilers in the CON and HS groups were injected intraperitoneally with saline. Twenty-four hours later, the broilers in the CON group were moved to environmental chambers controlled at 22°C for 2 h, and the broilers in the HS and GA groups were moved to environmental chambers controlled at 40°C for 2 h. The pH values of the pectoralis major after 30 min and 24 h of chilling after slaughter of HS and GA broilers were significantly lower (P stress caused significant increases in sera corticosterone and lactic dehydrogenase, the activity of malondialdehyde and superoxide dismutase, the expression of HSP90 and HSP70, and nuclear expression of GR protein in the pectoralis major (P stress induced a significant decrease in GR protein expression in the cytoplasm and GR mRNA expression. Furthermore, the low expression of HSP90 significantly increased levels of lactic dehydrogenase and malondialdehyde and GR protein expression in the cytoplasm under heat stress (P shock protein 90 was positively correlated with corticosterone and superoxide dismutase activities (P < 0.01), and HSP90 mRNA was negatively correlated with pH after chilling for 24 h. The results demonstrated that HSP90 plays a pivotal role in protecting cells from oxidation. ©2014 Poultry Science Association Inc.

  8. Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

    Directory of Open Access Journals (Sweden)

    De Marco Federico

    2010-03-01

    Full Text Available Abstract Background The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS, which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes. Results The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized. Conclusions Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

  9. Accumulation of small heat shock proteins, including mitochondrial HSP22, induced by oxidative stress and adaptive response in tomato cells

    International Nuclear Information System (INIS)

    Banzet, N.; Richaud, C.; Deveaux, Y.; Kazmaier, M.; Gagnon, J.; Triantaphylides, C.

    1998-01-01

    Changes in gene expression, by application of H2O2, O2.- generating agents (methyl viologen, digitonin) and gamma irradiation to tomato suspension cultures, were investigated and compared to the well-described heat shock response. Two-dimensional gel protein mapping analyses gave the first indication that at least small heat shock proteins (smHSP) accumulated in response to application of H2O2 and gamma irradiation, but not to O2.- generating agents. While some proteins seemed to be induced specifically by each treatment, only part of the heat shock response was observed. On the basis of Northern hybridization experiments performed with four heterologous cDNA, corresponding to classes I-IV of pea smHSP, it could be concluded that significant amounts of class I and II smHSP mRNA are induced by H2O2 and by irradiation. Taken together, these results demonstrate that in plants some HSP genes are inducible by oxidative stresses, as in micro-organisms and other eukaryotic cells. HSP22, the main stress protein that accumulates following H2O2 action or gamma irradiation, was also purified. Sequence homology of amino terminal and internal sequences, and immunoreactivity with Chenopodium rubrum mitochondrial smHSP antibody, indicated that the protein belongs to the recently discovered class of plant mitochondrial smHSP. Heat shock or a mild H2O2 pretreatment was also shown to lead to plant cell protection against oxidative injury. Therefore, the synthesis of these stress proteins can be considered as an adaptive mechanism in which mitochondrial protection could be essential

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

    Directory of Open Access Journals (Sweden)

    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.

  11. A PerR-like protein involved in response to oxidative stress in the extreme bacterium Deinococcus radiodurans

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chengzhi; Wang, Liangyan; Li, Tao; Lin, Lin; Dai, Shang; Tian, Bing, E-mail: tianbing@zju.edu.cn; Hua, Yuejin, E-mail: yjhua@zju.edu.cn

    2014-07-18

    Highlights: • We report a novel PerR-like protein of Fur family in D. radiodurans that is not annotated in the current database. • drperR responses to H{sub 2}O{sub 2} and functions as a negative regulator of katE and dps. • We provided implications on how to utilize sequenced genome data and the importance of genome data mining. • This study adds knowledge to complicated regulatory network that responds to ROS stress in D. radiodurans. - Abstract: Response and defense systems against reactive oxygen species (ROS) contribute to the remarkable resistance of Deinococcus radiodurans to oxidative stress induced by oxidants or radiation. However, mechanisms involved in ROS response and defense systems of D. radiodurans are not well understood. Fur family proteins are important in ROS response. Only a single Fur homolog is predicted by sequence similarity in the current D. radiodurans genome database. Our bioinformatics analysis demonstrated an additional guanine nucleotide in the genome of D. radiodurans that is not in the database, leading to the discovery of another Fur homolog DrPerR. Gene disruption mutant of DrPerR showed enhanced resistance to hydrogen peroxide (H{sub 2}O{sub 2}) and increased catalase activity in cell extracts. Real-time PCR results indicated that DrPerR functions as a repressor of the catalase gene katE. Meanwhile, derepression of dps (DNA-binding proteins from starved cells) gene under H{sub 2}O{sub 2} stress by DrPerR point to its regulatory role in metal ions hemostasis. Thus, DrPerR might function as a Fur homolog protein which is involved in ROS response and defense. These results help clarify the complicated regulatory network that responds to ROS stress in D. radiodurans.

  12. A PerR-like protein involved in response to oxidative stress in the extreme bacterium Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Liu, Chengzhi; Wang, Liangyan; Li, Tao; Lin, Lin; Dai, Shang; Tian, Bing; Hua, Yuejin

    2014-01-01

    Highlights: • We report a novel PerR-like protein of Fur family in D. radiodurans that is not annotated in the current database. • drperR responses to H 2 O 2 and functions as a negative regulator of katE and dps. • We provided implications on how to utilize sequenced genome data and the importance of genome data mining. • This study adds knowledge to complicated regulatory network that responds to ROS stress in D. radiodurans. - Abstract: Response and defense systems against reactive oxygen species (ROS) contribute to the remarkable resistance of Deinococcus radiodurans to oxidative stress induced by oxidants or radiation. However, mechanisms involved in ROS response and defense systems of D. radiodurans are not well understood. Fur family proteins are important in ROS response. Only a single Fur homolog is predicted by sequence similarity in the current D. radiodurans genome database. Our bioinformatics analysis demonstrated an additional guanine nucleotide in the genome of D. radiodurans that is not in the database, leading to the discovery of another Fur homolog DrPerR. Gene disruption mutant of DrPerR showed enhanced resistance to hydrogen peroxide (H 2 O 2 ) and increased catalase activity in cell extracts. Real-time PCR results indicated that DrPerR functions as a repressor of the catalase gene katE. Meanwhile, derepression of dps (DNA-binding proteins from starved cells) gene under H 2 O 2 stress by DrPerR point to its regulatory role in metal ions hemostasis. Thus, DrPerR might function as a Fur homolog protein which is involved in ROS response and defense. These results help clarify the complicated regulatory network that responds to ROS stress in D. radiodurans

  13. New insight into multifunctional role of peroxiredoxin family protein: Determination of DNA protection properties of bacterioferritin comigratory protein under hyperthermal and oxidative stresses

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sangmin, E-mail: taeinlee2011@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, South Korea (Korea, Republic of); Chung, Jeong Min [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, South Korea (Korea, Republic of); Yun, Hyung Joong; Won, Jonghan [Advanced Nano Surface Research Group, Korea Basic Science Institute, 169-148 Gwahak-ro, Daejeon, 305-333 (Korea, Republic of); Jung, Hyun Suk, E-mail: hsjung@kangwon.ac.kr [Department of Biochemistry, College of Natural Sciences, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, South Korea (Korea, Republic of)

    2016-01-22

    Bacterioferritin comigratory protein (BCP) is a monomeric conformer acting as a putative thiol-dependent bacterial peroxidase, however molecular basis of DNA-protection via DNA-binding has not been clearly understood. In this study, we characterized the DNA binding properties of BCP using various lengths and differently shaped architectures of DNA. An electrophoretic mobility shift assay and electron microscopy analysis showed that recombinant TkBCP bound to DNA of a circular shape (double-stranded DNA and single-stranded DNA) and a linear shape (16–1000 bp) as well as various architectures of DNA. In addition, DNA protection experiments indicated that TkBCP can protect DNA against hyperthermal and oxidative stress by removing highly reactive oxygen species (ROS) or by protecting DNA from thermal degradation. Based on these results, we suggest that TkBCP is a multi-functional DNA-binding protein which has DNA chaperon and antioxidant functions. - Highlights: • Bacterioferritin comigratory protein (BCP) protects DNA from oxidative stress by reducing ROS. • TkBCP does not only scavenge ROS, but also protect DNA from hyperthermal stress. • BCP potentially adopts the multi-functional role in DNA binding activities and anti-oxidant functions.

  14. New insight into multifunctional role of peroxiredoxin family protein: Determination of DNA protection properties of bacterioferritin comigratory protein under hyperthermal and oxidative stresses

    International Nuclear Information System (INIS)

    Lee, Sangmin; Chung, Jeong Min; Yun, Hyung Joong; Won, Jonghan; Jung, Hyun Suk

    2016-01-01

    Bacterioferritin comigratory protein (BCP) is a monomeric conformer acting as a putative thiol-dependent bacterial peroxidase, however molecular basis of DNA-protection via DNA-binding has not been clearly understood. In this study, we characterized the DNA binding properties of BCP using various lengths and differently shaped architectures of DNA. An electrophoretic mobility shift assay and electron microscopy analysis showed that recombinant TkBCP bound to DNA of a circular shape (double-stranded DNA and single-stranded DNA) and a linear shape (16–1000 bp) as well as various architectures of DNA. In addition, DNA protection experiments indicated that TkBCP can protect DNA against hyperthermal and oxidative stress by removing highly reactive oxygen species (ROS) or by protecting DNA from thermal degradation. Based on these results, we suggest that TkBCP is a multi-functional DNA-binding protein which has DNA chaperon and antioxidant functions. - Highlights: • Bacterioferritin comigratory protein (BCP) protects DNA from oxidative stress by reducing ROS. • TkBCP does not only scavenge ROS, but also protect DNA from hyperthermal stress. • BCP potentially adopts the multi-functional role in DNA binding activities and anti-oxidant functions.

  15. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

    Frijhoff, Jeroen; Winyard, Paul G; Zarkovic, Neven

    2015-01-01

    SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino ac....... The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker.......SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino...... acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous...

  16. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels.

    Science.gov (United States)

    El-Deeb, Wael M; Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI.

  17. Effectiveness of exercise and protein supplementation intervention on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia.

    Science.gov (United States)

    Shahar, Suzana; Kamaruddin, Norshafarina Shari; Badrasawi, Manal; Sakian, Noor Ibrahim Mohamed; Abd Manaf, Zahara; Yassin, Zaitun; Joseph, Leonard

    2013-01-01

    Sarcopenia, characterized as muscle loss that occurs with aging, is a major health problem in an aging population, due to its implications on mobility, quality of life, and fall risk. Protein supplementation could improve the physical fitness by increasing protein anabolism, and exercise has a documented evidence of positive effect on functional status among the elderly. However, the combined effect of both protein supplementation and exercise has not been investigated among sarcopenic elderly in the Asian population. Thus, this study aimed to determine the effectiveness of exercise intervention and protein supplementation either alone or in combination for 12 weeks, on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia. Sixty five sarcopenic elderly Malays aged 60-74 years were assigned to the control group, exercise group (ExG), protein supplementation group (PrG), or the combination of exercise and protein supplementation group. A significant interaction effect between body weight and body mass index (BMI) was observed, with the PrG (-2.1% body weight, -1.8% BMI) showing the highest reductions. Further, there was a decrease in % body fat (-4.5%) and an increase in fat-free mass (kg) (+5.7%) in the ExG after 12 weeks (P exercise program was found to improve muscle strength and body composition, while protein supplementation reduced body weight and increased upper body strength, among sarcopenic elderly in Malaysia.

  18. A Bacterial Biosensor for Oxidative Stress Using the Constitutively Expressed Redox-Sensitive Protein roGFP2

    Directory of Open Access Journals (Sweden)

    Carlos R. Arias-Barreiro

    2010-06-01

    Full Text Available A highly specific, high throughput-amenable bacterial biosensor for chemically induced cellular oxidation was developed using constitutively expressed redox-sensitive green fluorescent protein roGFP2 in E. coli (E. coli-roGFP2. Disulfide formation between two key cysteine residues of roGFP2 was assessed using a double-wavelength ratiometric approach. This study demonstrates that only a few minutes were required to detect oxidation using E. coli-roGFP2, in contrast to conventional bacterial oxidative stress sensors. Cellular oxidation induced by hydrogen peroxide, menadione, sodium selenite, zinc pyrithione, triphenyltin and naphthalene became detectable after 10 seconds and reached the maxima between 80 to 210 seconds, contrary to Cd2+, Cu2+, Pb2+, Zn2+ and sodium arsenite, which induced the oxidation maximum immediately. The lowest observable effect concentrations (in ppm were determined as 1.0 x 10−7 (arsenite, 1.0 x 10−4 (naphthalene, 1.0 x 10−4 (Cu2+, 3.8 x 10−4 (H2O2, 1.0 x 10−3 (Cd2+, 1.0 x 10−3 (Zn2+, 1.0 x 10−2 (menadione, 1.0 (triphenyltin, 1.56 (zinc pyrithione, 3.1 (selenite and 6.3 (Pb2+, respectively. Heavy metal-induced oxidation showed unclear response patterns, whereas concentration-dependent sigmoid curves were observed for other compounds. In vivo GSH content and in vitro roGFP2 oxidation assays together with E. coli-roGFP2 results suggest that roGFP2 is sensitive to redox potential change and thiol modification induced by environmental stressors. Based on redox-sensitive technology, E. coli-roGFP2 provides a fast comprehensive detection system for toxicants that induce cellular oxidation.

  19. Evaluation of salivary oxidate stress biomarkers, nitric oxide and C-reactive protein in patients with oral lichen planus and burning mouth syndrome.

    Science.gov (United States)

    Tvarijonaviciute, Asta; Aznar-Cayuela, Cristina; Rubio, Camila P; Ceron, José J; López-Jornet, Pia

    2017-05-01

    The aim of this study was to evaluate oxidative stress factors and C-reactive protein in the saliva of patients with oral lichen planus (OLP) and burning mouth syndrome (BMS). This consecutive, cross-sectional study included 20 patients with OLP, 19 with burning mouth syndrome (BMS), and 31 control subjects. The oral cavity of each patient was examined and patients responded to a quality of life questionnaire (OHIP-14) and the xerostomia inventory. The following parameters were measured in whole non-stimulated saliva: trolox equivalent antioxidant capacity (TEAC); total antioxidant capacity (TAC); cupric reducing antioxidant capacity (CUPRAC); ferric reducing ability of plasma (FRAP); C-reactive protein (CRP); nitric oxide; nitrates; and nitrites. The OLP group presented statistically significant differences in reactive oxygen species (ROS) (29 600 cps) in comparison with the control group (39 679 cps) (P < 0.05). In the BMS group, ROS was 29 707 cps with significant difference in comparison with the control group (P < 0.05). Significantly higher salivary nitric oxide (145.7 μmol) and nitrite (141.0 μmol) levels were found in OLP patients in comparison with control group (P < 0.05). Increases in nitric oxide and C-reactive protein were found in the saliva of OLP patients in comparison with BMS and control patients. Further studies are required to confirm these findings. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Alzheimer's Proteins, Oxidative Stress, and Mitochondrial Dysfunction Interplay in a Neuronal Model of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Antonella Bobba

    2010-01-01

    Full Text Available In this paper, we discuss the interplay between beta-amyloid (A peptide, Tau fragments, oxidative stress, and mitochondria in the neuronal model of cerebellar granule neurons (CGNs in which the molecular events reminiscent of AD are activated. The identification of the death route and the cause/effect relationships between the events leading to death could be helpful to manage the progression of apoptosis in neurodegeneration and to define antiapoptotic treatments acting on precocious steps of the death process. Mitochondrial dysfunction is among the earliest events linked to AD and might play a causative role in disease onset and progression. Recent studies on CGNs have shown that adenine nucleotide translocator (ANT impairment, due to interaction with toxic N-ter Tau fragment, contributes in a significant manner to bioenergetic failure and mitochondrial dysfunction. These findings open a window for new therapeutic strategies aimed at preserving and/or improving mitochondrial function.

  1. Universal stress proteins are important for oxidative and acid stress resistance and growth of Listeria monocytogenes EGD-e in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Christa Seifart Gomes

    Full Text Available BACKGROUND: Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species. METHODS AND FINDINGS: We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (Δlmo0515, Δlmo1580 and Δlmo2673 were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models. Tolerance to acidic stress was clearly reduced in Δlmo1580 and Δlmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in Δlmo1580 and Δlmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with Δlmo1580 or Δlmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection. CONCLUSION: This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions.

  2. dFOXO Activates Large and Small Heat Shock Protein Genes in Response to Oxidative Stress to Maintain Proteostasis in Drosophila.

    Science.gov (United States)

    Donovan, Marissa R; Marr, Michael T

    2016-09-02

    Maintaining protein homeostasis is critical for survival at the cellular and organismal level (Morimoto, R. I. (2011) Cold Spring Harb. Symp. Quant. Biol. 76, 91-99). Cells express a family of molecular chaperones, the heat shock proteins, during times of oxidative stress to protect against proteotoxicity. We have identified a second stress responsive transcription factor, dFOXO, that works alongside the heat shock transcription factor to activate transcription of both the small heat shock protein and the large heat shock protein genes. This expression likely protects cells from protein misfolding associated with oxidative stress. Here we identify the regions of the Hsp70 promoter essential for FOXO-dependent transcription using in vitro methods and find a physiological role for FOXO-dependent expression of heat shock proteins in vivo. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Inhibition of interaction between epigallocatechin-3-gallate and myofibrillar protein by cyclodextrin derivatives improves gel quality under oxidative stress.

    Science.gov (United States)

    Zhang, Yumeng; Chen, Lin; Lv, Yuanqi; Wang, Shuangxi; Suo, Zhiyao; Cheng, Xingguang; Xu, Xinglian; Zhou, Guanghong; Li, Zhixi; Feng, Xianchao

    2018-06-01

    High levels of polyphenols can interact with myofibrillar proteins (MPs), causing damage to a MP emulsion gel. In this study, β-cyclodextrins were used to reduce covalent and non-covalent interaction between epigallocatechin-3-gallate (EGCG) and MPs under oxidative stress. The loss of both thiol and free amine groups and the unfolding of MPs caused by EGCG (80 μM/g protein) were significantly prevented by β-cyclodextrins, and the structural stability and solubility were improved. MP emulsion gel treated with EGCG (80 μM/g protein) had the highest cooking loss (68.64%) and gel strength (0.51 N). Addition of β-cyclodextrins significantly reduced cooking loss (26.24-58.20%) and improved gel strength (0.31-0.41 N) of MP emulsion gel jeopardized by EGCG under oxidative stress. Damage to the emulsifying properties of MPs caused by EGCG was significantly prevented by addition of β-cyclodextrins. β-cyclodextrins reduced interaction between EGCG and MPs in the order Methyl-β-cyclodextrin > (2-Hydroxypropyl)-β-cyclodextrin > β-cyclodextrin. In absence of EGCG, addition of β-cyclodextrins partly protected MPs from oxidative attack and improved its solubility. It is concluded that β-cyclodextrins does not markedly reduce the antioxidant ability of EGCG according to carbonyl analysis, and can effectively increase EGCG loading to potentially provide more durable antioxidant effect for meat products during processing, transportation and storage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. 6-Hydroxydopamine Inhibits the Hepatitis C Virus through Alkylation of Host and Viral Proteins and the Induction of Oxidative Stress.

    Science.gov (United States)

    Lafreniere, Matthew A; Powdrill, Megan H; Singaravelu, Ragunath; Pezacki, John Paul

    2016-11-11

    Many viruses, including the hepatitis C virus (HCV), are dependent on the host RNA silencing pathway for replication. In this study, we screened small molecule probes, previously reported to disrupt loading of the RNA-induced silencing complex (RISC), including 6-hydroxydopamine (6-OHDA), suramin (SUR), and aurintricarboxylic acid (ATA), to examine their effects on viral replication. We found that 6-OHDA inhibited HCV replication; however, 6-OHDA was a less potent inhibitor of RISC than either SUR or ATA. By generating a novel chemical probe (6-OHDA-yne), we determined that 6-OHDA covalently modifies host and virus proteins. Moreover, 6-OHDA was shown to be an alkylating agent that is capable of generating adducts with a number of enzymes involved in the oxidative stress response. Furthermore, modification of viral enzymes with 6-OHDA and 6-OHDA-yne was found to inhibit their enzymatic activity. Our findings suggest that 6-OHDA is a probe for oxidative stress as well as protein alkylation, and these properties together contribute to the antiviral effects of this compound.

  5. Multidrug-resistance-associated protein plays a protective role in menadione-induced oxidative stress in endothelial cells.

    Science.gov (United States)

    Takahashi, Kyohei; Shibata, Tomohito; Oba, Tatsuya; Ishikawa, Tetsuya; Yoshikawa, Masahito; Tatsunami, Ryosuke; Takahashi, Kazuhiko; Tampo, Yoshiko

    2009-02-13

    Menadione, a redox-cycling quinone known to cause oxidative stress, binds to reduced glutathione (GSH) to form glutathione S-conjugate. Glutathione S-conjugates efflux is often mediated by multidrug-resistance-associated protein (MRP). We investigated the effect of a transporter inhibitor, MK571 (3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid), on menadione-induced oxidative stress in bovine aortic endothelial cells (BAECs). BAECs were treated with menadione and MK571, and cell viability was measured. Modulation of intracellular GSH levels was performed with buthionine sulfoximine and GSH ethyl ester treatments. Intracellular superoxide was estimated by dihydroethidium oxidation using fluorescence microscopy or flow cytometry. Expression of MRP was determined by flow cytometry using phycoerythrin-conjugated anti-MRP monoclonal antibody. Intracellular GSH depletion by buthionine sulfoximine promoted the loss of viability of BAECs exposed to menadione. Exogenous GSH, which does not permeate the cell membrane, or GSH ethyl ester protected BAECs against the loss of viability induced by menadione. The results suggest that GSH binds to menadione outside the cells as well as inside. Pretreatment of BAECs with MK571 dramatically increased intracellular levels of superoxide generated from menadione, indicating that menadione may accumulate in the intracellular milieu. Finally, we found that MK571 aggravated menadione-induced toxicity in BAECs and that MRP levels were increased in menadione-treated cells. We conclude that MRP plays a vital role in protecting BAECs against menadione-induced oxidative stress, presumably due to its ability to transport glutathione S-conjugate.

  6. MiR-17-5p Impairs Trafficking of H-ERG K+ Channel Protein by Targeting Multiple ER Stress-Related Chaperones during Chronic Oxidative Stress

    OpenAIRE

    Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

    2013-01-01

    BACKGROUND: To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Lucifer...

  7. Does oxidative stress shorten telomeres?

    NARCIS (Netherlands)

    Boonekamp, Jelle J.; Bauch, Christina; Mulder, Ellis; Verhulst, Simon

    Oxidative stress shortens telomeres in cell culture, but whether oxidative stress explains variation in telomere shortening in vivo at physiological oxidative stress levels is not well known. We therefore tested for correlations between six oxidative stress markers and telomere attrition in nestling

  8. Association of Oxidative Stress with Psychiatric Disorders.

    Science.gov (United States)

    Hassan, Waseem; Noreen, Hamsa; Castro-Gomes, Vitor; Mohammadzai, Imdadullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J

    2016-01-01

    When concentrations of both reactive oxygen species and reactive nitrogen species exceed the antioxidative capability of an organism, the cells undergo oxidative impairment. Impairments in membrane integrity and lipid and protein oxidation, protein mutilation, DNA damage, and neuronal dysfunction are some of the fundamental consequences of oxidative stress. The purpose of this work was to review the associations between oxidative stress and psychological disorders. The search terms were the following: "oxidative stress and affective disorders," "free radicals and neurodegenerative disorders," "oxidative stress and psychological disorders," "oxidative stress, free radicals, and psychiatric disorders," and "association of oxidative stress." These search terms were used in conjunction with each of the diagnostic categories of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders and World Health Organization's International Statistical Classification of Diseases and Related Health Problems. Genetic, pharmacological, biochemical, and preclinical therapeutic studies, case reports, and clinical trials were selected to explore the molecular aspects of psychological disorders that are associated with oxidative stress. We identified a broad spectrum of 83 degenerative syndromes and psychiatric disorders that were associated with oxidative stress. The multi-dimensional information identified herein supports the role of oxidative stress in various psychiatric disorders. We discuss the results from the perspective of developing novel therapeutic interventions.

  9. Staphylococcal response to oxidative stress

    Directory of Open Access Journals (Sweden)

    Rosmarie eGaupp

    2012-03-01

    Full Text Available Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria’s interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host.

  10. Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP.

    Directory of Open Access Journals (Sweden)

    Souvik Basak

    Full Text Available Oxidative damage to microbial hosts often occurs under stressful conditions during bioprocessing. Classical strain engineering approaches are usually both time-consuming and labor intensive. Here, we aim to improve E. coli performance under oxidative stress via engineering its global regulator cAMP receptor protein (CRP, which can directly or indirectly regulate redox-sensing regulators SoxR and OxyR, and other ~400 genes in E. coli. Error-prone PCR technique was employed to introduce modifications to CRP, and three mutants (OM1~OM3 were identified with improved tolerance via H(2O(2 enrichment selection. The best mutant OM3 could grow in 12 mM H(2O(2 with the growth rate of 0.6 h(-1, whereas the growth of wild type was completely inhibited at this H(2O(2 concentration. OM3 also elicited enhanced thermotolerance at 48°C as well as resistance against cumene hydroperoxide. The investigation about intracellular reactive oxygen species (ROS, which determines cell viability, indicated that the accumulation of ROS in OM3 was always lower than in WT with or without H(2O(2 treatment. Genome-wide DNA microarray analysis has shown not only CRP-regulated genes have demonstrated great transcriptional level changes (up to 8.9-fold, but also RpoS- and OxyR-regulated genes (up to 7.7-fold. qRT-PCR data and enzyme activity assay suggested that catalase (katE could be a major antioxidant enzyme in OM3 instead of alkyl hydroperoxide reductase or superoxide dismutase. To our knowledge, this is the first work on improving E. coli oxidative stress resistance by reframing its transcription machinery through its native global regulator. The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli.

  11. Heme degrading protein HemS is involved in oxidative stress response of Bartonella henselae.

    Directory of Open Access Journals (Sweden)

    MaFeng Liu

    Full Text Available Bartonellae are hemotropic bacteria, agents of emerging zoonoses. These bacteria are heme auxotroph Alphaproteobacteria which must import heme for supporting their growth, as they cannot synthesize it. Therefore, Bartonella genome encodes for a complete heme uptake system allowing the transportation of this compound across the outer membrane, the periplasm and the inner membranes. Heme has been proposed to be used as an iron source for Bartonella since these bacteria do not synthesize a complete system required for iron Fe³⁺ uptake. Similarly to other bacteria which use heme as an iron source, Bartonellae must transport this compound into the cytoplasm and degrade it to allow the release of iron from the tetrapyrrole ring. For Bartonella, the gene cluster devoted to the synthesis of the complete heme uptake system also contains a gene encoding for a polypeptide that shares homologies with heme trafficking or degrading enzymes. Using complementation of an E. coli mutant strain impaired in heme degradation, we demonstrated that HemS from Bartonella henselae expressed in E. coli allows the release of iron from heme. Purified HemS from B. henselae binds heme and can degrade it in the presence of a suitable electron donor, ascorbate or NADPH-cytochrome P450 reductase. Knocking down the expression of HemS in B. henselae reduces its ability to face H₂O₂ induced oxidative stress.

  12. Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts

    International Nuclear Information System (INIS)

    Keyse, S.M.; Tyrrell, R.M.

    1987-01-01

    We have analyzed the pattern of protein synthesis in solar near ultraviolet (334 nm, 365 nm) and near visible (405 nm) irradiated normal human skin fibroblasts. Two hours after irradiation we find that one major stress protein of approximately 32 kDa is induced in irradiated cells. This protein is not induced by ultraviolet radiation at wavelengths shorter than 334 nm and is not inducible by heat shock treatment of these cells. Although sodium arsenite, diamide, and menadione all induced a 32-kDa protein, they also induced the major heat shock proteins. In contrast, the oxidizing agent, hydrogen peroxide, induced the low molecular weight stress protein without causing induction of the major heat shock proteins. A comparison of the 32-kDa proteins induced by sodium arsenite, H 2 O 2 , and solar near ultraviolet radiation using chemical peptide mapping shows that they are closely related. These results imply that the pathways for induction of the heat shock response and the 32-kDa protein are not identical and suggest that, at least in the case of radiation and treatment with H 2 O 2 , the 32-kDa protein might be induced in response to cellular oxidative stress. This conclusion is supported by the observation that depletion of endogenous cellular glutathione prior to solar near ultraviolet irradiation lowers the fluence threshold for induction of the 32-kDa stress protein

  13. Effectiveness of exercise and protein supplementation intervention on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia

    Directory of Open Access Journals (Sweden)

    Shahar S

    2013-10-01

    Full Text Available Suzana Shahar,1 Norshafarina Shari Kamaruddin,2 Manal Badrasawi,1 Noor Ibrahim Mohamed Sakian,3 Zahara Abd Manaf,1 Zaitun Yassin,4 Leonard Joseph51Dietetic Programme, 2Biomedical Programme, 3Occupational Therapy Programme, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 4Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, 5Department of Physiotherapy, School of Healthcare Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, MalaysiaAbstract: Sarcopenia, characterized as muscle loss that occurs with aging, is a major health problem in an aging population, due to its implications on mobility, quality of life, and fall risk. Protein supplementation could improve the physical fitness by increasing protein anabolism, and exercise has a documented evidence of positive effect on functional status among the elderly. However, the combined effect of both protein supplementation and exercise has not been investigated among sarcopenic elderly in the Asian population. Thus, this study aimed to determine the effectiveness of exercise intervention and protein supplementation either alone or in combination for 12 weeks, on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia. Sixty five sarcopenic elderly Malays aged 60-74 years were assigned to the control group, exercise group (ExG, protein supplementation group (PrG, or the combination of exercise and protein supplementation group. A significant interaction effect between body weight and body mass index (BMI was observed, with the PrG (-2.1% body weight, -1.8% BMI showing the highest reductions. Further, there was a decrease in % body fat (-4.5% and an increase in fat-free mass (kg (+5.7% in the ExG after 12 weeks (P < 0.05. The highest increments in lower and upper body strength were observed in the Pr

  14. The Major Chromophore Arising from Glucose Degradation and Oxidative Stress Occurrence during Lens Proteins Glycation Induced by Glucose

    Directory of Open Access Journals (Sweden)

    Felipe Ávila

    2017-12-01

    Full Text Available Glucose autoxidation has been proposed as a key reaction associated with deleterious effects induced by hyperglycemia in the eye lens. Little is known about chromophores generated during glucose autoxidation. In this study, we analyzed the effect of oxidative and dicarbonyl stress in the generation of a major chromophore arising from glucose degradation (GDC and its association with oxidative damage in lens proteins. Glucose (5 mM was incubated with H2O2 (0.5–5 mM, Cu2+ (5–50 μM, glyoxal (0.5–5 mM or methylglyoxal (0.5–5 mM at pH 7.4, 5% O2, 37 °C, from 0 to 30 days. GDC concentration increased with incubation time, as well as when incubated in the presence of H2O2 and/or Cu2+, which were effective even at the lowest concentrations. Dicarbonylic compounds did not increase the levels of GDC during incubations. 1H, 13C and FT-IR spectra from the purified fraction containing the chromophore (detected by UV/vis spectroscopy showed oxidation products of glucose, including gluconic acid. Lens proteins solutions (10 mg/mL incubated with glucose (30 mM presented increased levels of carboxymethyl-lysine and hydrogen peroxide that were associated with GDC increase. Our results suggest a possible use of GDC as a marker of autoxidative reactions occurring during lens proteins glycation induced by glucose.

  15. Nitro-Oxidative Stress after Neuronal Ischemia Induces Protein Nitrotyrosination and Cell Death

    Directory of Open Access Journals (Sweden)

    Marta Tajes

    2013-01-01

    Full Text Available Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y, a murine glial (BV2, a human endothelial cell line (HUVEC, and in primary cultures of human cerebral myocytes (HC-VSMCs after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.

  16. Protein carbonyl: An oxidative stress marker in gingival crevicular fluid in healthy, gingivitis, and chronic periodontitis subjects

    Directory of Open Access Journals (Sweden)

    Avani R Pradeep

    2013-01-01

    Full Text Available Background: A defined role for reactive oxygen species (ROS in the tissue destruction that characterizes periodontitis has been described. Protein carbonyl (PC is the most widely used biomarker for oxidative damage to proteins, and reflects cellular damage induced by multiple forms of ROS. The purpose of this study is to determine the presence of PC in gingival crevicular fluid (GCF in healthy, gingivitis, and chronic periodontitis (CP subjects and to find an association, if any. Materials and Methods: A total number of 75 subjects (38 males and 37 females were selected based on their clinical parameters into three groups: Group 1 (25 healthy subjects, Group 2 (25 gingivitis subjects, and Group 3 (25 CP subjects. GCF samples were collected to estimate the levels of PC. Results: The PC concentration in GCF was highest in subjects with CP as compared to gingivitis and healthy subjects and a significant association was observed between GCF PC levels and all periodontal parameters. Conclusion: There was an increase in PC levels in GCF as the disease process progressed from healthy to gingivitis and CP, suggesting a role for increased oxidative stress in CP.

  17. Determination of protein-carbonyls and ubiquitin-mediated proteolysis as biomarkers of oxidative-stress in bivalvia and anthozoa

    International Nuclear Information System (INIS)

    Walker, Stephen Thomas

    2002-01-01

    This study describes the investigation of biomarkers of oxidative-stress in the bivalves Mytilus edulis and Dosinia lupinus, together with host and symbiont tissues of the scleractinian Anthozoa Agaricia agaricites. The biomarkers used were assay of total (via spectrophotometry) and individual (via Western blotting; Oxyblot kit) protein-carbonyls (PC=Os) and content of ubiquitin protein conjugates (UPC) via Western blotting (Bivalvia and Anthozoa) and immunohistochemistry (Anthozoa only). Additional assays for Bivalvia were Trolox equivalent antioxidant capacity (TEAC); and post γ-irradiation survival rates. Experimental stressors for Bivalvia were increased seawater temperature, H 2 O 2 and 60 Co γ-radiation (latter two were used in vivo and in vitro). Comparisons of clean and polluted marine sites are included. Stressors used for Anthozoa were increased solar irradiation concomitant with elevated seawater temperature. Results and conclusions were as follows: individual samples showed considerable variation, pooling of samples improved consistency. Controls for both biomarkers had detectable background levels in each phylum, against which relatively small differences were assessed. In M. edulis, no measurable differences in PC=Os could be determined when elevated seawater temperature or dilute H 2 O 2 ( 2 O 2 (30% v/v) produced a small difference. 60 Co γ-radiation produced clearer differences via Oxyblot and spectrophotometric assays. Comparison of four different tissues from the two bivalves found considerable species-specific and tissue-specific differences. Post-irradiation mortality between species was significantly different (<0.001), D. lupinus was more susceptible than M. edulis. TEAC values generally showed a decrease following irradiation (except for digestive gland). UPCs were clearly different between tissues and between species. PC=Os can be detected by DNPH-reactivity/Western blotting assay in host A. agaricites. UPCs can be assayed via Western

  18. Determination of protein-carbonyls and ubiquitin-mediated proteolysis as biomarkers of oxidative-stress in bivalvia and anthozoa

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Stephen Thomas

    2002-07-01

    This study describes the investigation of biomarkers of oxidative-stress in the bivalves Mytilus edulis and Dosinia lupinus, together with host and symbiont tissues of the scleractinian Anthozoa Agaricia agaricites. The biomarkers used were assay of total (via spectrophotometry) and individual (via Western blotting; Oxyblot kit) protein-carbonyls (PC=Os) and content of ubiquitin protein conjugates (UPC) via Western blotting (Bivalvia and Anthozoa) and immunohistochemistry (Anthozoa only). Additional assays for Bivalvia were Trolox equivalent antioxidant capacity (TEAC); and post {gamma}-irradiation survival rates. Experimental stressors for Bivalvia were increased seawater temperature, H{sub 2}O{sub 2} and {sup 60}Co {gamma}-radiation (latter two were used in vivo and in vitro). Comparisons of clean and polluted marine sites are included. Stressors used for Anthozoa were increased solar irradiation concomitant with elevated seawater temperature. Results and conclusions were as follows: individual samples showed considerable variation, pooling of samples improved consistency. Controls for both biomarkers had detectable background levels in each phylum, against which relatively small differences were assessed. In M. edulis, no measurable differences in PC=Os could be determined when elevated seawater temperature or dilute H{sub 2}O{sub 2} (<30% v/v) stressors were used, nor with between-site comparisons. Concentrated H{sub 2}O{sub 2} (30% v/v) produced a small difference. {sup 60}Co {gamma}-radiation produced clearer differences via Oxyblot and spectrophotometric assays. Comparison of four different tissues from the two bivalves found considerable species-specific and tissue-specific differences. Post-irradiation mortality between species was significantly different (<0.001), D. lupinus was more susceptible than M. edulis. TEAC values generally showed a decrease following irradiation (except for digestive gland). UPCs were clearly different between tissues and

  19. Temporal expression profiling of plasma proteins reveals oxidative stress in early stages of Type 1 Diabetes progression

    International Nuclear Information System (INIS)

    Liu, Chih-Wei; Bramer, Lisa; Computational Modeling); Webb-Robertson, Bobbie-Jo; Computational Modeling); Waugh, Kathleen; Rewers, Marian J.; Zhang, Qibin; Biochemistry)

    2017-01-01

    We report that blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n = 11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n = 10). To our knowledge, the current study represents the largest (> 2000 proteins measured) longitudinal expression profiles of human plasma proteome in T1D research. By applying statistical trend analysis on the temporal expression patterns between T1D and controls, and Benjamini-Hochberg procedure for multiple-testing correction, 13 protein groups were regarded as having statistically significant differences during the entire follow-up period. Moreover, 16 protein groups, which play pivotal roles in response to oxidative stress, have consistently abnormal expression trend before seroconversion to islet autoimmunity. Importantly, the expression trends of two key reactive oxygen species-decomposing enzymes, Catalase and Superoxide dismutase were verified independently by ELISA.

  20. Protein oxidation in aquatic foods

    DEFF Research Database (Denmark)

    Baron, Caroline P.

    2014-01-01

    The chapter discusses general considerations about protein oxidation and reviews the mechanisms involved in protein oxidation and consequences of protein oxidation on fish proteins. It presents two case studies, the first deals with protein and lipid oxidation in frozen rainbow trout......, and the second with oxidation in salted herring. The mechanisms responsible for initiation of protein oxidation are unclear, but it is generally accepted that free radical species initiating lipid oxidation can also initiate protein oxidation. The chapter focuses on interaction between protein and lipid...... oxidation. The protein carbonyl group measurement is the widely used method for estimating protein oxidation in foods and has been used in fish muscle. The chapter also talks about the impact of protein oxidation on protein functionality, fish muscle texture, and food nutritional value. Protein oxidation...

  1. Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response

    NARCIS (Netherlands)

    Cino, E.A.; Wong-ekkabut, J.; Karttunen, M.E.J.; Choy, W.-Y.

    2011-01-01

    Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTa) and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2), with a common binding partner, Kelch-like

  2. The p53/HSP70 inhibitor, 2-phenylethynesulfonamide, causes oxidative stress, unfolded protein response and apoptosis in rainbow trout cells

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Fanxing; Tee, Catherine; Liu, Michelle [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Sherry, James P. [Aquatic Contaminants Research Division, Environment Canada, Burlington, Ontario L7R 4A6 (Canada); Dixon, Brian; Duncker, Bernard P. [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada); Bols, Niels C., E-mail: ncbols@uwaterloo.ca [Department of Biology, University of Waterloo, Waterloo, Ontario N2L 3G1 (Canada)

    2014-01-15

    Highlights: •2-Phenylethynesulfonamide (PES) is an inhibitor of p53 and HSP 70 in mammals. •In the fish epithelial cell line, RTgill-W1, PES enhanced ROS generation and was cytotoxic. •RTgill-W1 death was by apoptosis and blocked by the anti-oxidant N-acetylcysteine. •This is the first report linking PES-induced cell death to ROS. •With this background PES should be useful for studying fish cell survival pathways. -- Abstract: The effect of 2-phenylethynesulfonamide (PES), which is a p53 and HSP70 inhibitor in mammalian cells, was studied on the rainbow trout (Oncorhynchus mykiss) gill epithelial cell line, RTgill-W1, in order to evaluate PES as a tool for understanding the cellular survival pathways operating in fish. As judged by three viability assays, fish cells were killed by 24 h exposures to PES, but cell death was blocked by the anti-oxidant N-acetylcysteine (NAC). Cell death had several hallmarks of apoptosis: DNA laddering, nuclear fragmentation, Annexin V staining, mitochondrial membrane potential decline, and caspases activation. Reactive oxygen species (ROS) production peaked in several hours after the addition of PES and before cell death. HSP70 and BiP levels were higher in cultures treated with PES for 24 h, but this was blocked by NAC. As well, PES treatment caused HSP70, BiP and p53 to accumulate in the detergent-insoluble fraction, and this too was prevented by NAC. Of several possible scenarios to explain the results, the following one is the simplest. PES enhances the generation of ROS, possibly by inhibiting the anti-oxidant actions of p53 and HSP70. ER stress arises from the ROS and from PES inhibiting the chaperone activities of HSP70. The ER stress in turn initiates the unfolded protein response (UPR), but this fails to restore ER homeostasis so proteins aggregate and cells die. Despite these multiple actions, PES should be useful for studying fish cellular survival pathways.

  3. Quantification of oxidative stress phenotypes based on high-throughput growth profiling of protein kinase and phosphatase knockouts

    DEFF Research Database (Denmark)

    Altıntaş, Ali; Martini, Jacopo; Mortensen, Uffe Hasbro

    2016-01-01

    Cellular responses to oxidative stress are important for restoring redox balance and ensuring cell survival. Genetic defects in response factors can lead to impaired response to oxidative damage and contribute to disease and aging. In single cell organisms, such as yeasts, the integrity of the ox...

  4. Effects of heat stress and probiotic supplementation on protein functionality and oxidative stability of ground chicken leg meat during display storage

    Science.gov (United States)

    The objective of this study was to evaluate effects of heat stress and probiotic supplementation on protein functionality and oxidative stability of ground chicken leg meat during display storage. Two hundred and forty 1-day-old male chicks (5 bird per pen) were randomly subjected to four treatments...

  5. Oxidative Stress in BPH.

    Science.gov (United States)

    Savas, M; Verit, A; Ciftci, H; Yeni, E; Aktan, E; Topal, U; Erel, O

    2009-01-01

    In the present study, we investigated the relationship between potency of oxidative stress and BPH and this may assist to contribute to the realistic explanation of the ethiopathogenesis of BPH. Seventy four newly diagnosed men with BPH (mean age: 54+/-11.2), who had not undergone any previous treatment for BPH, and 62 healthy volunteers (mean age: 55+/-14) were enrolled in the present study. To determine the antioxidative status of plasma, total antioxidant capacity (TAC) was calculated, and to determine the oxidative status of plasma (TOS) total peroxide levels were measured. The ratio of TAC to total peroxide was accepted as an indicator of oxidative stress (OSI). Data are presented as mean SD +/- unless specified. Student t-test and correlation analyses were used to evaluate the statistical significance differences in the median values recorded for all parameters between BPH and control group. Plasma TAC TOS were found in patients and controls (1.70 +/- 0.32, 1.68 +/- 0.19 micromol Trolox Equiv./L), (12.48 +/- 1.98, 12.40 +/- 1.14 micromol / L) respectively. OSI was calculated as 7.57 +/- 1.91, 7.48 +/- 1.33, respectively. Plasma TAC, TOS and OSI levels were not found to be significantly difference between patients and control subjects (p>0.05, p>0.05, p>0.05). The present study has shown that there were not relationship between potency of oxidative stress and BPH. Further well designed studies should be planned to find out whether the oxidative stress-related parameters play role in BPH as an interesting pathology in regard of the etiopathogenesis.

  6. Markers of protein oxidation

    DEFF Research Database (Denmark)

    Headlam, Henrietta A; Davies, Michael Jonathan

    2004-01-01

    Exposure of proteins to radicals in the presence of O2 gives both side-chain oxidation and backbone fragmentation. These processes can be interrelated, with initial side-chain oxidation giving rise to backbone damage via transfer reactions. We have shown previously that alkoxyl radicals formed...... of this process depends on the extent of oxidation at C-3 compared with other sites. HO*, generated by gamma radiolysis, gave the highest total carbonyl yield, with protein-bound carbonyls predominating over released. In contrast, metal ion/H2O2 systems, gave more released than bound carbonyls, with this ratio...... modulated by EDTA. This is ascribed to metal ion-protein interactions affecting the sites of initial oxidation. Hypochlorous acid gave low concentrations of released carbonyls, but high yields of protein-bound material. The peroxyl radical generator 2,2'-azobis(2-amidinopropane) hydrochloride...

  7. (−)-EPICATECHIN IMPROVES MITOCHONDRIAL RELATED PROTEIN LEVELS AND AMELIORATES OXIDATIVE STRESS IN DYSTROPHIC DELTA SARCOGLYCAN NULL MOUSE STRIATED MUSCLE

    Science.gov (United States)

    Ramirez-Sanchez, Israel; De los Santos, Sergio; Gonzalez-Basurto, Silvia; Canto, Patricia; Mendoza-Lorenzo, Patricia; Palma-Flores, Carlos; Ceballos-Reyes, Guillermo; Villarreal, Francisco; Zentella-Dehesa, Alejandro; Coral-Vazquez, Ramon

    2014-01-01

    Muscular dystrophies (MD) are a group of heterogeneous genetic disorders characterized by progressive striated muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for disease pathogenesis remains unclear. The presence of oxidative stress (OS) is known to contribute to the pathophysiology and severity of the MD. Mitochondrial dysfunction is observed in MD and likely represents an important determinant of increased OS. Experimental antioxidant therapies have been implemented with the aim of protecting against disease progression, but results from clinical trials have been disappointing. In this study, we explored the capacity of the cacao flavonoid (−)-epicatechin (Epi) to mitigate OS by acting as a positive regulator of mitochondrial structure/function endpoints and redox balance control systems in skeletal and cardiac muscles of dystrophic, δ-sarcoglycan (δ-SG) null mice. Wild type or δ-SG null 2.5 month old male mice were treated via oral gavage with either water (control animals) or Epi (1 mg/kg, twice/day) for 2 weeks. Results evidence a significant normalization of total protein carbonylation, recovery of reduced/oxidized glutathione (GSH/GSSG ratio) and enhanced superoxide dismutase 2, catalase and citrate synthase activities with Epi treatment. These effects were accompanied by increases in protein levels for thiolredoxin, glutathione peroxidase, superoxide dismutase 2, catalase and mitochondrial endpoints. Furthermore, we evidence decreases in heart and skeletal muscle fibrosis, accompanied with an improvement in skeletal muscle function with treatment. These results warrant the further investigation of Epi as a potential therapeutic agent to mitigate MD associated muscle degeneration. PMID:25284161

  8. Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease.

    Science.gov (United States)

    Uddin, Md Giash; Hossain, Mohammad Salim; Rahman, Md Atiqur; Uddin, A H M Mazbah; Bhuiyan, Md Shafiullah

    2017-08-01

    Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson's correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p CLD patients than in control subjects. The antioxidant vitamin C (p CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.

  9. Nutrients and Oxidative Stress: Friend or Foe?

    Science.gov (United States)

    Tan, Bee Ling; Norhaizan, Mohd Esa; Liew, Winnie-Pui-Pui

    2018-01-01

    There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF- κ B-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.

  10. Nutrients and Oxidative Stress: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Bee Ling Tan

    2018-01-01

    Full Text Available There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-κB- mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD, and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs. Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.

  11. Protein oxidation and peroxidation

    DEFF Research Database (Denmark)

    Davies, Michael Jonathan

    2016-01-01

    Proteins are major targets for radicals and two-electron oxidants in biological systems due to their abundance and high rate constants for reaction. With highly reactive radicals damage occurs at multiple side-chain and backbone sites. Less reactive species show greater selectivity with regard...... to the residues targeted and their spatial location. Modification can result in increased side-chain hydrophilicity, side-chain and backbone fragmentation, aggregation via covalent cross-linking or hydrophobic interactions, protein unfolding and altered conformation, altered interactions with biological partners...... and modified turnover. In the presence of O2, high yields of peroxyl radicals and peroxides (protein peroxidation) are formed; the latter account for up to 70% of the initial oxidant flux. Protein peroxides can oxidize both proteins and other targets. One-electron reduction results in additional radicals...

  12. Increased plasma levels of advanced oxidation protein products (AOPP) as a marker for oxidative stress in patients with active ulcerative colitis.

    Science.gov (United States)

    Alagozlu, Hakan; Gorgul, Ahmet; Bilgihan, Ayse; Tuncer, Candan; Unal, Selahattin

    2013-02-01

    After NADPH oxidase mediated radical formation, hypochloric acid (HOCl) is formed when Cl is used as a substrate by the myeloperoxidase enzyme. Myeloperoxidase is secreted from H2O2 activated leukocytes with polymorphic nuclei. The generation of HOCl also causes the formation of advanced oxidation protein products (AOPP) through damage to normal tissue and protein oxidation. AOPP has been identified as a marker of inflammation in many diseases. However, AOPP has not been investigated in ulcerative colitis. As a result of mucosal inflammation in ulcerative colitis, oxidative stress can occur. We aimed to determine whether plasma AOPP and oxidative stress markers are detectable in active ulcerative colitis. The patient group consisted of 59 patients who were diagnosed with ulcerative colitis in the clinic by histology and endoscopy. The patients were hospitalised and treated in the Gastroenterology Department of Gazi University Medical Facility. The 59 patients were separated into active and inactive groups according to the endoscopic activation index (EAI). Group I consisted of 33 active ulcerative colitis patients, Group II consisted of 26 inactive ulcerative colitis patients and Group III consisted of healthy control subjects. The disease activity of these patients were measured using the Rachmilewitz EAI based on rectosigmoidoscopic or colonoscopic findings. Patients with EAI scores greater than 4 were scored as having active disease (Group I). Patients with EAI0.05). The EAI value was 8.84±0.31 in Group I and 2.76±0.08 in Group II. There were statistically significant differences for EAI between groups (P<0.05). The correlation between AOPP and EAI in all patients with ulcerative colitis were statistically significant (P<0.05, r=0.61). The regression model in this correlation was statistically significant (y=49.68+10.75x, P<0.05). Based on our results, we suggest that AOPP could be used as a non invasive activation marker for ulcerative colitis patients

  13. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Directory of Open Access Journals (Sweden)

    Qi Wang

    Full Text Available BACKGROUND: To investigate if microRNAs (miRNAs play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. METHODS: We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+ current. RESULTS: H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2, with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. CONCLUSIONS: Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  14. MiR-17-5p impairs trafficking of H-ERG K+ channel protein by targeting multiple er stress-related chaperones during chronic oxidative stress.

    Science.gov (United States)

    Wang, Qi; Hu, Weina; Lei, Mingming; Wang, Yong; Yan, Bing; Liu, Jun; Zhang, Ren; Jin, Yuanzhe

    2013-01-01

    To investigate if microRNAs (miRNAs) play a role in regulating h-ERG trafficking in the setting of chronic oxidative stress as a common deleterious factor for many cardiac disorders. We treated neonatal rat ventricular myocytes and HEK293 cells with stable expression of h-ERG with H2O2 for 12 h and 48 h. Expression of miR-17-5p seed miRNAs was quantified by real-time RT-PCR. Protein levels of chaperones and h-ERG trafficking were measured by Western blot analysis. Luciferase reporter gene assay was used to study miRNA and target interactions. Whole-cell patch-clamp techniques were employed to record h-ERG K(+) current. H-ERG trafficking was impaired by H2O2 after 48 h treatment, accompanied by reciprocal changes of expression between miR-17-5p seed miRNAs and several chaperones (Hsp70, Hsc70, CANX, and Golga2), with the former upregulated and the latter downregulated. We established these chaperones as targets for miR-17-5p. Application miR-17-5p inhibitor rescued H2O2-induced impairment of h-ERG trafficking. Upregulation of endogenous by H2O2 or forced miR-17-5p expression either reduced h-ERG current. Sequestration of AP1 by its decoy molecule eliminated the upregulation of miR-17-5p, and ameliorated impairment of h-ERG trafficking. Collectively, deregulation of the miR-17-5p seed family miRNAs can cause severe impairment of h-ERG trafficking through targeting multiple ER stress-related chaperones, and activation of AP1 likely accounts for the deleterious upregulation of these miRNAs, in the setting of prolonged duration of oxidative stress. These findings revealed the role of miRNAs in h-ERG trafficking, which may contribute to the cardiac electrical disturbances associated with oxidative stress.

  15. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

    Takaaki Tomofuji; Koichiro Irie; Toshihiro Sanbe; Tetsuji Azuma; Daisuke Ekuni; Naofumi Tamaki; Tatsuo Yamamoto; Manabu Morita

    2009-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress). Such oxidation may be detrimental to systemic health. Fo...

  16. Bactericidal peptidoglycan recognition protein induces oxidative stress in Escherichia coli through a block in respiratory chain and increase in central carbon catabolism.

    Science.gov (United States)

    Kashyap, Des R; Kuzma, Marcin; Kowalczyk, Dominik A; Gupta, Dipika; Dziarski, Roman

    2017-09-01

    Mammalian Peptidoglycan Recognition Proteins (PGRPs) kill both Gram-positive and Gram-negative bacteria through simultaneous induction of oxidative, thiol and metal stress responses in bacteria. However, metabolic pathways through which PGRPs induce these bactericidal stress responses are unknown. We screened Keio collection of Escherichia coli deletion mutants and revealed that deleting genes for respiratory chain flavoproteins or for tricarboxylic acid (TCA) cycle resulted in increased resistance of E. coli to PGRP killing. PGRP-induced killing depended on the production of hydrogen peroxide, which required increased supply of NADH for respiratory chain oxidoreductases from central carbon catabolism (glycolysis and TCA cycle), and was controlled by cAMP-Crp. Bactericidal PGRP induced a rapid decrease in respiration, which suggested that the main source of increased production of hydrogen peroxide was a block in respiratory chain and diversion of electrons from NADH oxidoreductases to oxygen. CpxRA two-component system was a negative regulator of PGRP-induced oxidative stress. By contrast, PGRP-induced thiol stress (depletion of thiols) and metal stress (increase in intracellular free Zn 2+ through influx of extracellular Zn 2+ ) were mostly independent of oxidative stress. Thus, manipulating pathways that induce oxidative, thiol and metal stress in bacteria could be a useful strategy to design new approaches to antibacterial therapy. © 2017 John Wiley & Sons Ltd.

  17. Taurine: A Potential Ergogenic Aid for Preventing Muscle Damage and Protein Catabolism and Decreasing Oxidative Stress Produced by Endurance Exercise

    Directory of Open Access Journals (Sweden)

    Flávia G. De Carvalho

    2017-09-01

    Full Text Available The aim of this study was to evaluate the effects of taurine and chocolate milk supplementation on oxidative stress and protein metabolism markers, and aerobic parameters in triathletes.Methods: A double-blind, crossover study was conducted with 10 male triathletes, aged 30.9 ± 1.3 year, height 1.79 ± 0.01 m and body weight 77.45 ± 2.4 kg. Three grams of taurine and 400 ml of chocolate milk (TAUchoc, or a placebo (chocolate milk (CHOC was ingested post exercise for 8 weeks. Oxidative stress marker levels, and 24 h urinary nitrogen, creatinine, and urea excretion were measured before and after 8 weeks of training and supplementation with TAUchoc or CHOC. A maximal incremental running test on a treadmill was performed in order to evaluate aerobic parameters: Vmax, heart rate (HR and rate of perceived exertion (RPE.Results: TAUchoc treatment during the 8 weeks resulted in increased taurine plasma levels (PRE 201.32 ± 29.03 μmol/L and POST 234.36 ± 35.51 μmol/L, p = 0.01, decreased malondialdehyde levels (19.4%, p = 0.03 and urinary nitrogen excretion (−33%, p = 0.03, and promoted positive nitrogen balance (p = 0.01. There were no changes in reduced glutathione (TAUchoc PRE 0.72 ± 0.08 mmol/L and POST 0.83 ± 0.08 mmol/L; CHOC PRE 0.69 ± 0.08 mmol/L and POST 0.81 ± 0.06 mmol/L, vitamin E plasma levels (TAUchoc PRE 33.99 ± 2.52 μmol/L and 35.95 ± 2.80 μmol/L and CHOC PRE 31.48 ± 2.12 μmol/L and POST 33.77 ± 3.64 μmol/L, or aerobic parameters, which were obtained in the last phase of the maximal incremental running test (Vmax TAUchoc PRE 13 ± 1.4 km/h and POST 13.22 ± 1.34 km/h; CHOC PRE 13.11 ± 2.34 km/h and POST 13.11 ± 2.72 km/h, the heart rate values were TAUchoc PRE 181.89 ± 24.18 bpm and POST 168.89 ± 46.56 bpm; CHOC PRE 181.56 ± 2.14 bpm and POST 179.78 ± 3.4 bpm, and the RPE were TAUchoc PRE 8.33 ± 2.4 AU and POST 9.1 ± 2.1 AU; CHOC PRE 8.11 ± 4.94 AU and POST 8.78 ± 2.78 AU.Conclusion: Taurine supplementation

  18. Oxidative Stress in Myopia

    Directory of Open Access Journals (Sweden)

    Bosch-Morell Francisco

    2015-01-01

    Full Text Available Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem.

  19. Enterococcus faecalis zinc-responsive proteins mediate bacterial defence against zinc overload, lysozyme and oxidative stress

    NARCIS (Netherlands)

    C. Abrantes, Marta; Kok, Jan; de Fatima Silva Lopes, Maria

    2014-01-01

    Two Enterococcus faecalis genes encoding the P-type ATPase EF1400 and the putative SapB protein EF0759 were previously shown to be strongly upregulated in the presence of high concentrations of zinc. In the present work, we showed that a Zn(2+)-responsive DNA-binding motif (zim) is present in the

  20. Aging and oxidative stress reduce the response of human articular chondrocytes to insulin-like growth factor 1 and osteogenic protein 1.

    Science.gov (United States)

    Loeser, Richard F; Gandhi, Uma; Long, David L; Yin, Weihong; Chubinskaya, Susan

    2014-08-01

    To determine the effects of aging and oxidative stress on the response of human articular chondrocytes to insulin-like growth factor 1 (IGF-1) and osteogenic protein 1 (OP-1). Chondrocytes isolated from normal articular cartilage obtained from tissue donors were cultured in alginate beads or monolayer. Cells were stimulated with 50-100 ng/ml of IGF-1, OP-1, or both. Oxidative stress was induced using tert-butyl hydroperoxide. Sulfate incorporation was used to measure proteoglycan synthesis, and immunoblotting of cell lysates was performed to analyze cell signaling. Confocal microscopy was performed to measure nuclear translocation of Smad4. Chondrocytes isolated from the articular cartilage of tissue donors ranging in age from 24 years to 81 years demonstrated an age-related decline in proteoglycan synthesis stimulated by IGF-1 and IGF-1 plus OP-1. Induction of oxidative stress inhibited both IGF-1- and OP-1-stimulated proteoglycan synthesis. Signaling studies showed that oxidative stress inhibited IGF-1-stimulated Akt phosphorylation while increasing phosphorylation of ERK, and that these effects were greater in cells from older donors. Oxidative stress also increased p38 phosphorylation, which resulted in phosphorylation of Smad1 at the Ser(206) inhibitory site and reduced nuclear accumulation of Smad1. Oxidative stress also modestly reduced OP-1-stimulated nuclear translocation of Smad4. These results demonstrate an age-related reduction in the response of human chondrocytes to IGF-1 and OP-1, which are 2 important anabolic factors in cartilage, and suggest that oxidative stress may be a contributing factor by altering IGF-1 and OP-1 signaling. Copyright © 2014 by the American College of Rheumatology.

  1. Is the Oxidative Stress Really a Disease?

    Directory of Open Access Journals (Sweden)

    Fogarasi Erzsébet

    2016-03-01

    Full Text Available Oxidative stress is an imbalance between free radicals or other reactive species and the antioxidant activity of the organism. Oxidative stress can induce several illnesses such as cardiovascular disease, neurodegenerative disorders, diabetes, cancer, Alzheimer and Parkinson. The biomarkers of oxidative stress are used to test oxidative injury of biomolecules. The indicators of lipid peroxidation (malondialdehyde, 4-hydroxy- 2-nonenal, 2-propenal, isoprostanes, of protein oxidation (carbonylated proteins, tyrosine derivatives, of oxidative damage of DNA, and other biomarkers (glutathione level, metallothioneins, myeloperoxidase activity are the most used oxidative stress markers. Diseases caused by oxidative stress can be prevented with antioxidants. In human body are several enzymes with antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and spin traps. Antioxidants are synthetized in the organism (glutathione or arrive in the body by nutrition (ascorbic acid, vitamin E, carotenoids, flavonoids, resveratrol, xanthones. Different therapeutic strategies to reduce oxidative stress with the use of synthetic molecules such as nitrone-based antioxidants (phenyl-α-tert-butyl-nitrone (PBN, 2,4-disulphophenyl- N-tert-butylnitrone (NXY-059, stilbazulenyl nitrone (STAZN, which scavenge a wide variety of free radical species, increase endogenous antioxidant levels and inhibits free radical generation are also tested in animal models.

  2. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Chiou, Shyh-Shin, E-mail: chiouss@kmu.edu.tw [Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Department of Pediatrics, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China); Wang, Sophie Sheng-Wen; Wu, Deng-Chyang [Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Lin, Ying-Chu [School of Dentistry, College of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Kao, Li-Pin [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China)

    2013-07-26

    We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  3. A novel mTOR activating protein protects dopamine neurons against oxidative stress by repressing autophagy related cell death.

    Science.gov (United States)

    Choi, Kyou-Chan; Kim, Shin-Hee; Ha, Ji-Young; Kim, Sang-Tae; Son, Jin H

    2010-01-01

    Our previous microarray analysis identified a neuroprotective protein Oxi-alpha, that was down-regulated during oxidative stress (OS)-induced cell death in dopamine neurons [Neurochem. Res. (2004) vol. 29, pp. 1223]. Here we find that the phylogenetically conserved Oxi-alpha protects against OS by a novel mechanism: activation of the mammalian target of rapamycin (mTOR) kinase and subsequent repression of autophagic vacuole accumulation and cell death. To the best of our knowledge, Oxi-alpha is the first molecule discovered in dopamine neurons, which activates mTOR kinase. Indeed, the down-regulation of Oxi-alpha by OS suppresses the activation of mTOR kinase. The pathogenic effect of down-regulated Oxi-alpha was confirmed by gene-specific knockdown experiment, which resulted in not only the repression of mTOR kinase and the subsequent phosphorylation of p70 S6 kinase and 4E-BP1, but also enhanced susceptibility to OS. In accordance with these observations, treatment with rapamycin, an mTOR inhibitor and autophagy inducer, potentiated OS-induced cell death, while similar treatment with an autophagy inhibitor, 3-methyladenine protected the dopamine cells. Our findings present evidence for the presence of a novel class of molecule involved in autophagic cell death triggered by OS in dopamine neurons.

  4. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Directory of Open Access Journals (Sweden)

    Naoto Yamaguchi

    2013-07-01

    Full Text Available We report here that the Jun dimerization protein 2 (JDP2 plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2 and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS. JDP2 associates with Nrf2 and MafK (Nrf2-MafK to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  5. Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress.

    Science.gov (United States)

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain.

  6. A Novel Hemp Seed Meal Protein Hydrolysate Reduces Oxidative Stress Factors in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Abraham T. Girgih

    2014-12-01

    Full Text Available This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH in spontaneously hypertensive rats (SHR. Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old SHRs were divided into three groups (8 rats/group and fed diets that contained 0.0%, 0.5% or 1.0% (w/w HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC and superoxide dismutase (SOD, catalase (CAT and total peroxides (TPx levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05 increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity.

  7. Preconditioning with Azadirachta indica ameliorates cardiorenal dysfunction through reduction in oxidative stress and extracellular signal regulated protein kinase signalling

    Directory of Open Access Journals (Sweden)

    Temidayo Olutayo Omóbòwálé

    2016-10-01

    Conclusions: Together, A. indica and vitamin C prevented IRI-induced cardiorenal dysfunction via reduction in oxidative stress, improvement in antioxidant defence system and increase in the ERK1/2 expressions. Therefore, A. indica can be a useful chemopreventive agent in the prevention and treatment of conditions associated with intestinal ischaemia-reperfusion injury.

  8. Oxidative stress adaptation with acute, chronic, and repeated stress.

    Science.gov (United States)

    Pickering, Andrew M; Vojtovich, Lesya; Tower, John; A Davies, Kelvin J

    2013-02-01

    Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. A Molecular Web: Endoplasmic Reticulum Stress, Inflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Namrata eChaudhari

    2014-07-01

    Full Text Available Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded protein response (UPR through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS. Toxic accumulation of ROS within ER and mitochondria disturb fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways has been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease and others. In this review we have discussed the UPR signaling pathways, and networking between ER stress induced inflammatory pathways, oxidative stress and mitochondrial signaling events which further induce or exacerbate ER stress.

  10. Etiologies of sperm oxidative stress

    Directory of Open Access Journals (Sweden)

    Parvin Sabeti

    2016-04-01

    Full Text Available Sperm is particularly susceptible to reactive oxygen species (ROS during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions

  11. Effects of heat stress and probiotic supplementation on protein functionality and oxidative stability of ground chicken leg meat during display storage.

    Science.gov (United States)

    Kim, Hyun-Wook; Kim, Ji-Han; Yan, Feifei; Cheng, Heng-Wei; Brad Kim, Yuan H

    2017-12-01

    The present study aimed to evaluate the effects of heat stress and probiotic supplementation on protein functionality and oxidative stability of ground chicken leg during display storage. Two hundred and forty, 1-day-old male chicks (5 birds per pen) were subjected to four treatments in a 2 (thermoneutral condition at 21 °C and cyclic heat stress at 32-21-32 °C for 10 h day -1 ) × 2 (regular diet with 0 or 0.25 g kg -1 Bacillus subtilis) factorial design. Chickens were harvested at day 46, and pairs of whole legs were collected at 1 day postmortem. The chicken legs were deboned, ground, tray-packaged with oxygen-permeable film, and displayed for 3 days. Heat stress and probiotic supplementation had no impact on pH, water-holding capacity, color, protein functionality, lipid lipolysis and lipid/protein oxidation stability (P > 0.05). Display storage increased the pH and lipid oxidation of ground chicken legs (P chicken leg meat. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  12. Oxidative Stress Markers and C-Reactive Protein Are Related to Severity of Heart Failure in Patients with Dilated Cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Celina Wojciechowska

    2014-01-01

    Full Text Available Background. The aim of study was to determine relationships between functional capacity (NYHA class, left ventricle ejection fraction (LVEF, hemodynamic parameters, and biomarkers of redox state and inflammation in patients with dilated cardiomyopathy (DCM. Methods. DCM patients (n=109, aged 45.97±10.82 years, NYHA class IIV, and LVEF 2.94±7.1% were studied. Controls comprised age-matched healthy volunteers (n=28. Echocardiography and right heart catheterization were performed. Serum activities of superoxide dismutase isoenzymes (MnSOD and CuZnSOD, concentrations of uric acid (UA, malondialdehyde (MDA, and C-reactive protein (hs-CRP were measured. Results. MnSOD, UA, hs-CRP, and MDA were significantly higher in DCM patients compared to controls. Except MDA concentration, above parameters were higher in patients in III-IV NYHA class or with lower LVEF. hsCRP correlated with of MnSOD (P<0.05 and CuZnSOD activity (P<0.01. Both isoenzymes positively correlated with mPAP and pulmonary capillary wedge pressure (MnSOD, resp., P<0.01 and P<0.05 and CuZnSOD P<0.05; P<0.05. UA positively correlated with MnSOD (P<0.05, mPAP (P<0.05, and PVRI (P<0.05. The negative correlation between LVEF and UA (P<0.01 was detected. Conclusion. There are relationships among the severity of symptoms of heart failure, echocardiographic hemodynamic parameters, oxidative stress, and inflammatory activation. Increased MnSOD activity indicates the mitochondrial source of ROS in patients with advanced heart failure.

  13. Nutrigenetics and modulation of oxidative stress.

    Science.gov (United States)

    Da Costa, Laura A; Badawi, Alaa; El-Sohemy, Ahmed

    2012-01-01

    Oxidative stress develops as a result of an imbalance between the production and accumulation of reactive species and the body's ability to manage them using exogenous and endogenous antioxidants. Exogenous antioxidants obtained from the diet, including vitamin C, vitamin E, and carotenoids, have important roles in preventing and reducing oxidative stress. Individual genetic variation affecting proteins involved in the uptake, utilization and metabolism of these antioxidants may alter their serum levels, exposure to target cells and subsequent contribution to the extent of oxidative stress. Endogenous antioxidants include the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, paraoxanase, and glutathione S-transferase. These enzymes metabolize reactive species and their by-products, reducing oxidative stress. Variation in the genes coding these enzymes may impact their enzymatic antioxidant activity and, thus, the levels of reactive species, oxidative stress, and risk of disease development. Oxidative stress may contribute to the development of chronic disease, including osteoporosis, type 2 diabetes, neurodegenerative diseases, cardiovascular disease, and cancer. Indeed, polymorphisms in most of the genes that code for antioxidant enzymes have been associated with several types of cancer, although inconsistent findings between studies have been reported. These inconsistencies may, in part, be explained by interactions with the environment, such as modification by diet. In this review, we highlight some of the recent studies in the field of nutrigenetics, which have examined interactions between diet, genetic variation in antioxidant enzymes, and oxidative stress. Copyright © 2012 S. Karger AG, Basel.

  14. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

    Full Text Available Reactive oxygen species (ROS are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress. Such oxidation may be detrimental to systemic health. For instance, previous animal studies suggested that experimental periodontitis induces oxidative damage of the liver and descending aorta by increasing circulating oxidative stress. In addition, it has been revealed that clinical parameters in chronic periodontitis patients showed a significant improvement 2 months after periodontal treatment, which was accompanied by a significant reduction of reactive oxygen metabolites in plasma. Improvement of periodontitis by periodontal treatment could reduce the occurrence of circulating oxidative stress. Furthermore, recent studies indicate that the increase in circulating oxidative stress following diabetes mellitus and inappropriate nutrition damages periodontal tissues. In such cases, therapeutic approaches to systemic oxidative stress might be necessary to improve periodontal health.

  15. Biomarkers of oxidative stress study V: ozone exposure of rats and its effect on lipids, proteins, and DNA in plasma and urine.

    Science.gov (United States)

    Kadiiska, Maria B; Basu, Samar; Brot, Nathan; Cooper, Christopher; Saari Csallany, A; Davies, Michael J; George, Magdalene M; Murray, Dennis M; Jackson Roberts, L; Shigenaga, Mark K; Sohal, Rajindar S; Stocker, Roland; Van Thiel, David H; Wiswedel, Ingrid; Hatch, Gary E; Mason, Ronald P

    2013-08-01

    Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins, and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsistent results often reported in the literature might be due to the limitations of the available methods for measuring the various types of oxidative products. The time- and dose-dependent effects of ozone exposure on rat plasma lipid hydroperoxides, malondialdehyde, F2-isoprostanes, protein carbonyls, methionine oxidation, and tyrosine- and phenylalanine oxidation products, as well as urinary malondialdehyde and F2-isoprostanes were investigated with various techniques. The criterion used to recognize a marker in the model of ozone exposure was that a significant effect could be identified and measured in a biological fluid seen at both doses at more than one time point. No statistically significant differences between the experimental and the control groups at either ozone dose and time point studied could be identified in this study. Tissue samples were not included. Despite all the work accomplished in the BOSS study of ozone, no available product of oxidation in biological fluid has yet met the required criteria of being a biomarker. The current negative findings as a consequence of ozone exposure are of great importance, because they document that in complex systems, as the present in vivo experiment, the assays used may not provide meaningful data of ozone oxidation, especially in human studies. Published by Elsevier Inc.

  16. Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+

    DEFF Research Database (Denmark)

    Venco, Paola; Bonora, Massimo; Giorgi, Carlotta

    2015-01-01

    19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER) and MAM (Mitochondria Associated Membrane), while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein...... was able to relocate to the cytosol. On the contrary, mutant isoforms were not able to respond to oxidative stress. High mitochondrial calcium concentration and increased H2O2 induced apoptosis were found in fibroblasts derived from one patient as compared to controls. C19orf12 protein is a 17 k...... to rearrange in a structural domain, which is homologs to the N-terminal regulatory domain of the magnesium transporter MgtE, suggesting that C19orf12 may act as a regulatory protein for human MgtE transporters. The mutations here described affect respectively one glycine residue of the glycine zipper motifs...

  17. Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

    Science.gov (United States)

    Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

    2015-11-01

    The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

  18. Phosphorylation of Icariin Can Alleviate the Oxidative Stress Caused by the Duck Hepatitis Virus A through Mitogen-Activated Protein Kinases Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Wen Xiong

    2017-09-01

    Full Text Available The duck virus hepatitis (DVH caused by the duck hepatitis virus A (DHAV has produced extensive economic losses to the duck industry. The currently licensed commercial vaccine has shown some defects and does not completely prevent the DVH. Accordingly, a new alternative treatment for this disease is urgently needed. Previous studies have shown that icariin (ICA and its phosphorylated derivative (pICA possessed good anti-DHAV effects through direct and indirect antiviral pathways, such as antioxidative stress. But the antioxidant activity showed some differences between ICA and pICA. The aim of this study is to prove that ICA and pICA attenuate oxidative stress caused by DHAV in vitro and in vivo, and to investigate their mechanism of action to explain their differences in antioxidant activities. In vivo, the dynamic deaths, oxidative evaluation indexes and hepatic pathological change scores were detected. When was added the hinokitiol which showed the pro-oxidative effect as an intervention method, pICA still possessed more treatment effect than ICA. The strong correlation between mortality and oxidative stress proves that ICA and pICA alleviate oxidative stress caused by DHAV. This was also demonstrated by the addition of hydrogen peroxide (H2O2 as an intervention method in vitro. pICA can be more effective than ICA to improve duck embryonic hepatocytes (DEHs viability and reduce the virulence of DHAV. The strong correlation between TCID50 and oxidative stress demonstrates that ICA and pICA can achieve anti-DHAV effects by inhibiting oxidative stress. In addition, the superoxide dismutase (SOD and glutathione peroxidase (GSH-Px of ICA and pICA showed significant difference. pICA could significantly inhibit the phosphorylation of p38, extra cellular signal regulated Kinase (ERK 1/2 and c-Jun N-terminal kinase (JNK, which were related to mitogen-activated protein kinases (MAPKs signaling pathways. Ultimately, compared to ICA, pICA exhibited more

  19. BRCA1 and Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Yong Weon; Kang, Hyo Jin [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Bae, Insoo, E-mail: ib42@georgetown.edu [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States)

    2014-04-03

    The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS) is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1’s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers.

  20. Oxidative Stress and Antioxidant System in Periodontitis

    Science.gov (United States)

    Wang, Yue; Andrukhov, Oleh; Rausch-Fan, Xiaohui

    2017-01-01

    Periodontitis is a common inflammatory disease, which is initiated by bacterial infection and subsequently progressed by aberrant host response. It can result in the destruction of teeth supporting tissues and have an influence on systemic health. When periodontitis occurs, reactive oxygen species, which are overproduced mostly by hyperactive neutrophils, could not be balanced by antioxidant defense system and cause tissues damage. This is characterized by increased metabolites of lipid peroxidation, DNA damage and protein damage. Local and systemic activities of antioxidants can also be influenced by periodontitis. Total antioxidant capacity, total oxidant status and oxidative stress index have been used to evaluate the oxidative stress associated with periodontitis. Studies have confirmed that inflammatory response in periodontitis is associated with an increased local and systemic oxidative stress and compromised antioxidant capacity. Our review focuses on increased oxidative stress in periodontal disease, specifically, on the relationship between the local and systemic biomarkers of oxidative stress and periodontitis and their association with the pathogenesis of periodontitis. Also, the relationship between periodontitis and systemic inflammation, and the effects of periodontal therapy on oxidative stress parameters will be discussed. PMID:29180965

  1. The effect and influence of lumen holmium laser lithotripsy on serum oxidative stress proteins and inflammatory factors of ureteral calculi patients

    Directory of Open Access Journals (Sweden)

    Fan Zhang

    2016-09-01

    Full Text Available Objective: To investigate the effect and influence of lumen holmium laser lithotripsy on treating serum oxidative stress proteins and inflammatory factors of patients with ureteral calculi. Methods: A total of 120 cases of patients with ureteral calculi treated in our hospital from May 2010 to Nov 2014 were enrolled in this research for an analysis study. The effect and influence on serum oxidative stress proteins and inflammatory factors of lumen holmium laser lithotripsy on ureteral calculi patients were assayed. Then 120 cases of healthy subjects in our hospital at the same period were taken as control. Results: Among the 120 cases of ureteral calculi patients, 113 cases of patients showed successful operation, with a success rate of 94.2%. The average calculi-discharged time was (28.4 ± 11.2 d and the average operation time was (58.9 ± 10.7 min, while the postoperative hospital stay is (3.8 ± 1.2 d. The results also showed that the levels of NOX1. NOX3, NOX4 and NOX5, and levels of interleukin-2 (IL-2, IL-6, IL-10 and TNF-α of patients with ureteral calculi were significantly higher, compared with the control group, and these parameters were normalized greatly after operation with that the levels of them were significantly different from those before operation. Conclusion: Lumen holmium laser lithotripsy exerts a significant effect on ureteral calculi patients and the oxidative stress parameters and inflammatory factor were normalized greatly.

  2. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Asieh Hosseini

    2013-01-01

    Full Text Available Diabetic neuropathy (DN is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin, aldose reductase inhibitors (fidarestat, epalrestat, ranirestat, advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine, the hexosamine pathway inhibitor (benfotiamine, inhibitor of poly ADP-ribose polymerase (nicotinamide, and angiotensin-converting enzyme inhibitor (trandolapril. The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.

  3. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Science.gov (United States)

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

    Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

  4. Schizosaccharomyces pombe Homologs of Human DJ-1 Are Stationary Phase-Associated Proteins That Are Involved in Autophagy and Oxidative Stress Resistance.

    Directory of Open Access Journals (Sweden)

    Yang Su

    Full Text Available The Parkinson's disease protein DJ-1 is involved in various cellular functions including detoxification of dicarbonyl compounds, autophagy and oxidative stress response. DJ-1 homologs are widely found in both prokaryotes and eukaryotes, constituting a superfamily of proteins that appear to be involved in stress response. Schizosaccharomyces pombe contains six DJ-1 homologs, designated Hsp3101-Hsp3105 and Sdj1 (previously named SpDJ-1. Here we show that deletion of any one of these six genes somehow affects autophagy during prolonged stationary phase. Furthermore, deletions of each of these DJ-1 homologs result in reduced stationary phase survival. Deletion of sdj1 also increases the sensitivity of stationary-phase cells to oxidative stress induced by hydrogen peroxide (H2O2 whereas overexpression of sdj1 has the opposite effect. Consistent with their role in stationary phase, expression of hsp3101, hsp3102, hsp3105 and sdj1, and to a lesser extent hsp3103 and hsp3104, is increased in stationary phase. The induction of hsp3101, hsp3102, hsp3105 and sdj1 involves the Sty1-regulated transcription factor Atf1 but not the transcription factor Pap1. Our results firmly establish that S. pombe homologs of DJ-1 are stationary-phase associated proteins and are likely involved in autophagy and antioxidant defense in stationary phase of S. pombe cells.

  5. Effects of Metformin on Tissue Oxidative and Dicarbonyl Stress in Transgenic Spontaneously Hypertensive Rats Expressing Human C-Reactive Protein

    Czech Academy of Sciences Publication Activity Database

    Malínská, H.; Oliyarnyk, O.; Škop, V.; Šilhavý, Jan; Landa, Vladimír; Zídek, Václav; Mlejnek, Petr; Šimáková, Miroslava; Strnad, Hynek; Kazdová, L.; Pravenec, Michal

    2016-01-01

    Roč. 11, č. 3 (2016), e0150924 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LL1204; GA MZd(CZ) NT14325 Institutional support: RVO:67985823 ; RVO:68378050 Keywords : inflammation * spontaneously hypertensive rat * transgenic * C-reactive protein * dicarbonyl stress * metformin Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.806, year: 2016

  6. Cytoprotective role of the fatty acid binding protein 4 against oxidative and endoplasmic reticulum stress in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Kazuaki Kajimoto

    2014-01-01

    Full Text Available The fatty acid binding protein 4 (FABP4, one of the most abundant proteins in adipocytes, has been reported to have a proinflammatory function in macrophages. However, the physiological role of FABP4, which is constitutively expressed in adipocytes, has not been fully elucidated. Previously, we demonstrated that FABP4 was involved in the regulation of interleukin-6 (IL-6 and vascular endothelial growth factor (VEGF production in 3T3-L1 adipocytes. In this study, we examined the effects of FABP4 silencing on the oxidative and endoplasmic reticulum (ER stress in 3T3-L1 adipocytes. We found that the cellular reactive oxygen species (ROS and 8-nitro-cyclic GMP levels were significantly elevated in the differentiated 3T3-L1 adipocytes transfected with a small interfering RNA (siRNA against Fabp4, although the intracellular levels or enzyme activities of antioxidants including reduced glutathione (GSH, superoxide dismutase (SOD and glutathione S-transferase A4 (GSTA4 were not altered. An in vitro evaluation using the recombinant protein revealed that FABP4 itself functions as a scavenger protein against hydrogen peroxide (H2O2. FABP4-knockdown resulted in a significant lowering of cell viability of 3T3-L1 adipocytes against H2O2 treatment. Moreover, four kinds of markers related to the ER stress response including the endoplasmic reticulum to nucleus signaling 1 (Ern1, the signal sequence receptor α (Ssr1, the ORM1-like 3 (Ormdl3, and the spliced X-box binding protein 1 (Xbp1s, were all elevated as the result of the knockdown of FABP4. Consequently, FABP4 might have a new role as an antioxidant protein against H2O2 and contribute to cytoprotection against oxidative and ER stress in adipocytes.

  7. Oxidative stress resistance in Porphyromonas gingivalis

    Science.gov (United States)

    Henry, Leroy G; McKenzie, Rachelle ME; Robles, Antonette; Fletcher, Hansel M

    2012-01-01

    Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets. PMID:22439726

  8. Redox proteomics changes in the fungal pathogen Trichosporon asahii on arsenic exposure: identification of protein responses to metal-induced oxidative stress in an environmentally-sampled isolate.

    Directory of Open Access Journals (Sweden)

    Sidra Ilyas

    suggest extensive proteomic alterations in response to metal-induced oxidative stress in T. asahii. Amino acid metabolism, protein folding and degradation are principally affected.

  9. N-3 Polyunsaturated Fatty Acids Decrease the Protein Expression of Soluble Epoxide Hydrolase via Oxidative Stress-Induced P38 Kinase in Rat Endothelial Cells.

    Science.gov (United States)

    Okada, Takashi; Morino, Katsutaro; Nakagawa, Fumiyuki; Tawa, Masashi; Kondo, Keiko; Sekine, Osamu; Imamura, Takeshi; Okamura, Tomio; Ugi, Satoshi; Maegawa, Hiroshi

    2017-06-24

    N -3 polyunsaturated fatty acids (PUFAs) improve endothelial function. The arachidonic acid-derived metabolites (epoxyeicosatrienoic acids (EETs)) are part of the endothelial hyperpolarization factor and are vasodilators independent of nitric oxide. However, little is known regarding the regulation of EET concentration by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in blood vessels. Sprague-Dawley rats were fed either a control or fish oil diet for 3 weeks. Compared with the control, the fish oil diet improved acetylcholine-induced vasodilation and reduced the protein expression of soluble epoxide hydrolase (sEH), a key EET metabolic enzyme, in aortic strips. Both DHA and EPA suppressed sEH protein expression in rat aorta endothelial cells (RAECs). Furthermore, the concentration of 4-hydroxy hexenal (4-HHE), a lipid peroxidation product of n -3 PUFAs, increased in n -3 PUFA-treated RAECs. In addition, 4-HHE treatment suppressed sEH expression in RAECs, suggesting that 4-HHE (derived from n -3 PUFAs) is involved in this phenomenon. The suppression of sEH was attenuated by the p38 kinase inhibitor (SB203580) and by treatment with the antioxidant N-acetyl-L-cysteine. In conclusion, sEH expression decreased after n -3 PUFAs treatment, potentially through oxidative stress and p38 kinase. Mild oxidative stress induced by n -3 PUFAs may contribute to their cardio-protective effect.

  10. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

  11. Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity

    International Nuclear Information System (INIS)

    McGill, Mitchell R.; Williams, C. David; Xie, Yuchao; Ramachandran, Anup; Jaeschke, Hartmut

    2012-01-01

    Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the West. In mice, APAP hepatotoxicity can be rapidly induced with a single dose. Because it is both clinically relevant and experimentally convenient, APAP intoxication has become a popular model of liver injury. Early data demonstrated that rats are resistant to APAP toxicity. As a result, mice are the preferred species for mechanistic studies. Furthermore, recent work has shown that the mechanisms of APAP toxicity in humans are similar to mice. Nevertheless, some investigators still use rats. New mechanistic information from the last forty years invites a reevaluation of the differences between these species. Comparison may provide interesting insights and confirm or exclude the rat as an option for APAP studies. To this end, we treated rats and mice with APAP and measured parameters of liver injury, APAP metabolism, oxidative stress, and activation of the c-Jun N-terminal kinase (JNK). Consistent with earlier data, we found that rats were highly resistant to APAP toxicity. Although overall APAP metabolism was similar in both species, mitochondrial protein adducts were significantly lower in rats. Accordingly, rats also had less oxidative stress. Finally, while mice showed extensive activation and mitochondrial translocation of JNK, this could not be detected in rat livers. These data support the hypothesis that mitochondrial dysfunction is critical for the development of necrosis after APAP treatment. Because mitochondrial damage also occurs in humans, rats are not a clinically relevant species for studies of APAP hepatotoxicity. Highlights: ► Acetaminophen overdose causes severe liver injury only in mice but not in rats. ► APAP causes hepatic GSH depletion and protein adduct formation in rats and mice. ► Less protein adducts were measured in rat liver mitochondria compared to mouse. ► No oxidant stress, peroxynitrite formation or JNK activation was present in rats. ► The

  12. Emery-Dreifuss Muscular Dystrophy-Associated Mutant Forms of Lamin A Recruit the Stress Responsive Protein Ankrd2 into the Nucleus, Affecting the Cellular Response to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Silvia Angori

    2017-05-01

    Full Text Available Background: Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2 is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear. Methods: Experiments were performed in EDMD2-lamin A overexpressing cell lines and EDMD2-affected human myotubes. Oxidative stress was produced by H2O2 treatment. Co-immunoprecipitation, cellular subfractionation and immunofluorescence analysis were used to validate the relation between Ankrd2 and forms of lamin A; cellular sensibility to stress was monitored by the analysis of Reactive Oxygen Species (ROS release and cell viability. Results: Our data demonstrate that oxidative stress induces the formation of a complex between Ankrd2 and lamin A. However, EDMD2-lamin A mutants were able to bind and mislocalize Ankrd2 in the nucleus even under basal conditions. Nonetheless, cells co-expressing Ankrd2 and EDMD2-lamin A mutants were more sensitive to oxidative stress than the Ankrd2-wild type lamin A counterpart. Conclusions: For the first time, we present evidence that in muscle fibers from patients affected by EDMD2, Ankrd2 has an unusual nuclear localization. By introducing a plausible mechanism ruling this accumulation, our data hint at a novel function of Ankrd2 in the pathogenesis of EDMD2-affected cells.

  13. Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in pancreatic tumour AR42J cells.

    Science.gov (United States)

    Santofimia-Castaño, Patricia; Izquierdo-Alvarez, Alicia; Plaza-Davila, María; Martinez-Ruiz, Antonio; Fernandez-Bermejo, Miguel; Mateos-Rodriguez, Jose M; Salido, Gines M; Gonzalez, Antonio

    2018-01-01

    Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free-Ca 2+ concentration ([Ca 2+ ] c ), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen-activated protein kinases were analyzed. Our results show that ebselen evoked a concentration-dependent increase in [Ca 2+ ] c . The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin-evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X-box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen-activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells. © 2017 Wiley Periodicals, Inc.

  14. Mild oxidative stress induces redistribution of BACE1 in non-apoptotic conditions and promotes the amyloidogenic processing of Alzheimer's disease amyloid precursor protein.

    Directory of Open Access Journals (Sweden)

    Jiang-Li Tan

    Full Text Available BACE1 is responsible for β-secretase cleavage of the amyloid precursor protein (APP, which represents the first step in the production of amyloid β (Aβ peptides. Previous reports, by us and others, have indicated that the levels of BACE1 protein and activity are increased in the brain cortex of patients with Alzheimer's disease (AD. The association between oxidative stress (OS and AD has prompted investigations that support the potentiation of BACE1 expression and enzymatic activity by OS. Here, we have established conditions to analyse the effects of mild, non-lethal OS on BACE1 in primary neuronal cultures, independently from apoptotic mechanisms that were shown to impair BACE1 turnover. Six-hour treatment of mouse primary cortical cells with 10-40 µM hydrogen peroxide did not significantly compromise cell viability but it did produce mild oxidative stress (mOS, as shown by the increased levels of reactive radical species and activation of p38 stress kinase. The endogenous levels of BACE1 mRNA and protein were not significantly altered in these conditions, whereas a toxic H2O2 concentration (100 µM caused an increase in BACE1 protein levels. Notably, mOS conditions resulted in increased levels of the BACE1 C-terminal cleavage product of APP, β-CTF. Subcellular fractionation techniques showed that mOS caused a major rearrangement of BACE1 localization from light to denser fractions, resulting in an increased distribution of BACE1 in fractions containing APP and markers for trans-Golgi network and early endosomes. Collectively, these data demonstrate that mOS does not modify BACE1 expression but alters BACE1 subcellular compartmentalization to favour the amyloidogenic processing of APP, and thus offer new insight in the early molecular events of AD pathogenesis.

  15. Obesity, reproduction and oxidative stress

    Directory of Open Access Journals (Sweden)

    Tamara V. Zhuk

    2017-12-01

    Full Text Available The prevalence of obesity and overweight is one of the most pressing problems nowadays. Obesity as a comorbid condition affects all body systems. Obesity has been reported to be a risk factor not only for cardiovascular diseases and oncopathology, but also for fertility problems, many obstetric and perinatal complications worsening the maternal and infant health. The balance between the oxidative and antioxidant system is one of the indicators of the state of human homeostasis. Today it is proved that obesity is associated with an increase in oxidative stress and a decrease in antioxidant protection. This review reveals a close relationship between obesity, oxidative stress and reproductive problems.

  16. The dynamic changes of the plasma membrane proteins and the protective roles of nitric oxide in rice subjected to heavy metal cadmium stress

    Directory of Open Access Journals (Sweden)

    Liming eYang

    2016-02-01

    Full Text Available The heavy metal cadmium is a common environmental contaminant in soils and has adverse effects on crop growth and development. The signaling processes in plants that initiate cellular responses to environmental stress have been shown to be located in the plasma membrane (PM. A better understanding of the PM proteome in response to environmental stress might provide new insights for improving stress-tolerant crops. Nitric oxide (NO is reported to be involved in the plant response to cadmium (Cd stress. To further investigate how NO modulates protein changes in the plasma membrane during Cd stress, a quantitative proteomics approach based on isobaric tags for relative and absolute quantification (iTRAQ was used to identify differentially regulated proteins from the rice plasma membrane after Cd or Cd and NO treatment. Sixty-six differentially expressed proteins were identified, of which, many function as transporters, ATPases, kinases, metabolic enzymes, phosphatases and phospholipases. Among these, the abundance of phospholipase D (PLD was altered substantially after the treatment of both Cd and Cd and NO. Transient expression of the PLD fused with green fluorescent peptide (GFP in rice protoplasts showed that the Cd and NO treatment promoted the accumulation of PLD in the plasma membrane. Addition of NO also enhanced Cd-induced PLD activity and the accumulation of phosphatidic acid (PA produced through PLD activity. Meanwhile, NO elevated the activities of antioxidant enzymes and caused the accumulation of glutathione both which function to reduce Cd-induced H2O2 accumulation. Taken together, we suggest that NO signaling is associated with the accumulation of antioxidant enzymes, glutathione and PA which increases cadmium tolerance in rice via the antioxidant defense system.

  17. Thermotolerance, oxidative stress, apoptosis, heat-shock proteins and damages to reproductive cells of insecticide-susceptible and -resistant strains of the diamondback moth Plutella xylostella.

    Science.gov (United States)

    Zhang, L J; Chen, J L; Yang, B L; Kong, X G; Bourguet, D; Wu, G

    2017-08-01

    In this study, we investigated thermotolerance, several physiological responses and damage to reproductive cells in chlorpyrifos-resistant (Rc) and -susceptible (Sm) strains of the diamondback moth, Plutella xylostella subjected to heat stress. The chlorpyrifos resistance of these strains was mediated by a modified acetylcholinesterase encoded by an allele, ace1R, of the ace1 gene. Adults of the Rc strain were less heat resistant than those of the Sm strain; they also had lower levels of enzymatic activity against oxidative damage, higher reactive oxygen species contents, weaker upregulation of two heat shock protein (hsp) genes (hsp69s and hsp20), and stronger upregulation of two apoptotic genes (caspase-7 and -9). The damage to sperm and ovary cells was greater in Rc adults than in Sm adults and was temperature sensitive. The lower fitness of the resistant strain, compared with the susceptible strain, is probably due to higher levels of oxidative stress and apoptosis, which also have deleterious effects on several life history traits. The greater injury observed in conditions of heat stress may be due to both the stronger upregulation of caspase genes and weaker upregulation of hsp genes in resistant than in susceptible individuals.

  18. Effect of heat stress and recovery on viability, oxidative damage, and heat shock protein expression in hepatic cells of grass carp (Ctenopharyngodon idellus).

    Science.gov (United States)

    Cui, Yanting; Liu, Bo; Xie, Jun; Xu, Pao; Habte-Tsion, H-Michael; Zhang, Yuanyuan

    2014-06-01

    In this study, we investigated the effects of hyperthermia and recovery on cell viability, lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA), total antioxidant capacity (T-AOC), and heat shock protein (HSP60, 70, and 90) mRNA expression in the hepatic cells of the grass carp, Ctenopharyngodon idellus. Triplicate groups of cultured cells were exposed to 30, 32, or 34 °C for 0.5 h and then immediately incubated at 27 °C in 5 % CO2 for 6, 12, 24, or 48 h. Hyperthermia stress greatly reduced cell viability and increased LDH release. Cell damage declined after recovery. Hyperthermia stress increased the lipid peroxide levels and reduced the antioxidant capacity (e.g., reduced SOD and T-AOC) of the cells. However, oxidative damage declined as the recovery period increased, and the levels of MDA, SOD, and T-AOC were restored. After cells were exposed to 32 °C, the expression of HSP60 after recovery for 1, 2, and 4 h (P recovery for 0.5 and 1 h (P recovery were significantly higher (P recovery period, the variations in HSP gene expression reflected the transition period from a state of cellular growth to one of the cellular repairs. In conclusion, hyperthermia depresses cell viability, induces oxidative damage, and increases HSP expression, which plays an important role during hyperthermic stress in grass carp hepatic cells.

  19. The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment.

    Science.gov (United States)

    Versari, Silvia; Longinotti, Giulia; Barenghi, Livia; Maier, Jeanette Anne Marie; Bradamante, Silvia

    2013-11-01

    Exposure to microgravity generates alterations that are similar to those involved in age-related diseases, such as cardiovascular deconditioning, bone loss, muscle atrophy, and immune response impairment. Endothelial dysfunction is the common denominator. To shed light on the underlying mechanism, we participated in the Progress 40P mission with Spaceflight of Human Umbilical Vein Endothelial Cells (HUVECs): an Integrated Experiment (SPHINX), which consisted of 12 in-flight and 12 ground-based control modules and lasted 10 d. Postflight microarray analysis revealed 1023 significantly modulated genes, the majority of which are involved in cell adhesion, oxidative phosphorylation, stress responses, cell cycle, and apoptosis. Thioredoxin-interacting protein was the most up-regulated (33-fold), heat-shock proteins 70 and 90 the most down-regulated (5.6-fold). Ion channels (TPCN1, KCNG2, KCNJ14, KCNG1, KCNT1, TRPM1, CLCN4, CLCA2), mitochondrial oxidative phosphorylation, and focal adhesion were widely affected. Cytokine detection in the culture media indicated significant increased secretion of interleukin-1α and interleukin-1β. Nitric oxide was found not modulated. Our data suggest that in cultured HUVECs, microgravity affects the same molecular machinery responsible for sensing alterations of flow and generates a prooxidative environment that activates inflammatory responses, alters endothelial behavior, and promotes senescence.

  20. Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-{sup 19}F-NMR

    Energy Technology Data Exchange (ETDEWEB)

    Dickinson, Elizabeth, E-mail: elizabeth.dickinson@york.ac.uk [University of York, Department of Chemistry (United Kingdom); Arnold, John R. P. [Selby College (United Kingdom); Fisher, Julie [University of Leeds, School of Chemistry (United Kingdom)

    2017-02-15

    The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using {sup 19}F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane.

  1. Determination of glucose exchange rates and permeability of erythrocyte membrane in preeclampsia and subsequent oxidative stress-related protein damage using dynamic-"1"9F-NMR

    International Nuclear Information System (INIS)

    Dickinson, Elizabeth; Arnold, John R. P.; Fisher, Julie

    2017-01-01

    The cause of the pregnancy condition preeclampsia (PE) is thought to be endothelial dysfunction caused by oxidative stress. As abnormal glucose tolerance has also been associated with PE, we use a fluorinated-mimic of this metabolite to establish whether any oxidative damage to lipids and proteins in the erythrocyte membrane has increased cell membrane permeability. Data were acquired using "1"9F Dynamic-NMR (DNMR) to measure exchange of 3-fluoro-3-deoxyglucose (3-FDG) across the membrane of erythrocytes from 10 pregnant women (5 healthy control women, and 5 from women suffering from PE). Magnetisation transfer was measured using the 1D selective inversion and 2D EXSY pulse sequences, over a range of time delays. Integrated intensities from these experiments were used in matrix diagonalisation to estimate the values of the rate constants of exchange and membrane permeability. No significant differences were observed for the rate of exchange of 3-FDG and membrane permeability between healthy pregnant women and those suffering from PE, leading us to conclude that no oxidative damage had occurred at this carrier-protein site in the membrane.

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

    Science.gov (United States)

    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.

  3. SCR96, a small cysteine-rich secretory protein of Phytophthora cactorum, can trigger cell death in the Solanaceae and is important for pathogenicity and oxidative stress tolerance.

    Science.gov (United States)

    Chen, Xiao-Ren; Li, Yan-Peng; Li, Qi-Yuan; Xing, Yu-Ping; Liu, Bei-Bei; Tong, Yun-Hui; Xu, Jing-You

    2016-05-01

    Peptides and small molecules produced by both the plant pathogen Phytophthora and host plants in the apoplastic space mediate the relationship between the interplaying organisms. Various Phytophthora apoplastic effectors, including small cysteine-rich (SCR) secretory proteins, have been identified, but their roles during interaction remain to be determined. Here, we identified an SCR effector encoded by scr96, one of three novel genes encoding SCR proteins in P. cactorum with similarity to the P. cactorum phytotoxic protein PcF. Together with the other two genes, scr96 was transcriptionally induced throughout the developmental and infection stages of the pathogen. These genes triggered plant cell death (PCD) in the Solanaceae, including Nicotiana benthamiana and tomato. The scr96 gene did not show single nucleotide polymorphisms in a collection of P. cactorum isolates from different countries and host plants, suggesting that its role is essential and non-redundant during infection. Homologues of SCR96 were identified only in oomycetes, but not in fungi and other organisms. A stable protoplast transformation protocol was adapted for P. cactorum using green fluorescent protein as a marker. The silencing of scr96 in P. cactorum caused gene-silenced transformants to lose their pathogenicity on host plants and these transformants were significantly more sensitive to oxidative stress. Transient expression of scr96 partially recovered the virulence of gene-silenced transformants on plants. Overall, our results indicate that the P. cactorum scr96 gene encodes an important virulence factor that not only causes PCD in host plants, but is also important for pathogenicity and oxidative stress tolerance. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  4. Toxicity and oxidative stress of different forms of organic selenium (Se) and dietary protein in mallard (Anas platyrhynchos) ducklings

    Science.gov (United States)

    Hoffman, D.; Heinz, G.; Eisemann, J.; Pendleton, G.

    1994-01-01

    High concentrations of Se have been found in aquatic food chains associated with irrigation drainwater and toxicity to fish and wildlife. Earlier studies have compared toxicities of Se as selenite and as seleno-DL-methionine (DL) in mallards. This study compares DL, seleno-L-methionine (L), selenized yeast (Y) and selenized wheat (W). Day-old mallard ducklings received an untreated diet (controls) containing 75% wheat (22% protein) or the same diet containing 15 or 30 ppm Se in the above forms. After 2 weeks blood and liver samples were collected for biochemical assays and Se analysis. All forms of selenium caused significant increases in plasma and hepatic glutathione peroxidase activities. Se as L was the most toxic, resulting in high mortality (64%) and impaired growth (>50%) and the greatest increase in ratio of oxidized to reduced glutathione with 30 ppm in the diet. Se as Y accumulated the least in liver. In a subsequent experiment with 30% dietary protein Se as L was less toxic.

  5. Oxidative stress drives CD8+ T-cell skin trafficking in patients with vitiligo through CXCL16 upregulation by activating the unfolded protein response in keratinocytes.

    Science.gov (United States)

    Li, Shuli; Zhu, Guannan; Yang, Yuqi; Jian, Zhe; Guo, Sen; Dai, Wei; Shi, Qiong; Ge, Rui; Ma, Jingjing; Liu, Ling; Li, Kai; Luan, Qi; Wang, Gang; Gao, Tianwen; Li, Chunying

    2017-07-01

    In patients with vitiligo, an increased reactive oxygen species (ROS) level has been proved to be a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment, such as keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and was recently found to mediate homing of CD8 + T cells in human skin. We sought to explicate the effect of oxidative stress on human keratinocytes and its capacity to drive CD8 + T-cell trafficking through CXCL16 regulation. We first detected putative T-cell skin-homing chemokines and ROS in serum and lesions of patients with vitiligo. The production of candidate chemokines was detected by using quantitative real-time PCR and ELISA in keratinocytes exposed to H 2 O 2 . Furthermore, the involved mediators were analyzed by using quantitative real-time PCR, Western blotting, ELISA, and immunofluorescence. Next, we tested the chemotactic migration of CD8 + T cells from patients with vitiligo mediated by the CXCL16-CXCR6 pair using the transwell assay. CXCL16 expression increased and showed a positive correlation with oxidative stress levels in serum and lesions of patients with vitiligo. The H 2 O 2 -induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways: kinase RNA (PKR)-like ER kinase-eukaryotic initiation factor 2α and inositol-requiring enzyme 1α-X-box binding protein 1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6 + CD8 + T cells derived from patients with vitiligo. CXCR6 + CD8 + T-cell skin infiltration is accompanied by melanocyte loss in lesions of patients with vitiligo. Our study demonstrated that CXCL16-CXCR6 mediates CD8 + T-cell skin trafficking under oxidative stress in patients with vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least in part, caused by unfolded protein response

  6. [Vitamins and oxidative stress].

    Science.gov (United States)

    Kodentsova, V M; Vrzhesinskaia, O A; Mazo, V K

    2013-01-01

    The central and local stress limiting systems, including the antioxidant defense system involved in defending the organism at the cellular and systemic levels from excess activation response to stress influence, leading to damaging effects. The development of stress, regardless of its nature [cold, increased physical activity, aging, the development of many pathologies (cardiovascular, neurodegenerative diseases, diseases of the gastrointestinal tract, ischemia, the effects of burns), immobilization, hypobaric hypoxia, hyperoxia, radiation effects etc.] leads to a deterioration of the vitamin status (vitamins E, A, C). Damaging effect on the antioxidant defense system is more pronounced compared to the stress response in animals with an isolated deficiency of vitamins C, A, E, B1 or B6 and the combined vitamins deficiency in the diet. Addition missing vitamin or vitamins restores the performance of antioxidant system. Thus, the role of vitamins in adaptation to stressors is evident. However, vitamins C, E and beta-carotene in high doses, significantly higher than the physiological needs of the organism, may be not only antioxidants, but may have also prooxidant properties. Perhaps this explains the lack of positive effects of antioxidant vitamins used in extreme doses for a long time described in some publications. There is no doubt that to justify the current optimal doses of antioxidant vitamins and other dietary antioxidants specially-designed studies, including biochemical testing of initial vitamin and antioxidant status of the organism, as well as monitoring their change over time are required.

  7. Rice bran protein hydrolysates reduce arterial stiffening, vascular remodeling and oxidative stress in rats fed a high-carbohydrate and high-fat diet.

    Science.gov (United States)

    Senaphan, Ketmanee; Sangartit, Weerapon; Pakdeechote, Poungrat; Kukongviriyapan, Veerapol; Pannangpetch, Patchareewan; Thawornchinsombut, Supawan; Greenwald, Stephen E; Kukongviriyapan, Upa

    2018-02-01

    Rice bran protein hydrolysates (RBPH) contain highly nutritional proteins and antioxidant compounds which show benefits against metabolic syndrome (MetS). Increased arterial stiffness and the components of MetS have been shown to be associated with an increased risk of cardiovascular disease. This study aimed to investigate whether RBPH could alleviate the metabolic disorders, arterial stiffening, vascular remodeling, and oxidative stress in rats fed a high-carbohydrate and high-fat (HCHF) diet. Male Sprague-Dawley rats were fed either a standard chow and tap water or a HCHF diet and 15 % fructose solution for 16 weeks. HCHF rats were treated orally with RBPH (250 or 500 mg/kg/day) for the final 6 weeks of the experimental period. Rats fed with HCHF diet had hyperglycemia, insulin resistance, dyslipidemia, hypertension, increased aortic pulse wave velocity, aortic wall hypertrophy and vascular remodeling with increased MMP-2 and MMP-9 expression. RBPH supplementation significantly alleviated these alterations (P stress was also alleviated after RBPH treatment by decreasing plasma malondialdehyde, reducing superoxide production and suppressing p47 phox NADPH oxidase expression in the vascular tissues of HCHF rats. RBPH increased plasma nitrate/nitrite level and up-regulated eNOS expression in the aortas of HCHF-diet-fed rats, indicating that RBPH increased NO production. RBPH mitigate the deleterious effects of HCHF through potential mechanisms involving enhanced NO bioavailability, anti-ACE, anti-inflammatory and antioxidant properties. RBPH could be used as dietary supplements to minimize oxidative stress and vascular alterations triggered by MetS.

  8. Mutations of C19orf12, coding for a transmembrane glycine zipper containing mitochondrial protein, cause mis-localization of the protein, inability to respond to oxidative stress and increased mitochondrial Ca2+.

    Directory of Open Access Journals (Sweden)

    Paola eVenco

    2015-05-01

    Full Text Available Mutations in C19orf12 have been identified in patients affected by Neurodegeneration with Brain Iron Accumulation (NBIA, a clinical entity characterized by iron accumulation in the basal ganglia. By using western blot analysis with specific antibody and confocal studies, we showed that wild-type C19orf12 protein was not exclusively present in mitochondria, but also in the Endoplasmic Reticulum (ER and MAM (Mitochondria Associated Membrane, while mutant C19orf12 variants presented a different localization. Moreover, after induction of oxidative stress, a GFP-tagged C19orf12 wild-type protein was able to relocate to the cytosol. On the contrary, mutant isoforms were not able to respond to oxidative stress. High mitochondrial calcium concentration and increased H2O2 induced apoptosis were found in fibroblasts derived from one patient as compared to controls.C19orf12 protein is a 17kDa mitochondrial membrane-associated protein whose function is still unknown. Our in silico investigation suggests that, the glycine zipper motifs of C19orf12 form helical regions spanning the membrane. The N- and C-terminal regions with respect to the transmembrane portion, on the contrary, are predicted to rearrange in a structural domain, which is homologues to the N-terminal regulatory domain of the magnesium transporter MgtE, suggesting that C19orf12 may act as a regulatory protein for human MgtE transporters. The mutations here described affect respectively one glycine residue of the glycine zipper motifs, which are involved in dimerization of transmembrane helices and predicted to impair the correct localization of the protein into the membranes, and one residue present in the regulatory domain, which is important for protein-protein interaction.

  9. Fanconi anemia proteins and endogenous stresses

    Energy Technology Data Exchange (ETDEWEB)

    Pang Qishen [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States); Andreassen, Paul R., E-mail: Paul.Andreassen@cchmc.org [Division of Experimental Hematology and Cancer Biology, Cincinnati Children' s Research Foundation, Cincinnati, OH (United States); Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH (United States)

    2009-07-31

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  10. Fanconi anemia proteins and endogenous stresses

    International Nuclear Information System (INIS)

    Pang Qishen; Andreassen, Paul R.

    2009-01-01

    Each of the thirteen identified Fanconi anemia (FA) genes is required for resistance to DNA interstrand crosslinking agents, such as mitomycin C, cisplatin, and melphalan. While these agents are excellent tools for understanding the function of FA proteins in DNA repair, it is uncertain whether a defect in the removal of DNA interstrand crosslinks (ICLs) is the basis for the pathophysiology of FA. For example, DNA interstrand crosslinking agents induce other types of DNA damage, in addition to ICLs. Further, other DNA-damaging agents, such as ionizing or ultraviolet radiation, activate the FA pathway, leading to monoubiquitination of FANCD2 and FANCI. Also, FA patients display congenital abnormalities, hematologic deficiencies, and a predisposition to cancer in the absence of an environmental source of ICLs that is external to cells. Here we consider potential sources of endogenous DNA damage, or endogenous stresses, to which FA proteins may respond. These include ICLs formed by products of lipid peroxidation, and other forms of oxidative DNA damage. FA proteins may also potentially respond to telomere shortening or replication stress. Defining these endogenous sources of DNA damage or stresses is critical for understanding the pathogenesis of deficiencies for FA proteins. We propose that FA proteins are centrally involved in the response to replication stress, including replication stress arising from oxidative DNA damage.

  11. Influence of a polyphenol-enriched protein powder on exercise-induced inflammation and oxidative stress in athletes: a randomized trial using a metabolomics approach.

    Directory of Open Access Journals (Sweden)

    David C Nieman

    Full Text Available Polyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training.Water soluble polyphenols from blueberry and green tea extracts were captured onto a polyphenol soy protein complex (PSPC. Subjects were recruited, and included 38 long-distance runners ages 19-45 years who regularly competed in road races. Runners successfully completing orientation and baseline testing (N = 35 were randomized to 40 g/d PSPC (N = 17 (2,136 mg/d gallic acid equivalents or placebo (N = 18 for 17 d using double-blinded methods and a parallel group design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO2max. Blood samples were collected pre- and post-14 d supplementation, and immediately and 14 h after the third day of running in subjects completing all aspects of the study (N = 16 PSPC, N = 15 placebo, and analyzed using a metabolomics platform with GC-MS and LC-MS.Metabolites characteristic of gut bacteria metabolism of polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4-hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively, P<0.05, an effect which persisted for 14-h post-exercise. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14-h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05. Established biomarkers for inflammation (CRP, cytokines and oxidative stress (protein carbonyls did not differ between groups.PSPC supplementation over a 17-d period did not alter established biomarkers for inflammation and oxidative stress but was linked to an enhanced gut-derived phenolic signature and ketogenesis in runners during recovery from 3-d heavy exertion.ClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT01775384.

  12. Recombinant heat shock protein 27 (HSP27/HSPB1) protects against cadmium-induced oxidative stress and toxicity in human cervical cancer cells.

    Science.gov (United States)

    Alvarez-Olmedo, Daiana G; Biaggio, Veronica S; Koumbadinga, Geremy A; Gómez, Nidia N; Shi, Chunhua; Ciocca, Daniel R; Batulan, Zarah; Fanelli, Mariel A; O'Brien, Edward R

    2017-05-01

    Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity. Here, we report that the harmful effects of Cd correlated with changes in oxidative stress markers: upregulation of reactive oxygen species, reduction in nitric oxide (NO) bioavailability, increment in lipid peroxidation, peroxynitrite (PN), and protein nitration; intracellular HSP27 was reduced. Treatments with Cd (100 μM) for 24 h or with the peroxynitrite donor, SIN-1, decreased HSP27 levels (~50%), suggesting that PN formation is responsible for the reduction of HSP27. Pre-treatments of the cells either with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) (a pharmacological inhibitor of NO synthase) or with recombinant HSP27 (rHSP27) attenuated the disruption of the cellular metabolism induced by Cd, increasing in a 55 and 52%, respectively, the cell viability measured by CCK-8. Cd induced necrotic cell death pathways, although apoptosis was also activated; pre-treatment with L-NAME or rHSP27 mitigated cell death. Our findings show for the first time a direct relationship between Cd-induced toxicity and PN production and a role for rHSP27 as a potential therapeutic agent that may counteract Cd toxicity.

  13. Imoxin attenuates high fructose-induced oxidative stress and apoptosis in renal epithelial cells via downregulation of protein kinase R pathway.

    Science.gov (United States)

    Kalra, Jaspreet; Mangali, Suresh Babu; Bhat, Audesh; Dhar, Indu; Udumula, Mary Priyanka; Dhar, Arti

    2018-02-11

    Double-stranded RNA (dsRNA)-activated protein kinase R (PKR), a ubiquitously expressed serine/threonine kinase, is a key inducer of inflammation, insulin resistance, and glucose homeostasis in obesity. Recent studies have demonstrated that PKR can respond to metabolic stress in mice as well as in humans. However, the underlying molecular mechanism is not fully understood. The aim of this study was to examine the effect of high fructose (HF) in cultured renal tubular epithelial cells (NRK-52E) derived from rat kidney and to investigate whether inhibition of PKR could prevent any deleterious effects of HF in these cells. PKR expression was determined by immunofluorescence staining and Western blotting. Oxidative damage and apoptosis were measured by flow cytometry. HF-treated renal cells developed a significant increase in PKR expression. A significant increase in reactive oxygen species generation and apoptosis was also observed in HF-treated cultured renal epithelial cells. All these effects of HF were attenuated by a selective PKR inhibitor, imoxin (C16). In conclusion, our study demonstrates PKR induces oxidative stress and apoptosis, is a significant contributor involved in vascular complications and is a possible mediator of HF-induced hypertension. Inhibition of PKR pathway can be used as a therapeutic strategy for the treatment of cardiovascular and metabolic disorders. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  14. Ablation of the mitochondrial complex IV assembly protein Surf1 leads to increased expression of the UPRMT and increased resistance to oxidative stress in primary cultures of fibroblasts

    Directory of Open Access Journals (Sweden)

    Gavin Pharaoh

    2016-08-01

    Full Text Available Mice deficient in the electron transport chain (ETC complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPRMT and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPRMT in response to reduced cytochrome c oxidase activity in Surf1−/− mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1−/− mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1−/− mice have increased expression of UPRMT components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1−/− mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1−/− fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1−/− fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPRMT in cell survival.

  15. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    21–25 ... Decreased total antioxidant levels and increased oxidative stress in South ... antioxidant-rich diet and lifestyle changes in T2DM patients would help to avert the .... glycation of proteins and the formation of advanced glycosylation.

  16. Salvianolic acid B Relieves Oxidative Stress in Glucose Absorption ...

    African Journals Online (AJOL)

    Absorption and Utilization of Mice Fed High-Sugar Diet ... Salvianolic acid B, Blood glucose, Reactive oxygen species, Oxidative stress, Sugar diet. ... protein expression in human aortic smooth ... induced by glucose uptake and metabolism [8].

  17. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    International Nuclear Information System (INIS)

    Malaviya, Rama; Laskin, Jeffrey D.; Laskin, Debra L.

    2014-01-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic

  18. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  19. Nitric oxide stress and activation of AMP-activated protein kinase impair β-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.

    Science.gov (United States)

    Tong, X; Kono, T; Evans-Molina, C

    2015-06-18

    The sarcoendoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) concentration gradient between the cytosol and ER lumen in the pancreatic β-cell, and the integrity of this gradient has a central role in regulated insulin production and secretion, maintenance of ER function and β-cell survival. We have previously demonstrated loss of β-cell SERCA2b expression under diabetic conditions. To define the mechanisms underlying this, INS-1 cells and rat islets were treated with the proinflammatory cytokine interleukin-1β (IL-1β) combined with or without cycloheximide or actinomycin D. IL-1β treatment led to increased inducible nitric oxide synthase (iNOS) gene and protein expression, which occurred concurrently with the activation of AMP-activated protein kinase (AMPK). IL-1β led to decreased SERCA2b mRNA and protein expression, whereas time-course experiments revealed a reduction in protein half-life with no change in mRNA stability. Moreover, SERCA2b protein but not mRNA levels were rescued by treatment with the NOS inhibitor l-NMMA (NG-monomethyl L-arginine), whereas the NO donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) and the AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) recapitulated the effects of IL-1β on SERCA2b protein stability. Similarly, IL-1β-induced reductions in SERCA2b expression were rescued by pharmacological inhibition of AMPK with compound C or by transduction of a dominant-negative form of AMPK, whereas β-cell death was prevented in parallel. Finally, to determine a functional relationship between NO and AMPK signaling and SERCA2b activity, fura-2/AM (fura-2-acetoxymethylester) Ca(2+) imaging experiments were performed in INS-1 cells. Consistent with observed changes in SERCA2b expression, IL-1β, SNAP and AICAR increased cytosolic Ca(2+) and decreased ER Ca(2+) levels, suggesting congruent modulation of SERCA activity under these conditions. In aggregate, these results show that SERCA2b

  20. Shifts in renin-angiotensin system components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa region of streptozotocin-induced diabetic mice.

    Science.gov (United States)

    Qian, Xiaobing; Lin, Leilei; Zong, Yao; Yuan, Yongguang; Dong, Yanmin; Fu, Yue; Shao, Wanwen; Li, Yujie; Gao, Qianying

    2018-03-01

    This study aimed to analyse shifts in renin-angiotensin system (RAS) components, angiogenesis, and oxidative stress-related protein expression in the lamina cribrosa (LC) region in streptozotocin (STZ)-induced diabetic mice. Six months after diabetes induction, the retinal vessels of male C57BL/6 J mice were observed by colour photography, fundus fluorescein angiography (FFA), and immunofluorescent staining following incubation with CD31. Immunofluorescence for glial fibrillary acidic protein (GFAP), alpha-smooth muscle actin (α-SMA),and NG2 was also performed. Angiotensin-converting enzyme 1 (ACE1), angiotensin II type I receptor (AT1R), renin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and haeme oxygenase 1 (HO-1) expression levels were confirmed by immunohistochemical and western blotting analyses. Compared with control mice, diabetic mice had significantly higher blood glucose concentrations (p diabetic mice; however, immunostaining of whole-mount retinas revealed an increased number of retinal vessels. Furthermore, histopathological staining showed significant reduction in the whole retinal thickness. GFAP expression was slightly higher, whereas fewer NG2 + pericytes were observed in diabetic mice than in control mice. ACE1, AT1R, renin, HIF-1α, VEGF, VEGFR2, and HO-1 expression were up-regulated in the LC of the STZ-induced diabetic mice. Collectively, ACE 1, AT1R, HIF-1α, VEGF, VEGFR2, and HO-1 activation in the LC region in diabetic mice may be involved in diabetes via the RAS and induction of angiogenesis and oxidative stress.

  1. Protective Effects of Maillard Reaction Products of Whey Protein Concentrate against Oxidative Stress through an Nrf2-Dependent Pathway in HepG2 Cells.

    Science.gov (United States)

    Pyo, Min Cheol; Yang, Sung-Yong; Chun, Su-Hyun; Oh, Nam Su; Lee, Kwang-Won

    2016-09-01

    Whey protein concentrate (WPC), which contains α-lactalbumin and β-lactoglobulin, is utilized widely in the food industry. The Maillard reaction is a complex reaction that produces Maillard reaction products (MRPs), which are associated with the formation of antioxidant compounds. In this study, the hepatoprotection activity of MRPs of WPC against oxidative stress through the nuclear factor-E2-related factor 2 (Nrf2)-dependent antioxidant pathway in HepG2 cells was examined. Glucose-whey protein concentrate conjugate (Glc-WPC) was obtained from Maillard reaction between WPC and glucose. The fluorescence intensity of Glc-WPC increased after 7 d compared to native WPC, and resulted in loss of 48% of the free amino groups of WPC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) patterns of Glc-WPC showed the presence of a high-molecular-weight portion. Treatment of HepG2 cells with Glc-WPC increased cell viability in the presence of oxidative stress, inhibited the generation of intracellular reactive oxygen species by tert-butyl hydroperoxide (t-BHP), and increased the glutathione level. Nrf2 translocation and Nrf2, reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H)-quinone oxidoreductase 1 (NOQ1), heme oxygenase-1 (HO-1), glutamate-L-cysteine ligase (GCL)M and GCLC mRNA levels were increased by Glc-WPC. Also, Glc-WPC increased the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK). The results of this study demonstrate that Glc-WPC activates the Nrf2-dependent pathway through the phosphorylation of ERK1/2 and JNK in HepG2 cells, and induces production of antioxidant enzymes and phase II enzymes.

  2. Protein stress and stress proteins: implications in aging and disease

    Indian Academy of Sciences (India)

    Madhu Sudhan

    2007-04-02

    Apr 2, 2007 ... (iii) modulating protein activity via stabilization and/or maturation to ... Resistance to any physical stress is correlated with longevity in many, if not all .... range of pathologies including cancer, diabetes, immune- problems and ...

  3. Deciphering the interplay between cysteine synthase and thiol cascade proteins in modulating Amphotericin B resistance and survival of Leishmania donovani under oxidative stress

    Directory of Open Access Journals (Sweden)

    Kuljit Singh

    2017-08-01

    Full Text Available Leishmania donovani is the causative organism of the neglected human disease known as visceral leishmaniasis which is often fatal, if left untreated. The cysteine biosynthesis pathway of Leishmania may serve as a potential drug target because it is different from human host and regulates downstream components of redox metabolism of the parasites; essential for their survival, pathogenicity and drug resistance. However, despite the apparent dependency of redox metabolism of cysteine biosynthesis pathway, the role of L. donovani cysteine synthase (LdCS in drug resistance and redox homeostasis has been unexplored. Herein, we report that over-expression of LdCS in Amphotericin B (Amp B sensitive strain (S1-OE modulates resistance towards oxidative stress and drug pressure. We observed that antioxidant enzyme activities were up-regulated in S1-OE parasites and these parasites alleviate intracellular reactive oxygen species (ROS efficiently by maintaining the reduced thiol pool. In contrast to S1-OE parasites, Amp B sensitive strain (S1 showed higher levels of ROS which was positively correlated with the protein carbonylation levels and negatively correlated with cell viability. Moreover, further investigations showed that LdCS over-expression also augments the ROS-primed induction of LdCS-GFP as well as endogenous LdCS and thiol pathway proteins (LdTryS, LdTryR and LdcTXN in L. donovani parasites; which probably aids in stress tolerance and drug resistance. In addition, the expression of LdCS was found to be up-regulated in Amp B resistant isolates and during infective stationary stages of growth and consistent with these observations, our ex vivo infectivity studies confirmed that LdCS over-expression enhances the infectivity of L. donovani parasites. Our results reveal a novel crosstalk between LdCS and thiol metabolic pathway proteins and demonstrate the crucial role of LdCS in drug resistance and redox homeostasis of Leishmania. Keywords

  4. Hypoxia, Oxidative Stress and Fat

    Directory of Open Access Journals (Sweden)

    Nikolaus Netzer

    2015-06-01

    Full Text Available Metabolic disturbances in white adipose tissue in obese individuals contribute to the pathogenesis of insulin resistance and the development of type 2 diabetes mellitus. Impaired insulin action in adipocytes is associated with elevated lipolysis and increased free fatty acids leading to ectopic fat deposition in liver and skeletal muscle. Chronic adipose tissue hypoxia has been suggested to be part of pathomechanisms causing dysfunction of adipocytes. Hypoxia can provoke oxidative stress in human and animal adipocytes and reduce the production of beneficial adipokines, such as adiponectin. However, time-dose responses to hypoxia relativize the effects of hypoxic stress. Long-term exposure of fat cells to hypoxia can lead to the production of beneficial substances such as leptin. Knowledge of time-dose responses of hypoxia on white adipose tissue and the time course of generation of oxidative stress in adipocytes is still scarce. This paper reviews the potential links between adipose tissue hypoxia, oxidative stress, mitochondrial dysfunction, and low-grade inflammation caused by adipocyte hypertrophy, macrophage infiltration and production of inflammatory mediators.

  5. Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts

    DEFF Research Database (Denmark)

    Le Boulch, Marine; Ahmed, Emad K; Rogowska-Wrzesinska, Adelina

    2018-01-01

    Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi-pro...

  6. Overexpression of a Medicago truncatula stress-associated protein gene (MtSAP1) leads to nitric oxide accumulation and confers osmotic and salt stress tolerance in transgenic tobacco.

    Science.gov (United States)

    Charrier, Aurélie; Planchet, Elisabeth; Cerveau, Delphine; Gimeno-Gilles, Christine; Verdu, Isabelle; Limami, Anis M; Lelièvre, Eric

    2012-08-01

    The impact of Medicago truncatula stress-associated protein gene (MtSAP1) overexpression has been investigated in Nicotiana tabacum transgenic seedlings. Under optimal conditions, transgenic lines overexpressing MtSAP1 revealed better plant development and higher chlorophyll content as compared to wild type seedlings. Interestingly, transgenic lines showed a stronger accumulation of nitric oxide (NO), a signaling molecule involved in growth and development processes. This NO production seemed to be partially nitrate reductase dependent. Due to the fact that NO has been also reported to play a role in tolerance acquisition of plants to abiotic stresses, the responses of MtSAP1 overexpressors to osmotic and salt stress have been studied. Compared to the wild type, transgenic lines were less affected in their growth and development. Moreover, NO content in MtSAP1 overexpressors was always higher than that detected in wild seedlings under stress conditions. It seems that this better tolerance induced by MtSAP1 overexpression could be associated with this higher NO production that would enable seedlings to reach a high protection level to prepare them to cope with abiotic stresses.

  7. Mycoplasma hyopneumoniae-derived lipid-associated membrane proteins induce apoptosis in porcine alveolar macrophage via increasing nitric oxide production, oxidative stress, and caspase-3 activation.

    Science.gov (United States)

    Bai, Fangfang; Ni, Bo; Liu, Maojun; Feng, Zhixin; Xiong, Qiyan; Xiao, Shaobo; Shao, Guoqing

    2013-09-15

    Mycoplasma hyopneumoniae is the primary etiological agent of enzootic pneumonia in swine. Lipid-associated membrane proteins (LAMP) of mycoplasma are the main pathogenicity factors in mycoplasma diseases. In this study, we investigated the effects of M. hyopneumoniae LAMP on porcine alveolar macrophage (PAM) 3D4/21 cell line. Apoptotic features, such as chromatin condensation and apoptotic bodies, were observed in LAMP-treated PAM 3D4/21 cells. Moreover, LAMP significantly increased the number of TUNEL positive apoptotic cells in PAM 3D4/21 cells compared with the untreated control. In addition, flow cytometric analysis using dual staining with annexin-V-FITC and propidium iodide (PI) showed that LAMP of M. hyopneumoniae induced a time-dependent apoptosis in PAM 3D4/21 cells. Moreover, increased levels of superoxide anion production and activated caspase-3 in PAM 3D4/21 cells were observed after exposure to LAMP. Increased production of nitric oxide (NO) was also confirmed in the cell supernatants. Besides, apoptotic rates increase and caspase-3 activation were suppressed by NOS inhibitor or antioxidant. It is suggested that LAMP of M. hyopneumoniae induced apoptosis in porcine alveolar macrophage via NO production, superoxide anion production, and caspase-3 activation. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Oxidative stress and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Javier eBlesa

    2015-07-01

    Full Text Available Parkinson disease is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in Parkinson’s Disease. Environmental factors, such as neurotoxins, insecticides like rotenone, pesticides like Paraquat, dopamine itself and genetic mutations in Parkinson’s Disease related proteins contribute to mitochondrial dysfunction which precedes reactive oxygen species formation. In this mini review, we give an update of the classical pathways involving these mechanisms of neurodegeneration, the biochemical and molecular events that mediate or regulate DA neuronal vulnerability, and the role of PD-related gene products in modulating cellular responses to oxidative stress in the course of the neurodegenerative process.

  9. Insight into PreImplantation Factor (PIF* mechanism for embryo protection and development: target oxidative stress and protein misfolding (PDI and HSP through essential RIKP [corrected] binding site.

    Directory of Open Access Journals (Sweden)

    Eytan R Barnea

    Full Text Available Endogenous PIF, upon which embryo development is dependent, is secreted only by viable mammalian embryos, and absent in non-viable ones. Synthetic PIF (sPIF administration promotes singly cultured embryos development and protects against their demise caused by embryo-toxic serum. To identify and characterize critical sPIF-embryo protein interactions novel biochemical and bio-analytical methods were specifically devised.FITC-PIF uptake/binding by cultured murine and equine embryos was examined and compared with scrambled FITC-PIF (control. Murine embryo (d10 lysates were fractionated by reversed-phase HPLC, fractions printed onto microarray slides and probed with Biotin-PIF, IDE and Kv1.3 antibodies, using fluorescence detection. sPIF-based affinity column was developed to extract and identify PIF-protein interactions from lysates using peptide mass spectrometry (LC/MS/MS. In silico evaluation examined binding of PIF to critical targets, using mutation analysis.PIF directly targets viable cultured embryos as compared with control peptide, which failed to bind. Multistep Biotin-PIF targets were confirmed by single-step PIF-affinity column based isolation. PIF binds protein disulfide isomerases a prolyl-4-hydroxylase β-subunit, (PDI, PDIA4, PDIA6-like containing the antioxidant thioredoxin domain. PIF also binds protective heat shock proteins (70&90, co-chaperone, BAG-3. Remarkably, PIF targets a common RIKP [corrected] site in PDI and HSP proteins. Further, single PIF amino acid mutation significantly reduced peptide-protein target bonding. PIF binds promiscuous tubulins, neuron backbones and ACTA-1,2 visceral proteins. Significant anti-IDE, while limited anti-Kv1.3b antibody-binding to Biotin-PIF positive lysates HPLC fractions were documented.Collectively, data identifies PIF shared targets on PDI and HSP in the embryo. Such are known to play a critical role in protecting against oxidative stress and protein misfolding. PIF-affinity-column is a

  10. Oxidative stress and male reproductive health

    Directory of Open Access Journals (Sweden)

    Robert J Aitken

    2014-02-01

    Full Text Available One of the major causes of defective sperm function is oxidative stress, which not only disrupts the integrity of sperm DNA but also limits the fertilizing potential of these cells as a result of collateral damage to proteins and lipids in the sperm plasma membrane. The origins of such oxidative stress appear to involve the sperm mitochondria, which have a tendency to generate high levels of superoxide anion as a prelude to entering the intrinsic apoptotic cascade. Unfortunately, these cells have very little capacity to respond to such an attack because they only possess the first enzyme in the base excision repair (BER pathway, 8-oxoguanine glycosylase 1 (OGG1. The latter successfully creates an abasic site, but the spermatozoa cannot process the oxidative lesion further because they lack the downstream proteins (APE1, XRCC1 needed to complete the repair process. It is the responsibility of the oocyte to continue the BER pathway prior to initiation of S-phase of the first mitotic division. If a mistake is made by the oocyte at this stage of development, a mutation will be created that will be represented in every cell in the body. Such mechanisms may explain the increase in childhood cancers and other diseases observed in the offspring of males who have suffered oxidative stress in their germ line as a consequence of age, environmental or lifestyle factors. The high prevalence of oxidative DNA damage in the spermatozoa of male infertility patients may have implications for the health of children conceivedin vitro and serves as a driver for current research into the origins of free radical generation in the germ line.

  11. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women.

    Science.gov (United States)

    Asemi, Zatollah; Samimi, Mansooreh; Tabassi, Zohreh; Shakeri, Hossein; Esmaillzadeh, Ahmad

    2013-09-01

    Unfavorable metabolic profiles and oxidative stress in pregnancy are associated with several complications. This study was conducted to determine the effects of vitamin D supplementation on serum concentrations of high-sensitivity C-reactive protein (hs-CRP), metabolic profiles, and biomarkers of oxidative stress in healthy pregnant women. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 pregnant women aged 18-40 y old at 25 wk of gestation. Participants were randomly assigned to receive either 400 IU/d cholecalciferol supplements (n = 24) or placebo (n = 24) for 9 wk. Fasting blood samples were taken at study baseline and after 9 wk of intervention to quantify serum concentrations of hs-CRP, lipid concentrations, insulin, and biomarkers of oxidative stress. After 9 wk of intervention, the increases in serum 25-hydroxyvitamin D and calcium concentrations were greater in the vitamin D group (+3.7 μg/L and +0.20 mg/dL, respectively) than in the placebo group (-1.2 μg/L and -0.12 mg/dL, respectively; P insulin concentrations (vitamin D vs. placebo groups: -1.0 vs. +2.6 μIU/mL; P-interaction = 0.04) and a significant increase in the Quantitative Insulin Sensitivity Check Index score (vitamin D vs. placebo groups: +0.02 vs. -0.02; P-interaction = 0.006), plasma total antioxidant capacity (vitamin D vs. placebo groups: +152 vs. -20 mmol/L; P-interaction = 0.002), and total glutathione concentrations (vitamin D vs. placebo groups: +205 vs. -32 μmol/L; P-interaction = 0.02) compared with placebo. Intake of vitamin D supplements led to a significant decrease in fasting plasma glucose (vitamin D vs. placebo groups: -0.65 vs. -0.12 mmol/L; P-interaction = 0.01), systolic blood pressure (vitamin D vs. placebo groups: -0.2 vs. +5.5 mm Hg; P-interaction = 0.01), and diastolic blood pressure (vitamin D vs. placebo groups: -0.4 vs. +3.1 mm Hg; P-interaction = 0.01) compared with placebo. In conclusion, vitamin D supplementation for 9 wk

  12. Implantation of Neural Probes in the Brain Elicits Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Evon S. Ereifej

    2018-02-01

    Full Text Available Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp, and Stearoyl-Coenzyme A desaturase 1 (Scd1 were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1 relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage

  13. Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation

    OpenAIRE

    Celi, Pietro; Gabai, Gianfranco

    2015-01-01

    This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functi...

  14. Oxidant/antioxidant balance in animal nutrition and health: the role of protein oxidation

    OpenAIRE

    Pietro eCeli; Pietro eCeli; Gianfranco eGabai

    2015-01-01

    This review examines the role that oxidative stress, and protein oxidation in particular, plays in nutrition, metabolism and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional m...

  15. Oxidative stress, aging, and diseases

    Directory of Open Access Journals (Sweden)

    Liguori I

    2018-04-01

    Full Text Available Ilaria Liguori,1 Gennaro Russo,1 Francesco Curcio,1 Giulia Bulli,1 Luisa Aran,1 David Della-Morte,2,3 Gaetano Gargiulo,4 Gianluca Testa,1,5 Francesco Cacciatore,1,6 Domenico Bonaduce,1 Pasquale Abete1 1Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy; 2Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 3San Raffaele Roma Open University, Rome, Italy; 4Division of Internal Medicine, AOU San Giovanni di Dio e Ruggi di Aragona, Salerno, Italy; 5Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy; 6Azienda Ospedaliera dei Colli, Monaldi Hospital, Heart Transplantation Unit, Naples, Italy Abstract: Reactive oxygen and nitrogen species (RONS are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer, including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of

  16. [Oxidative stress in station service workers].

    Science.gov (United States)

    Basso, A; Elia, G; Petrozzi, M T; Zefferino, R

    2004-01-01

    The aim of this study is to identify an oxidative stress in service station workers. Previous studies verified an increased incidence of leukemia and myeloma, however other authors haven't verified it. There are reports of nasal, pharyngeal, laryngeal, and lung cancer in service station workers. Our study wants to evaluate the oxidative balance in the fuel workers. We studied 44 subjects with gasoline exposure and 29 control subjects. We determined the blood concentrations of Glutathione reduced and oxidized, Protein sulfhydrylic (PSH) Vitamine E, Vitamine C, Malondialdehyde, Protein oxidized (OX-PROT) and beta carotene. The t test was performed to analyze the differences between the means, the Chi square was used to evaluate the statistical significance of associations between variable categorical (redox index). The Anova test excluded the confusing effect of age, smoke and alcohol habit. The mean age of the workers was 36.6 years, instead the control group was 38. In the workers Glutathione reduced, Vit. E and Beta carotene were lower than in the control subjects, this difference was statistically significant (p < 0.01). The Malondialdehyde concentration was higher in the workers higher than in the control group, but this difference wasn't statistically significant. Our data demonstrated Glutathione, Vit. E, and Beta carotene are useful to verify a reduction of the antioxidant activity. The only marker of the presence of oxidative injury that correlated to work exposure was the malondialdehyde. The redox index was surest marker. The limit of our study is the number of control group, it was little and lower than workers. Conclusively we believe it's useful to continue our studies and, if our results are going to be confirmed, we retain that stress oxidative determination would be verified in occupational medicine using these markers, especially to study exposure of the fuel workers who were investigated less and, in our opinion, would receive more attention.

  17. Oxidative stress and the high altitude environment

    Directory of Open Access Journals (Sweden)

    Jakub Krzeszowiak

    2013-03-01

    Full Text Available In the recent years there has been considerable interest in mountain sports, including mountaineering, owing to the general availability of climbing clothing and equipment as well trainings and professional literature. This raised a new question for the environmental and mountain medicine: Is mountaineering harmful to health? Potential hazards include the conditions existing in the alpine environment, i.e. lower atmospheric pressure leading to the development of hypobaric hypoxia, extreme physical effort, increased UV radiation, lack of access to fresh food, and mental stress. A reasonable measure of harmfulness of these factors is to determine the increase in the level of oxidative stress. Alpine environment can stimulate the antioxidant enzyme system but under specific circumstances it may exceed its capabilities with simultaneous consumption of low-molecular antioxidants resulting in increased generation of reactive oxygen species (ROS. This situation is referred to as oxidative stress. Rapid and uncontrolled proliferation of reactive oxygen species leads to a number of adverse changes, resulting in the above-average damage to the lipid structures of cell membranes (peroxidation, proteins (denaturation, and nucleic acids. Such situation within the human body cannot take place without resultant systemic consequences. This explains the malaise of people returning from high altitude and a marked decrease in their physical fitness. In addition, a theory is put forward that the increase in the level of oxidative stress is one of the factors responsible for the onset of acute mountain sickness (AMS. However, such statement requires further investigation because the currently available literature is inconclusive. This article presents the causes and effects of development of oxidative stress in the high mountains.

  18. Oxidative stress signaling to chromatin in health and disease

    KAUST Repository

    Kreuz, Sarah

    2016-06-20

    Oxidative stress has a significant impact on the development and progression of common human pathologies, including cancer, diabetes, hypertension and neurodegenerative diseases. Increasing evidence suggests that oxidative stress globally influences chromatin structure, DNA methylation, enzymatic and non-enzymatic post-translational modifications of histones and DNA-binding proteins. The effects of oxidative stress on these chromatin alterations mediate a number of cellular changes, including modulation of gene expression, cell death, cell survival and mutagenesis, which are disease-driving mechanisms in human pathologies. Targeting oxidative stress-dependent pathways is thus a promising strategy for the prevention and treatment of these diseases. We summarize recent research developments connecting oxidative stress and chromatin regulation.

  19. Chinese mitten crab (Eriocheir sinensis) iron-sulphur cluster assembly protein 2 (EsIscA2) is differentially regulated after immune and oxidative stress challenges.

    Science.gov (United States)

    Zhang, Peng; Liu, Yu; Wang, Min; Dong, Miren; Liu, Zhaoqun; Jia, Zhihao; Wang, Weilin; Zhang, Anguo; Wang, Lingling; Song, Linsheng

    2018-07-01

    stimulation (p < 0.05). When the primary cultured crab hemocytes were incubated with different concentrations of H 2 O 2 for 15 min, the expression level of EsIscA2 mRNA was significantly repressed to the 0.34-0.44-fold of that in the control group. After A. hydrophila stimulation, the mRNA expression of EsGrx2 was up-regulated at 3 h (3.22-fold compared to control group, p < 0.05) and reached the peak at 12 h (4.88-fold, p < 0.05). All these results suggested that EsIscA2 had iron-binding capabilities as observed in IscA proteins from other organisms, supporting the role of EsIscA2 as a mitochondrial iron donor for ISC synthesis in Chinese mitten crab. Its differential mRNA expression after immune and oxidative stress challenges suggested the adaptations of ISC synthesis rates to these stress conditions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Oxidative stress in ageing of hair.

    Science.gov (United States)

    Trüeb, Ralph M

    2009-01-01

    Experimental evidence supports the hypothesis that oxidative stress plays a major role in the ageing process. Reactive oxygen species are generated by a multitude of endogenous and environmental challenges. Reactive oxygen species or free radicals are highly reactive molecules that can directly damage cellular structural membranes, lipids, proteins, and DNA. The body possesses endogenous defence mechanisms, such as antioxidative enzymes and non-enzymatic antioxidative molecules, protecting it from free radicals by reducing and neutralizing them. With age, the production of free radicals increases, while the endogenous defence mechanisms decrease. This imbalance leads to the progressive damage of cellular structures, presumably resulting in the ageing phenotype. Ageing of hair manifests as decrease of melanocyte function or graying, and decrease in hair production or alopecia. There is circumstantial evidence that oxidative stress may be a pivotal mechanism contributing to hair graying and hair loss. New insights into the role and prevention of oxidative stress could open new strategies for intervention and reversal of the hair graying process and age-dependent alopecia.

  1. Regulation of death induction and chemosensitizing action of 3-bromopyruvate in myeloid leukemia cells: energy depletion, oxidative stress, and protein kinase activity modulation.

    Science.gov (United States)

    Calviño, Eva; Estañ, María Cristina; Sánchez-Martín, Carlos; Brea, Rocío; de Blas, Elena; Boyano-Adánez, María del Carmen; Rial, Eduardo; Aller, Patricio

    2014-02-01

    3-Bromopyruvate (3-BrP) is an alkylating, energy-depleting drug that is of interest in antitumor therapies, although the mechanisms underlying its cytotoxicity are ill-defined. We show here that 3-BrP causes concentration-dependent cell death of HL60 and other human myeloid leukemia cells, inducing both apoptosis and necrosis at 20-30 μM and a pure necrotic response at 60 μM. Low concentrations of 3-BrP (10-20 μM) brought about a rapid inhibition of glycolysis, which at higher concentrations was followed by the inhibition of mitochondrial respiration. The combination of these effects causes concentration-dependent ATP depletion, although this cannot explain the lethality at intermediate 3-BrP concentrations (20-30 μM). The oxidative stress caused by exposure to 3-BrP was evident as a moderate overproduction of reactive oxygen species and a concentration-dependent depletion of glutathione, which was an important determinant of 3-BrP toxicity. In addition, 3-BrP caused glutathione-dependent stimulation of p38 mitogen-activated protein kinase (MAPK), mitogen-induced extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK), and protein kinase B (Akt)/mammalian target of rapamycin/p70S6K phosphorylation or activation, as well as rapid LKB-1/AMP kinase (AMPK) activation, which was later followed by Akt-mediated inactivation. Experiments with pharmacological inhibitors revealed that p38 MAPK activation enhances 3-BrP toxicity, which is conversely restrained by ERK and Akt activity. Finally, 3-BrP was seen to cooperate with antitumor agents like arsenic trioxide and curcumin in causing cell death, a response apparently mediated by both the generation of oxidative stress induced by 3-BrP and the attenuation of Akt and ERK activation by curcumin. In summary, 3-BrP cytotoxicity is the result of several combined regulatory mechanisms that might represent important targets to improve therapeutic efficacy.

  2. Protein oxidation in muscle foods: A review

    DEFF Research Database (Denmark)

    Lund, Marianne; Heinonen, Marina; Baron, Caroline P.

    2011-01-01

    insight into the reactions involved in the oxidative modifications undergone by muscle proteins. Moreover, a variety of products derived from oxidized muscle proteins, including cross-links and carbonyls, have been identified. The impact of oxidation on protein functionality and on specific meat quality...... and consequences of Pox in muscle foods. The efficiency of different anti-oxidant strategies against the oxidation of muscle proteins is also reported.......Protein oxidation in living tissues is known to play an essential role in the pathogenesis of relevant degenerative diseases, whereas the occurrence and impact of protein oxidation (Pox) in food systems have been ignored for decades. Currently, the increasing interest among food scientists...

  3. Glucose-regulated protein 75 determines ER–mitochondrial coupling and sensitivity to oxidative stress in neuronal cells

    NARCIS (Netherlands)

    Honrath, Birgit; Metz, Isabell; Bendridi, Nadia; Rieusset, Jennifer; Culmsee, Carsten; Dolga, Amalia Mihalea

    2017-01-01

    The crosstalk between different organelles allows for the exchange of proteins, lipids and ions. Endoplasmic reticulum (ER) and mitochondria are physically linked and signal through the mitochondria-associated membrane (MAM) to regulate the transfer of Ca2+ from ER stores into the mitochondrial

  4. HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

    Directory of Open Access Journals (Sweden)

    Khadija Rebbani

    2016-01-01

    Full Text Available About 150 million people worldwide are chronically infected with hepatitis C virus (HCV. The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24 is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.

  5. Oxidative stress in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Shyamal K Goswami

    2015-01-01

    Full Text Available Oxidative stress caused by various oxygen containing free radicals and reactive species (collectively called "Reactive Oxygen Species" or ROS has long been attributed to cardiovascular diseases. In human body, major oxidizing species are super oxide, hydrogen peroxide, hydroxyl radical, peroxy nitrite etc. ROS are produced from distinct cellular sources, enzymatic and non-enzymatic; have specific physicochemical properties and often have specific cellular targets. Although early studies in nineteen sixties and seventies highlighted the deleterious effects of these species, later it was established that they also act as physiological modulators of cellular functions and diseases occur only when ROS production is deregulated. One of the major sources of cellular ROS is Nicotinamide adenine dinucleotide phosphate oxidases (Noxes that are expressed in almost all cell types. Superoxide and hydrogen peroxide generated from them under various conditions act as signal transducers. Due to their immense importance in cellular physiology, various Nox inhibitors are now being developed as therapeutics. Another free radical of importance in cardiovascular system is nitric oxide (a reactive nitrogen species generated from nitric oxide synthase(s. It plays a critical role in cardiac function and its dysregulated generation along with superoxide leads to the formation of peroxynitrite a highly deleterious agent. Despite overwhelming evidences of association between increased level of ROS and cardiovascular diseases, antioxidant therapies using vitamins and omega 3 fatty acids have largely been unsuccessful till date. Also, there are major discrepancies between studies with laboratory animals and human trials. It thus appears that the biology of ROS is far complex than anticipated before. A comprehensive understanding of the redox biology of diseases is thus needed for developing targeted therapeutics.

  6. Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells.

    Science.gov (United States)

    Yao, Takako; Fujimura, Tsutomu; Murayama, Kimie; Okumura, Ko; Seko, Yoshinori

    2017-10-18

    We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself.

  7. Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats.

    Science.gov (United States)

    Nasri, Rim; Abdelhedi, Ola; Jemil, Ines; Daoued, Ines; Hamden, Khaled; Kallel, Choumous; Elfeki, Abdelfattah; Lamri-Senhadji, Myriem; Boualga, Ahmed; Nasri, Moncef; Karra-Châabouni, Maha

    2015-12-05

    This study investigated the therapeutic potential of undigested goby fish (Zosterisessor ophiocephalus) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Liver Growth Factor (LGF Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

    Directory of Open Access Journals (Sweden)

    Lucía Calatrava-Ferreras

    2016-12-01

    Full Text Available Friedreich’s ataxia (FA is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF, which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXNYG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 μg/mouse exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold and heart (1.2-fold. LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.

  9. Oxidative Stress in Cystinosis Patients

    Directory of Open Access Journals (Sweden)

    Maria Helena Vaisbich

    2011-09-01

    Full Text Available Background/Aims: Nephropathic cystinosis (NC is a severe systemic disease and cysteamine improves its prognosis. Lysosomal cystine accumulation is the hallmark of cystinosis and is regarded as the primary defect due to mutations in the CTNS gene. However, there is great evidence that cystine accumulation itself is not responsible for all abnormalities observed in NC. Studies have demonstrated altered ATP metabolism, increased apoptosis, and cell oxidation. An increased number of autophagosomes and autophagic vacuoles have been observed in cystinotic fibroblasts and renal epithelial cells, suggesting that altered autophagy plays a role in NC, leading to increased production of reactive oxygen species. Therefore, cystinosis patients can be more susceptible to oxidative stress (OS and it can contribute to the progression of the renal disease. Our goal was to evaluate a marker of OS (serum TBARS in NC children, and to compare the results with those observed in healthy controls and correlated with renal function parameters. Methods: The study included patients aged under 18 years, with good adherence to the treatment and out of renal replacement therapy. The following parameters were evaluated: serum creatinine, BUN, creatinine clearance estimated by stature and serum TBARS levels. Results: We selected 20 patients aged 8.0 ±3.6 years and observed serum TBARS levels of 4.03 ±1.02 nmol/ml. Serum TBARS levels in the 43 healthy controls, aged 7.4 ±1.1 years, were 1.60 ±0.04 nmol/ml. There was a significant difference between the plasma TBARS levels among the 2 groups (p Conclusion: An increased level of serum TBARS in patients with NC was observed and this abnormality was not correlated with the renal function status degree. This is the first report that shows increased oxidative stress in serum of NC patients.

  10. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells

    Directory of Open Access Journals (Sweden)

    Müller Sylke

    2009-05-01

    Full Text Available Abstract Background Plasmodium falciparum-parasitized red blood cells (RBCs are equipped with protective antioxidant enzymes and heat shock proteins (HSPs. The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Methods Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. Results In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of

  11. Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

    Science.gov (United States)

    Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

    2009-05-29

    Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of

  12. Impact of Oxidative Stress in Fetal Programming

    OpenAIRE

    Thompson, Loren P.; Al-Hasan, Yazan

    2012-01-01

    Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that pr...

  13. Impact of Oxidative Stress in Fetal Programming

    Directory of Open Access Journals (Sweden)

    Loren P. Thompson

    2012-01-01

    Full Text Available Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

  14. Oxidant/Antioxidant Balance in Animal Nutrition and Health: The Role of Protein Oxidation.

    Science.gov (United States)

    Celi, Pietro; Gabai, Gianfranco

    2015-01-01

    This review examines the role that oxidative stress (OS), and protein oxidation in particular, plays in nutrition, metabolism, and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions, such as respiratory diseases and parasitic infection; however, some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions, such as reproduction, nutrition, metabolism, lactation, gut health, and neonatal physiology. As the characterization of the mechanisms by which OS may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins.

  15. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins.

    Directory of Open Access Journals (Sweden)

    Chunxiang Yao

    Full Text Available Reactive protein cysteine thiolates are instrumental in redox regulation. Oxidants, such as hydrogen peroxide (H2O2, react with thiolates to form oxidative post-translational modifications, enabling physiological redox signaling. Cardiac disease and aging are associated with oxidative stress which can impair redox signaling by altering essential cysteine thiolates. We previously found that cardiac-specific overexpression of catalase (Cat, an enzyme that detoxifies excess H2O2, protected from oxidative stress and delayed cardiac aging in mice. Using redox proteomics and systems biology, we sought to identify the cysteines that could play a key role in cardiac disease and aging. With a 'Tandem Mass Tag' (TMT labeling strategy and mass spectrometry, we investigated differential reversible cysteine oxidation in the cardiac proteome of wild type and Cat transgenic (Tg mice. Reversible cysteine oxidation was measured as thiol occupancy, the ratio of total available versus reversibly oxidized cysteine thiols. Catalase overexpression globally decreased thiol occupancy by ≥1.3 fold in 82 proteins, including numerous mitochondrial and contractile proteins. Systems biology analysis assigned the majority of proteins with differentially modified thiols in Cat Tg mice to pathways of aging and cardiac disease, including cellular stress response, proteostasis, and apoptosis. In addition, Cat Tg mice exhibited diminished protein glutathione adducts and decreased H2O2 production from mitochondrial complex I and II, suggesting improved function of cardiac mitochondria. In conclusion, our data suggest that catalase may alleviate cardiac disease and aging by moderating global protein cysteine thiol oxidation.

  16. Assessment of the degree of oxidative stress injury, renin-angiotensin system activity and podocyte loss after combined treatment of keto acid with low protein diet for patients with diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Yuan-Hua Xu

    2016-03-01

    Full Text Available Objective: To analyze the degree of oxidative stress injury, RAS activity and podocyte loss after patients with diabetic nephropathy received keto acid combined with low protein diet. Methods: A total of 106 cases of patients with diabetic nephropathy who received hospital treatment in our hospital from September 2012 to July 2015 were selected as research subjects and randomly divided into observation group and control group according to different treatment, each group with 53 cases. Control group received low protein diet treatment alone, observation group received keto acid combined with low protein diet treatment, and then the degree of oxidative stress injury, RAS activity and podocyte loss of two groups were compared. Results: Serum MDA and AOPP levels of observation group after treatment were lower than those of control group, and levels of SOD and T-AOC were higher than those of control group; PRA, Ang栻 and Aldosterone levels of observation group after treatment were lower than those of control group; mRNA expression levels of podocin and synaptopodin in urine sediment of observation group after treatment were lower than those of control group. Conclusion: Keto acid combined with low protein diet treatment for patients with diabetic nephropathy can reduce the degree of oxidative stress injury and RAS activity, decrease podocyte loss and optimize patients’ condition.

  17. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

    Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

  18. Oxidative stress, thyroid dysfunction & Down syndrome

    Directory of Open Access Journals (Sweden)

    Carlos Campos

    2015-01-01

    Full Text Available Down syndrome (DS is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation. Thyroid dysfunction is the most typical endocrine abnormality in patients with DS. It is well known that thyroid dysfunction is highly prevalent in children and adults with DS and that both hypothyroidism and hyperthyroidism are more common in patients with DS than in the general population. Increasing evidence has shown that DS individuals are under unusual increased oxidative stress, which may be involved in the higher prevalence and severity of a number of pathologies associated with the syndrome, as well as the accelerated ageing observed in these individuals. The gene for Cu/Zn superoxide dismutase (SOD1 is coded on chromosome 21 and it is overexpressed (~50% resulting in an increase of reactive oxygen species (ROS due to overproduction of hydrogen peroxide (H 2 O 2 . ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS.

  19. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Science.gov (United States)

    Duan, Xiaochun; Wen, Zunjia; Shen, Haitao; Shen, Meifen

    2016-01-01

    Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH). Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI) following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER) stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches. PMID:27190572

  20. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Xiaochun Duan

    2016-01-01

    Full Text Available Hemorrhagic stroke is a common and severe neurological disorder and is associated with high rates of mortality and morbidity, especially for intracerebral hemorrhage (ICH. Increasing evidence demonstrates that oxidative stress responses participate in the pathophysiological processes of secondary brain injury (SBI following ICH. The mechanisms involved in interoperable systems include endoplasmic reticulum (ER stress, neuronal apoptosis and necrosis, inflammation, and autophagy. In this review, we summarized some promising advances in the field of oxidative stress and ICH, including contained animal and human investigations. We also discussed the role of oxidative stress, systemic oxidative stress responses, and some research of potential therapeutic options aimed at reducing oxidative stress to protect the neuronal function after ICH, focusing on the challenges of translation between preclinical and clinical studies, and potential post-ICH antioxidative therapeutic approaches.

  1. Less Stress : Oxidative stress and glutathione kinetics in preterm infants

    NARCIS (Netherlands)

    D. Rook (Denise)

    2013-01-01

    textabstractDue to immature antioxidant defenses, preterm infants are at susceptible to oxidative stress, which is associated with bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia. The general aim of this thesis was to study oxidative stress in preterm infants

  2. [Biological consequences of oxidative stress induced by pesticides].

    Science.gov (United States)

    Grosicka-Maciąg, Emilia

    2011-06-17

    Pesticides are used to protect plants and numerous plant products. They are also utilized in several industrial branches. These compounds are highly toxic to living organisms. In spite of close supervision in the use of pesticides there is a serious risk that these agents are able to spread into the environment and contaminate water, soil, food, and feedstuffs. Recently, more and more studies have been focused on understanding the toxic mechanisms of pesticide actions. The data indicate that the toxic action of pesticides may include the induction of oxidative stress and accumulation of free radicals in the cell. Long-lasting or acute oxidative stress disturbs cell metabolism and is able to produce permanent changes in the structure of proteins, lipids, and DNA. The proteins that are oxidized may lose or enhance their activity. Moreover, the proteins oxidized are able to form aggregates that inhibit the systems responsible for protein degradation and lead to alterations of proteins in the cell. Once oxidized, lipids have the capacity to damage and depolarize cytoplasmic membranes. Free oxygen radicals are harmful to DNA including damage to single nitric bases, DNA strand breaks and adduct production. Many studies indicate that oxidative stress may accelerate development of numerous diseases including cancer and neurodegenerative ones such as Alzheimer’s and Parkinson’s disease and may also be responsible for infertility.

  3. Assessment of the degree of oxidative stress injury, renin-angiotensin system activity and podocyte loss after combined treatment of keto acid with low protein diet for patients with diabetic nephropathy

    OpenAIRE

    Yuan-Hua Xu; Mei Wang

    2016-01-01

    Objective: To analyze the degree of oxidative stress injury, RAS activity and podocyte loss after patients with diabetic nephropathy received keto acid combined with low protein diet. Methods: A total of 106 cases of patients with diabetic nephropathy who received hospital treatment in our hospital from September 2012 to July 2015 were selected as research subjects and randomly divided into observation group and control group according to different treatment, each group with 53...

  4. Isolation and characterization of a metallothionein-1 protein in Chloris virgata Swartz that enhances stress tolerances to oxidative, salinity and carbonate stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Nishiuchi, Shunsaku; Liu, Shenkui; Takano, Tetsuo

    2007-08-01

    Chloris virgata Swartz (C. virgata) is a gramineous wild plant that is found in alkaline soil areas in northeast China and is highly tolerant to carbonate stress. We constructed a cDNA library from C. virgata seedlings treated with NaHCO(3), and isolated a type 1 metallothionein (MT1) gene (ChlMT1: AB294238) from the library. The amino acid sequence of ChlMT1 contained 12 cysteine residues that constituted the Cys-X-Cys (X = amino acid except Cys) motifs in the N- and C-terminal regions. Northern hybridization showed that expression of ChlMT1 was induced by several abiotic stresses, from salts (NaCl and NaHCO(3)), a ROS inducer (paraquat), and metals (CuSO(4), ZnSO(4), and CoCl(2)). ChlMT1 expression in leaf was induced by 200 mM NaCl and 100 mM NaHCO(3). About 5 microM Paraquat, 500 microM Zn(2+), and 500 microM Co(2+) also induced expression of ChlMT1 in leaf after 6 h, and 100 microM Cu(2+) induced it after 24 h. Saccharomyces cerevisiae when transformed with the ChlMT1 gene had dramatically increased tolerances to salts (NaCl and NaHCO(3)) and ROS.

  5. Oxidative stress in primary glomerular diseases

    DEFF Research Database (Denmark)

    Markan, Suchita; Kohli, Harbir Singh; Sud, Kamal

    2008-01-01

    To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure.......To evaluate the status of oxidative stress in patients with different primary glomerular diseases (PGD) which have differential predisposition to renal failure....

  6. Primary and secondary oxidative stress in Bacillus

    NARCIS (Netherlands)

    Mols, Maarten; Abee, Tjakko

    Coping with oxidative stress originating from oxidizing compounds or reactive oxygen species (ROS), associated with the exposure to agents that cause environmental stresses, is one of the prerequisites for an aerobic lifestyle of Bacillus spp. such as B. subtilis, B. cereus and B. anthracis. This

  7. Primary and secondary oxidative stress in Bacillus

    NARCIS (Netherlands)

    Mols, J.M.; Abee, T.

    2011-01-01

    Coping with oxidative stress originating from oxidizing compounds or reactive oxygen species (ROS), associated with the exposure to agents that cause environmental stresses, is one of the prerequisites for an aerobic lifestyle of Bacillus spp. such as B. subtilis, B. cereus and B. anthracis. This

  8. A STUDY OF OXIDATIVE STRESS IN DIABETES

    Directory of Open Access Journals (Sweden)

    Babu Rao

    2015-06-01

    Full Text Available Non - enzymatic free radical mediated oxidation of biological molecules, membranes and tissues is associated with a variety of pathological events such as cancer, aging and diabetes mellitus . [1] Increased oxidative stress is seen in both types of diabetes me llitus namely type 1 and type 2, irrespective of duration, complications and treatment. In diabetes mellitus, oxidative stress seems primarily due to both an increased plasma free radical concentration and a sharp decline in antioxidant defences . [1] Among the causes of enhanced free radical production, hyperglycemia and hyper insulinemia seem to play a major role , [2,3] Hyperglycemia is the more easily modifiable factor among the two and good glycemic control can reduce the oxidative stress. Controversy pers ists regarding the other possible mechanisms of increased oxidative stress in diabetes and whether oxidative stress normalizes with adequate metabolic control alone. The role of oxidative stress and diabetic complications has been extensively investigated. Oxidative stress has been suggested to be involved in the genesis of both macro and micro angiopathy [4,5] Prospective trials are now underway addressing the controversial issues of possible role of pharmacological antioxidants in preventing or at least de laying the onset of diabetic complications.

  9. Power of Proteomics in Linking Oxidative Stress and Female Infertility

    Science.gov (United States)

    Gupta, Sajal; Sharma, Rakesh; Agarwal, Ashok

    2014-01-01

    Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions. PMID:24900998

  10. Power of Proteomics in Linking Oxidative Stress and Female Infertility

    Directory of Open Access Journals (Sweden)

    Sajal Gupta

    2014-01-01

    Full Text Available Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM, cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.

  11. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome.

    Science.gov (United States)

    Madani, Zohra; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J; Ait Yahia, Dalila

    2012-02-01

    The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective

  12. Influence of oxidative stress on disease development

    Directory of Open Access Journals (Sweden)

    Božić Tatjana

    2013-01-01

    Full Text Available There is ever increasing data indicating the vmast contribution of oxidative stress to the pathogenesis of numerous diseases (atherosclerosis, hypertension, heart failure, diabetes mellitus, stroke, rheumatoid arthritis, and others. Thus, in the pathogenesis of atherosclerosis the primary role is held by reactive oxygen species that are synthetized by endothelial cells of arterial blood vessels, leukocytes and macrophages. Furthermore, native particles of lipoproteins of small density become atherogenic through oxidation caused by reactive oxygen species. The oxidation of small-density lipoproteins stimulates the inflammatory process, and it in turn steps up adhesion and the inflow of monocytes and affects the synthesis and release of numerous proinflammatory cytokines involved in the further course of the process. One of the reasons for the development of arterial hypertension is the simultaneous activation of NAD(PH oxidase and 12/15-lipoxygenase, since it results in the stepped up production of reactive oxygen species. These stimulate the production of matrix metalloproteinase 2, which lead to vascular remodelling and to increased apoptosis of heart muscle cells. Stepped up apoptosis is linked with myocardial infarction, cardiomyopathies and the development of heart failure. The sensitivity of β-cells of the endocrine part of the pancreas to reactive oxygen species favor the naturally low concentrations of the collectors of free radicals in them, as well as an increase in the concentration of proinflammatory cytokines, glucosis and lipids that induce a reduction in the mass and function of β-cells. Hyperglycemia in diabetes mellitus causes tissue damage through non-enzyme glycosylation of intracellular and extracellular proteins, which results in: reduced enzyme activity, damaged nucleic acid, disrupted natural decomposition of proteins, and activation of cytotoxic pathways. These processes are the basis of the pathogenesis of numerous

  13. Oxidative stress in patients with endodontic pathologies

    Directory of Open Access Journals (Sweden)

    Vengerfeldt V

    2017-08-01

    Full Text Available Veiko Vengerfeldt,1 Reet Mändar,2,3 Mare Saag,1 Anneli Piir,2 Tiiu Kullisaar2 1Institute of Dental Sciences, Faculty of Medicine, University of Tartu, 2Institute of Biomedicine and Translational Medicine, Faculty of Medicine, University of Tartu, 3Competence Centre on Health Technologies, Tartu, Estonia Background: Apical periodontitis (AP is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful.Purpose: To compare oxidative stress (OxS levels in the saliva and the endodontium (root canal [RC] contents in patients with different endodontic pathologies and in endodontically healthy subjects.Patients and methods: The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP, 26 with posttreatment or secondary chronic apical periodontitis (sCAP, eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material were collected under strict aseptic conditions using the Hedström file. The samples were frozen to −80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI] were detected in the saliva and the endodontium. Results: The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p=0.004; OSI 6.0 vs 10.4, p<0

  14. Interferon-¿ regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.

    2002-01-01

    Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...

  15. Oxidative stress and maternal obesity: feto-placental unit interaction.

    Science.gov (United States)

    Malti, N; Merzouk, H; Merzouk, S A; Loukidi, B; Karaouzene, N; Malti, A; Narce, M

    2014-06-01

    To determine oxidative stress markers in maternal obesity during pregnancy and to evaluate feto-placental unit interaction, especially predictors of fetal metabolic alterations. 40 obese pregnant women (prepregnancy BMI > 30 kg/m²) were compared to 50 control pregnant women. Maternal, cord blood and placenta samples were collected at delivery. Biochemical parameters (total cholesterol and triglycerides) and oxidative stress markers (malondialdehyde, carbonyl proteins, superoxide anion expressed as reduced Nitroblue Tetrazolium, nitric oxide expressed as nitrite, reduced glutathione, catalase, superoxide dismutase) were assayed by biochemical methods. Maternal, fetal and placental triglyceride levels were increased in obese group compared to control. Maternal malondialdehyde, carbonyl proteins, nitric oxide and superoxide anion levels were high while reduced glutathione concentrations and superoxide dismutase activity were low in obesity. In the placenta and in newborns of these obese mothers, variations of redox balance were also observed indicating high oxidative stress. Maternal and placental interaction constituted a strong predictor of fetal redox variations in obese pregnancies. Maternal obesity compromised placental metabolism and antioxidant status which strongly impacted fetal redox balance. Oxidative stress may be one of the key downstream mediators that initiate programming of the offspring. Maternal obesity is associated with metabolic alterations and dysregulation of redox balance in the mother-placenta - fetus unit. These perturbations could lead to maternal and fetal complications and should be carefully considered. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Photodynamic Therapy Oxidative Stress as a Molecular Switch Controlling Therapeutic Gene Expression for the Treatment of Locally Recurrent Breast Carcinoma

    National Research Council Canada - National Science Library

    Gomer, Charles

    2002-01-01

    ... a procedure offering local tumoricidal activity. We have demonstrated that PDT-mediated oxidative stress is a strong transcriptional inducer of stress proteins belonging to the heat shock protein (hsp...

  17. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

    Ageing is a process characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-related diseases and death. Several hundred theories have attempted to explain this phenomenon. One of the most popular is the 'oxidative stress theory', originally termed the 'free radical theory'. The endocrine system seems to have a role in the modulation of oxidative stress; however, much less is known about the role that oxidative stress might have in the ageing of the endocrine system and the induction of age-related endocrine diseases. This Review outlines the interactions between hormones and oxidative metabolism and the potential effects of oxidative stress on ageing of endocrine organs. Many different mechanisms that link oxidative stress and ageing are discussed, all of which converge on the induction or regulation of inflammation. All these mechanisms, including cell senescence, mitochondrial dysfunction and microRNA dysregulation, as well as inflammation itself, could be targets of future studies aimed at clarifying the effects of oxidative stress on ageing of endocrine glands.

  18. Oxidative stress and histopathological changes induced by ...

    African Journals Online (AJOL)

    These authors contributed equally to this work. Abstract: ... Oxidative stress has been proposed as a pos- sible mechanism involved .... to the Natural Health Institute of Health Guidelines for. Animal Care and ..... Journal of American College of.

  19. Post-Electrophoretic Identification of Oxidized Proteins

    Science.gov (United States)

    Conrad, Craig C; Talent, John M; Malakowsky, Christina A

    1999-01-01

    The oxidative modification of proteins has been shown to play a major role in a number of human diseases. However, the ability to identify specific proteins that are most susceptible to oxidative modifications is difficult. Separation of proteins using polyacrylamide gel electrophoresis (PAGE) offers the analytical potential for the recovery, amino acid sequencing, and identification of thousands of individual proteins from cells and tissues. We have developed a method to allow underivatized proteins to be electroblotted onto PVDF membranes before derivatization and staining. Since both the protein and oxidation proteins are quantifiable, the specific oxidation index of each protein can be determined. The optimal sequence and conditions for the staining process are (a) electrophoresis, (b) electroblotting onto PVDF membranes, (c) derivatization of carbonyls with 2,4-DNP, (d) immunostaining with anti DNP antibody, and (e) protein staining with colloidal gold. PMID:12734585

  20. Food-derived bioactive peptides on inflammation and oxidative stress.

    Science.gov (United States)

    Chakrabarti, Subhadeep; Jahandideh, Forough; Wu, Jianping

    2014-01-01

    Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions. Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

  1. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    Full Text Available

    Inflammation is a common response in the human liver. It is involved in chronic hepatitis, cirrhosis, steatosis, ischemiareperfusion damage, hepatocarcinomas and in the development of metastasis. Reactive oxygen species (ROS production is part of the inflammatory processes. It is implicated in many physiological and pathological situations and can induce mutations in key cancer genes. Normally, this process is prevented by DNA repair enzymatic systems that maintain sequence fidelity during DNA replication. However, overproduction of free radicals in chronic inflammatory diseases is thought to saturate the ability of the cell to repair DNA damage prior to replications. Inflammation-induced genetic damage is not unique to the liver, and it might contribute to the development of mutations in several organs. An example is the chronic inflammatory response in ulcerative colitis that ultimately could lead to neoplasia.

    There is compelling evidence to suggest that most known environmental risk factors for HCC development lead to generation of reactive oxygen species (ROS. Indeed, hepatitis C virus (HCV, alcohol and hepatitis B virus (HBV have all been associated with oxidative stress. Direct production of oxidative stress by HCV core protein has been shown. A link between oxidative stress and liver pathogenesis is also supported by the successful use of antioxidant therapy to treat liver injury caused by chronic HCV infection, although it is not currently used for effective therapy. Ethanol metabolism via the alcohol dehydrogenase pathway and microsomal ethanol oxidizing system contribute substantially to the production of acetaldehyde and generation of ROS. HBx via its association with mitochondria has been shown to induce oxidative stress which in turn leads to activation of a

  2. Influence of Oxidative Stress on Stored Platelets

    Directory of Open Access Journals (Sweden)

    K. Manasa

    2016-01-01

    Full Text Available Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions.

  3. Oxidant/antioxidant balance in animal nutrition and health: the role of protein oxidation

    Directory of Open Access Journals (Sweden)

    Pietro eCeli

    2015-10-01

    Full Text Available This review examines the role that oxidative stress, and protein oxidation in particular, plays in nutrition, metabolism and health of farm animals. The route by which redox homeostasis is involved in some important physiological functions and the implications of the impairment of oxidative status on animal health and diseases is also examined. Proteins have various and, at the same time, unique biological functions and their oxidation can result in structural changes and various functional modifications. Protein oxidation seems to be involved in pathological conditions such as respiratory diseases and parasitic infection; however some studies also suggest that protein oxidation plays a crucial role in the regulation of important physiological functions such as reproduction, nutrition, metabolism, lactation, gut health and neonatal physiology. As the characterization of the mechanisms by which oxidative stress may influence metabolism and health is attracting considerable scientific interest, the aim of this review is to present veterinary scientists and clinicians with various aspects of oxidative damage to proteins.

  4. Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation

    Directory of Open Access Journals (Sweden)

    Thomas L. Lynch

    2015-01-01

    Full Text Available Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C. However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM expressing a homozygous MYBPC3 mutation (cMyBP-C(t/t was used, compared to wild-type (WT mice. Echocardiography confirmed decreased percentage of fractional shortening in DCM versus WT hearts. Histopathological analysis indicated a significant increase in myocardial disarray and fibrosis while the second harmonic generation imaging revealed disorganized sarcomeric structure and myocyte damage in DCM hearts when compared to WT hearts. Intriguingly, DCM mouse heart homogenates had decreased glutathione (GSH/GSSG ratio and increased protein carbonyl and lipid malondialdehyde content compared to WT heart homogenates, consistent with elevated oxidative stress. Importantly, a similar result was observed in human cardiomyopathy heart homogenate samples. These results were further supported by reduced signals for mitochondrial semiquinone radicals and Fe-S clusters in DCM mouse hearts measured using electron paramagnetic resonance spectroscopy. In conclusion, we demonstrate elevated oxidative stress in MYPBC3-mutated DCM mice, which may exacerbate the development of heart failure.

  5. Haptoglobin is required to prevent oxidative stress and muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Enrico Bertaggia

    Full Text Available BACKGROUND: Oxidative stress (OS plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/- to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD, OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

  6. Oxidative stress and antioxidant defenses in pregnant women.

    Science.gov (United States)

    Leal, Claudio A M; Schetinger, Maria R C; Leal, Daniela B R; Morsch, Vera M; da Silva, Aleksandro Schafer; Rezer, João F P; de Bairros, André Valle; Jaques, Jeandre Augusto Dos Santos

    2011-01-01

    Oxidative stress (OS) is defined as an imbalance in the production of reactive oxygen species and the capacity of antioxidant defenses. The objective of this work was to investigate OS and antioxidant capacity in pregnant women. Parameters of the oxidative status and antioxidant capacity in serum and whole blood were evaluated in thirty-nine women with normal pregnancy. The assessment of antioxidants indicated an increase in superoxide dismutase and catalase activities (P0.05) in protein carbonylation. This study demonstrates that there is a change in the pro-oxidant and antioxidant defenses associated with body and circulation changes that are inherent to the pregnancy process.

  7. Oxidative Stress and Anesthesia in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Peivandi Yazdi A

    2014-04-01

    Full Text Available Free radical and peroxide production lead to intracellular damage. On the other hand, free radicals are used by the human immune system to defend against pathogens. The aging process could be limited by oxidative stress in the short term. Chronic diseases like diabetes mellitus (DM are full-stress conditions in which remarkable metabolic functional destructions might happen. There is strong evidence regarding antioxidant impairment in diabetes. Performing a particular method for anesthesia in diabetic patients might prevent or modify excessive free radical formation and oxidative stress. It seems that prescribing antioxidant drugs could promote wound healing in diabetics.  

  8. Oxidative Stress, Prooxidants, and Antioxidants: The Interplay

    Directory of Open Access Journals (Sweden)

    Anu Rahal

    2014-01-01

    Full Text Available Oxidative stress is a normal phenomenon in the body. Under normal conditions, the physiologically important intracellular levels of reactive oxygen species (ROS are maintained at low levels by various enzyme systems participating in the in vivo redox homeostasis. Therefore, oxidative stress can also be viewed as an imbalance between the prooxidants and antioxidants in the body. For the last two decades, oxidative stress has been one of the most burning topics among the biological researchers all over the world. Several reasons can be assigned to justify its importance: knowledge about reactive oxygen and nitrogen species production and metabolism; identification of biomarkers for oxidative damage; evidence relating manifestation of chronic and some acute health problems to oxidative stress; identification of various dietary antioxidants present in plant foods as bioactive molecules; and so on. This review discusses the importance of oxidative stress in the body growth and development as well as proteomic and genomic evidences of its relationship with disease development, incidence of malignancies and autoimmune disorders, increased susceptibility to bacterial, viral, and parasitic diseases, and an interplay with prooxidants and antioxidants for maintaining a sound health, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue.

  9. OXIDATIVE STRESS AND VASCULAR DAMAGE IN HYPOXIA PROCESSES. MALONDIALDEHYDE (MDA AS BIOMARKER FOR OXIDATIVE DAMAGE

    Directory of Open Access Journals (Sweden)

    Muñiz P

    2014-05-01

    Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

  10. Simvastatin and oxidative stress in humans

    DEFF Research Database (Denmark)

    Rasmussen, Sanne Tofte; Andersen, Jon Thor Trærup; Nielsen, Torben Kjær

    2016-01-01

    in mitochondrial respiratory complexes I and II and might thereby reduce the formation of reactive oxygen species, which have been implicated in the pathogenesis of arteriosclerosis. Therefore, we hypothesized that simvastatin may reduce oxidative stress in humans in vivo. We conducted a randomized, double......-blinded, placebo-controlled study in which subjects were treated with either 40 mg of simvastatin or placebo for 14 days. The endpoints were six biomarkers for oxidative stress, which represent intracellular oxidative stress to nucleic acids, lipid peroxidation and plasma antioxidants, that were measured in urine.......1% in the placebo group for DNA oxidation and 7.3% in the simvastatin group compared to 3.4% in the placebo group. The differences in biomarkers related to plasma were not statistically significant between the treatments groups, with the exception of total vitamin E levels, which, as expected, were reduced...

  11. Hepatic oxidative stress in ovariectomized transgenic mice expressing the hepatitis C virus polyprotein is augmented through suppression of adenosine monophosphate-activated protein kinase/proliferator-activated receptor gamma co-activator 1 alpha signaling.

    Science.gov (United States)

    Tomiyama, Yasuyuki; Nishina, Sohji; Hara, Yuichi; Kawase, Tomoya; Hino, Keisuke

    2014-10-01

    Oxidative stress plays an important role in hepatocarcinogenesis of hepatitis C virus (HCV)-related chronic liver diseases. Despite the evidence of an increased proportion of females among elderly patients with HCV-related hepatocellular carcinoma (HCC), it remains unknown whether HCV augments hepatic oxidative stress in postmenopausal women. The aim of this study was to determine whether oxidative stress was augmented in ovariectomized (OVX) transgenic mice expressing the HCV polyprotein and to investigate its underlying mechanisms. OVX and sham-operated female transgenic mice expressing the HCV polyprotein and non-transgenic littermates were assessed for the production of reactive oxygen species (ROS), expression of inflammatory cytokines and antioxidant potential in the liver. Compared with OVX non-transgenic mice, OVX transgenic mice showed marked hepatic steatosis and ROS production without increased induction of inflammatory cytokines, but there was no increase in ROS-detoxifying enzymes such as superoxide dismutase 2 and glutathione peroxidase 1. In accordance with these results, OVX transgenic mice showed less activation of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), which is required for the induction of ROS-detoxifying enzymes, and no activation of adenosine monophosphate-activated protein kinase-α (AMPKα), which regulates the activity of PGC-1α. Our study demonstrated that hepatic oxidative stress was augmented in OVX transgenic mice expressing the HCV polyprotein by attenuation of antioxidant potential through inhibition of AMPK/PGC-1α signaling. These results may account in part for the mechanisms by which HCV-infected women are at high risk for HCC development when some period has passed after menopause. © 2013 The Japan Society of Hepatology.

  12. Matrix metalloproteinase-2 and -9 are induced differently by metal nanoparticles in human monocytes: The role of oxidative stress and protein tyrosine kinase activation

    International Nuclear Information System (INIS)

    Wan Rong; Mo Yiqun; Zhang Xing; Chien Sufan; Tollerud, David J.; Zhang Qunwei

    2008-01-01

    after exposure to Nano-Co, but not to Nano-TiO 2 . However, neither Nano-Co nor Nano-TiO 2 exposure led to any transcriptional change of TIMP-1. The decrease of TIMP-2 after exposure to Nano-Co was also inhibited by pre-treatment with ROS scavengers or inhibitors. Our results also showed that pre-treatment of U937 cells with AP-1 inhibitor, curcumin, or the PTK specific inhibitor, herbimycin A or genistein, prior to exposure to Nano-Co, significantly abolished Nano-Co-induced pro-MMP-2 and-9 activity. Our results suggest that Nano-Co causes an imbalance between the expression and activity of MMPs and their inhibitors which is mediated by the AP-1 and tyrosine kinase pathways due to oxidative stress

  13. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Liang-Jun Yan

    2014-01-01

    Full Text Available Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH, respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

  14. Stress proteins, autoimmunity, and autoimmune disease.

    Science.gov (United States)

    Winfield, J B; Jarjour, W N

    1991-01-01

    At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and

  15. Oxidative stress in patients with endodontic pathologies.

    Science.gov (United States)

    Vengerfeldt, Veiko; Mändar, Reet; Saag, Mare; Piir, Anneli; Kullisaar, Tiiu

    2017-01-01

    Apical periodontitis (AP) is an inflammatory disease affecting periradicular tissues. It is a widespread condition but its etiopathogenetic mechanisms have not been completely elucidated and the current treatment options are not always successful. To compare oxidative stress (OxS) levels in the saliva and the endodontium (root canal [RC] contents) in patients with different endodontic pathologies and in endodontically healthy subjects. The study group of this comparison study included 22 subjects with primary chronic apical periodontitis (pCAP), 26 with posttreatment or secondary chronic apical periodontitis (sCAP), eight with acute periapical abscess, 13 with irreversible pulpitis, and 17 healthy controls. Resting saliva samples were collected before clinical treatment. Pulp samples (remnants of the pulp, tooth tissue, and/or previous root filling material) were collected under strict aseptic conditions using the Hedström file. The samples were frozen to -80°C until analysis. OxS markers (myeloperoxidase [MPO], oxidative stress index [OSI], 8-isoprostanes [8-EPI]) were detected in the saliva and the endodontium. The highest MPO and 8-EPI levels were seen in pCAP and pulpitis, while the highest levels of OSI were seen in pCAP and abscess patients, as well as the saliva of sCAP patients. Controls showed the lowest OxS levels in both RC contents and saliva. Significant positive correlations between OxS markers, periapical index, and pain were revealed. Patients with pain had significantly higher OxS levels in both the endodontium (MPO median 27.9 vs 72.6 ng/mg protein, p =0.004; OSI 6.0 vs 10.4, p <0.001; 8-EPI 50.0 vs 75.0 pg/mL, p <0.001) and saliva (MPO 34.2 vs 117.5 ng/mg protein, p <0.001; 8-EPI 50.0 vs 112.8 pg/mL, p <0.001) compared to pain-free subjects. OxS is an important pathomechanism in endodontic pathologies that is evident at both the local (RC contents) and systemic (saliva) level. OxS is significantly associated with dental pain and bone

  16. Oxidative Stress in Patients With Nongenital Warts

    Directory of Open Access Journals (Sweden)

    Sezai Sasmaz

    2005-01-01

    Full Text Available Comparison of oxidative stress status between subjects with or without warts is absent in the literature. In this study, we evaluated 31 consecutive patients with warts (15 female, 16 male and 36 control cases with no evidence of disease to determine the effects of oxidative stress in patients with warts. The patients were classified according to the wart type, duration, number, and location of lesions. We measured the indicators of oxidative stress such as catalase (CAT, glucose-6-phosphate dehydrogenase (G6PD, superoxide dismutase (SOD, and malondialdehyde (MDA in the venous blood by spectrophotometry. There was a statistically significant increase in levels of CAT, G6PD, SOD activities and MDA in the patients with warts compared to the control group (P<.05. However, we could not define a statistically significant correlation between these increased enzyme activities and MDA levels and the type, the duration, the number, and the location of lesions. We determined possible suppression of T cells during oxidative stress that might have a negative effect on the prognosis of the disease. Therefore, we propose an argument for the appropriateness to give priority to immunomodulatory treatment alternatives instead of destructive methods in patients with demonstrated oxidative stress.

  17. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yosuke Kayama

    2015-10-01

    Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

  18. Oxidative stress markers imbalance in late-life depression.

    Science.gov (United States)

    Diniz, Breno S; Mendes-Silva, Ana Paula; Silva, Lucelia Barroso; Bertola, Laiss; Vieira, Monica Costa; Ferreira, Jessica Diniz; Nicolau, Mariana; Bristot, Giovana; da Rosa, Eduarda Dias; Teixeira, Antonio L; Kapczinski, Flavio

    2018-03-20

    Oxidative stress has been implicated in the pathophysiology of mood disorders in young adults. However, there is few data to support its role in the elderly. The primary aim of this study was to evaluate whether subjects with late-life depression (LLD) presented with changes in oxidative stress response in comparison with the non-depressed control group. We then explored how oxidative stress markers associated with specific features of LLD, in particular cognitive performance and age of onset of major depressive disorder in these individuals. We included a convenience sample of 124 individuals, 77 with LLD and 47 non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, and glutathione S-transferase (GST) activity. We found that participants with LLD had significantly higher free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity (p = 0.006) compared to controls. Free 8-isoprostane levels were also significantly correlated with worse scores in the initiation/perseverance (r = -0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the total scores (r = -0.21, p = 0.04) on the DRS. Our study provides robust evidence of the imbalance between oxidative stress damage, in particular lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD, and cognitive impairment in this population. Interventions aiming to reduce oxidative stress damage can have a potential neuroprotective effect for LLD subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Association between prenatal psychological stress and oxidative stress during pregnancy.

    Science.gov (United States)

    Eick, Stephanie M; Barrett, Emily S; van 't Erve, Thomas J; Nguyen, Ruby H N; Bush, Nicole R; Milne, Ginger; Swan, Shanna H; Ferguson, Kelly K

    2018-03-30

    Prenatal psychological stress during pregnancy has been associated with adverse reproductive outcomes. A growing animal literature supports an association between psychological stress and oxidative stress. We assessed this relationship in pregnant women, hypothesising that psychological stress is associated with higher concentrations of oxidative stress biomarkers during pregnancy. Psychosocial status and stressful life events (SLE) were self-reported. 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) was measured as a biomarker of oxidative stress in urine samples at median 32 weeks' gestation. We examined SLEs individually (ever vs never) and in summary (any vs none) and psychosocial status as measured by individual subscales and in summary (poor vs good). Linear models estimated associations between these parameters and urinary 8-iso-PGF 2α concentrations after adjusting for covariates. The geometric mean of 8-iso-PGF 2α was significantly higher among pregnant women who were non-White, smokers, had less than a college education, higher pre-pregnancy BMI and were unmarried. Having ever had a death in the family (n = 39) during pregnancy was associated with a 22.9% increase in 8-iso-PGF 2α in unadjusted models (95% confidence interval [CI] 1.50, 48.8). Poor psychosocial status was associated with a 13.1% (95% CI 2.43, 25.0) greater mean 8-iso-PGF 2α in unadjusted analyses. Associations were attenuated, but remained suggestive, after covariate adjustment. These data suggest that 8-iso-PGF 2α is elevated in pregnant women with who are at a sociodemographic disadvantage and who have higher psychological stress in pregnancy. Previous studies have observed that 8-iso-PGF 2α levels are associated with adverse birth outcomes, oxidative stress could be a mediator in these relationships. © 2018 John Wiley & Sons Ltd.

  20. Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Fereshteh Ahmadinejad

    2017-07-01

    Full Text Available Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively, collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase and nitric oxide synthase (NOS. Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA used routinely in the treatment of Parkinson’s disease (not as a free radical scavenger, and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1. Although they share the targets in reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis.

  1. Oxidative costs of reproduction: Oxidative stress in mice fed standard and low antioxidant diets.

    Science.gov (United States)

    Vaanholt, L M; Milne, A; Zheng, Y; Hambly, C; Mitchell, S E; Valencak, T G; Allison, D B; Speakman, J R

    2016-02-01

    Lactation is one of the most energetically expensive behaviours, and trade-offs may exist between the energy devoted to it and somatic maintenance, including protection against oxidative damage. However, conflicting data exist for the effects of reproduction on oxidative stress. In the wild, a positive relationship is often observed, but in laboratory studies oxidative damage is often lower in lactating than in non-breeding animals. We hypothesised that this discrepancy may exist because during lactation food intake increases many-fold resulting in a large increase in the intake of dietary antioxidants which are typically high in laboratory rodent chow where they are added as a preservative. We supplied lactating and non-breeding control mice with either a standard or low antioxidant diet and studied how this affected the activity of endogenous antioxidants (catalase, superoxide dismutase; SOD, and glutathione peroxidise; GPx) and oxidative damage to proteins (protein carbonyls, PC) in liver and brain tissue. The low antioxidant diet did not significantly affect activities of antioxidant enzymes in brain or liver, and generally did not result in increased protein damage, except in livers of control mice on low antioxidant diet. Catalase activity, but not GPx or SOD, was decreased in both control and lactating mice on the low antioxidant diet. Lactating mice had significantly reduced oxidative damage to both liver and brain compared to control mice, independent of the diet they were given. In conclusion, antioxidant content of the diet did not affect oxidative stress in control or reproductive mice, and cannot explain the previously observed reduction in oxidative stress in lactating mammals studied in the laboratory. The reduced oxidative stress in the livers of lactating mice even under low antioxidant diet treatment was consistent with the 'shielding' hypothesis. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Acetaminophen inhibits neuronal inflammation and protects neurons from oxidative stress

    Directory of Open Access Journals (Sweden)

    Grammas Paula

    2009-03-01

    Full Text Available Abstract Background Recent studies have demonstrated a link between the inflammatory response, increased cytokine formation, and neurodegeneration in the brain. The beneficial effects of anti-inflammatory drugs in neurodegenerative diseases, such as Alzheimer's disease (AD, have been documented. Increasing evidence suggests that acetaminophen has unappreciated anti-oxidant and anti-inflammatory properties. The objectives of this study are to determine the effects of acetaminophen on cultured brain neuronal survival and inflammatory factor expression when exposed to oxidative stress. Methods Cerebral cortical cultured neurons are pretreated with acetaminophen and then exposed to the superoxide-generating compound menadione (5 μM. Cell survival is assessed by MTT assay and inflammatory protein (tumor necrosis factor alpha, interleukin-1, macrophage inflammatory protein alpha, and RANTES release quantitated by ELISA. Expression of pro- and anti-apoptotic proteins is assessed by western blots. Results Acetaminophen has pro-survival effects on neurons in culture. Menadione, a superoxide releasing oxidant stressor, causes a significant (p Conclusion These data show that acetaminophen has anti-oxidant and anti-inflammatory effects on neurons and suggest a heretofore unappreciated therapeutic potential for this drug in neurodegenerative diseases such as AD that are characterized by oxidant and inflammatory stress.

  3. Human surfactant protein D alters oxidative stress and HMGA1 expression to induce p53 apoptotic pathway in eosinophil leukemic cell line.

    Directory of Open Access Journals (Sweden)

    Lakshna Mahajan

    Full Text Available Surfactant protein D (SP-D, an innate immune molecule, has an indispensable role in host defense and regulation of inflammation. Immune related functions regulated by SP-D include agglutination of pathogens, phagocytosis, oxidative burst, antigen presentation, T lymphocyte proliferation, cytokine secretion, induction of apoptosis and clearance of apoptotic cells. The present study unravels a novel ability of SP-D to reduce the viability of leukemic cells (eosinophilic leukemic cell line, AML14.3D10; acute myeloid leukemia cell line, THP-1; acute lymphoid leukemia cell lines, Jurkat, Raji; and human breast epithelial cell line, MCF-7, and explains the underlying mechanisms. SP-D and a recombinant fragment of human SP-D (rhSP-D induced G2/M phase cell cycle arrest, and dose and time-dependent apoptosis in the AML14.3D10 eosinophilic leukemia cell line. Levels of various apoptotic markers viz. activated p53, cleaved caspase-9 and PARP, along with G2/M checkpoints (p21 and Tyr15 phosphorylation of cdc2 showed significant increase in these cells. We further attempted to elucidate the underlying mechanisms of rhSP-D induced apoptosis using proteomic analysis. This approach identified large scale molecular changes initiated by SP-D in a human cell for the first time. Among others, the proteomics analysis highlighted a decreased expression of survival related proteins such as HMGA1, overexpression of proteins to protect the cells from oxidative burst, while a drastic decrease in mitochondrial antioxidant defense system. rhSP-D mediated enhanced oxidative burst in AML14.3D10 cells was confirmed, while antioxidant, N-acetyl-L-cysteine, abrogated the rhSP-D induced apoptosis. The rhSP-D mediated reduced viability was specific to the cancer cell lines and viability of human PBMCs from healthy controls was not affected. The study suggests involvement of SP-D in host's immunosurveillance and therapeutic potential of rhSP-D in the eosinophilic leukemia and

  4. [Role of green tea in oxidative stress prevention].

    Science.gov (United States)

    Metro, D; Muraca, U; Manasseri, L

    2006-01-01

    Oxidative stress is a condition caused by an increase of Reactive Oxygen Species (ROS) or by a shortage of the mechanisms of cellular protection and antioxidant defence. ROS have a potential oxidative effect towards various cellular macromolecules: proteins, nucleic acids, proteoglycans, lipids, with consequent damages in several cellular districts and promotion of the ageing process of the organism. However, some substances are able to prevent and/or reduce the damages caused by ROS; therefore, they are defined antioxidant. The present research studied, in a group of subjects, the antioxidant effects of the green tea, that was administered with fruit and vegetables in a strictly controlled diet. 50 subjects were selected and requested to daily consume 2-3 fruit portions (especially pineapple), 3-5 portions of vegetables (especially tomato) and 2-3 glasses of green tea for about 2 months to integrate the controlled basic diet. Some indicators of the oxidative stress were measured in the plasma before and after the integration period. The integration of a basic diet with supplements of fruit, vegetables and green tea turned out to be able in increasing both plasmatic total antioxidant capacity and endogenous antioxidant levels and to reduce the lipid peroxidation of the membranes, suggesting a reduction of the oxidative stress. These data suggest that an adequate supplement of antioxidants can prevent oxidative stress and correlated pathologies.

  5. RNA Recognition and Stress Granule Formation by TIA Proteins

    Science.gov (United States)

    Waris, Saboora; Wilce, Matthew Charles James; Wilce, Jacqueline Anne

    2014-01-01

    Stress granule (SG) formation is a primary mechanism through which gene expression is rapidly modulated when the eukaryotic cell undergoes cellular stresses (including heat, oxidative, viral infection, starvation). In particular, the sequestration of specifically targeted translationally stalled mRNAs into SGs limits the expression of a subset of genes, but allows the expression of heatshock proteins that have a protective effect in the cell. The importance of SGs is seen in several disease states in which SG function is disrupted. Fundamental to SG formation are the T cell restricted intracellular antigen (TIA) proteins (TIA-1 and TIA-1 related protein (TIAR)), that both directly bind to target RNA and self-associate to seed the formation of SGs. Here a summary is provided of the current understanding of the way in which TIA proteins target specific mRNA, and how TIA self-association is triggered under conditions of cellular stress. PMID:25522169

  6. Oxidative stress parameters in localized scleroderma patients.

    Science.gov (United States)

    Kilinc, F; Sener, S; Akbaş, A; Metin, A; Kirbaş, S; Neselioglu, S; Erel, O

    2016-11-01

    Localized scleroderma (LS) (morphea) is a chronic, inflammatory skin disease with unknown cause that progresses with sclerosis in the skin and/or subcutaneous tissues. Its pathogenesis is not completely understood. Oxidative stress is suggested to have a role in the pathogenesis of localized scleroderma. We have aimed to determine the relationship of morphea lesions with oxidative stress. The total oxidant capacity (TOC), total antioxidant capacity (TAC), paroxonase (PON) and arylesterase (ARES) activity parameters of PON 1 enzyme levels in the serum were investigated in 13 LS patients (generalized and plaque type) and 13 healthy controls. TOC values of the patient group were found higher than the TOC values of the control group (p < 0.01). ARES values of the patient group was found to be higher than the control group (p < 0.0001). OSI was significantly higher in the patient group when compared to the control (p < 0.005). Oxidative stress seems to be effective in the pathogenesis. ARES levels have increased in morphea patients regarding to the oxidative stress and its reduction. Further controlled studies are required in wider series.

  7. Heat stress proteins in hypertension

    International Nuclear Information System (INIS)

    Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

    1986-01-01

    It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46 0 C during 5 min in a hot water bath. The cells were then labeled with ( 75 Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension

  8. Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation.

    Science.gov (United States)

    Liu, Yong; He, Yizhou; Jin, Aiwen; Tikunov, Andrey P; Zhou, Lishi; Tollini, Laura A; Leslie, Patrick; Kim, Tae-Hyung; Li, Lei O; Coleman, Rosalind A; Gu, Zhennan; Chen, Yong Q; Macdonald, Jeffrey M; Graves, Lee M; Zhang, Yanping

    2014-06-10

    The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis. Although the Mdm2(C305F) mutation does not significantly affect growth and development in mice, this mutation promotes fat accumulation under normal feeding conditions and hepatosteatosis under acute fasting conditions. We show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2 interaction, and induces p53-mediated transactivation of malonyl-CoA decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl-CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to decreased oxidative respiration and increased fatty acid accumulation in the liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor responsible for stimulating fatty acid oxidation in response to nutrient depletion.

  9. Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants.

    Science.gov (United States)

    Lee, Seung-Yup; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

    2013-10-01

    The brain is an organ predisposed to oxidative/nitrosative stress. This is especially true in the case of aging as well as several neurodegenerative diseases. Under such circumstances, a decline in the normal antioxidant defense mechanisms leads to an increase in the vulnerability of the brain to the deleterious effects of oxidative damage. Highly reactive oxygen/nitrogen species damage lipids, proteins, and mitochondrial and neuronal genes. Unless antioxidant defenses react appropriately to damage inflicted by radicals, neurons may experience microalteration, microdysfunction, and degeneration. We reviewed how oxidative and nitrosative stresses contribute to the pathogenesis of depressive disorders and reviewed the clinical implications of various antioxidants as future targets for antidepressant treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Stress proteins and the immune response.

    Science.gov (United States)

    Moseley, P

    2000-07-25

    The heat shock or stress response is one of the most highly conserved adaptive responses in nature. In single cell organisms, the stress response confers tolerance to a variety of stresses including hyperthermia, hyperoxia, hypoxia, and other perturbations, which alter protein synthesis. This tolerance phenomenon is also extremely important in the multicellular organism, resulting in not only thermal tolerance, but also resistance to stresses of the whole organism such as ischemia-reperfusion injury. Moreover, recent data indicates that these stress proteins have the ability to modulate the cellular immune response. Although the terms heat shock proteins (HSPs) and stress proteins are often used interchangeably, the term stress proteins includes the HSPs, the glucose-regulated proteins (GRPs) and ubiquitin. The stress proteins may be grouped by molecular weight ranging from the large 110 kDa HSP110 to ubiquitin at 8 kDa. These proteins serve as cellular chaperones, participating in protein synthesis and transport through the various cellular compartments. Because these proteins have unique cellular localizations, the chaperone function of the stress proteins often involves a transfer of peptides between stress proteins as the peptide is moved between cellular compartments. For example, HSP70 is a cytosolic and nuclear chaperone, which is critical for the transfer of cellular peptides in the mitochondrion through a hand-off that involves mitochondrial HSP60 at the inner mitochondrial membrane. Similarly, cytosolic proteins are transferred from HSP70 to gp96 as they move into the endoplasmic reticulum. The central role of the stress proteins in the transfer of peptides through the cell may be responsible for the recently recognized importance of the stress proteins in the modulation of the immune system [Feder, M.E., Hofmann, G.E., 1999. Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu. Rev. Physiol. 61

  11. The effects of anesthetic agents on oxidative stress

    Science.gov (United States)

    Yakan, Selvinaz; Düzgüner, Vesile

    2016-04-01

    Oxidative stress can be defined as the instability between antioxidant defense of the body and the production of free radical that causes peroxydation on the lipid layer. Free radicals are reactive oxygen species that are produced in the course of normal metabolisms of aerobe organisms and they may cause disorders in cell structure and organelles by interacting macromolecules, like lipid, protein, nucleic acids. Therefore, they may cause cardiovascular, immune system, liver, kidney illnesses and many other illnesses like cancer, aging, cataract, diabetes. It is known that many drugs used for the purpose of anesthetizing may cause lipid peroxidation in organism. For these reasons, determining the Oxidative stress index of anaesthetic stress chosen in the ones that are exposed to long term anaesthetic agents and anaesthesia appliccations, is so substantial.

  12. Oxidative stress in normal hematopoietic stem cells and leukemia.

    Science.gov (United States)

    Samimi, Azin; Kalantari, Heybatullah; Lorestani, Marzieh Zeinvand; Shirzad, Reza; Saki, Najmaldin

    2018-04-01

    Leukemia is developed following the abnormal proliferation of immature hematopoietic cells in the blood when hematopoietic stem cells lose the ability to turn into mature cells at different stages of maturation and differentiation. Leukemia initiating cells are specifically dependent upon the suppression of oxidative stress in the hypoglycemic bone marrow (BM) environment to be able to start their activities. Relevant literature was identified by a PubMed search (2000-2017) of English-language literature using the terms 'oxidative stress,' 'reactive oxygen species,' 'hematopoietic stem cell,' and 'leukemia.' The generation and degradation of free radicals is a main component of the metabolism in aerobic organisms. A certain level of ROS is required for proper cellular function, but values outside this range will result in oxidative stress (OS). Long-term overactivity of reactive oxygen species (ROS) has harmful effects on the function of cells and their vital macromolecules, including the transformation of proteins into autoantigens and increased degradation of protein/DNA, which eventually leads to the change in pathways involved in the development of cancer and several other disorders. According to the metabolic disorders of cancer, the relationship between OS changes, the viability of cancer cells, and their response to chemotherapeutic agents affecting this pathway are undeniable. Recently, studies have been conducted to determine the effect of herbal agents and cancer chemotherapy drugs on oxidative stress pathways. By emphasizing the role of oxidative stress on stem cells in the incidence of leukemia, this paper attempts to state and summarize this subject. © 2018 APMIS. Published by John Wiley & Sons Ltd.

  13. Oxidized tissue proteins after intestinal reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Schanaider Alberto

    2005-01-01

    Full Text Available PURPOSE: To analyse if the carbonyl proteins measurement could be validated as a method that allows the identification of an intestinal oxidative stress after ischemia and reperfusion injury. METHODS: Twenty-five male Wistar rats (n =21 weighting 200 to 250g were divided into three groups. Group I - control (n = 10. Group II - sham (n = 5 and Group III (n = 10 subjected to 60 minutes of intestinal ischemia and equal period of reperfusion. For this purpose it was clamped the superior mesenteric artery in its distal third. Histological changes and carbonyl protein levels were determined in the samples of all groups. In group III, samples of both normal and reperfused ileal segment were studied. RESULTS: All the reperfused segments showed mucosal and submucosal swelling and inflammatory infiltrate of the lamina propria. Levels of carbonyl protein rose in group III, including in the non-ischemic segments. The sensitivity and specificity of the carbonyl protein tissue levels were respectively 94% and 88%. CONCLUSION: The carbonyl protein method is a useful biologic marker of oxidative stress after the phenomenon of intestinal ischemia and reperfusion in rats. It was also noteworthy that the effects of oxidative stress could be seen far from the locus of the primary injury.

  14. Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress.

    Science.gov (United States)

    Shayesteh, Reyhaneh; Kamalinejad, Mohammad; Adiban, Hasan; Kardan, Azin; Keyhanfar, Fariborz; Eskandari, Mohammad Reza

    2017-10-01

    Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin ( Cucurbita moschata ) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect. Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes. Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress. Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Genetics of Oxidative Stress in Obesity

    Directory of Open Access Journals (Sweden)

    Azahara I. Rupérez

    2014-02-01

    Full Text Available Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

  16. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

    Berg, Ronan M G; Møller, Kirsten; Bailey, Damian M

    2011-01-01

    Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...

  17. Oxidative Stress Control by Apicomplexan Parasites

    Directory of Open Access Journals (Sweden)

    Soraya S. Bosch

    2015-01-01

    Full Text Available Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis.

  18. Oxidative stress and histopathological changes induced by ...

    African Journals Online (AJOL)

    Background: Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism.

  19. Tobacco smoking and oxidative stress to DNA

    DEFF Research Database (Denmark)

    Ellegaard, Pernille Kempel; Poulsen, Henrik Enghusen

    2016-01-01

    Oxidative stress to DNA from smoking was investigated in one randomized smoking cessation study and in 36 cohort studies from excretion of urinary 8-oxo-7-hydrodeoxyguanosine (8-oxodG). Meta-analysis of the 36 cohort studies showed smoking associated with a 15.7% (95% CL 11.0:20.3, p < 0.0001) in...

  20. Genetics of oxidative stress in obesity.

    Science.gov (United States)

    Rupérez, Azahara I; Gil, Angel; Aguilera, Concepción M

    2014-02-20

    Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

  1. Mitochondrial oxidative stress causes hyperphosphorylation of tau.

    Directory of Open Access Journals (Sweden)

    Simon Melov

    2007-06-01

    Full Text Available Age-related neurodegenerative disease has been mechanistically linked with mitochondrial dysfunction via damage from reactive oxygen species produced within the cell. We determined whether increased mitochondrial oxidative stress could modulate or regulate two of the key neurochemical hallmarks of Alzheimer's disease (AD: tau phosphorylation, and beta-amyloid deposition. Mice lacking superoxide dismutase 2 (SOD2 die within the first week of life, and develop a complex heterogeneous phenotype arising from mitochondrial dysfunction and oxidative stress. Treatment of these mice with catalytic antioxidants increases their lifespan and rescues the peripheral phenotypes, while uncovering central nervous system pathology. We examined sod2 null mice differentially treated with high and low doses of a catalytic antioxidant and observed striking elevations in the levels of tau phosphorylation (at Ser-396 and other phospho-epitopes of tau in the low-dose antioxidant treated mice at AD-associated residues. This hyperphosphorylation of tau was prevented with an increased dose of the antioxidant, previously reported to be sufficient to prevent neuropathology. We then genetically combined a well-characterized mouse model of AD (Tg2576 with heterozygous sod2 knockout mice to study the interactions between mitochondrial oxidative stress and cerebral Ass load. We found that mitochondrial SOD2 deficiency exacerbates amyloid burden and significantly reduces metal levels in the brain, while increasing levels of Ser-396 phosphorylated tau. These findings mechanistically link mitochondrial oxidative stress with the pathological features of AD.

  2. Hepatic Antioxidant, Oxidative Stress And Histopathological ...

    African Journals Online (AJOL)

    Hepatic Antioxidant, Oxidative Stress And Histopathological Changes Induced By Nicotine In A Gender Based Study In Adult Rats. ... Antioxidant status was assessed in liver by measuring the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and ...

  3. Oxidative stress and mechanisms of ochronosis in alkaptonuria.

    Science.gov (United States)

    Braconi, Daniela; Millucci, Lia; Bernardini, Giulia; Santucci, Annalisa

    2015-11-01

    Alkaptonuria (AKU) is a rare metabolic disease due to a deficient activity of the enzyme homogentisate 1,2-dioxygenase (HGD), involved in Phe and Tyr catabolism. Due to such a deficiency, AKU patients undergo accumulation of the metabolite homogentisic acid (HGA), which is prone to oxidation/polymerization reactions causing the production of a melanin-like pigment. Once the pigment is deposited onto connective tissues (mainly in joints, spine, and cardiac valves), a classical bluish-brown discoloration is imparted, leading to a phenomenon known as "ochronosis", the hallmark of AKU. A clarification of the molecular mechanisms for the production and deposition of the ochronotic pigment in AKU started only recently with a range of in vitro and ex vivo human models used for the study of HGA-induced effects. Thanks to redox-proteomic analyses, it was found that HGA could induce significant oxidation of a number of serum and chondrocyte proteins. Further investigations allowed highlighting how HGA-induced proteome alteration, lipid peroxidation, thiol depletion, and amyloid production could contribute to oxidative stress generation and protein oxidation in AKU. This review briefly summarizes the most recent findings on HGA-induced oxidative stress in AKU, helping in the clarification of the molecular mechanisms of ochronosis and potentially providing the basis for its pharmacological treatment. Future work should be undertaken in order to validate in vivo the results so far obtained in in vitro AKU models. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. IGF-1, oxidative stress, and atheroprotection

    Science.gov (United States)

    Higashi, Yusuke; Sukhanov, Sergiy; Anwar, Asif; Shai, Shaw-Yung; Delafontaine, Patrice

    2009-01-01

    Atherosclerosis is a chronic inflammatory disease in which early endothelial dysfunction and subintimal modified lipoprotein deposition progress to complex, advanced lesions that are predisposed to erosion, rupture and thrombosis. Oxidative stress plays a critical role not only in initial lesion formation but also in lesion progression and destabilization. While growth factors are thought to promote vascular smooth muscle cell proliferation and migration, thereby increasing neointima, recent animal studies indicate that IGF-1 exerts pleiotropic anti-oxidant effects along with anti-inflammatory effects that together reduce atherosclerotic burden. This review discusses the effects of IGF-1 in vascular injury and atherosclerosis models, emphasizing the relationship between oxidative stress and potential atheroprotective actions of IGF-1. PMID:20071192

  5. Serum Polychlorinated Biphenyls Increase and Oxidative Stress Decreases with a Protein-Pacing Caloric Restriction Diet in Obese Men and Women.

    Science.gov (United States)

    He, Feng; Zuo, Li; Ward, Emery; Arciero, Paul J

    2017-01-10

    The purposes were to compare the effects of a: (1) 12-week P-CR weight loss (WL) diet (Phase 1) between obese men and women and; (2) 52-week modified P-CR (mP-CR) vs. heart healthy (HH) weight maintenance (WM) diet (Phase 2) on serum PCBs and oxidative stress biomarkers (thiobarbituric acid reactive substances, TBARS; total antioxidant capacity, TAC) in 40 obese participants (men, n = 21; women, n = 19). Participants received dietary counseling and monitoring of compliance. PCBs, TBARS, and TAC were assessed at weeks -1 (CON), 12 (WL), and 64 (WM). Following WL (Week 12), concomitant with reductions in TBARS (0.24 ± 0.15 vs. 0.18 ± 0.11 µM; p 0.42, p < 0.05) and negatively correlated with body weight, fat mass, and abdominal fat ( r < -0.46, p < 0.02). Our results support mobilization of stored PCBs as well as enhanced redox status following a 12-week P-CR WL diet. Additionally, a 52-week mP-CR WM diet demonstrated an advantage in preventing weight gain relapse accompanied by an increase in circulating PCBs compared to a traditional HH diet.

  6. Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

    Directory of Open Access Journals (Sweden)

    He Peiyuan

    2017-01-01

    Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

  7. Piracetam improves mitochondrial dysfunction following oxidative stress

    Science.gov (United States)

    Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

  8. Oxidative stress induced inflammation initiates functional decline of tear production.

    Directory of Open Access Journals (Sweden)

    Yuichi Uchino

    Full Text Available Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1 using a modified tetracycline system (Tet-On/Off system. This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b(560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC in humans. The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.

  9. Oxidative Stress and Huntington's Disease: The Good, The Bad, and The Ugly.

    Science.gov (United States)

    Kumar, Amit; Ratan, Rajiv R

    2016-10-01

    Redox homeostasis is crucial for proper cellular functions, including receptor tyrosine kinase signaling, protein folding, and xenobiotic detoxification. Under basal conditions, there is a balance between oxidants and antioxidants. This balance facilitates the ability of oxidants, such as reactive oxygen species, to play critical regulatory functions through a direct modification of a small number of amino acids (e.g. cysteine) on signaling proteins. These signaling functions leverage tight spatial, amplitude, and temporal control of oxidant concentrations. However, when oxidants overwhelm the antioxidant capacity, they lead to a harmful condition of oxidative stress. Oxidative stress has long been held to be one of the key players in disease progression for Huntington's disease (HD). In this review, we will critically review this evidence, drawing some intermediate conclusions, and ultimately provide a framework for thinking about the role of oxidative stress in the pathophysiology of HD.

  10. Progranulin causes adipose insulin resistance via increased autophagy resulting from activated oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Guo, Qinyue; Xu, Lin; Li, Huixia; Sun, Hongzhi; Liu, Jiali; Wu, Shufang; Zhou, Bo

    2017-01-31

    Progranulin (PGRN) has recently emerged as an important regulator for insulin resistance. However, the direct effect of progranulin in adipose insulin resistance associated with the autophagy mechanism is not fully understood. In the present study, progranulin was administered to 3T3-L1 adipocytes and C57BL/6 J mice with/without specific inhibitors of oxidative stress and endoplasmic reticulum stress, and metabolic parameters, oxidative stress, endoplasmic reticulum stress and autophagy markers were assessed. Progranulin treatment increased iNOS expression, NO synthesis and ROS generation, and elevated protein expressions of CHOP, GRP78 and the phosphorylation of PERK, and caused a significant increase in Atg7 and LC3-II protein expression and a decreased p62 expression, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake, demonstrating that progranulin activated oxidative stress and ER stress, elevated autophagy and induced insulin insensitivity in adipocytes and adipose tissue of mice. Interestingly, inhibition of iNOS and ER stress both reversed progranulin-induced stress response and increased autophagy, protecting against insulin resistance in adipocytes. Furthermore, the administration of the ER stress inhibitor 4-phenyl butyric acid reversed the negative effect of progranulin in vivo. Our findings showed the clinical potential of the novel adipokine progranulin in the regulation of insulin resistance, suggesting that progranulin might mediate adipose insulin resistance, at least in part, by inducing autophagy via activated oxidative stress and ER stress.

  11. Protective effect of surface layer proteins isolated from four Lactobacillus strains on hydrogen-peroxide-induced HT-29 cells oxidative stress.

    Science.gov (United States)

    Zhao, Bin-Bin; Meng, Jun; Zhang, Qiu-Xiang; Kang, Ting-Ting; Lu, Rong-Rong

    2017-09-01

    The objective of this study was to explore the antioxidant effect of the surface layer proteins (SLPs) and their mechanism. We investigated four SLPs which were extracted from L. casei zhang, L. rhamnosus, L. gasseri and L. acidophilus NCFM respectively using LiCl. The protective effect of SLPs on H 2 O 2 -induced HT-29 cells oxidative injury was investigated. As results, SLPs (100μg/mL) could significantly mitigate HT-29 cells cytotoxicity, improve the activities of total antioxidant capacity (T-AOC), catalase (CAT) and superoxide dismutase (SOD), decrease the contents of malondialdehyde (MDA) and lactate dehydrogenase (LDH), compared with H 2 O 2 -induced group (Pproteins of caspase-3 and caspase-9 (Pcells induced by H 2 O 2 , and the mechanism could be attributed to SLPs' ability to enhance the activity of the intracellular antioxidant enzyme system, reduce ROS accumulation and to inhibit apoptosis by regulating mitochondrial pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

    Science.gov (United States)

    Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz

    2015-01-01

    Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds. PMID:25748174

  13. The two Dps proteins, NpDps2 and NpDps5, are involved in light-induced oxidative stress tolerance in the N2-fixing cyanobacterium Nostoc punctiforme.

    Science.gov (United States)

    Moparthi, Vamsi K; Li, Xin; Vavitsas, Konstantinos; Dzhygyr, Ievgen; Sandh, Gustaf; Magnuson, Ann; Stensjö, Karin

    2016-11-01

    Cyanobacteria are photosynthetic prokaryotes that are considered biotechnologically prominent organisms for production of high-value compounds. Cyanobacteria are subject to high-light intensities, which is a challenge that needs to be addressed in design of efficient bio-engineered photosynthetic organisms. Dps proteins are members of the ferritin superfamily and are omnipresent in prokaryotes. They play a major role in oxidative stress protection and iron homeostasis. The filamentous, heterocyst-forming Nostoc punctiforme, has five Dps proteins. In this study we elucidated the role of these Dps proteins in acclimation to high light intensity, the gene loci organization and the transcriptional regulation of all five dps genes in N. punctiforme was revealed, and dps-deletion mutant strains were used in physiological characterization. Two mutants defective in Dps2 and Dps5 activity displayed a reduced fitness under increased illumination, as well as a differential Photosystem (PS) stoichiometry, with an elevated Photosystem II to Photosystem I ratio in the dps5 deletion strain. This work establishes a Dps-mediated link between light tolerance, H 2 O 2 detoxification, and iron homeostasis, and provides further evidence on the non-redundant role of multiple Dps proteins in this multicellular cyanobacterium. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Comparative analyses reveal different consequences of two oxidative stress inducers, gamma irradiation and potassium tellurite, in the extremophile Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Narasimha, Anaganti; Basu, Bhakti; Apte, Shree Kumar

    2014-01-01

    Proteomic and mass spectrometric analyses revealed differential responses of D. radiodurans to two oxidative stressors. While both elicited oxidative stress alleviation response, major divergence was observed at the level of DNA repair, metabolic pathways and protein homeostasis. Response to gamma irradiation was focused on DNA repair and ROS scavenging but supported metabolism as well as protein homeostasis. Tellurite, induced oxidative stress alleviation but decreased reducing affected and adversely affected metabolism and protein homeostasis

  15. Oxidative stress signaling to chromatin in health and disease

    KAUST Repository

    Kreuz, Sarah; Fischle, Wolfgang

    2016-01-01

    Oxidative stress has a significant impact on the development and progression of common human pathologies, including cancer, diabetes, hypertension and neurodegenerative diseases. Increasing evidence suggests that oxidative stress globally influences

  16. Study on the serum oxidative stress status in silicosis patients

    African Journals Online (AJOL)

    Administrator

    2011-09-07

    Sep 7, 2011 ... oxidative stress parameters were investigated in silicosis patients and controls group. 128 silicosis ... to help clinicians to further delineate the role of oxidative- stress .... in age, working duration smoking, total cholesterol, ALT,.

  17. Protective effects of flavonoids from corn silk on oxidative stress ...

    African Journals Online (AJOL)

    Protective effects of flavonoids from corn silk on oxidative stress induced by ... The present study aims at exploring the effects of flavonoids from corn silk (FCS) on oxidative stress induced by exhaustive exercise in mice. ... from 32 Countries:.

  18. Biochemical basis of the high resistance to oxidative stress in ...

    Indian Academy of Sciences (India)

    Unknown

    581. Keywords. Apoptosis; D. discoideum; oxidative stress; antioxidant enzymes; lipid peroxidation ..... multiple toxic effects of oxidative stress that is related to several pathological conditions ... culture. This work was supported by a grant to RB.

  19. Effects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial.

    Science.gov (United States)

    Kitabchi, Abbas E; McDaniel, Kristin A; Wan, Jim Y; Tylavsky, Frances A; Jacovino, Crystal A; Sands, Chris W; Nyenwe, Ebenezer A; Stentz, Frankie B

    2013-07-01

    To study the effects of high-protein versus high-carbohydrate diets on various metabolic end points (glucoregulation, oxidative stress [dichlorofluorescein], lipid peroxidation [malondialdehyde], proinflammatory cytokines [tumor necrosis factor-α and interleukin-6], adipokines, and resting energy expenditure [REE]) with high protein-low carbohydrate (HP) and high carbohydrate-low protein (HC) diets at baseline and after 6 months of dietary intervention. We recruited obese, premenopausal women aged 20-50 years with no diabetes or prediabetes who were randomized to HC (55% carbohydrates, 30% fat, and 15% protein) or HP (40% carbohydrates, 30% fat, and 30% protein) diets for 6 months. The diets were provided in prepackaged food, which provided 500 kcal restrictions per day. The above metabolic end points were measured with HP and HC diet at baseline and after 6 months of dietary intervention. After 6 months of the HP versus HC diet (12 in each group), the following changes were significantly different by Wilcoxon rank sum test for the following parameters: dichlorofluorescein (-0.8 vs. -0.3 µmol/L, P vs. -0.2 μmol/L, P = 0.0004), C-reactive protein (-2.1 vs. -0.8 mg/L, P = 0.0003), E-selectin (-8.6 vs. -3.7 ng/mL, P = 0.0007), adiponectin (1,284 vs. 504 ng/mL, P = 0.0011), tumor necrosis factor-α (-1.8 vs. -0.9 pg/mL, P vs. -0.4 pg/mL, P vs. 0.16 mmol/L, P = 0.0002), REE (259 vs. 26 kcal, P vs. 0.9, P vs. 2.1, P < 0.0001). To our knowledge, this is the first report on the significant advantages of a 6-month hypocaloric HP diet versus hypocaloric HC diet on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in normal, obese females without diabetes.

  20. Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity.

    Science.gov (United States)

    Aschbacher, Kirstin; O'Donovan, Aoife; Wolkowitz, Owen M; Dhabhar, Firdaus S; Su, Yali; Epel, Elissa

    2013-09-01

    Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (pstress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress

  1. Plant Polyphenol Antioxidants and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    INES URQUIAGA

    2000-01-01

    Full Text Available In recent years there has been a remarkable increment in scientific articles dealing with oxidative stress. Several reasons justify this trend: knowledge about reactive oxygen and nitrogen species metabolism; definition of markers for oxidative damage; evidence linking chronic diseases and oxidative stress; identification of flavonoids and other dietary polyphenol antioxidants present in plant foods as bioactive molecules; and data supporting the idea that health benefits associated with fruits, vegetables and red wine in the diet are probably linked to the polyphenol antioxidants they contain.In this review we examine some of the evidence linking chronic diseases and oxidative stress, the distribution and basic structure of plant polyphenol antioxidants, some biological effects of polyphenols, and data related to their bioavailability and the metabolic changes they undergo in the intestinal lumen and after absorption into the organism.Finally, we consider some of the challenges that research in this area currently faces, with particular emphasis on the contributions made at the International Symposium "Biology and Pathology of Free Radicals: Plant and Wine Polyphenol Antioxidants" held July 29-30, 1999, at the Catholic University, Santiago, Chile and collected in this special issue of Biological Research

  2. Oxidative stress in chemical toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Kappus, H.

    1986-05-01

    The toxic effect of compounds which undergo redox cycling enzymatic one-electron reduction are reviewed. First of all, the enzymatic reduction of these compounds leads to reactive intermediates, mainly radicals which react with oxygen, whereby superoxide anion radicals are formed. Further oxygen metabolites are hydrogen peroxide, singlet oxygen and hydroxyl radicals. The role of these oxygen metabolites in toxicity is discussed. The occurrence of lipid peroxidation during redox cycling of quinonoide compounds, e.g., adriamycin, and the possible relationship to their toxicity is critically evaluated. It is shown that iron ions play a crucial role in lipid peroxidation induced by redox cycling compounds. DNA damage by metal chelates, e.g., bleomycin, is discussed on the basis of findings that enzymatic redox cycling of a bleomycin-iron complex has been observed. The involvement of hydroxyl radicals in bleomycin-induced DNA damage occurring during redox cycling in cell nuclei is claimed. Redox cycling of other substances, e.g., aromatic amines, is discussed in relation to carcinogenesis. Other chemical groups, e.g., nitroaromatic compounds, hydroxylamines and azo compounds are included. Other targets for oxygen radical attack, e.g., proteins, are also dealt with. It is concluded that oxygen radical formation by redox cycling may be a critical event in toxic effects of several compounds if the protective mechanisms of cells are overwhelmed.

  3. Oxidative and nitrosative stress in trichloroethene-mediated autoimmune response

    International Nuclear Information System (INIS)

    Wang Gangduo; Cai Ping; Ansari, G.A.S.; Khan, M. Firoze

    2007-01-01

    Reactive oxygen and nitrogen species (RONS) are implicated in the pathogenesis of several autoimmune diseases. Also, increased lipid peroxidation and protein nitration are reported in systemic autoimmune diseases. Lipid peroxidation-derived aldehydes (LPDAs) such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are highly reactive and bind proteins covalently, but their potential to elicit an autoimmune response and contribution to disease pathogenesis remain unclear. Similarly, nitration of protein could also contribute to disease pathogenesis. To assess the status of lipid peroxidation and/or RONS, autoimmune-prone female MRL+/+ mice (5-week old) were treated with trichloroethene (TCE), an environmental contaminant known to induce autoimmune response, for 48 weeks (0.5 mg/ml via drinking water), and formation of antibodies to LPDA-protein adducts was followed in the sera of control and TCE-treated mice. TCE treatment led to greater formation of both anti-MDA- and -HNE-protein adduct antibodies and higher serum iNOS and nitrotyrosine levels. The increase in TCE-induced oxidative stress was associated with increases in anti-nuclear-, anti-ssDNA- and anti-dsDNA-antibodies. These findings suggest that TCE exposure not only leads to oxidative/nitrosative stress, but is also associated with induction/exacerbation of autoimmune response in MRL+/+ mice. Further interventional studies are needed to establish a causal role of RONS in TCE-mediated autoimmunity

  4. Protein cysteine oxidation in redox signaling

    DEFF Research Database (Denmark)

    Forman, Henry Jay; Davies, Michael J; Krämer, Anna C

    2017-01-01

    Oxidation of critical signaling protein cysteines regulated by H2O2 has been considered to involve sulfenic acid (RSOH) formation. RSOH may subsequently form either a sulfenyl amide (RSNHR') with a neighboring amide, or a mixed disulfide (RSSR') with another protein cysteine or glutathione. Previ...

  5. Oxidative Stress and Periodontal Disease in Obesity.

    Science.gov (United States)

    Dursun, Erhan; Akalin, Ferda Alev; Genc, Tolga; Cinar, Nese; Erel, Ozcan; Yildiz, Bulent Okan

    2016-03-01

    Periodontal disease is a chronic inflammatory disease of the jaws and is more prevalent in obesity. Local and systemic oxidative stress may be an early link between periodontal disease and obesity. The primary aim of this study was to detect whether increased periodontal disease susceptibility in obese individuals is associated with local and systemic oxidative stress. Accordingly; we analyzed periodontal status and systemic (serum) and local (gingival crevicular fluid [GCF]) oxidative status markers in young obese women in comparison with age-matched lean women.Twenty obese and 20 lean women participated. Periodontal condition was determined by clinical periodontal indices including probing depth, clinical attachment level, gingival index, gingival bleeding index, and plaque index. Anthropometric, hormonal, and metabolic measurements were also performed. Blood and GCF sampling was performed at the same time after an overnight fasting. Serum and GCF total antioxidant capacity (TAOC), and total oxidant status (TOS) levels were determined, and oxidative stress index (OSI) was calculated.Clinical periodontal analyses showed higher gingival index and gingival bleeding index in the obese group (P = 0.001 for both) with no significant difference in probing depth, clinical attachment level, and plaque index between the obese and the lean women. Oxidant status analyses revealed lower GCF and serum TAOC, and higher GCF and serum OSI values in the obese women (P < 0.05 for all). GCF TOS was higher in the obese women (P < 0.05), whereas there was a nonsignificant trend for higher serum TOS in obese women (P = 0.074). GCF TAOC values showed a negative correlation with body mass index, whereas GCF OSI was positively correlated with fasting insulin and low-density lipoprotein-cholesterol levels (P < 0.05 for all). Clinical periodontal indices showed significant correlations with body mass index, insulin, and lipid levels, and also oxidant status markers

  6. Protein stress and stress proteins: implications in aging and disease

    Indian Academy of Sciences (India)

    Madhu Sudhan

    2007-04-02

    Apr 2, 2007 ... age-related disease by DAF-16 and heat-shock factor; Science. 300 1142–1145. Macario A J and Conway de Macario E 2005 Sick chaperones, cellular stress, and disease; N. Engl. J. Med. 353 1489–1501. Massey A C, Kaushik S, Sovak G, Kiffin R and Cuervo A M 2006. Consequences of the selective ...

  7. Nitric oxide in the stress axis.

    Science.gov (United States)

    López-Figueroa, M O; Day, H E; Akil, H; Watson, S J

    1998-10-01

    In recent years nitric oxide (NO) has emerged as a unique biological messenger. NO is a highly diffusible gas, synthesized from L-arginine by the enzyme nitric oxide synthase (NOS). Three unique subtypes of NOS have been described, each with a specific distribution profile in the brain and periphery. NOS subtype I is present, among other areas, in the hippocampus, hypothalamus, pituitary and adrenal gland. Together these structures form the limbic-hypothalamic-pituitary-adrenal (LHPA) or stress axis, activation of which is one of the defining features of a stress response. Evidence suggests that NO may modulate the release of the stress hormones ACTH and corticosterone, and NOS activity and transcription is increased in the LHPA axis following various stressful stimuli. Furthermore, following activation of the stress axis, glucocorticoids are thought to down-regulate the transcription and activity of NOS via a feedback mechanism. Taken together, current data indicate a role for NO in the regulation of the LHPA axis, although at present this role is not well defined. It has been suggested that NO may act as a cellular communicator in plasticity and development, to facilitate the activation or the release of other neurotransmitters, to mediate immune responses, and/or as a vasodilator in the regulation of blood flow. In the following review we summarize some of the latest insights into the function of NO, with special attention to its relationship with the LHPA axis.

  8. Biochemical basis of the high resistance to oxidative stress

    Indian Academy of Sciences (India)

    Aerobic organisms experience oxidative stress due to generation of reactive oxygen species during normal aerobic metabolism. In addition, several chemicals also generate reactive oxygen species which induce oxidative stress. Thus oxidative stress constitutes a major threat to organisms living in aerobic environments.

  9. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    International Nuclear Information System (INIS)

    Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2013-01-01

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P 450 inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate

  10. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  11. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  12. Wet-cupping removes oxidants and decreases oxidative stress.

    Science.gov (United States)

    Tagil, Suleyman Murat; Celik, Huseyin Tugrul; Ciftci, Sefa; Kazanci, Fatmanur Hacievliyagil; Arslan, Muzeyyen; Erdamar, Nazan; Kesik, Yunus; Erdamar, Husamettin; Dane, Senol

    2014-12-01

    Wet-cupping therapy is one of the oldest known medical techniques. Although it is widely used in various conditions such as acute\\chronic inflammation, infectious diseases, and immune system disorders, its mechanism of action is not fully known. In this study, we investigated the oxidative status as the first step to elucidate possible mechanisms of action of wet cupping. Wet cupping therapy is implemented to 31 healthy volunteers. Venous blood samples and Wet cupping blood samples were taken concurrently. Serum nitricoxide, malondialdehyde levels and activity of superoxide dismutase and myeloperoxidase were measured spectrophotometrically. Wet cupping blood had higher activity of myeloperoxidase, lower activity of superoxide dismutase, higher levels of malondialdehyde and nitricoxide compared to the venous blood. Wet cupping removes oxidants and decreases oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Ascorbate/menadione-induced oxidative stress kills cancer cells that express normal or mutated forms of the oncogenic protein Bcr-Abl. An in vitro and in vivo mechanistic study.

    Science.gov (United States)

    Beck, Raphaël; Pedrosa, Rozangela Curi; Dejeans, Nicolas; Glorieux, Christophe; Levêque, Philippe; Gallez, Bernard; Taper, Henryk; Eeckhoudt, Stéphane; Knoops, Laurent; Calderon, Pedro Buc; Verrax, Julien

    2011-10-01

    Numerous studies suggest that generation of oxidative stress could be useful in cancer treatment. In this study, we evaluated, in vitro and in vivo, the antitumor potential of oxidative stress induced by ascorbate/menadione (asc/men). This combination of a reducing agent (ascorbate) and a redox active quinone (menadione) generates redox cycling leading to formation of reactive oxygen species (ROS). Asc/men was tested in several cell types including K562 cells (a stable human-derived leukemia cell line), freshly isolated leukocytes from patients with chronic myeloid leukemia, BaF3 cells (a murine pro-B cell line) transfected with Bcr-Abl and peripheral blood leukocytes derived from healthy donors. Although these latter cells were resistant to asc/men, survival of all the other cell lines was markedly reduced, including the BaF3 cells expressing either wild-type or mutated Bcr-Abl. In a standard in vivo model of subcutaneous tumor transplantation, asc/men provoked a significant delay in the proliferation of K562 and BaF3 cells expressing the T315I mutated form of Bcr-Abl. No effect of asc/men was observed when these latter cells were injected into blood of mice most probably because of the high antioxidant potential of red blood cells, as shown by in vitro experiments. We postulate that cancer cells are more sensitive to asc/men than healthy cells because of their lack of antioxidant enzymes, mainly catalase. The mechanism underlying this cytotoxicity involves the oxidative cleavage of Hsp90 with a subsequent loss of its chaperone function thus leading to degradation of wild-type and mutated Bcr-Abl protein.

  14. Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic pain and disinhibition of the spinal nociceptive circuitry.

    Science.gov (United States)

    Ge, Yanhu; Jiao, Yingfu; Li, Peiying; Xiang, Zhenghua; Li, Zhi; Wang, Long; Li, Wenqian; Gao, Hao; Shao, Jiayun; Wen, Daxiang; Yu, Weifeng

    2018-05-01

    The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress. Other important findings in this study including the following: (1) nociceptive behavior was alleviated in SNL rat as long as tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2) inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3) blocking protein disulfide isomerase pharmacologically reduced ER stress and nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER stress were mainly neurons; and (5) whole-cell recordings made in slide preparations revealed significant inhibition of GABA-ergic interneuron activity in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together, results of the current study demonstrate that coregulation of ER stress and oxidative stress played an important role in neuropathic pain process. Inhibiting SDH ER stress could be a potential novel strategy to manage neuropathic pain.

  15. Influence of Oxidative Stress on Stored Platelets

    OpenAIRE

    K. Manasa; R. Vani

    2016-01-01

    Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS) is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platele...

  16. Oxidative stress and Parkinson’s Disease

    OpenAIRE

    Javier eBlesa; Javier eBlesa; Javier eBlesa; Ines eTrigo-Damas; Ines eTrigo-Damas; Anna eQuiroga-Varela; Vernice Ruffin Jackson-Lewis

    2015-01-01

    Parkinson disease is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in Parkinson’s Disease. Environmental factors, such as neuro...

  17. Piracetam improves mitochondrial dysfunction following oxidative stress

    OpenAIRE

    Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

    2005-01-01

    Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging.Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction fol...

  18. Chrononutrition against Oxidative Stress in Aging

    Directory of Open Access Journals (Sweden)

    M. Garrido

    2013-01-01

    Full Text Available Free radicals and oxidative stress have been recognized as important factors in the biology of aging and in many age-associated degenerative diseases. Antioxidant systems deteriorate during aging. It is, thus, considered that one way to reduce the rate of aging and the risk of chronic disease is to avoid the formation of free radicals and reduce oxidative stress by strengthening antioxidant defences. Phytochemicals present in fruits, vegetables, grains, and other foodstuffs have been linked to reducing the risk of major oxidative stress-induced diseases. Some dietary components of foods possess biological activities which influence circadian rhythms in humans. Chrononutrition studies have shown that not only the content of food, but also the time of ingestion contributes to the natural functioning of the circadian system. Dietary interventions with antioxidant-enriched foods taking into account the principles of chrononutrition are of particular interest for the elderly since they may help amplify the already powerful benefits of phytochemicals as natural instruments with which to prevent or delay the onset of common age-related diseases.

  19. Adaptive stress response to menadione-induced oxidative stress in Saccharomyces cerevisiae KNU5377.

    Science.gov (United States)

    Kim, Il-Sup; Sohn, Ho-Yong; Jin, Ingnyol

    2011-10-01

    The molecular mechanisms involved in the ability of yeast cells to adapt and respond to oxidative stress are of great interest to the pharmaceutical, medical, food, and fermentation industries. In this study, we investigated the time-dependent, cellular redox homeostasis ability to adapt to menadione-induced oxidative stress, using biochemical and proteomic approaches in Saccharomyces cerevisiae KNU5377. Time-dependent cell viability was inversely proportional to endogenous amounts of ROS measured by a fluorescence assay with 2',7'-dichlorofluorescin diacetate (DCFHDA), and was hypersensitive when cells were exposed to the compound for 60 min. Morphological changes, protein oxidation and lipid peroxidation were also observed. To overcome the unfavorable conditions due to the presence of menadione, yeast cells activated a variety of cell rescue proteins including antioxidant enzymes, molecular chaperones, energy-generating metabolic enzymes, and antioxidant molecules such as trehalose. Thus, these results show that menadione causes ROS generation and high accumulation of cellular ROS levels, which affects cell viability and cell morphology and there is a correlation between resistance to menadione and the high induction of cell rescue proteins after cells enter into this physiological state, which provides a clue about the complex and dynamic stress response in yeast cells.

  20. Symbiosis-induced adaptation to oxidative stress.

    Science.gov (United States)

    Richier, Sophie; Furla, Paola; Plantivaux, Amandine; Merle, Pierre-Laurent; Allemand, Denis

    2005-01-01

    Cnidarians in symbiosis with photosynthetic protists must withstand daily hyperoxic/anoxic transitions within their host cells. Comparative studies between symbiotic (Anemonia viridis) and non-symbiotic (Actinia schmidti) sea anemones show striking differences in their response to oxidative stress. First, the basal expression of SOD is very different. Symbiotic animal cells have a higher isoform diversity (number and classes) and a higher activity than the non-symbiotic cells. Second, the symbiotic animal cells of A. viridis also maintain unaltered basal values for cellular damage when exposed to experimental hyperoxia (100% O(2)) or to experimental thermal stress (elevated temperature +7 degrees C above ambient). Under such conditions, A. schmidti modifies its SOD activity significantly. Electrophoretic patterns diversify, global activities diminish and cell damage biomarkers increase. These data suggest symbiotic cells adapt to stress while non-symbiotic cells remain acutely sensitive. In addition to being toxic, high O(2) partial pressure (P(O(2))) may also constitute a preconditioning step for symbiotic animal cells, leading to an adaptation to the hyperoxic condition and, thus, to oxidative stress. Furthermore, in aposymbiotic animal cells of A. viridis, repression of some animal SOD isoforms is observed. Meanwhile, in cultured symbionts, new activity bands are induced, suggesting that the host might protect its zooxanthellae in hospite. Similar results have been observed in other symbiotic organisms, such as the sea anemone Aiptasia pulchella and the scleractinian coral Stylophora pistillata. Molecular or physical interactions between the two symbiotic partners may explain such variations in SOD activity and might confer oxidative stress tolerance to the animal host.

  1. Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs.

    Science.gov (United States)

    Balbaa, Mahmoud; Abdulmalek, Shaymaa A; Khalil, Sofia

    2017-01-01

    oxidative stress, the pro-inflammatory mediators and amyloidogenic pathway. Moreover, it lowers the insulin receptor inhibitory effect of IOMe-AG538 and modifies the insulin-signaling pathway. Therefore, it prevents the neurotoxicity, amyloid plaque formation and Tau hyper-phosphorylation and restores AD-related miRNA normal levels. These data suggest that NSO or its combined treatments with anti-diabetic drugs have a possible benefit as disease modifying agents for the insulin resistance in the brain through enhancing brain insulin signaling pathway.

  2. Ghrelin protects against depleted uranium-induced apoptosis of MC3T3-E1 cells through oxidative stress-mediated p38-mitogen-activated protein kinase pathway

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-01

    Depleted uranium (DU) mainly accumulates in the bone over the long term. Osteoblast cells are responsible for the formation of bone, and they are sensitive to DU damage. However, studies investigating methods of reducing DU damage in osteoblasts are rarely reported. Ghrelin is a stomach hormone that stimulates growth hormones released from the hypothalamic–pituitary axis, and it is believed to play an important physiological role in bone metabolism. This study evaluates the impact of ghrelin on DU-induced apoptosis of the osteoblast MC3T3-E1 and investigates its underlying mechanisms. The results show that ghrelin relieved the intracellular oxidative stress induced by DU, eliminated reactive oxygen species (ROS) and reduced lipid peroxidation by increasing intracellular GSH levels; in addition, ghrelin effectively suppressed apoptosis, enhanced mitochondrial membrane potential, and inhibited cytochrome c release and caspase-3 activation after DU exposure. Moreover, ghrelin significantly reduced the expression of DU-induced phosphorylated p38-mitogen-activated protein kinase (MAPK). A specific inhibitor (SB203580) or specific siRNA of p38-MAPK could significantly suppress DU-induced apoptosis and related signals, whereas ROS production was not affected. In addition, ghrelin receptor inhibition could reduce the anti-apoptosis effect of ghrelin on DU and reverse the effect of ghrelin on intracellular ROS and p38-MAPK after DU exposure. These results suggest that ghrelin can suppress DU-induced apoptosis of MC3T3-E1 cells, reduce DU-induced oxidative stress by interacting with its receptor, and inhibit downstream p38-MAPK activation, thereby suppressing the mitochondrial-dependent apoptosis pathway. - Highlights: • Ghrelin suppressed DU-induced apoptosis of MC3T3-E1 cells. • Ghrelin inhibited DU-induced oxidative stress and further p38-MAPK activation. • Ghrelin further suppressed mitochondrial-dependent apoptosis pathway. • The anti-oxidation effect of

  3. Serum Polychlorinated Biphenyls Increase and Oxidative Stress Decreases with a Protein-Pacing Caloric Restriction Diet in Obese Men and Women

    Directory of Open Access Journals (Sweden)

    Feng He

    2017-01-01

    Full Text Available The purposes were to compare the effects of a: (1 12-week P-CR weight loss (WL diet (Phase 1 between obese men and women and; (2 52-week modified P-CR (mP-CR vs. heart healthy (HH weight maintenance (WM diet (Phase 2 on serum PCBs and oxidative stress biomarkers (thiobarbituric acid reactive substances, TBARS; total antioxidant capacity, TAC in 40 obese participants (men, n = 21; women, n = 19. Participants received dietary counseling and monitoring of compliance. PCBs, TBARS, and TAC were assessed at weeks −1 (CON, 12 (WL, and 64 (WM. Following WL (Week 12, concomitant with reductions in TBARS (0.24 ± 0.15 vs. 0.18 ± 0.11 µM; p < 0.01, PCB serum concentrations (86.7 ± 45.6 vs. 115.6 ± 65.9 ng/g lipid; p < 0.01 and TAC (18.9 ± 2.6 vs. 19.9 ± 2.3 nmol/mL; p < 0.02 were increased similarly in men and women. At the end of WM (Week 64, a significant effect of time × group interaction was observed for % change in PCB 170 and 187; whereby mP-CR values were higher compared to HH (PCB170: 19.31% ± 26.48% vs. −6.61% ± 28.88%, p = 0.02; PCB187: −3.04% ± 17.78% vs. −21.4% ± 27.31%, p = 0.04. PCB changes were positively correlated with TBARS levels (r > 0.42, p < 0.05 and negatively correlated with body weight, fat mass, and abdominal fat (r < −0.46, p < 0.02. Our results support mobilization of stored PCBs as well as enhanced redox status following a 12-week P-CR WL diet. Additionally, a 52-week mP-CR WM diet demonstrated an advantage in preventing weight gain relapse accompanied by an increase in circulating PCBs compared to a traditional HH diet.

  4. Iron, Oxidative Stress and Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Taifeng Zhuang

    2014-09-01

    Full Text Available Both iron deficiency and hyperglycemia are highly prevalent globally for pregnant women. Iron supplementation is recommended during pregnancy to control iron deficiency. The purposes of the review are to assess the oxidative effects of iron supplementation and the potential relationship between iron nutrition and gestational diabetes. High doses of iron (~relative to 60 mg or more daily for adult humans can induce lipid peroxidation in vitro and in animal studies. Pharmaceutical doses of iron supplements (e.g., 10× RDA or more for oral supplements or direct iron supplementation via injection or addition to the cell culture medium for a short or long duration will induce DNA damage. Higher heme-iron intake or iron status measured by various biomarkers, especially serum ferritin, might contribute to greater risk of gestational diabetes, which may be mediated by iron oxidative stress though lipid oxidation and/or DNA damage. However, information is lacking about the effect of low dose iron supplementation (≤60 mg daily on lipid peroxidation, DNA damage and gestational diabetes. Randomized trials of low-dose iron supplementation (≤60 mg daily for pregnant women are warranted to test the relationship between iron oxidative stress and insulin resistance/gestational diabetes, especially for iron-replete women.

  5. Diethyl Phthalate Causes Oxidative Stress: An in Vitro Study

    Directory of Open Access Journals (Sweden)

    Heena Prajapati

    2014-03-01

    Full Text Available Background: Phthalates are a group of multifunctional chemicals. Diethyl phthalate (DEP is one of the most frequently used phthalates in solvents and fixatives for numerous industrial products. Method: The present experiment was designed to assess oxidative stress, if any, caused by diethyl phthalate. For this the homogenates of liver and kidney were treated with different concentrations ( 10-40 µg/mL of DEP. 10% liver and kidney homogenates were prepared in phosphate buffered saline and used for estimation of lipid peroxidation.In final step lipid peroxidation and total protein content were analyzed. Results: The result revealed significant and dose - dependent increase in lipid peroxidation, whereas protein content reduced significantly. Maximum increase in LPO and decrease in protein content was observed at 40 µg/mL of DEP concentration. Conclusion: From this study, it can be concluded that different concentrations of DEP leads to dose- dependent significant increase in lipid peroxidation and decrease protein content.So at the different concentration of DEP cause oxidative stress.

  6. Analysis and Chemistry of Novel Protein Oxidation Markers in Vivo.

    Science.gov (United States)

    Henning, Christian; Liehr, Kristin; Girndt, Matthias; Ulrich, Christof; Glomb, Marcus A

    2018-05-09

    Proteins continually undergo spontaneous oxidation reactions, which lead to changes in structure and function. The quantitative assessment of protein oxidation adducts provides information on the level of exposure to reactive precursor compounds with a high oxidizing potential and reactive oxygen species (ROS). In the present work, we introduce N 6 -(2-hydroxyethyl)lysine as a novel marker based on the ratio of glycolaldehyde and its oxidized form glyoxal. The high analytical potential was proven with a first set of patients undergoing hemodialysis versus healthy controls, in comparison with well-established parameters for oxidative stress. In vitro experiments with N 1 - t-BOC-lysine and N 1 - t-BOC-arginine enlightened the mechanistic relationship of glycolaldehyde and glyoxal. Oxidation was strongly dependent on the catalytic action of the ε-amino moiety of lysine. Investigations on the formation of N 6 -carboxymethyl lysine revealed glycolaldehyde-imine as the more reactive precursor, even though an additional oxidative step is required. As a result, a novel and very effective alternative mechanism was unraveled.

  7. Oxidative stress markers at birth: Analyses of a neonatal population.

    Science.gov (United States)

    Giuffrè, Mario; Rizzo, Manfredi; Scaturro, Giusy; Pitruzzella, Alessandro; Marino Gammazza, Antonella; Cappello, Francesco; Corsello, Giovanni; Li Volti, Giovanni

    2015-01-01

    In order to further understand neonatal stress and, thus, control it efficaciously, there is a need for more information on the manifestations of stress at the molecular level in the newborn, with particular regard to oxidants, and anti-oxidant and anti-stress mechanisms, including mitochondrial heat shock protein-chaperones such as Hsp60. We investigated patterns of anti-oxidants, biomarkers of oxidative stress, and Hsp60 levels in sera from newborns and found significant associations between glutathione (GSH) levels and gestational age, delivery modality, and lipid hydroperoxydes (LOOH) level. LOOH levels and spontaneous (vaginal) delivery were independently associated with increased GSH levels when these were above the median. Hsp60 and LOOH levels were positively correlated whereas Hsp60 and GSH levels were inversely correlated in spontaneously delivered newborns; in contrast, Hsp60 and GSH levels were positively correlated in newborns delivered by cesarea. Our results point to new directions in the search for definite patterns of GSH, LOOH, and Hsp60 in the newborn's serum that might have functional and diagnostic significance and that could help in the monitoring of newborn health during and after delivery. In addition, the data provide a starting basis for investigating the precise roles and interplay of GSH and Hsp60 in the maintenance of an optimal redox balance at birth to cope with the stress inherent to delivery, and also for investigating the predictive value of any given pattern of GSH, LOOH, and Hsp60 at birth with regard to health status and risk of disease in adult life. Copyright © 2015 Elsevier GmbH. All rights reserved.

  8. Dietary antioxidents and oxidative stress in predialysis chronic kidney disease patients.

    Science.gov (United States)

    L Gupta, Krishan; Sahni, Nancy

    2012-10-01

    Dietary antioxidants are important in protecting against human diseases. Oxidative stress, a non- traditional risk factors of cardio-vascular disease is far more prevalent in chronic kidney disease (CKD) patients than in normal subjects. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Oxidative stress could be a consequence of an increase in reactive oxygen species as well as a decrease in antioxidant defenses. Among the important factors that can be involved in triggering oxidative stress is insufficient dietary intake of antioxidants. Malnourished CKD patients are reported to have more oxidative stress than well nourished ones. Moving beyond the importance of assessment of dietary protein and energy in pre dialysis CKD patients to the assessment of dietary antioxidants is of utmost importance to help combat enhanced oxidative stress levels in such patients.

  9. Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

    Science.gov (United States)

    Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Oxidative stress participates in age-related changes in rat lumbar intervertebral discs.

    Science.gov (United States)

    Hou, Gang; Lu, Huading; Chen, Mingjuan; Yao, Hui; Zhao, Huiqing

    2014-01-01

    Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Oxidative Stress in Patients with Drug Resistant Partial Complex Seizure

    Directory of Open Access Journals (Sweden)

    Lourdes Lorigados Pedre

    2018-06-01

    Full Text Available Oxidative stress (OS has been implicated as a pathophysiological mechanism of drug-resistant epilepsy, but little is known about the relationship between OS markers and clinical parameters, such as the number of drugs, age onset of seizure and frequency of seizures per month. The current study’s aim was to evaluate several oxidative stress markers and antioxidants in 18 drug-resistant partial complex seizure (DRPCS patients compared to a control group (age and sex matched, and the results were related to clinical variables. We examined malondialdehyde (MDA, advanced oxidation protein products (AOPP, advanced glycation end products (AGEs, nitric oxide (NO, uric acid, superoxide dismutase (SOD, glutathione, vitamin C, 4-hydroxy-2-nonenal (4-HNE and nitrotyrosine (3-NT. All markers except 4-HNE and 3-NT were studied by spectrophotometry. The expressions of 4-HNE and 3-NT were evaluated by Western blot analysis. MDA levels in patients were significantly increased (p ≤ 0.0001 while AOPP levels were similar to the control group. AGEs, NO and uric acid concentrations were significantly decreased (p ≤ 0.004, p ≤ 0.005, p ≤ 0.0001, respectively. Expressions of 3-NT and 4-HNE were increased (p ≤ 0.005 similarly to SOD activity (p = 0.0001, whereas vitamin C was considerably diminished (p = 0.0001. Glutathione levels were similar to the control group. There was a positive correlation between NO and MDA with the number of drugs. The expression of 3-NT was positively related with the frequency of seizures per month. There was a negative relationship between MDA and age at onset of seizures, as well as vitamin C with seizure frequency/month. We detected an imbalance in the redox state in patients with DRCPS, supporting oxidative stress as a relevant mechanism in this pathology. Thus, it is apparent that some oxidant and antioxidant parameters are closely linked with clinical variables.

  12. Role of oxidative stress in female reproduction

    Directory of Open Access Journals (Sweden)

    Sharma Rakesh K

    2005-07-01

    Full Text Available Abstract In a healthy body, ROS (reactive oxygen species and antioxidants remain in balance. When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS occurs. OS influences the entire reproductive lifespan of a woman and even thereafter (i.e. menopause. OS results from an imbalance between prooxidants (free radical species and the body's scavenging ability (antioxidants. ROS are a double-edged sword – they serve as key signal molecules in physiological processes but also have a role in pathological processes involving the female reproductive tract. ROS affect multiple physiological processes from oocyte maturation to fertilization, embryo development and pregnancy. It has been suggested that OS modulates the age-related decline in fertility. It plays a role during pregnancy and normal parturition and in initiation of preterm labor. Most ovarian cancers appear in the surface epithelium, and repetitive ovulation has been thought to be a causative factor. Ovulation-induced oxidative base damage and damage to DNA of the ovarian epithelium can be prevented by antioxidants. There is growing literature on the effects of OS in female reproduction with involvement in the pathophsiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as abortions. Numerous studies have shown that OS plays a role in the pathoysiology of infertility and assisted fertility. There is some evidence of its role in endometriosis, tubal and peritoneal factor infertility and unexplained infertility. This article reviews the role OS plays in normal cycling ovaries, follicular development and cyclical endometrial changes. It also discusses OS-related female infertility and how it influences the outcomes of assisted reproductive techniques. The review comprehensively explores the literature for evidence of the role of oxidative stress in conditions such as abortions, preeclampsia, hydatidiform mole, fetal

  13. Nitrosative stress and nitrated proteins in trichloroethene-mediated autoimmunity.

    Directory of Open Access Journals (Sweden)

    Gangduo Wang

    Full Text Available Exposure to trichloroethene (TCE, a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼ 250 mg/kg/day via drinking water. TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies.

  14. Conservation of Oxidative Protein Stabilization in an Insect Homologue of Parkinsonism-Associated Protein DJ-1

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Jiusheng; Prahlad, Janani; Wilson, Mark A. (UNL)

    2012-08-21

    DJ-1 is a conserved, disease-associated protein that protects against oxidative stress and mitochondrial damage in multiple organisms. Human DJ-1 contains a functionally essential cysteine residue (Cys106) whose oxidation is important for regulating protein function by an unknown mechanism. This residue is well-conserved in other DJ-1 homologues, including two (DJ-1{alpha} and DJ-1{beta}) in Drosophila melanogaster. Because D. melanogaster is a powerful model system for studying DJ-1 function, we have determined the crystal structure and impact of cysteine oxidation on Drosophila DJ-1{beta}. The structure of D. melanogaster DJ-1{beta} is similar to that of human DJ-1, although two important residues in the human protein, Met26 and His126, are not conserved in DJ-1{beta}. His126 in human DJ-1 is substituted with a tyrosine in DJ-1{beta}, and this residue is not able to compose a putative catalytic dyad with Cys106 that was proposed to be important in the human protein. The reactive cysteine in DJ-1 is oxidized readily to the cysteine-sulfinic acid in both flies and humans, and this may regulate the cytoprotective function of the protein. We show that the oxidation of this conserved cysteine residue to its sulfinate form (Cys-SO{sub 2{sup -}}) results in considerable thermal stabilization of both Drosophila DJ-1{beta} and human DJ-1. Therefore, protein stabilization is one potential mechanism by which cysteine oxidation may regulate DJ-1 function in vivo. More generally, most close DJ-1 homologues are likely stabilized by cysteine-sulfinic acid formation but destabilized by further oxidation, suggesting that they are biphasically regulated by oxidative modification.

  15. Oxidative Stress and DNA Methylation in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Krishna Vanaja Donkena

    2010-01-01

    Full Text Available The protective effects of fruits, vegetables, and other foods on prostate cancer may be due to their antioxidant properties. An imbalance in the oxidative stress/antioxidant status is observed in prostate cancer patients. Genome oxidative damage in prostate cancer patients is associated with higher lipid peroxidation and lower antioxidant levels. Oxygen radicals are associated with different steps of carcinogenesis, including structural DNA damage, epigenetic changes, and protein and lipid alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin-associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy.

  16. Oxidative stress and toxicity of gold nanoparticles in Mytilus edulis

    International Nuclear Information System (INIS)

    Tedesco, Sara; Doyle, Hugh; Blasco, Julian; Redmond, Gareth; Sheehan, David

    2010-01-01

    Gold nanoparticles (AuNP) have potential applications in drug delivery, cancer diagnosis and therapy, food industry and environment remediation. However, little is known about their potential toxicity or fate in the environment. Mytilus edulis was exposed in tanks to750 ppb AuNP (average diameter 5.3 ± 1 nm) for 24 h to study in vivo biological effects of nanoparticles. Traditional biomarkers and an affinity procedure selective for thiol-containing proteins followed by two-dimensional electrophoresis (2DE) separations were used to study toxicity and oxidative stress responses. Results were compared to those obtained for treatment with cadmium chloride, a well known pro-oxidant. M. edulis mainly accumulated AuNP in digestive gland which also showed higher lipid peroxidation. One-dimensional SDS/PAGE (1DE) and 2DE analysis of digestive gland samples revealed decreased thiol-containing proteins for AuNP. Lysosomal membrane stability measured in haemolymph gave lower values for neutral red retention time (NRRT) in both treatments but was greater in AuNP. Oxidative stress occurred within 24 h of AuNP exposure in M. edulis. Previously we showed that larger diameter AuNP caused modest effects, indicating that nanoparticle size is a key factor in biological responses to nanoparticles. This study suggests that M. edulis is a suitable model animal for environmental toxicology studies of nanoparticles.

  17. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  18. Smog induces oxidative stress and microbiota disruption.

    Science.gov (United States)

    Wong, Tit-Yee

    2017-04-01

    Smog is created through the interactions between pollutants in the air, fog, and sunlight. Air pollutants, such as carbon monoxide, heavy metals, nitrogen oxides, ozone, sulfur dioxide, volatile organic vapors, and particulate matters, can induce oxidative stress in human directly or indirectly through the formation of reactive oxygen species. The outermost boundary of human skin and mucous layers are covered by a complex network of human-associated microbes. The relation between these microbial communities and their human host are mostly mutualistic. These microbes not only provide nutrients, vitamins, and protection against other pathogens, they also influence human's physical, immunological, nutritional, and mental developments. Elements in smog can induce oxidative stress to these microbes, leading to community collapse. Disruption of these mutualistic microbiota may introduce unexpected health risks, especially among the newborns and young children. Besides reducing the burning of fossil fuels as the ultimate solution of smog formation, advanced methods by using various physical, chemical, and biological means to reduce sulfur and nitrogen contains in fossil fuels could lower smog formation. Additionally, information on microbiota disruption, based on functional genomics, culturomics, and general ecological principles, should be included in the risk assessment of prolonged smog exposure to the health of human populations. Copyright © 2017. Published by Elsevier B.V.

  19. Oxidative Stress in Oral Diseases: Understanding Its Relation with Other Systemic Diseases

    Directory of Open Access Journals (Sweden)

    Jaya Kumar

    2017-09-01

    Full Text Available Oxidative stress occurs in diabetes, various cancers, liver diseases, stroke, rheumatoid arthritis, chronic inflammation, and other degenerative diseases related to the nervous system. The free radicals have deleterious effect on various organs of the body. This is due to lipid peroxidation and irreversible protein modification that leads to cellular apoptosis or programmed cell death. During recent years, there is a rise in the oral diseases related to oxidative stress. Oxidative stress in oral disease is related to other systemic diseases in the body such as periodontitis, cardiovascular, pancreatic, gastric, and liver diseases. In the present review, we discuss the various pathways that mediate oxidative cellular damage. Numerous pathways mediate oxidative cellular damage and these include caspase pathway, PERK/NRF2 pathway, NADPH oxidase 4 pathways and JNK/mitogen-activated protein (MAP kinase pathway. We also discuss the role of inflammatory markers, lipid peroxidation, and role of oxygen species linked to oxidative stress. Knowledge of different pathways, role of inflammatory markers, and importance of low-density lipoprotein, fibrinogen, creatinine, nitric oxide, nitrates, and highly sensitive C-reactive proteins may be helpful in understanding the pathogenesis and plan better treatment for oral diseases which involve oxidative stress.

  20. Oxidative Stress Induces Senescence in Cultured RPE Cells.

    Science.gov (United States)

    Aryan, Nona; Betts-Obregon, Brandi S; Perry, George; Tsin, Andrew T

    2016-01-01

    The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period [at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide]. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, cells with a high level of positive senescence-indicator SA-Beta-Gal-positive staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 MCM and at 800 MCM). Our data suggests that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence.

  1. Relationship between mitochondrial dysfunction, oxidative stress and diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Song Yue

    2014-12-01

    Full Text Available As one of the serious complications of diabetes, diabetic retinopathy(DRhas become a main eye disease which causes blindness. The occurrence and development of DR is related to many factors. The pathogenesis is complicated, and the mechanism has not been clear. Early data suggest that the occurrence and development of DR has relations with many factors such as blood sugar level, diabetes duration and the environment. Among the factors, mitochondrial dysfunction and oxidative stress is the important mechanisms of DR and has become research focus in recent years. Consequences of mitochondrial dysfunction within cells include elevation of the rate of reactive oxygen species(ROSproduction due to damage of electron transport chain proteins, mitochondrial DNA(mtDNAdamage, and loss of metabolic capacity. Clear understanding on the mechanism of mitochondrial functional change under high sugar level and oxidative stress response in the occurrence and development of DR is of great significance on prevention and cure of DR. In this article, the development of mitochondrial metabolism and oxidative stress of DR is reviewed.

  2. [Serum markers of oxidative stress in infertile women with endometriosis].

    Science.gov (United States)

    Andrade, Aline Zyman de; Rodrigues, Jhenifer Kliemchen; Dib, Luciana Azôr; Romão, Gustavo Salata; Ferriani, Rui Alberto; Jordão Junior, Alceu Afonso; Navarro, Paula Andrea de Albuquerque Salles

    2010-06-01

    to compare serum markers of oxidative stress between infertile patients with and without endometriosis and to assess the association of these markers with disease staging. this was a prospective study conducted on 112 consecutive infertile, non-obese patients younger than 39 years, divided into two groups: Endometriosis (n=48, 26 with minimal and mild endometriosis - Stage I/II, and 22 with moderate and severe endometriosis - Stage III/IV) and Control (n=64, with tubal and/or male factor infertility). Blood samples were collected during the early follicular phase of the menstrual cycle for the analysis of serum malondialdehyde, glutathione and total hydroxyperoxide levels by spectrophotometry and of vitamin E by high performance liquid chromatography. The results were compared between the endometriosis and control groups, stage I/II endometriosis and control, stage III/IV endometriosis and control, and between the two endometriosis subgroups. The level of significance was set at 5% (p Control Group (8.0 ± 2 µMol/g protein) and among patients with stage III/IV disease (9.7 ± 2.3 µMol/g protein) compared to patients with stage I/II disease (8.2 ± 1.0 µMol/g protein). No significant differences in serum malondialdehyde levels were observed between groups. we demonstrated a positive association between infertility related to endometriosis, advanced disease stage and increased serum hydroxyperoxide levels, suggesting an increased production of reactive species in women with endometriosis. These data, taken together with the reduction of serum vitamin E and glutathione levels, suggest the occurrence of systemic oxidative stress in women with infertility associated with endometriosis. The reproductive and metabolic implications of oxidative stress should be assessed in future studies.

  3. Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

    Directory of Open Access Journals (Sweden)

    Marcel Jaqueto

    Full Text Available Abstract Introduction: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH is also implicated. Objective: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Methods: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. Results: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. Conclusion: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism.

  4. Effect of non-surgical periodontal therapy on C-reactive protein, oxidative stress, and matrix metalloproteinase (MMP)-9 and MMP-2 levels in patients with type 2 diabetes: a randomized controlled study.

    Science.gov (United States)

    Koromantzos, Panagiotis A; Makrilakis, Konstantinos; Dereka, Xanthippi; Offenbacher, Steven; Katsilambros, Nicholas; Vrotsos, Ioannis A; Madianos, Phoebus N

    2012-01-01

    It is well accepted that glycemic control in patients with diabetes mellitus (DM) is affected by systemic inflammation and oxidative stress. The effect of periodontal therapy on these systemic factors may be related to improvement on glycemic status. The aim of the present study is to assess over a period of 6 months the effect of non-surgical periodontal therapy on serum levels of high-sensitivity C-reactive protein (hsCRP), d-8-iso prostaglandin F2a (d-8-iso) as a marker of oxidative stress, and matrix metalloproteinase (MMP)-2 and MMP-9 on patients with type 2 DM. Sixty participants with type 2 DM and moderate to severe periodontal disease were randomized into intervention (IG) and control (CG) groups. IG received scaling and root planing, whereas CG received supragingival cleaning at baseline and scaling and root planing at 6 months. Participants of both groups were evaluated at baseline and 1, 3, and 6 months. Periodontal data recorded at each visit included probing depth, clinical attachment loss, bleeding on probing, and gingival index. Blood was collected at each visit for the assay of serum glycated hemoglobin A1c (A1c), hsCRP, d-8-iso, MMP-2, and MMP-9. Although there was a trend to a reduction in hsCRP, d-8-iso and MMP-9 it did not reach statistical significance. MMP-2 levels remained unchanged after periodontal treatment. Effective non-surgical periodontal treatment of participants with type 2 DM and moderate to severe periodontal disease improved significantly A1c levels but did not result in a statistically significant improvement in hsCRP, d-8-iso, MMP-2, and MMP-9 levels.

  5. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    International Nuclear Information System (INIS)

    Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

    2015-01-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  6. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Wei [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Fu, Jianfang [Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Shun [Reproductive Medicine Center, Department of Gynecology and Obstetrics, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Zhao, Jie [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi' an 710032 (China); Xie, Nianlin, E-mail: xienianlin@126.com [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Cai, Guoqing, E-mail: firstchair@fmmu.edu.cn [Department of Gynaecology and Obstetrics, Xijing Hospital, Fourth Military Medical University, Xi' an 710032 (China)

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  7. Advances in metal-induced oxidative stress and human disease

    International Nuclear Information System (INIS)

    Jomova, Klaudia; Valko, Marian

    2011-01-01

    Detailed studies in the past two decades have shown that redox active metals like iron (Fe), copper (Cu), chromium (Cr), cobalt (Co) and other metals undergo redox cycling reactions and possess the ability to produce reactive radicals such as superoxide anion radical and nitric oxide in biological systems. Disruption of metal ion homeostasis may lead to oxidative stress, a state where increased formation of reactive oxygen species (ROS) overwhelms body antioxidant protection and subsequently induces DNA damage, lipid peroxidation, protein modification and other effects, all symptomatic for numerous diseases, involving cancer, cardiovascular disease, diabetes, atherosclerosis, neurological disorders (Alzheimer's disease, Parkinson's disease), chronic inflammation and others. The underlying mechanism of action for all these metals involves formation of the superoxide radical, hydroxyl radical (mainly via Fenton reaction) and other ROS, finally producing mutagenic and carcinogenic malondialdehyde (MDA), 4-hydroxynonenal (HNE) and other exocyclic DNA adducts. On the other hand, the redox inactive metals, such as cadmium (Cd), arsenic (As) and lead (Pb) show their toxic effects via bonding to sulphydryl groups of proteins and depletion of glutathione. Interestingly, for arsenic an alternative mechanism of action based on the formation of hydrogen peroxide under physiological conditions has been proposed. A special position among metals is occupied by the redox inert metal zinc (Zn). Zn is an essential component of numerous proteins involved in the defense against oxidative stress. It has been shown, that depletion of Zn may enhance DNA damage via impairments of DNA repair mechanisms. In addition, Zn has an impact on the immune system and possesses neuroprotective properties. The mechanism of metal-induced formation of free radicals is tightly influenced by the action of cellular antioxidants. Many low-molecular weight antioxidants (ascorbic acid (vitamin C), alpha

  8. Persistent response of Fanconi anemia haematopoietic stem and progenitor cells to oxidative stress.

    Science.gov (United States)

    Li, Yibo; Amarachintha, Surya; Wilson, Andrew F; Li, Xue; Du, Wei

    2017-06-18

    Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress. Mechanistically, we demonstrated that accumulation of unrepaired DNA damage, particularly in oxidative damage-sensitive genes, was responsible for the long-lasting response in FA HSPCs. Furthermore, genetic correction of Fanca deficiency almost completely abolished the persistent oxidative stress-induced G 2 /M arrest and DNA damage response in vivo. Our study suggests that FA pathway is an integral part of a versatile cellular mechanism by which HSPCs respond to oxidative stress.

  9. Oxidative stress associated with exercise, psychological stress and life-style factors

    DEFF Research Database (Denmark)

    Møller, P; Wallin, H; Knudsen, Lisbeth E.

    1996-01-01

    generation. Here, we review the effect of alcohol, air pollution, cigarette smoke, diet, exercise, non-ionizing radiation (UV and microwaves) and psychological stress on the development of oxidative stress. Regular exercise and carbohydrate-rich diets seem to increase the resistance against oxidative stress....... Air pollution, alcohol, cigarette smoke, non-ionizing radiation and psychological stress seem to increase oxidative stress. Alcohol in lower doses may act as an antioxidant on low density lipoproteins and thereby have an anti-atherosclerotic property....

  10. Oxidative and nitrosative stress markers in bus drivers.

    Science.gov (United States)

    Rossner, Pavel; Svecova, Vlasta; Milcova, Alena; Lnenickova, Zdena; Solansky, Ivo; Santella, Regina M; Sram, Radim J

    2007-04-01

    Exposure to ambient air pollution is associated with many diseases. Oxidative and nitrosative stress are believed to be two of the major sources of particulate matter (PM)-mediated adverse health effects. PM in ambient air arises from industry, local heating, and vehicle emissions and poses a serious problem mainly in large cities. In the present study we analyzed the level of oxidative and nitrosative stress among 50 bus drivers from Prague, Czech Republic, and 50 matching controls. We assessed simultaneously the levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) and 8-oxodeoxyguanosine (8-oxodG) in urine and protein carbonyl groups and 3-nitrotyrosine (NT) in blood plasma. For the analysis of all four markers we used ELISA techniques. We observed significantly increased levels of oxidative and nitrosative stress markers in bus drivers. The median levels (min, max) of individual markers in bus drivers versus controls were as follows: 8-oxodG: 7.79 (2.64-12.34)nmol/mmol versus 6.12 (0.70-11.38)nmol/mmol creatinine (p<0.01); 15-F(2t)-IsoP: 0.81 (0.38-1.55)nmol/mmol versus 0.68 (0.39-1.79)nmol/mmol creatinine (p<0.01); carbonyl levels: 14.1 (11.8-19.0)nmol/ml versus 12.9 (9.8-16.6)nmol/ml plasma (p<0.001); NT: 694 (471-3228)nmol/l versus 537 (268-13833)nmol/l plasma (p<0.001). 15-F(2t)-IsoP levels correlated with vitamin E (R=0.23, p<0.05), vitamin C (R=-0.33, p<0.01) and cotinine (R=0.47, p<0.001) levels. Vitamin E levels also positively correlated with 8-oxodG (R=0.27, p=0.01) and protein carbonyl levels (R=0.32, p<0.001). Both oxidative and nitrosative stress markers positively correlated with PM2.5 and PM10 exposure. In conclusion, our study indicates that exposure to PM2.5 and PM10 results in increased oxidative and nitrosative stress.

  11. Relationships between inflammation, adiponectin, and oxidative stress in metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Shu-Ju Chen

    Full Text Available Metabolic syndrome (MS represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72. The control group (n = 105 comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP and interleukin-6 (IL-6, adiponectin, an oxidative stress marker (malondialdehyde, and antioxidant enzymes activities [catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GPx] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L, or IL-6 (≥1.50 pg/mL or a lower level of adiponectin (<7.90 µg/mL were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.

  12. S-adenosyl-L-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Brown, James Mike [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States); Kuhlman, Christopher [Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson, AZ (United States); Terneus, Marcus V. [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States); Labenski, Matthew T. [Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson, AZ (United States); Lamyaithong, Andre Benja; Ball, John G. [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States); Lau, Serrine S. [Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona Health Sciences Center, Tucson, AZ (United States); Valentovic, Monica A., E-mail: Valentov@marshall.edu [Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Huntington, WV (United States)

    2014-12-01

    Acetaminophen (APAP) hepatotoxicity is protected by S-adenosyl-L-methionine (SAMe) treatment 1 hour (h) after APAP in C57/Bl6 mice. This study examined protein carbonylation as well as mitochondrial and cytosolic protein adduction by 4-hydroxynonenal (4-HNE) using mass spectrometry (MS) analysis. Additional studies investigated the leakage of mitochondrial proteins and 4-HNE adduction of these proteins. Male C57/Bl6 mice (n = 5/group) were divided into the following groups and treated as indicated: Veh (15 ml/kg water, ip), SAMe (1.25 mmol/kg, ip), APAP (250 mg/kg), and SAMe given 1 h after APAP (S + A). APAP toxicity was confirmed by an increase (p < 0.05) in plasma ALT (U/l) and liver weight/10 g body weight relative to the Veh, SAMe and S + A groups 4 h following APAP treatment. SAMe administered 1 h post-APAP partially corrected APAP hepatotoxicity as ALT and liver weight/10 g body weights were lower in the S + A group compared the APAP group. APAP induced leakage of the mitochondrial protein, carbamoyl phosphate synthase-1 (CPS-1) into the cytosol and which was reduced in the S + A group. SAMe further reduced the extent of APAP mediated 4-HNE adduction of CPS-1. MS analysis of hepatic and mitochondrial subcellular fractions identified proteins from APAP treated mice. Site specific 4-HNE adducts were identified on mitochondrial proteins sarcosine dehydrogenase and carbamoyl phosphate synthase-1 (CPS-1). In summary, APAP is associated with 4-HNE adduction of proteins as identified by MS analysis and that CPS-1 leakage was greater in APAP treated mice. SAMe reduced the extent of 4-HNE adduction of proteins as well as leakage of CPS-1. - Highlights: • Acetaminophen (APAP) toxicity protected by S-adenosylmethionine (SAMe) • 4-Hydroxynonenal adducted to sarcosine dehydrogenase • 4-Hydroxynonenal adducted to carbamoyl phosphate synthetase-1 • SAMe reduced APAP mediated CPS-1 mitochondrial leakage.

  13. S-adenosyl-L-methionine protection of acetaminophen mediated oxidative stress and identification of hepatic 4-hydroxynonenal protein adducts by mass spectrometry

    International Nuclear Information System (INIS)

    Brown, James Mike; Kuhlman, Christopher; Terneus, Marcus V.; Labenski, Matthew T.; Lamyaithong, Andre Benja; Ball, John G.; Lau, Serrine S.; Valentovic, Monica A.

    2014-01-01

    Acetaminophen (APAP) hepatotoxicity is protected by S-adenosyl-L-methionine (SAMe) treatment 1 hour (h) after APAP in C57/Bl6 mice. This study examined protein carbonylation as well as mitochondrial and cytosolic protein adduction by 4-hydroxynonenal (4-HNE) using mass spectrometry (MS) analysis. Additional studies investigated the leakage of mitochondrial proteins and 4-HNE adduction of these proteins. Male C57/Bl6 mice (n = 5/group) were divided into the following groups and treated as indicated: Veh (15 ml/kg water, ip), SAMe (1.25 mmol/kg, ip), APAP (250 mg/kg), and SAMe given 1 h after APAP (S + A). APAP toxicity was confirmed by an increase (p < 0.05) in plasma ALT (U/l) and liver weight/10 g body weight relative to the Veh, SAMe and S + A groups 4 h following APAP treatment. SAMe administered 1 h post-APAP partially corrected APAP hepatotoxicity as ALT and liver weight/10 g body weights were lower in the S + A group compared the APAP group. APAP induced leakage of the mitochondrial protein, carbamoyl phosphate synthase-1 (CPS-1) into the cytosol and which was reduced in the S + A group. SAMe further reduced the extent of APAP mediated 4-HNE adduction of CPS-1. MS analysis of hepatic and mitochondrial subcellular fractions identified proteins from APAP treated mice. Site specific 4-HNE adducts were identified on mitochondrial proteins sarcosine dehydrogenase and carbamoyl phosphate synthase-1 (CPS-1). In summary, APAP is associated with 4-HNE adduction of proteins as identified by MS analysis and that CPS-1 leakage was greater in APAP treated mice. SAMe reduced the extent of 4-HNE adduction of proteins as well as leakage of CPS-1. - Highlights: • Acetaminophen (APAP) toxicity protected by S-adenosylmethionine (SAMe) • 4-Hydroxynonenal adducted to sarcosine dehydrogenase • 4-Hydroxynonenal adducted to carbamoyl phosphate synthetase-1 • SAMe reduced APAP mediated CPS-1 mitochondrial leakage

  14. Oxidative stress tolerance of early stage diabetic endothelial progenitor cell

    Directory of Open Access Journals (Sweden)

    Dewi Sukmawati

    2015-06-01

    Conclusions: Primitive BM-EPCs showed vasculogenic dysfunction in early diabetes. However the oxidative stress is not denoted as the major initiating factor of its cause. Our results suggest that primitive BM-KSL cell has the ability to compensate oxidative stress levels in early diabetes by increasing the expression of anti-oxidative enzymes.

  15. Free radicals, reactive oxygen species, oxidative stress and its classification.

    Science.gov (United States)

    Lushchak, Volodymyr I

    2014-12-05

    Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Oxidative stress in normal and diabetic rats.

    Science.gov (United States)

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pC18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected.

  17. Oxidative stress in ischemia and reperfusion

    DEFF Research Database (Denmark)

    Sinning, Christoph; Westermann, Dirk; Clemmensen, Peter

    2017-01-01

    Oxidative stress remains a major contributor to myocardial injury after ischemia followed by reperfusion (I/R) as the reperfusion of the myocardial infarction (MI) area inevitably leads to a cascade of I/R injury. This review focused on concepts of the antioxidative defense system and elucidates......, the different mechanisms through which myocardial protection can be addressed, like ischemic postconditioning in myocardial infarction or adjunctive measures like targeted temperature management as well as new theories, including the role of iron in I/R injury, will be discussed....

  18. Menopause as risk factor for oxidative stress.

    Science.gov (United States)

    Sánchez-Rodríguez, Martha A; Zacarías-Flores, Mariano; Arronte-Rosales, Alicia; Correa-Muñoz, Elsa; Mendoza-Núñez, Víctor Manuel

    2012-03-01

    The aim of this study was to determine the influence of menopause (hypoestrogenism) as a risk factor for oxidative stress. We carried out a cross-sectional study with 187 perimenopausal women from Mexico City, including 94 premenopausal (mean ± SD age, 44.9 ± 4.0 y; estrogen, 95.8 ± 65.7 pg/mL; follicle-stimulating hormone, 13.6 ± 16.9 mIU/mL) and 93 postmenopausal (mean ± SD age, 52.5 ± 3.3 y; estrogen, 12.8 ± 6.8 pg/mL; follicle-stimulating hormone, 51.4 ± 26.9 mIU/mL) women. We measured lipoperoxides using a thiobarbituric acid-reacting substance assay, erythrocyte superoxide dismutase and glutathione peroxidase activities, and the total antioxidant status with the Randox kit. An alternative cutoff value for lipoperoxide level of 0.320 μmol/L or higher was defined on the basis of the 90th percentile of young healthy participants. All women answered the Menopause Rating Scale, the Athens Insomnia Scale, and a structured questionnaire about pro-oxidant factors, that is, smoking, consumption of caffeinated and alcoholic beverages, and physical activity. Finally, we measured weight and height and calculated body mass index. The lipoperoxide levels were significantly higher in the postmenopausal group than in the premenopausal group (0.357 ± 0.05 vs 0.331 ± 0.05 μmol/L, P = 0.001). Using logistic regression to control pro-oxidant variables, we found that menopause was the main risk factor for oxidative stress (odds ratio, 2.62; 95% CI, 1.35-5.11; P menopause rating score, insomnia score, and lipoperoxides, and this relationship was most evident in the postmenopausal group (menopause scale, r = 0.327 [P = 0.001]; insomnia scale, r = 0.209 [P < 0.05]). Our findings suggest that the depletion of estrogen in postmenopause could cause oxidative stress in addition to the known symptoms.

  19. Cadmium induced oxidative stress in Dunaliella salina | Moradshahi ...

    African Journals Online (AJOL)

    The unicellular green algae Dunaliella salina contains various antioxidants which protect the cell from oxidative damage due to environmental stresses such as heavy metal stress. In the present study, the response of D. salina at the stationary growth phase to oxidative stress generated by cadmium chloride was ...

  20. Statins Prevent Dextrose-Induced Endoplasmic Reticulum Stress and Oxidative Stress in Endothelial and HepG2 Cells.

    Science.gov (United States)

    Kojanian, Hagop; Szafran-Swietlik, Anna; Onstead-Haas, Luisa M; Haas, Michael J; Mooradian, Arshag D

    Statins have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. However, antioxidant vitamins, unlike statins, are not as cardioprotective, and this paradox has been explained by failure of vitamin antioxidants to ameliorate endoplasmic reticulum (ER) stress. To determine whether statins prevent dextrose-induced ER stress in addition to their antioxidative effects, human umbilical vein endothelial cells and HepG2 hepatocytes were treated with 27.5 mM dextrose in the presence of simvastatin (lipophilic statin that is a prodrug) and pravastatin (water-soluble active drug), and oxidative stress, ER stress, and cell death were measured. Superoxide generation was measured using 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride. ER stress was measured using the placental alkaline phosphatase assay and Western blot of glucose-regulated protein 75, c-jun-N-terminal kinase, phospho-JNK, eukaryotic initiating factor 2α and phospho-eIF2α, and X-box binding protein 1 mRNA splicing. Cell viability was measured by propidium iodide staining. Superoxide anion production, ER stress, and cell death induced by 27.5 mM dextrose were inhibited by therapeutic concentrations of simvastatin and pravastatin. The salutary effects of statins on endothelial cells in reducing both ER stress and oxidative stress observed with pravastatin and the prodrug simvastatin suggest that the effects may be independent of cholesterol-lowering activity.

  1. Extremely radioresistant microbe Deinococcus radiodurans does not survive tellurite-mediated oxidative stress: revelation of molecular basis

    International Nuclear Information System (INIS)

    Apte, Shree Kumar; Narasimha, Anaganti; Basu, Bhakti

    2014-01-01

    Deinococcus radiodurans exhibits extraordinary resistance to gamma radiation as well as oxidative stress. Comparison of tellurite stress with gamma irradiation, both of which impart severe oxidative stress, revealed that tellurite induced less ROS and caused less oxidative damage to proteins, but was much more lethal to D. radiodurans than gamma irradiation. The proteomic changes induced by tellurite exposure were mapped by two dimensional protein electrophoresis followed by mass spectrometry. Seventy proteins belonging to major functional categories of oxidative stress alleviation, protein translation/folding and metabolism were identified. Tellurite responsive proteome dynamics displayed (i) up-regulation of proteins involved in tellurite stress resistance and oxidative stress alleviation, dehydrogenases involved in generation of reducing potential, and chaperones (such DnaK), and (ii) down regulation of key glycolysis and TCA cycle enzymes, proteins involved in protein translation/folding and energy production. Tellurite stress also resulted in nearly 50% loss in the cellular reducing potential within 1h of exposure while gamma irradiation had no such effect. The findings provide a better insight into the mechanism of tellurite toxicity, beyond metal mediated oxidative stress, in this extremophile. (author)

  2. The dynamic changes of the plasma membrane proteins and the protective roles of nitric oxide in rice subjected to heavy metal cadmium stress

    Science.gov (United States)

    The heavy metal cadmium is a common environmental contaminant in soils and has adverse effects on crop growth and development. The signaling processes in plants that initiate cellular responses to environmental stress have been shown to be located in the plasma membrane (PM). A better understanding ...

  3. The Apoplastic Secretome of Trichoderma virens During Interaction With Maize Roots Shows an Inhibition of Plant Defence and Scavenging Oxidative Stress Secreted Proteins

    Directory of Open Access Journals (Sweden)

    Guillermo Nogueira-Lopez

    2018-04-01

    Full Text Available In Nature, almost every plant is colonized by fungi. Trichoderma virens is a biocontrol fungus which has the capacity to behave as an opportunistic plant endophyte. Even though many plants are colonized by this symbiont, the exact mechanisms by which Trichoderma masks its entrance into its plant host remain unknown, but likely involve the secretion of different families of proteins into the apoplast that may play crucial roles in the suppression of plant immune responses. In this study, we investigated T. virens colonization of maize roots under hydroponic conditions, evidencing inter- and intracellular colonization by the fungus and modifications in root morphology and coloration. Moreover, we show that upon host penetration, T. virens secretes into the apoplast an arsenal of proteins to facilitate inter- and intracellular colonization of maize root tissues. Using a gel-free shotgun proteomics approach, 95 and 43 secretory proteins were identified from maize and T. virens, respectively. A reduction in the maize secretome (36% was induced by T. virens, including two major groups, glycosyl hydrolases and peroxidases. Furthermore, T. virens secreted proteins were mainly involved in cell wall hydrolysis, scavenging of reactive oxygen species and secondary metabolism, as well as putative effector-like proteins. Levels of peroxidase activity were reduced in the inoculated roots, suggesting a strategy used by T. virens to manipulate host immune responses. The results provide an insight into the crosstalk in the apoplast which is essential to maintain the T. virens-plant interaction.

  4. Oxidative Stress and Antioxidants in the Diagnosis and Therapy of Periodontitis

    Directory of Open Access Journals (Sweden)

    L'ubomíra Tóthová

    2017-12-01

    Full Text Available Oxidative stress has been implicated in the pathogenesis of numerous diseases. However, large interventional studies with antioxidants failed to show benefits in the prevention or treatment of cardiovascular diseases, cancer, or diabetes mellitus. Numerous clinical studies have confirmed the association of oxidative stress markers and periodontitis. Technical and biological variability is high for most of the analyzed markers and none of them seems to be optimal for routine clinical use. In a research setting, analysis of a palette of oxidative stress markers is needed to cover lipid peroxidation, protein oxidation, and the antioxidant status. The source of reactive oxygen species and their role in the pathogenesis of periodontitis remains unclear. Interventional experiments indicate that oxidative stress might be more than just a simple consequence of the inflammation. Small studies have confirmed that some antioxidants could have therapeutic value at least as an addition to the standard non-surgical treatment of periodontitis. A clear evidence for the efficiency of antioxidant treatment in large patient cohorts is lacking. Potentially, because lowering of oxidative stress markers might be a secondary effect of anti-inflammatory or antibacterial agents. As the field of research of oxidative stress in periodontitis gains attraction and the number of relevant published papers is increasing a systematic overview of the conducted observational and interventional studies is needed. This review summarizes the currently available literature linking oxidative stress and periodontitis and points toward the potential of adjuvant antioxidant treatment, especially in cases where standard treatment fails to improve the periodontal status.

  5. Oxidative Stress and Antioxidants in the Diagnosis and Therapy of Periodontitis

    Science.gov (United States)

    Tóthová, L'ubomíra; Celec, Peter

    2017-01-01

    Oxidative stress has been implicated in the pathogenesis of numerous diseases. However, large interventional studies with antioxidants failed to show benefits in the prevention or treatment of cardiovascular diseases, cancer, or diabetes mellitus. Numerous clinical studies have confirmed the association of oxidative stress markers and periodontitis. Technical and biological variability is high for most of the analyzed markers and none of them seems to be optimal for routine clinical use. In a research setting, analysis of a palette of oxidative stress markers is needed to cover lipid peroxidation, protein oxidation, and the antioxidant status. The source of reactive oxygen species and their role in the pathogenesis of periodontitis remains unclear. Interventional experiments indicate that oxidative stress might be more than just a simple consequence of the inflammation. Small studies have confirmed that some antioxidants could have therapeutic value at least as an addition to the standard non-surgical treatment of periodontitis. A clear evidence for the efficiency of antioxidant treatment in large patient cohorts is lacking. Potentially, because lowering of oxidative stress markers might be a secondary effect of anti-inflammatory or antibacterial agents. As the field of research of oxidative stress in periodontitis gains attraction and the number of relevant published papers is increasing a systematic overview of the conducted observational and interventional studies is needed. This review summarizes the currently available literature linking oxidative stress and periodontitis and points toward the potential of adjuvant antioxidant treatment, especially in cases where standard treatment fails to improve the periodontal status. PMID:29311982

  6. Nutritionally Mediated Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Alexandra Muñoz

    2013-01-01

    Full Text Available There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation.

  7. Melamine Induces Oxidative Stress in Mouse Ovary.

    Directory of Open Access Journals (Sweden)

    Xiao-Xin Dai

    Full Text Available Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GPX were analyzed, and the concentration of malondialdehyde (MDA were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway.

  8. OXIDATIVE STRESS IN MUSCLE GROWTH AND ADAPTATION TO PHYSICAL EXERCISE

    Directory of Open Access Journals (Sweden)

    Ihor Yurkevych

    2015-05-01

    Full Text Available In a few last decades oxidative stress detected in a variety of physiological processes where reactive oxygen species (ROS and reactive nitrogen species (RNS play a central role. They are directly involved in oxidation of proteins, lipids and nucleic acids. In certain concentrations they are necessary for cell division, proliferation and apoptosis. Contractile muscle tissue at aerobic conditions form high ROS flow that may modulate a variety of cell functions, for example proliferation. However, slight increase in ROS level provide hormetic effect which may participate in adaptation to heavy weight training resulted in hypertrophy and proliferation of skeletal muscle fibers. This review will discuss ROS types, sites of generation, strategies to increase force production and achieve skeletal muscle hypertrophy.

  9. Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

    Science.gov (United States)

    Okusaga, Olaoluwa O

    2014-08-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

  10. Laboratory assessment of oxidative stress in semen

    Directory of Open Access Journals (Sweden)

    Ashok Agarwal

    2018-03-01

    Full Text Available Objectives: To evaluate different laboratory assessments of oxidative stress (OS in semen and identify a cost-efficient and highly sensitive instrument capable of providing a comprehensive measure of OS in a clinical setting, as early intervention and an accurate diagnostic test are important because they help maintain a balance of free radicals and antioxidants; otherwise, excessive OS could lead to sperm damage and result in male infertility. Materials and methods: A systematic literature search was performed through a MedLine database search using the keywords ‘semen’ AND ‘oxygen reduction potential’. We also reviewed the references of retrieved articles to search for other potentially relevant research articles and additional book chapters discussing laboratory assessments for OS, ranging from 1994 to 2017. A total of 29 articles and book chapters involving OS-related laboratory assays were included. We excluded animal studies and articles written in languages other than English. Results: Direct laboratory techniques include: chemiluminescence, nitro blue tetrazolium, cytochrome C reduction test, fluorescein probe, electron spin resonance and oxidation–reduction potential (ORP. Indirect laboratory techniques include: measurement of Endtz test, lipid peroxidation, chemokines, antioxidants/micronutrients/vitamins, ascorbate, total antioxidant capacity, or DNA damage. Each of these laboratory techniques has its advantages and disadvantages. Conclusion: Traditional OS laboratory assessments have their limitations. Amongst the prevalent laboratory techniques, ORP is novel and better option as it can be easily used in a clinical setting to provide a comprehensive review of OS. However, more studies are needed to evaluate its reproducibility across various laboratory centres. Keywords: Semen, male infertility, Oxidative stress, Chemiluminescence, Total antioxidant capacity, Oxidation-reduction potential

  11. Effects of l-carnitine on oxidative stress parameters in ...

    African Journals Online (AJOL)

    Emel Peri Canbolat

    2016-08-10

    Aug 10, 2016 ... Nitric oxide (NO), malondialdehyde (MDA), total antioxidant status (TAS), total oxidative stress .... Erel's method was used for measuring TOS.19 TOS was ..... antioxidant capacity using a new generation, more stable ABTS.

  12. Effect of moxifloxacin on oxidative stress, paraoxonase-1 (PON1 ...

    African Journals Online (AJOL)

    oxidative stress in patients with multiple drug-resistant tuberculosis (MDR-TB). Methods: A total ofof ... seriously affects the quality of life and prognosis. [6]. ... balance between pro-oxidants and antioxidant ..... original work is properly credited.

  13. Fatty acids and oxidative stress in psychiatric disorders

    OpenAIRE

    Tonello Lucio; Cocchi Massimo; Tsaluchidu Sofia; Puri Basant K

    2008-01-01

    Abstract Background The aim of this study was to determine whether there is published evidence for increased oxidative stress in neuropsychiatric disorders. Methods A PubMed search was carried out using the MeSH search term 'oxidative stress' in conjunction with each of the DSM-IV-TR diagnostic categories of the American Psychiatric Association in order to identify potential studies. Results There was published evidence of increased oxidative stress in the following DSM-IV-TR diagnostic categ...

  14. Involvement of inositol biosynthesis and nitric oxide in the mediation of UV-B induced oxidative stress

    Directory of Open Access Journals (Sweden)

    Dmytro I Lytvyn

    2016-04-01

    Full Text Available The involvement of NO-signaling in ultraviolet B (UV-B induced oxidative stress in plants is an open question. Inositol biosynthesis contributes to numerous cellular functions, including the regulation of plants tolerance to stress. This work reveals the involvement of inositol-3-phosphate synthase 1 (IPS1, a key enzyme for biosynthesis of myo-inositol and its derivatives, in the response to NO-dependent oxidative stress in Arabidopsis. Homozygous mutants deficient for IPS1 (atips1 and wild-type plants were transformed with a reduction-oxidation-sensitive green fluorescent protein 2 (grx1-rogfp2 and used for the dynamic measurement of UV-B-induced and SNP (sodium nitroprusside-mediated oxidative stresses by confocal microscopy. atips1 mutants displayed greater tissue-specific resistance to the action of UV-B than the wild type. SNP can act both as an oxidant or repairer depending on the applied concentration, but mutant plants were more tolerant than the wild type to nitrosative effects of high concentration of SNP. Additionally, pretreatment with low concentrations of SNP (10, 100 μM before UV-B irradiation resulted in a tissue-specific protective effect that was enhanced in atips1. We conclude that the interplay between nitric oxide and inositol signaling can be involved in the mediation of UV-B-initiated oxidative stress in the plant cell.

  15. Nuclear transport of heat shock proteins in stressed cells

    International Nuclear Information System (INIS)

    Chughtai, Zahoor Saeed

    2001-01-01

    Nuclear import of proteins that are too large to passively enter the nucleus requires soluble factors, energy , and a nuclear localization signal (NLS). Nuclear protein transport can be regulated, and different forms of stress affect nucleocytoplasmic trafficking. As such, import of proteins containing a classical NLS is inhibited in starving yeast cells. In contrast, the heat shock protein hsp70 Ssa4p concentrates in nuclei upon starvation. Nuclear concentration of Ssa4p in starving cells is reversible, and transfer of nutrient-depleted cells to fresh medium induces Ssa4p nuclear export. This export reaction represents an active process that is sensitive to oxidative stress. Upon starvation, the N-terminal domain of Ssa4p mediates Ssa4p nuclear accumulation, and a short hydrophobic sequence, termed Star (for starvation), is sufficient to localize the reporter proteins green fluorescent protein or β-gaIactosidase to nuclei. To determine whether nuclear accumulation of Star-β-galactosidase depends on a specific nuclear carrier, I have analyzed its distribution in mutant yeast strains that carry a deletion of a single β-importin gene. With this assay I have identified Nmd5p as a β-importin required to concentrate Star-β-galactosidase in nuclei of stationary phase cells. (author)

  16. Nuclear transport of heat shock proteins in stressed cells

    Energy Technology Data Exchange (ETDEWEB)

    Chughtai, Zahoor Saeed

    2001-07-01

    Nuclear import of proteins that are too large to passively enter the nucleus requires soluble factors, energy , and a nuclear localization signal (NLS). Nuclear protein transport can be regulated, and different forms of stress affect nucleocytoplasmic trafficking. As such, import of proteins containing a classical NLS is inhibited in starving yeast cells. In contrast, the heat shock protein hsp70 Ssa4p concentrates in nuclei upon starvation. Nuclear concentration of Ssa4p in starving cells is reversible, and transfer of nutrient-depleted cells to fresh medium induces Ssa4p nuclear export. This export reaction represents an active process that is sensitive to oxidative stress. Upon starvation, the N-terminal domain of Ssa4p mediates Ssa4p nuclear accumulation, and a short hydrophobic sequence, termed Star (for starvation), is sufficient to localize the reporter proteins green fluorescent protein or {beta}-gaIactosidase to nuclei. To determine whether nuclear accumulation of Star-{beta}-galactosidase depends on a specific nuclear carrier, I have analyzed its distribution in mutant yeast strains that carry a deletion of a single {beta}-importin gene. With this assay I have identified Nmd5p as a {beta}-importin required to concentrate Star-{beta}-galactosidase in nuclei of stationary phase cells. (author)

  17. Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

    Science.gov (United States)

    Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

    2018-08-01

    Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

  18. Evaluating the Oxidative Stress in Inflammation: Role of Melatonin

    Directory of Open Access Journals (Sweden)

    Aroha Sánchez

    2015-07-01

    Full Text Available Oxygen is used by eukaryotic cells for metabolic transformations and energy production in mitochondria. Under physiological conditions, there is a constant endogenous production of intermediates of reactive oxygen (ROI and nitrogen species (RNI that interact as signaling molecules in physiological mechanisms. When these species are not eliminated by antioxidants or are produced in excess, oxidative stress arises. Oxidative stress can damage proteins, lipids, DNA, and organelles. It is a process directly linked to inflammation; in fact, inflammatory cells secrete a large number of cytokines and chemokines responsible for the production of ROI and RNI in phagocytic and nonphagocytic cells through the activation of protein kinases signaling. Currently, there is a wide variety of diseases capable of producing inflammatory manifestations. While, in the short term, most of these diseases are not fatal they have a major impact on life quality. Since there is a direct relationship between chronic inflammation and many emerging disorders like cancer, oral diseases, kidney diseases, fibromyalgia, gastrointestinal chronic diseases or rheumatics diseases, the aim of this review is to describe the use and role of melatonin, a hormone secreted by the pineal gland, that works directly and indirectly as a free radical scavenger, like a potent antioxidant.

  19. Oxidative Stress, Synaptic Dysfunction, and Alzheimer's Disease.

    Science.gov (United States)

    Tönnies, Eric; Trushina, Eugenia

    2017-01-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD. Increased production of reactive oxygen species (ROS) associated with age- and disease-dependent loss of mitochondrial function, altered metal homeostasis, and reduced antioxidant defense directly affect synaptic activity and neurotransmission in neurons leading to cognitive dysfunction. In addition, molecular targets affected by ROS include nuclear and mitochondrial DNA, lipids, proteins, calcium homeostasis, mitochondrial dynamics and function, cellular architecture, receptor trafficking and endocytosis, and energy homeostasis. Abnormal cellular metabolism in turn could affect the production and accumulation of amyloid-β (Aβ) and hyperphosphorylated Tau protein, which independently could exacerbate mitochondrial dysfunction and ROS production, thereby contributing to a vicious cycle. While mounting evidence implicates ROS in the AD etiology, clinical trials with antioxidant therapies have not produced consistent results. In this review, we will discuss the role of oxidative stress in synaptic dysfunction in AD, innovative therapeutic strategies evolved based on a better understanding of the complexity of molecular mechanisms of AD, and the dual role ROS play in health and disease.

  20. Serum markers of inflammation and oxidative stress in sarcopenia.

    Science.gov (United States)

    Can, Busra; Kara, Ozgur; Kizilarslanoglu, Muhammet Cemal; Arik, Gunes; Aycicek, Gozde Sengul; Sumer, Fatih; Civelek, Ramazan; Demirtas, Canan; Ulger, Zekeriya

    2017-08-01

    Sarcopenia is a geriatric syndrome characterized by the presence of low muscle mass and function. Possible mechanisms underlying sarcopenia include oxidative stress and elevation of inflammatory cytokines. The aim of the study was to evaluate the relationship between sarcopenia and biomarkers that may be involved in its pathogenesis and hence early detection. A total of 72 patients (36 sarcopenic and 36 non-sarcopenic) were included in the study. An experienced geriatric team applied comprehensive geriatric assessment to all patients. Anthropometric measures, gait speed and handgrip strength were recorded. Bioelectrical impedance analysis was used to assess skeletal muscle mass. In addition to routine clinical laboratory tests, serum adiponectin, thioredoxin-1 and pentraxin-3 levels were measured. Sarcopenia was defined according to the European Working Group on Sarcopenia in older Adults as the presence of low muscle mass and low muscle function or muscle performance. Sarcopenic patients were more likely to be functionally dependent and had lower scores on comprehensive geriatric assessment tools. Erythrocyte sedimentation rate (ESR) and C-reactive protein levels were significantly higher in the sarcopenic group. There was no significant difference in serum levels of thioredoxin-1 and pentraxin-3. Sarcopenic patients had lower levels of hemoglobin, albumin, total protein, calcium, triglycerides, uric acid and adiponectin (p sarcopenia whereas ESR was positively correlated. The present study demonstrated an association of sarcopenia with inflammatory markers CRP, ESR and adiponectin. Long-term prospective studies are warranted to confirm the relationship between markers oxidative stress and age related muscle decline.

  1. Oxidative stress at high altitude: genotype–phenotype correlations

    Directory of Open Access Journals (Sweden)

    Pandey P

    2014-05-01

    Full Text Available Priyanka Pandey,1,2 MA Qadar Pasha1,2 1CSIR-Institute of Genomics and Integrative Biology, Delhi, India; 2Department of Biotechnology, University of Pune, Ganeshkhind, Pune, India Abstract: It has been well-documented that the hypobaric hypoxic environment at high altitude (HA causes stress to both the permanent residents of HA and the sojourners. This oxidative stress primarily disturbs the oxygen-sensing and vascular homeostasis pathways, thereby upsetting normal human physiology, especially in sojourners. These environmental challenges have caused dynamic evolutionary changes within natives of HA, allowing them to develop adaptive plasticity. This review focuses on the genomic and biochemical features of the molecules involved in the oxygen-sensing and vascular homeostasis pathways with respect to HA pulmonary edema (HAPE and adaptation. We review the role of genetic markers such as HIF-prolyl hydroxylase 2, endothelial PAS domain-containing protein 1, endothelial nitric oxide synthase, endothelin 1, cytochrome b-245 alpha polypeptide, and glutathione S-transferase pi 1, as well as three circulatory biomarkers (nitric oxide, endothelin 1, and 8-iso-prostaglandin F2α, by highlighting approaches such as candidate gene and genome-wide, adopted in deciphering the pathways. A disagreement between the two approaches has also been highlighted. In addition, we discuss that an overrepresentation of wild-type alleles in HA natives and mutant alleles of same polymorphisms in HAPE patients implies that the allelic variants at the same locus are involved in adaptation and HAPE, respectively. Moreover, healthy sojourners present a number of genomic features similar to HA natives, further strengthening the concept of genetic predisposition. A trend in correlation between protective and risk alleles and altered levels of circulatory markers clearly documents the phenomenon of genotype–phenotype correlations. We conclude that the genetic and biochemical

  2. Inflammation and oxidative stress markers in diabetes and hypertension

    Directory of Open Access Journals (Sweden)

    Pouvreau C

    2018-02-01

    Full Text Available Chloé Pouvreau,1 Antoine Dayre,1 Eugene G Butkowski,2 Beverlie de Jong,2 Herbert F Jelinek2,3 1Faculty of Sciences, University of Poitiers, Poitiers, France; 2School of Community Health, Charles Sturt University, Albury, NSW, Australia; 3Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, Australia Background: Inflammation and oxidative stress are important factors associated with chronic disease such as essential hypertension (HTN and type 2 diabetes mellitus (T2DM. However, the association of inflammation and oxidative stress in HTN with T2DM as a comorbidity is inconclusive due to the multifactorial nature of these cardiometabolic diseases. Methodology: The influence of pathophysiological factors include genetics, age of patient, and disease progression change throughout the lifespan and require further investigation. The study population included 256 participants attending a rural health screening program who were tested for markers of inflammation, oxidative stress, and coagulation/fibrinolysis. Demographic and clinical variables included, age, gender, systolic and diastolic blood pressures, blood glucose, hemoglobin A1c, estimated glomerular filtration rate, and cholesterol profile. Data were tested for normality, and nonparametric statistics were applied to analyze the sample with significance set at p<0.05. Results: Of the inflammatory markers, interleukin-1β (IL-1β and IL-10 were significantly different between the control and hypertensive group (p<0.03 and between the HTN+T2DM compared to the HTN group (p<0.05. Significant results for oxidative stress were observed for urinary 8-iso-PGF2α and insulin-like growth factor 1 (IGF-1 between the control and the HTN+T2DM group (p<0.01. Glutathione (GSH was also significant between the HTN and HTN+T2DM group (p<0.05. Investigation of the progression of HTN also found significant changes in the inflammatory markers IGF-1, monocyte chemoattractant protein 1 (MCP-1, and

  3. Anti-oxidative effects of Rooibos tea (Aspalathus linearis on immobilization-induced oxidative stress in rat brain.

    Directory of Open Access Journals (Sweden)

    In-Sun Hong

    Full Text Available Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea's ability to (i reverse the increase in stress-related metabolites (5-HIAA and FFA, (ii prevent lipid peroxidation (LPO, (iii restore stress-induced protein degradation (PD, (iv regulate glutathione metabolism (GSH and GSH/GSSG ratio, and (v modulate changes in the activities of antioxidant enzymes (SOD and CAT.

  4. Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Sonia Sifuentes-Franco

    2018-01-01

    Full Text Available Diabetic nephropathy (DN is the second most frequent and prevalent complication of diabetes mellitus (DM. The increase in the production of oxidative stress (OS is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids. OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM in DN. The reactive oxygen species (ROS play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN.

  5. Potential disruption of protein-protein interactions by graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Mei [Department of Physics, Institute of Quantitative Biology, Zhejiang University, Hangzhou 310027 (China); Kang, Hongsuk; Luan, Binquan [Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Yang, Zaixing [Institute of Quantitative Biology and Medicine, SRMP and RAD-X, and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123 (China); Zhou, Ruhong, E-mail: ruhong@us.ibm.com [Department of Physics, Institute of Quantitative Biology, Zhejiang University, Hangzhou 310027 (China); Computational Biological Center, IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Department of Chemistry, Columbia University, New York, New York 10027 (United States)

    2016-06-14

    Graphene oxide (GO) is a promising novel nanomaterial with a wide range of potential biomedical applications due to its many intriguing properties. However, very little research has been conducted to study its possible adverse effects on protein-protein interactions (and thus subsequent toxicity to human). Here, the potential cytotoxicity of GO is investigated at molecular level using large-scale, all-atom molecular dynamics simulations to explore the interaction mechanism between a protein dimer and a GO nanosheet oxidized at different levels. Our theoretical results reveal that GO nanosheet could intercalate between the two monomers of HIV-1 integrase dimer, disrupting the protein-protein interactions and eventually lead to dimer disassociation as graphene does [B. Luan et al., ACS Nano 9(1), 663 (2015)], albeit its insertion process is slower when compared with graphene due to the additional steric and attractive interactions. This study helps to better understand the toxicity of GO to cell functions which could shed light on how to improve its biocompatibility and biosafety for its wide potential biomedical applications.

  6. Potential disruption of protein-protein interactions by graphene oxide

    International Nuclear Information System (INIS)

    Feng, Mei; Kang, Hongsuk; Luan, Binquan; Yang, Zaixing; Zhou, Ruhong

    2016-01-01

    Graphene oxide (GO) is a promising novel nanomaterial with a wide range of potential biomedical applications due to its many intriguing properties. However, very little research has been conducted to study its possible adverse effects on protein-protein interactions (and thus subsequent toxicity to human). Here, the potential cytotoxicity of GO is investigated at molecular level using large-scale, all-atom molecular dynamics simulations to explore the interaction mechanism between a protein dimer and a GO nanosheet oxidized at different levels. Our theoretical results reveal that GO nanosheet could intercalate between the two monomers of HIV-1 integrase dimer, disrupting the protein-protein interactions and eventually lead to dimer disassociation as graphene does [B. Luan et al., ACS Nano 9(1), 663 (2015)], albeit its insertion process is slower when compared with graphene due to the additional steric and attractive interactions. This study helps to better understand the toxicity of GO to cell functions which could shed light on how to improve its biocompatibility and biosafety for its wide potential biomedical applications.

  7. Fighting Oxidative Stress: Increased Resistance of Male Rat Cerebellum at Weaning Induced by Low Omega 6/Omega 3 Ratio in a Protein-Deficient Diet.

    Science.gov (United States)

    Augusto, Ricielle Lopes; Isaac, Alinny Rosendo; Silva-Júnior, Ivanildo Inácio da; Santana, David Filipe de; Ferreira, Diorginis José Soares; Lagranha, Claudia Jacques; Gonçalves-Pimentel, Catarina; Rodrigues, Marcelo Cairrão Araujo; Andrade-da-Costa, Belmira Lara da Silveira

    2017-02-01

    The cerebellum is vulnerable to malnutrition effects. Notwithstanding, it is able to incorporate higher amount of docosahexaenoic acid (DHA) than the cerebral cortex (Cx) when low n-6/n-3 fatty acid ratio is present in a multideficient diet. Considering importance of DHA for brain redox balance, we hypothesize that this cerebellum feature improves its antioxidant status compared to the Cx. A chronic malnutrition status was induced on dams before mating and kept until weaning or adulthood (offspring). A group nutritionally rehabilitated from weaning was also analyzed. Morphometric parameters, total-superoxide dismutase (t-SOD) and catalase activities, lipoperoxidation (LP), nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, reactive oxygen species (ROS), and reduced nicotinamide adenine dinucleotide/phosphate levels were assessed. Both ROS and LP levels were increased (∼53 %) in the Cx of malnourished young animals while the opposite was seen in the cerebellum (72 and 20 % of the control, respectively). Consistently, lower (∼35 %) and higher t-SOD (∼153 %) and catalase (CAT) (∼38 %) activities were respectively detected in the Cx and cerebellum compared to the control. In malnourished adult animals, redox balance was maintained in the cerebellum and recovered in the Cx (lower ROS and LP levels and higher GSH/GSSG ratio). NO production was impaired by malnutrition at either age, mainly in the cerebellum. The findings suggest that despite a multinutrient deficiency and a modified structural development, a low dietary n-6/n-3 ratio favors early antioxidant resources in the male cerebellum and indicates an important role of astrocytes in the redox balance recovery of Cx in adulthood.

  8. Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.

    Science.gov (United States)

    Findeisen, Hannes M; Pearson, Kevin J; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; de Cabo, Rafael; Bruemmer, Dennis

    2011-04-14

    Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.

  9. Measurement of exercise-induced oxidative stress in lymphocytes.

    Science.gov (United States)

    Turner, James E; Bosch, Jos A; Aldred, Sarah

    2011-10-01

    Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

  10. Effects of 12-week combined exercise therapy on oxidative stress in female fibromyalgia patients.

    Science.gov (United States)

    Sarıfakıoğlu, Banu; Güzelant, Aliye Yıldırım; Güzel, Eda Celik; Güzel, Savaş; Kızıler, Ali Rıza

    2014-10-01

    The aims of this study were to investigate the effect of exercise therapy on the oxidative stress in fibromyalgia patients and relationship between oxidative stress and fibromyalgia symptoms. Thirty women diagnosed with fibromyalgia according to the American College of Rheumatology preliminary criteria, and 23 healthy women whose age- and weight-matched women were enrolled the study. Pain intensity with visual analog scale (VAS), the number of tender points, the fibromyalgia impact questionnaire (FIQ), the Beck depression inventory (BDI) were evaluated. The oxidative stress parameters thiobarbituric acid reactive substances, protein carbonyls, and nitric oxide, and antioxidant parameters thiols and catalase were investigated in patients and control group. After, combined aerobic and strengthen exercise regimen was given to fibromyalgia group. Exercise therapy consisted of a warming period of 10 min, aerobic exercises period of 20 min, muscle strengthening exercises for 20 min, and 10 min cooling down period. Therapy was lasting 1 h three times per week over a 12-week period. All parameters were reevaluated after the treatment in the patient group. The oxidative stress parameters levels were significantly higher, and antioxidant parameters were significantly lower in patients with fibromyalgia than in the controls. VAS, FIQ, and BDI scores decreased significantly with exercise therapy. The exercise improved all parameters of oxidative stress and antioxidant parameters. Also, all clinical parameters were improved with exercise. We should focus on oxidative stress in the treatment for fibromyalgia with the main objective of reducing oxidative load.

  11. Oxidatively generated DNA/RNA damage in psychological stress states

    DEFF Research Database (Denmark)

    Jørgensen, Anders

    2013-01-01

    age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8...... between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased......Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several...

  12. Short communication: Camel milk ameliorates inflammatory responses and oxidative stress and downregulates mitogen-activated protein kinase signaling pathways in lipopolysaccharide-induced acute respiratory distress syndrome in rats.

    Science.gov (United States)

    Zhu, Wei-Wei; Kong, Gui-Qing; Ma, Ming-Ming; Li, Yan; Huang, Xiao; Wang, Li-Peng; Peng, Zhen-Yi; Zhang, Xiao-Hua; Liu, Xiang-Yong; Wang, Xiao-Zhi

    2016-01-01

    Acute respiratory distress syndrome (ARDS) is a complex syndrome disorder with high mortality rate. Camel milk (CM) contains antiinflammatory and antioxidant properties and protects against numerous diseases. This study aimed to demonstrate the function of CM in lipopolysaccharide (LPS)-induced ARDS in rats. Camel milk reduced the lung wet:dry weight ratio and significantly reduced LPS-induced increases in neutrophil infiltration, interstitial and intra-alveolar edema, thickness of the alveolar wall, and lung injury scores of lung tissues. It also had antiinflammatory and antioxidant effects on LPS-induced ARDS. After LPS stimulation, the levels of proinflammatory cytokines (tumor necrosis factor-α, IL-10, and IL-1β) in serum and oxidative stress markers (malondialdehyde, myeloperoxidase, and total antioxidant capacity) in lung tissue were notably attenuated by CM. Camel milk also downregulated mitogen-activated protein kinase signaling pathways. Given these results, CM is a potential complementary food for ARDS treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Assessing protein oxidation by inorganic nanoparticles with enzyme-linked immunosorbent assay (ELISA).

    Science.gov (United States)

    Sun, Wenjie; Luna-Velasco, Antonia; Sierra-Alvarez, Reyes; Field, Jim A

    2013-03-01

    Growth in the nanotechnology industry is leading to increased production of engineered nanoparticles (NPs). This has given rise to concerns about the potential adverse and toxic effects to biological system and the environment. An important mechanism of NP toxicity is oxidative stress caused by the formation of reactive oxygen species (ROS) or via direct oxidation of biomolecules. In this study, a protein oxidation assay was developed as an indicator of biomolecule oxidation by NPs. The oxidation of the protein, bovine serum albumin (BSA) was evaluated with an enzyme-linked immunosorbent assay (ELISA) to measure the protein carbonyl derivatives formed from protein oxidation. The results showed that some NPs such as Cu(0), CuO, Mn(2)O(3), and Fe(0) caused oxidation of BSA; whereas, many of the other NPs tested were not reactive or very slowly reactive with BSA. The mechanisms involved in the oxidation of BSA protein by the reactive NPs could be attributed to the combined effects of ROS-dependent and direct protein oxidation mechanisms. The ELISA assay is a promising method for the assessment of protein oxidation by NPs, which can provide insights on NP toxicity mechanisms. Copyright © 2012 Wiley Periodicals, Inc.

  14. The allosteric behavior of Fur mediates oxidative stress signal transduction in Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Simone ePelliciari

    2015-08-01

    Full Text Available The microaerophilic gastric pathogen Helicobacter pylori is exposed to oxidative stress originating from the aerobic environment, the oxidative burst of phagocytes and the formation of reactive oxygen species, catalyzed by iron excess. Accordingly, the expression of genes involved in oxidative stress defense have been repeatedly linked to the ferric uptake regulator Fur. Moreover, mutations in the Fur protein affect the resistance to metronidazole, likely due to loss-of-function in the regulation of genes involved in redox control. Although many advances in the molecular understanding of HpFur function were made, little is known about the mechanisms that enable Fur to mediate the responses to oxidative stress.Here we show that iron-inducible, apo-Fur repressed genes, such as pfr and hydA, are induced shortly after oxidative stress, while their oxidative induction is lost in a fur knockout strain. On the contrary, holo-Fur repressed genes, such as frpB1 and fecA1, vary modestly in response to oxidative stress. This indicates that the oxidative stress signal specifically targets apo-Fur repressed genes, rather than impairing indiscriminately the regulatory function of Fur. Footprinting analyses showed that the oxidative signal strongly impairs the binding affinity of Fur towards apo-operators, while the binding towards holo-operators is less affected. Further evidence is presented that a reduced state of Fur is needed to maintain apo-repression, while oxidative conditions shift the preferred binding architecture of Fur towards the holo-operator binding conformation, even in the absence of iron. Together the results demonstrate that the allosteric regulation of Fur enables transduction of oxidative stress signals in H. pylori, supporting the concept that apo-Fur repressed genes can be considered oxidation inducible Fur regulatory targets. These findings may have important implications in the study of H. pylori treatment and resistance to

  15. Biofabrication of Zinc Oxide Nanoparticle from Ochradenus baccatus Leaves: Broad-Spectrum Antibiofilm Activity, Protein Binding Studies, and In Vivo Toxicity and Stress Studies

    Directory of Open Access Journals (Sweden)

    Nasser A. Al-Shabib

    2018-01-01

    Full Text Available Biofilms are complex aggregation of cells that are embedded in EPS matrix. These microcolonies are highly resistant to drugs and are associated with various diseases. Biofilms have greatly affected the food safety by causing severe losses due to food contamination and spoilage. Therefore, novel antibiofilm agents are needed. This study investigates the antibiofilm and protein binding activity of zinc nanoparticles (ZnNPs synthesized from leaf extract of Ochradenus baccatus. Standard physical techniques, including UV-visible spectroscopy Fourier transform infrared spectroscopy and X-ray diffraction and transmission electron microscopy, were used to characterize the synthesized OB-ZnNPs. Synthesized OB-ZnNPs demonstrated significant biofilm inhibition in human and food-borne pathogens (Chromobacterium violaceum, Escherichia coli, P. aeruginosa, Klebsiella pneumoniae, Serratia marcescens, and Listeria monocytogenes at subinhibitory concentrations. OB-ZnNPs significantly reduced the virulence factors like violacein, prodigiosin, and alginate and impaired swarming migration and EPS production. OB-ZnNPs demonstrated efficient binding with HSA protein and no change in their structure or stability was observed. In addition, in vivo toxicity evaluation confirmed that OB-ZnNPs possessed no serious toxic effect even at higher doses. Moreover, they were found to have excellent antioxidant properties that can be employed in the fields of food safety and medicine. Hence, it is envisaged that the OB-ZnNPs can be used as potential nanomaterials to combat drug resistant bacterial infections and prevent contamination/spoilage of food.

  16. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Sha Li

    2015-11-01

    Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  17. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  18. Mitochondrial oxidative stress and cardiac ageing.

    Science.gov (United States)

    Martín-Fernández, Beatriz; Gredilla, Ricardo

    According with different international organizations, cardiovascular diseases are becoming the first cause of death in western countries. Although exposure to different risk factors, particularly those related to lifestyle, contribute to the etiopathogenesis of cardiac disorders, the increase in average lifespan and aging are considered major determinants of cardiac diseases events. Mitochondria and oxidative stress have been pointed out as relevant factors both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy and diabetic cardiomyopathy. During aging, cellular processes related with mitochondrial function, such as bioenergetics, apoptosis and inflammation are altered leading to cardiac dysfunction. Increasing our knowledge about the mitochondrial mechanisms related with the aging process, will provide new strategies in order to improve this process, particularly the cardiovascular ones. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Financial strain is associated with increased oxidative stress levels: the Women's Health and Aging Studies.

    Science.gov (United States)

    Palta, Priya; Szanton, Sarah L; Semba, Richard D; Thorpe, Roland J; Varadhan, Ravi; Fried, Linda P

    2015-01-01

    Elevated oxidative stress levels may be one mechanism contributing to poor health outcomes. Financial strain and oxidative stress are each predictors of morbidity and mortality, but little research has investigated their relationship. Community-dwelling older adults (n = 728) from the Women's Health and Aging Studies I and II were included in this cross-sectional analysis. Financial strain was ascertained as an ordinal response to: "At the end of the month, do you have more than enough money left over, just enough, or not enough?" Oxidative stress was measured using serum protein carbonyl concentrations. Linear regression was used to quantify the relationship between financial strain and oxidative stress. Participants who reported high financial strain exhibited 13.4% higher protein carbonyl concentrations compared to individuals who reported low financial strain (p = 0.002). High financial strain may be associated with increased oxidative stress, suggesting that oxidative stress could mediate associations between financial strain and poor health. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

    Science.gov (United States)

    Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

    2014-12-01

    Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Sport and oxidative stress in oncological patients.

    Science.gov (United States)

    Knop, K; Schwan, R; Bongartz, M; Bloch, W; Brixius, K; Baumann, F

    2011-12-01

    Oxidative stress is thought to be an important factor in the onset, progression and recurrence of cancer. In order to investigate how it is influenced by physical activity, we measured oxidative stress and antioxidative capacity (aoC) in 12 women with breast cancer and 6 men with prostate cancer, before and after long hiking trips. Before the hike, the men had a ROS-concentration of 1.8±0.6 mM H2O2 and an aoC of 0.7±0.6 mM Trolox-equivalent (Tro), while the women had a ROS-concentration of 3.1±0.7 mM H2O2 and an aoC of 1.2±0.2 mM Tro. After the hike, women showed no significant change in ROS and a significant increase in aoC (1.3±0.2 mM Tro), while the ROS concentration in men increased significantly (2.1±0.3 mM H2O2) and their aoC decreased (0.25±0.1 mM Tro). After a regenerative phase, the ROS concentration of the men decreased to 1.7±0.4 mM H2O2 and their aoC recovered significantly (1.2±0.4 mM Tro), while the women presented no significant change in the concentration of H2O2 but showed an ulterior increase in antioxidant capacity (2.05±0.43 mM Tro). From this data we conclude that physical training programs as for example long distance hiking trips can improve the aoC in the blood of oncological patients. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Selenite protects Caenorhabditis elegans from oxidative stress via DAF-16 and TRXR-1.

    Science.gov (United States)

    Li, Wen-Hsuan; Shi, Yeu-Ching; Chang, Chun-Han; Huang, Chi-Wei; Hsiu-Chuan Liao, Vivian

    2014-04-01

    Selenium is an essential micronutrient. In the present study, trace amount of selenite (0.01 μM) was evaluated for oxidative stress resistance and potential associated factors in Caenorhabditis elegans. Selenite-treated C. elegans showed an increased survival under oxidative stress and thermal stress compared to untreated controls. Further studies demonstrated that the significant stress resistance of selenite on C. elegans could be attributed to its in vivo free radical-scavenging ability. We also found that the oxidative and thermal stress resistance phenotypes by selenite were absent from the forkhead transcription factor daf-16 mutant worms. Moreover, selenite influenced the subcellular distribution of DAF-16 in C. elegans. Furthermore, selenite increased mRNA levels of stress-resistance-related proteins, including superoxide dismutase-3 and heat shock protein-16.2. Additionally, selenite (0.01 μM) upregulated expressions of transgenic C. elegans carrying sod-3::green fluorescent protein (GFP) and hsp-16.2::GFP, whereas this effect was abolished by feeding daf-16 RNA interference in C. elegans. Finally, unlike the wild-type N2 worms, the oxidative stress resistance phenotypes by selenite were both absent from the C. elegans selenoprotein trxr-1 mutant worms and trxr-1 mutants feeding with daf-16 RNA interference. These findings suggest that the antioxidant effects of selenite in C. elegans are mediated via DAF-16 and TRXR-1. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Hypochlorous and peracetic acid induced oxidation of dairy proteins.

    Science.gov (United States)

    Kerkaert, Barbara; Mestdagh, Frédéric; Cucu, Tatiana; Aedo, Philip Roger; Ling, Shen Yan; De Meulenaer, Bruno

    2011-02-09

    Hypochlorous and peracetic acids, both known disinfectants in the food industry, were compared for their oxidative capacity toward dairy proteins. Whey proteins and caseins were oxidized under well controlled conditions at pH 8 as a function of the sanitizing concentration. Different markers for protein oxidation were monitored. The results established that the protein carbonyl content was a rather unspecific marker for protein oxidation, which did not allow one to differentiate the oxidant used especially at the lower concentrations. Cysteine, tryptophan, and methionine were proven to be the most vulnerable amino acids for degradation upon hypochlorous and peracetic acid treatment, while tyrosine was only prone to degradation in the presence of hypochlorous acid. Hypochlorous acid induced oxidation gave rise to protein aggregation, while during peracetic acid induced oxidation, no high molecular weight aggregates were observed. Protein aggregation upon hypochlorous acid oxidation could primarily be linked to tryptophan and tyrosine degradation.

  4. Moderate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruption.

    Directory of Open Access Journals (Sweden)

    Christoph M Zehendner

    Full Text Available Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR on the evolution of reactive oxygen species (ROS and blood-brain barrier (BBB integrity in brain endothelial cells (BEC. BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC or towards occlusion of the arteria cerebri media (MCAO with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF, MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1 and claudin 5 (Cl5, decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role

  5. Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress.

    Science.gov (United States)

    Zhang, Yin Hua

    2017-01-01

    Nitric oxide (NO) is an imperative regulator of the cardiovascular system and is a critical mechanism in preventing the pathogenesis and progression of the diseased heart. The scenario of bioavailable NO in the myocardium is complex: 1) NO is derived from both endogenous NO synthases (endothelial, neuronal, and/or inducible NOSs [eNOS, nNOS, and/or iNOS]) and exogenous sources (entero-salivary NO pathway) and the amount of NO from exogenous sources varies significantly; 2) NOSs are located at discrete compartments of cardiac myocytes and are regulated by distinctive mechanisms under stress; 3) NO regulates diverse target proteins through different modes of post-transcriptional modification (soluble guanylate cyclase [sGC]/cyclic guanosine monophosphate [cGMP]/protein kinase G [PKG]-dependent phosphorylation, S -nitrosylation, and transnitrosylation); 4) the downstream effectors of NO are multidimensional and vary from ion channels in the plasma membrane to signalling proteins and enzymes in the mitochondria, cytosol, nucleus, and myofilament; 5) NOS produces several radicals in addition to NO (e.g. superoxide, hydrogen peroxide, peroxynitrite, and different NO-related derivatives) and triggers redox-dependent responses. However, nNOS inhibits cardiac oxidases to reduce the sources of oxidative stress in diseased hearts. Recent consensus indicates the importance of nNOS protein in cardiac protection under pathological stress. In addition, a dietary regime with high nitrate intake from fruit and vegetables together with unsaturated fatty acids is strongly associated with reduced cardiovascular events. Collectively, NO-dependent mechanisms in healthy and diseased hearts are better understood and shed light on the therapeutic prospects for NO and NOSs in clinical applications for fatal human heart diseases.

  6. Differential p53 engagement in response to oxidative and oncogenic stresses in Fanconi anemia mice

    OpenAIRE

    Rani, Reena; Li, Jie; Pang, Qishen

    2008-01-01

    Members of the Fanconi anemia (FA) protein family are involved in repair of genetic damage caused by DNA cross-linkers. It is not clear whether the FA proteins function in oxidative DNA damage and oncogenic stress response. Here we report that deficiency in the Fanca gene in mice elicits a p53-dependent growth arrest and DNA damage response to oxidative DNA damage and oncogenic stress. Using a Fanca-/- Trp53-/- double knockout model and a functionally switchable p53 retrovirus, we define the ...

  7. Eales′ disease: Oxidant stress and weak antioxidant defence

    Directory of Open Access Journals (Sweden)

    Ramakrishnan S

    2007-01-01

    Full Text Available Eales′ disease (ED is an idiopathic retinal periphlebitis characterized by capillary non-perfusion and neovascularization. In addition to the existing system, a new staging system has been proposed by Saxena et al . Immunological, molecular biological and biochemical studies have indicated the role of human leucocyte antigen, retinal S antigen autoimmunity, Mycobacterium tuberculosis genome, free radical damage and possibly hyperhomocysteinemia in its etiopathogenesis, which appears multifactorial. Oxidant stress has been shown by increase in the levels of thiobarbituric acid reactive substances (lipid oxidation in the vitreous, erythrocytes, platelets, and monocytes. A decrease in vitamins E and C both in active and healed vasculitis, superoxide dismutase, glutathione, and glutathione peroxidase showed a weakened antioxidant defence. Epiretinal membrane from patients of ED who underwent surgery showed, by immunolocalization, presence of carboxy methyl lysine, an advanced glycation end product formed by glycoxidation and is involved in angiogenesis. OH· free radical accumulation in monocytes has been directly shown by electron spin resonance spectrometry. Free radical damage to DNA and of protein was shown by the accumulation of 8 hydroxy 2 deoxyguanosine (in leucocytes and nitrotyrosine (in monocytes, respectively. Nitrosative stress was shown by increased expression of inducible nitric oxide synthase in monocytes in which levels of iron and copper were increased while those of zinc decreased. A novel 88 kDa protein was found in serum and vitreous in inflammatory condition and had antioxidant function. Platelet fluidity was also affected. Oral, methotrexate in low dosage (12.5 mg/week for 12 weeks as well as oral vitamin E (400 IU and C (500 mg daily for 8 weeks are reported to have beneficial effects.

  8. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    Science.gov (United States)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  9. Oxidative stress and superoxide dismutase activity in brain of rats ...

    African Journals Online (AJOL)

    The present study was envisaged to investigate the possible role of oxidative stress in permethrin neurotoxicity and to evaluate the protective effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as thiobarbituric acid reacting substances (TBARS) was found to ...

  10. Oxidative stress in diabetic patients with retinopathy | Kundu ...

    African Journals Online (AJOL)

    Background: Diabetes mellitus (DM) is known to induce oxidative stress along with deranging various metabolisms; one of the late complications of diabetes mellitus is diabetic retinopathy, which is a leading cause of acquired blindness. Poor glycemic control and oxidative stress have been attributed to the development of ...

  11. Adiponectin, leptin and oxidative stress in preeclampsia in Egyptian ...

    African Journals Online (AJOL)

    Adiponectin and Leptin are closely related adipokines that are associated with the oxidative stresses and endothelial dysfunction and proposed to participate in preeclampsia (PE) pathogenesis. This study is to determine changes in serum levels of adiponectin, leptin and oxidative stress in PE women in order to speculate a ...

  12. Decreased total antioxidant levels and increased oxidative stress in ...

    African Journals Online (AJOL)

    Background: Chronic hyperglycaemia in diabetes mellitus leads to increased lipid peroxidation in the body, followed by the development of chronic complications due to oxidative stress. Objective: The aim of this study was to compare total antioxidant (TAO) levels and oxidative stress in type 2 diabetes mellitus (T2DM) ...

  13. Analysis of protein oxidation in serum of fetal and newborn piglets and the influence of iron dextran on induction of protein carbonyls.

    Science.gov (United States)

    Methods were employed to evaluate serum biomarkers associated with protein oxidative stress and damage, to determine potential sources of metabolic stress in baby pigs. Protein carbonyls in serum were converted to dinitrophenyl (DNP) derivatives with DNP-hydrazine, precipitated with TCA, extracted i...

  14. Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium.

    Science.gov (United States)

    Betzen, Christian; White, Robin; Zehendner, Christoph M; Pietrowski, Eweline; Bender, Bianca; Luhmann, Heiko J; Kuhlmann, Christoph R W

    2009-10-15

    N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was observed via in-cell Western. The functionality of the expressed NMDA-R was determined by measuring DiBAC fluorescence in ROS-preexposed cells upon stimulation with the specific agonist NMDA. Finally, the effects on barrier integrity were evaluated using the ECIS system to detect changes in monolayer impedance upon NMDA-R stimulation after exposure to ROS. The expression of NR1 significantly (p<0.001) increased 72 h after 30 min exposure to superoxide (+33.8+/-7.5%), peroxynitrite (+84.9+/-10.7%), or hydrogen peroxide (+92.8+/-7.6%), resulting in increased cellular response to NMDA-R stimulation and diminished monolayer impedance. We conclude that oxidative stress upregulates NMDA-R on cerebrovascular endothelium and thus heightens susceptibility to glutamate-induced BBB disruption.

  15. Oxidative stress treatment for clinical trials in neurodegenerative diseases.

    Science.gov (United States)

    Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

    2011-01-01

    Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine.

  16. Cellular and exosome mediated molecular defense mechanism in bovine granulosa cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed Saeed-Zidane

    Full Text Available Various environmental insults including diseases, heat and oxidative stress could lead to abnormal growth, functions and apoptosis in granulosa cells during ovarian follicle growth and oocyte maturation. Despite the fact that cells exposed to oxidative stress are responding transcriptionally, the potential release of transcripts associated with oxidative stress response into extracellular space through exosomes is not yet determined. Therefore, here we aimed to investigate the effect of oxidative stress in bovine granulosa cells in vitro on the cellular and exosome mediated defense mechanisms. Bovine granulosa cells were aspirated from ovarian follicles and cultured in DMEM/F-12 Ham culture medium supplemented with 10% exosome-depleted fetal bovine serum. In the first experiment sub-confluent cells were treated with 5 μM H2O2 for 40 min to induce oxidative stress. Thereafter, cells were subjected to ROS and mitochondrial staining, cell proliferation and cell cycle assays. Furthermore, gene and protein expression analysis were performed in H2O2-challenged versus control group 24 hr post-treatment using qRT-PCR and immune blotting or immunocytochemistry assay, respectively. Moreover, exosomes were isolated from spent media using ultracentrifugation procedure, and subsequently used for RNA isolation and qRT-PCR. In the second experiment, exosomes released by granulosa cells under oxidative stress (StressExo or those released by granulosa cells without oxidative stress (NormalExo were co-incubated with bovine granulosa cells in vitro to proof the potential horizontal transfer of defense molecules from exosomes to granulosa cells and investigate any phenotype changes. Exposure of bovine granulosa cells to H2O2 induced the accumulation of ROS, reduced mitochondrial activity, increased expression of Nrf2 and its downstream antioxidant genes (both mRNA and protein, altered the cell cycle transitions and induced cellular apoptosis. Granulosa cells

  17. Differential trafficking of oxidized LDL and oxidized LDL immune complexes in macrophages: impact on oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed M Al Gadban

    2010-09-01

    Full Text Available Oxidized low-density lipoproteins (oxLDL and oxLDL-containing immune complexes (oxLDL-IC contribute to formation of lipid-laden macrophages (foam cells. It has been shown that oxLDL-IC are considerably more efficient than oxLDL in induction of foam cell formation, inflammatory cytokines secretion, and cell survival promotion. Whereas oxLDL is taken up by several scavenger receptors, oxLDL-IC are predominantly internalized through the FCgamma receptor I (FCgamma RI. This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress.Fluorescently labeled lipid and protein moieties of oxLDL co-localized within endosomal and lysosomal compartments in U937 human monocytic cells. In contrast, the lipid moiety of oxLDL-IC was detected in the endosomal compartment, whereas its apolipoprotein moiety advanced to the lysosomal compartment. Cells treated with oxLDL-IC prior to oxLDL demonstrated co-localization of internalized lipid moieties from both oxLDL and oxLDL-IC in the endosomal compartment. This sequential treatment likely inhibited oxLDL lipid moieties from trafficking to the lysosomal compartment. In RAW 264.7 macrophages, oxLDL-IC but not oxLDL induced GFP-tagged heat shock protein 70 (HSP70 and HSP70B', which co-localized with the lipid moiety of oxLDL-IC in the endosomal compartment. This suggests that HSP70 family members might prevent the degradation of the internalized lipid moiety of oxLDL-IC by delaying its advancement to the lysosome. The data also showed that mitochondrial membrane potential was decreased and generation of reactive oxygen and nitrogen species was increased in U937 cell treated with oxLDL compared to oxLDL-IC.Findings suggest that lipid and apolipoprotein moieties of oxLDL-IC traffic to separate cellular compartments, and that HSP70/70B' might sequester the lipid moiety of oxLDL-IC in the endosomal compartment. This mechanism could

  18. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes*

    Science.gov (United States)

    Collins, John A.; Wood, Scott T.; Nelson, Kimberly J.; Rowe, Meredith A.; Carlson, Cathy S.; Chubinskaya, Susan; Poole, Leslie B.; Furdui, Cristina M.; Loeser, Richard F.

    2016-01-01

    Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1–3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. PMID:26797130

  19. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  20. Influence of acute exercise of varying intensity and duration on postprandial oxidative stress.

    Science.gov (United States)

    Canale, Robert E; Farney, Tyler M; McCarthy, Cameron G; Bloomer, Richard J

    2014-09-01

    Aerobic exercise can reduce postprandial lipemia, and possibly oxidative stress, when performed prior to a lipid-rich meal. To compare the impact of acute exercise on postprandial oxidative stress. We compared aerobic and anaerobic exercise bouts of different intensities and durations on postprandial blood triglycerides (TAG), oxidative stress biomarkers (malondialdehyde, hydrogen peroxide, advanced oxidation protein products), and antioxidant status (trolox equivalent antioxidant capacity, superoxide dismutase, catalase, glutathione peroxidase). Twelve trained men (21-35 years) underwent four conditions: (1) No exercise rest; (2) 60-min aerobic exercise at 70% heart rate reserve; (3) five 60-s sprints at 100% max capacity; and (4) ten 15-s sprints at 200% max capacity. All exercise bouts were performed on a cycle ergometer. A high-fat meal was consumed 1 h after exercise cessation. Blood samples were collected pre-meal and 2 and 4 h post-meal and analyzed for TAG, oxidative stress biomarkers, and antioxidant status. No significant interaction or condition effects were noted for any variable (p > 0.05), with acute exercise having little to no effect on the magnitude of postprandial oxidative stress. In a sample of healthy, well-trained men, neither aerobic nor anaerobic exercise attenuates postprandial oxidative stress in response to a high-fat meal.

  1. Oxidative stress response after laparoscopic versus conventional sigmoid resection

    DEFF Research Database (Denmark)

    Madsen, Michael Tvilling; Kücükakin, Bülent; Lykkesfeldt, Jens

    2012-01-01

    Surgery is accompanied by a surgical stress response, which results in increased morbidity and mortality. Oxidative stress is a part of the surgical stress response. Minimally invasive laparoscopic surgery may result in reduced oxidative stress compared with open surgery. Nineteen patients...... scheduled for sigmoid resection were randomly allocated to open or laparoscopic sigmoid resection in a double-blind, prospective clinical trial. Three biochemical markers of oxidative stress (malondialdehyde, ascorbic acid, and dehydroascorbic acid) were measured at 6 different time points (preoperatively......, 1 h, 6 h, 24 h, 48 h, and 72 h postoperatively). There were no statistical significant differences between laparoscopic and open surgery for any of the 3 oxidative stress parameters. Malondialdehyde was reduced 1 hour postoperatively (P...

  2. Clinical Perspective of Oxidative Stress in Sporadic ALS

    Science.gov (United States)

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  3. Higher oxidative stress in skeletal muscle of McArdle disease patients

    Directory of Open Access Journals (Sweden)

    Jan J. Kaczor

    2017-09-01

    Full Text Available McArdle disease (MCD is an autosomal recessive condition resulting from skeletal muscle glycogen phosphorylase deficiency. The resultant block in glycogenolysis leads to an increased flux through the xanthine oxidase pathway (myogenic hyperuricemia and could lead to an increase in oxidative stress. We examined markers of oxidative stress (8-isoprostane and protein carbonyls, NAD(PH-oxidase, xanthine oxidase and antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase activity in skeletal muscle of MCD patients (N = 12 and controls (N = 12. Eight-isoprostanes and protein carbonyls were higher in MCD patients as compared to controls (p < 0.05. There was a compensatory up-regulation of catalase protein content and activity (p < 0.05, mitochondrial superoxide dismutase (MnSOD protein content (p < 0.01 and activity (p < 0.05 in MCD patients, yet this increase was not sufficient to protect the muscle against elevated oxidative damage. These results suggest that oxidative stress in McArdle patients occurs and future studies should evaluate a potential role for oxidative stress contributing to acute pathology (rhabdomyolysis and possibly later onset fixed myopathy.

  4. Peripheral markers of oxidative stress in chronic mercuric chloride intoxication

    Directory of Open Access Journals (Sweden)

    Gutierrez L.L.P.

    2006-01-01

    Full Text Available The present study was designed to evaluate the time course changes in peripheral markers of oxidative stress in a chronic HgCl2 intoxication model. Twenty male adult Wistar rats were treated subcutaneously daily for 30 days and divided into two groups of 10 animals each: Hg, which received HgCl2 (0.16 mg kg-1 day-1, and control, receiving the same volume of saline solution. Blood was collected at the first, second and fourth weeks of Hg administration to evaluate lipid peroxidation (LPO, total radical trapping antioxidant potential (TRAP, and superoxide dismutase (Cu,Zn-SOD, glutathione peroxidase (GPx, glutathione-S-transferase (GST, and catalase (CAT. HgCl2 administration induced a rise (by 26% in LPO compared to control (143 ± 10 cps/mg hemoglobin in the second week and no difference was found at the end of the treatment. At that time, GST and GPx were higher (14 and 24%, respectively in the Hg group, and Cu,Zn-SOD was lower (54% compared to control. At the end of the treatment, Cu,Zn-SOD and CAT were higher (43 and 10%, respectively in the Hg group compared to control (4.6 ± 0.3 U/mg protein; 37 ± 0.9 pmol/mg protein, respectively. TRAP was lower (69% in the first week compared to control (43.8 ± 1.9 mM Trolox. These data provide evidence that HgCl2 administration is accompanied by systemic oxidative damage in the initial phase of the process, which leads to adaptive changes in the antioxidant reserve, thus decreasing the oxidative injury at the end of 30 days of HgCl2 administration. These results suggest that a preventive treatment with antioxidants would help to avoid oxidative damage in subjects with chronic intoxication.

  5. Evaluation of oxidative stress in D-serine induced nephrotoxicity

    International Nuclear Information System (INIS)

    Orozco-Ibarra, Marisol; Medina-Campos, Omar Noel; Sanchez-Gonzalez, Dolores Javier; Martinez-Martinez, Claudia Maria; Floriano-Sanchez, Esau; Santamaria, Abel; Ramirez, Victoria; Bobadilla, Norma A.; Pedraza-Chaverri, Jose

    2007-01-01

    It has been suggested that oxidative stress is involved in D-serine-induced nephrotoxicity. The purpose of this study was to assess if oxidative stress is involved in this experimental model using several approaches including (a) the determination of several markers of oxidative stress and the activity of some antioxidant enzymes in kidney and (b) the use of compounds with antioxidant or prooxidant effects. Rats were sacrificed at several periods of time (from 3 to 24 h) after a single i.p. injection of D-serine (400 mg/kg). Control rats were injected with L-serine (400 mg/kg) and sacrificed 24 h after. The following markers were used to assess the temporal aspects of renal damage: (a) urea nitrogen (BUN) and creatinine in blood serum, (b) kidney injury molecule (KIM-1) mRNA levels, and (c) tubular necrotic damage. In addition, creatinine clearance, proteinuria, and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) were measured 24 h after D-serine injection. Protein carbonyl content, malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), fluorescent products of lipid peroxidation, reactive oxygen species (ROS), glutathione (GSH) content, and heme oxygenase-1 (HO-1) expression were measured as markers of oxidative stress in the kidney. Additional experiments were performed using the following compounds with antioxidant or pro-oxidant effects before D-serine injection: (a) α-phenyl-tert-butyl-nitrone (PBN), a spin trapping agent; (b) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron(III) (FeTPPS), a soluble complex able to metabolize peroxynitrite; (c) aminotriazole (ATZ), a catalase (CAT) inhibitor; (d) stannous chloride (SnCl 2 ), an HO-1 inductor; (e) tin mesoporphyrin (SnMP), an HO inhibitor. In the time-course study, serum creatinine and BUN increased significantly on 15-24 and 20-24 h, respectively, and KIM-1 mRNA levels increased significantly on 6-24 h. Histological analyses revealed tubular necrosis at 12 h. The activity of antioxidant enzymes

  6. Exposure of rat hippocampal astrocytes to Ziram increases oxidative stress.

    Science.gov (United States)

    Matei, Ann-Marie; Trombetta, Louis D

    2016-04-01

    Pesticides have been shown in several studies to be the leading candidates of environmental toxins and may contribute to the pathogenesis of several neurodegenerative diseases. Ziram (zinc-bis(dimethyldithiocarbamate)) is an agricultural dithiocarbamate fungicide that is used to treat a variety of plant diseases. In spite of their generally acknowledged low toxicity, dithiocarbamates are known to cause a wide range of neurobehavioral effects as well as neuropathological changes in the brain. Astrocytes play a key role in normal brain physiology and in the pathology of the nervous system. This investigation studied the effects of 1.0 µM Ziram on rat hippocampal astrocytes. The thiobarbituric acid reactive substance assay performed showed a significant increase in malondialdehyde, a product of lipid peroxidation, in the Ziram-treated cells. Biochemical analysis also revealed a significant increase in the induction of 70 kDa heat shock and heme oxygenase 1 stress proteins. In addition, an increase of glutathione peroxidase (GPx) and a significant increase in oxidized glutathione (GSSG) were observed in the Ziram-treated cells. The ratio GSH to GSSG calculated from the treated cells was also decreased. Light and transmission electron microscopy supported the biochemical findings in Ziram-treated astrocytes. This data suggest that the cytotoxic effects observed with Ziram treatments may be related to the increase of oxidative stress. © The Author(s) 2013.

  7. Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity

    International Nuclear Information System (INIS)

    Ichihara, Sahoko; Yamada, Yoshiji; Kawai, Yoshichika; Osawa, Toshihiko; Furuhashi, Koichi; Duan Zhiwen; Ichihara, Gaku

    2007-01-01

    Cardiotoxicity is a treatment-limiting side effect of the anticancer drug doxorubicin (DOX). We have now investigated the roles of oxidative stress and signaling by the protein kinase Akt in DOX-induced cardiotoxicity as well as the effects on such toxicity both of fenofibrate, an agonist of peroxisome proliferator-activated receptor-α, and of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), an antioxidant. Mice injected intraperitoneally with DOX were treated for 4 days with fenofibrate or PEG-SOD. Fenofibrate and PEG-SOD each prevented the induction of cardiac dysfunction by DOX. Both drugs also inhibited the activation of the transcription factor NF-κB and increase in lipid peroxidation in the left ventricle induced by DOX, whereas only PEG-SOD inhibited the DOX-induced activation of Akt and Akt-regulated gene expression. These results suggest that fenofibrate and PEG-SOD prevented cardiac dysfunction induced by DOX through normalization of oxidative stress and redox-regulated NF-κB signaling

  8. Hypertension and physical exercise: The role of oxidative stress.

    Science.gov (United States)

    Korsager Larsen, Monica; Matchkov, Vladimir V

    2016-01-01

    Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress and endothelial function. The aim of this review is to investigate the effect of oxidative stress in relation to hypertension and physical exercise, including the role of NO in the pathogenesis of hypertension. Endothelial dysfunction and decreased NO levels have been found to have the adverse effects in the correlation between oxidative stress and hypertension. Most of the previous studies found that aerobic exercise significantly decreased blood pressure and oxidative stress in hypertensive subjects, but the intense aerobic exercise can also injure endothelial cells. Isometric exercise decreases normally only systolic blood pressure. An alternative exercise, Tai chi significantly decreases blood pressure and oxidative stress in normotensive elderly, but the effect in hypertensive subjects has not yet been studied. Physical exercise and especially aerobic training can be suggested as an effective intervention in the prevention and treatment of hypertension and cardiovascular disease via reduction in oxidative stress. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Oxidation of Proteins in Plants-Mechanisms and Consequences

    DEFF Research Database (Denmark)

    Sweetlove, Lee J; Møller, Ian M

    2009-01-01

    The production of reactive oxygen and reactive nitrogen species in plant cells can lead to a variety of modifications of proteins through oxidation of amino acid side groups. The widespread occurrence of such modifications is becoming appreciated as new proteomic approaches allow their systematic....... A view that such modifications could have signalling ramifications is emerging. However, in many cases there is a lack of information as to the effect of oxidation on protein activity or function. Severe protein oxidation is costly to the cell since oxidatively damaged proteins need to be degraded...... of modified proteins by affinity purification. Although there are several technical caveats with such approaches, they have been useful in documenting the extent of oxidative modification of proteins and have highlighted a number of proteins where oxidative modification is critical for protein function...

  10. Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts.

    Science.gov (United States)

    Sitte, N; Merker, K; von Zglinicki, T; Grune, T

    2000-03-01

    One of the highlights of age-related changes of cellular metabolism is the accumulation of oxidized proteins. The aging process on a cellular level can be treated either as the ongoing proliferation until a certain number of cell divisions is reached (the Hayflick limit) or as the aging of nondividing cells, that is, the age-related changes in cells without proliferation. The present investigation was undertaken to reveal the changes in protein turnover, proteasome activity, and protein oxidation status during proliferative senescence. We were able to demonstrate that the activity of the cytosolic proteasomal system declines dramatically during the proliferative senescence of human MRC-5 fibroblasts. Regardless of the loss in activity, it could be demonstrated that there are no changes in the transcription and translation of proteasomal subunits. This decline in proteasome activity was accompanied by an increased concentration of oxidized proteins. Cells at higher proliferation stages were no longer able to respond with increased degradation of endogenous [(35)S]-Met-radiolabeled proteins after hydrogen peroxide- or quinone-induced oxidative stress. It could be demonstrated that oxidized proteins in senescent human MRC-5 fibroblasts are not as quickly removed as they are in young cells. Therefore, our study demonstrates that the accumulation of oxidized proteins and decline in protein turnover and activity of the proteasomal system are not only a process of postmitotic aging but also occur during proliferative senescence and result in an increased half-life of oxidized proteins.

  11. Connection between markers of cholestasis and intensity of oxidative modification of proteins in patients with choledocholithiasis

    Directory of Open Access Journals (Sweden)

    Zoran Damnjanović

    2014-03-01

    Full Text Available The aim of this study was to examine the connection between cholestatic markers and the oxidative protein modification intensity in patients with choledocholithiasis. All the participants were subjected to clinical, laboratory and ultrasonic check-up at the Internal Department of the Military Hospital in Niš, Serbia. The parameters of oxidative stress: carbonyl groups, a measure of oxidative protein modification, and biochemical markers of cholestasis were determined by standard biochemical methods. The concentration of total (r=0.41, p<0.05, direct (r=0.49, p<+0.01 and indirect (r=0.41, p<0.05 bilirubin was in statistically significant positive linear correlation with the intensity of oxidative modification of proteins, while the other biochemical markers of cholestasis did not show such correlation. Total, direct and indirect bilirubins showed a significant positive correlation with oxidative protein modification, assessed through the levels of carbonyl groups in patients with choledocholithiasis.

  12. Oxidative Stress as an Important Factor in the Pathophysiology of alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Tanise Gemelli,

    2013-06-01

    Full Text Available Oxidative stress has been associated to play a crucial role in the pathogenesis of many diseases, including neurodegenerative diseases. Alzheimer's disease is an age-related neurodegenerative disorder, which is recognized as the most common form of dementia. In this article, the aim was to review the involvement of oxidative stress on Alzheimer's disease. Alzheimer's disease is histopathologically characterized by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles, the presence of oligomers of amyloid-? peptide and loss of synapses. Moreover, the brain and the nervous system are more prone to oxidative stress and oxidative damage influences the neurodegenerative diseases. However, increased oxidative damage, mitochondrial dysfunction, accumulation of oxidized aggregated proteins, inflammation, and defects in proteins constitute complex intertwined pathologies that lead to neuronal cell death. Mitochondrial mutations on deoxyribonucleic acid and oxidative stress contribute to aging, affecting different cell signaling systems, as well as the connectivity and neuronal cell death may lead to the largest risk factor for neurodegenerative diseases such as Alzheimer's Disease.

  13. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    Science.gov (United States)

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.

    Directory of Open Access Journals (Sweden)

    Rajendra Upadhya

    Full Text Available The ability of the opportunistic fungal pathogen Cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. To cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macrophages, C. neoformans has developed multilayered redundant molecular responses to neutralize the stress, to repair the damage and to eventually grow inside the hostile environment of the phagosome. We used microarray analysis of cells treated with hydrogen peroxide (H(2O(2 at multiple time points in a nutrient defined medium to identify a transcriptional signature associated with oxidative stress. We discovered that the composition of the medium in which fungal cells were grown and treated had a profound effect on their capacity to degrade exogenous H(2O(2. We determined the kinetics of H(2O(2 breakdown by growing yeast cells under different conditions and accordingly selected an appropriate media composition and range of time points for isolating RNA for hybridization. Microarray analysis revealed a robust transient transcriptional response and the intensity of the global response was consistent with the kinetics of H(2O(2 breakdown by treated cells. Gene ontology analysis of differentially expressed genes related to oxidation-reduction, metabolic process and protein catabolic processes identified potential roles of mitochondrial function and protein ubiquitination in oxidative stress resistance. Interestingly, the metabolic pathway adaptation of C. neoformans to H(2O(2 treatment was remarkably distinct from the response of other fungal organisms to oxidative stress. We also identified the induction of an antifungal drug resistance response upon the treatment of C. neoformans with H(2O(2. These results highlight the complexity of the oxidative stress response and offer possible new avenues for improving our understanding of mechanisms of oxidative stress resistance in C. neoformans.

  15. Role of selenium toxicity and oxidative stress in aquatic birds

    Science.gov (United States)

    Hoffman, D.J.

    2002-01-01

    hepatic GSH peroxidase, depletion of hepatic protein bound thiols and total thiols, but a small increase in GSH. Diving ducks in the San Francisco Bay area exhibited a positive correlation between hepatic Se concentration and GSH peroxidase activity (r=0.63, Pbirds. Further selenium nutritional interaction studies may also help to illucidate the mechanism of selenium induced teratogenesis, by optimizing GSH and other antioxidant defense mechanisms in a manner that would stabilize or raise the cell's threshold for susceptibility to toxic attack from excess selenium. It is concluded that Se-related manifestations of oxidative stress may serve as useful bioindicators of Se exposure and toxicity in wild aquatic birds.

  16. γ-Glutamyl semialdehyde and 2-amino-adipic semialdehyde: biomarkers of oxidative damage to proteins

    DEFF Research Database (Denmark)

    Daneshvar, B.; Frandsen, H.; Autrup, Herman

    1997-01-01

    proteins collected from eight different mammalian species was found to be inversely proportional to their maximum lifespan potential. The content of AAS in plasma proteins of untreated adult rats showed a positive correlation with the age of the rat. In young rats a negative correlation with age was found......Reactive oxygen species are formed in the body by several natural processes and by induced oxidative stress. The reactive oxygen species may react with the various biomolecules of the body, including proteins. In order to assess the impact of oxidative damage to proteins, we have tried to identify...

  17. Oxidative stress specifically downregulates survivin to promote breast tumour formation.

    Science.gov (United States)

    Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

    2013-03-05

    Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, sugges