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Sample records for oxidative stress survival

  1. Salmonella Rapidly Regulates Membrane Permeability To Survive Oxidative Stress

    PubMed Central

    van der Heijden, Joris; Reynolds, Lisa A.; Deng, Wanyin; Mills, Allan; Scholz, Roland; Imami, Koshi; Foster, Leonard J.; Duong, Franck

    2016-01-01

    ABSTRACT The outer membrane (OM) of Gram-negative bacteria provides protection against toxic molecules, including reactive oxygen species (ROS). Decreased OM permeability can promote bacterial survival under harsh circumstances and protects against antibiotics. To better understand the regulation of OM permeability, we studied the real-time influx of hydrogen peroxide in Salmonella bacteria and discovered two novel mechanisms by which they rapidly control OM permeability. We found that pores in two major OM proteins, OmpA and OmpC, could be rapidly opened or closed when oxidative stress is encountered and that the underlying mechanisms rely on the formation of disulfide bonds in the periplasmic domain of OmpA and TrxA, respectively. Additionally, we found that a Salmonella mutant showing increased OM permeability was killed more effectively by treatment with antibiotics. Together, these results demonstrate that Gram-negative bacteria regulate the influx of ROS for defense against oxidative stress and reveal novel targets that can be therapeutically targeted to increase bacterial killing by conventional antibiotics. PMID:27507830

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

    PubMed

    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. PMID:27422326

  3. Oxidative Stress Promotes Peroxiredoxin Hyperoxidation and Attenuates Pro-survival Signaling in Aging Chondrocytes.

    PubMed

    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

    2016-03-25

    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 observedin situin 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

  4. Novel thiazolidinedione mitoNEET ligand-1 acutely improves cardiac stem cell survival under oxidative stress.

    PubMed

    Logan, Suzanna J; Yin, Liya; Geldenhuys, Werner J; Enrick, Molly K; Stevanov, Kelly M; Carroll, Richard T; Ohanyan, Vahagn A; Kolz, Christopher L; Chilian, William M

    2015-03-01

    Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD. Accordingly, manipulation of stem cell mitochondrial metabolism may be an effective strategy to improve survival of stem cells under oxidative stress. MitoNEET is a redox-sensitive, mitochondrial target of thiazolidinediones (TZDs), and influences cellular oxidative capacity. Pharmacological targeting of mitoNEET with the novel TZD, mitoNEET Ligand-1 (NL-1), improved cardiac stem cell (CSC) survival compared to vehicle (0.1% DMSO) during in vitro oxidative stress (H2O2). 10 μM NL-1 also reduced CSC maximal oxygen consumption rate (OCR) compared to vehicle. Following treatment with dexamethasone, CSC maximal OCR increased compared to baseline, but NL-1 prevented this effect. Smooth muscle α-actin expression increased significantly in CSC following differentiation compared to baseline, irrespective of NL-1 treatment. When CSCs were treated with glucose oxidase for 7 days, NL-1 significantly improved cell survival compared to vehicle (trypan blue exclusion). NL-1 treatment of cells isolated from mitoNEET knockout mice did not increase CSC survival with H2O2 treatment. Following intramyocardial injection of CSCs into Zucker obese fatty rats, NL-1 significantly improved CSC survival after 24 h, but not after 10 days. These data suggest that pharmacological targeting of mitoNEET with TZDs may acutely protect stem cells following transplantation into an oxidative environment. Continued treatment or manipulation of mitochondrial metabolism may be necessary to produce long-term benefits related to stem cell therapies. PMID:25725808

  5. The Campylobacter jejuni Ferric Uptake Regulator Promotes Acid Survival and Cross-Protection against Oxidative Stress.

    PubMed

    Askoura, Momen; Sarvan, Sabina; Couture, Jean-François; Stintzi, Alain

    2016-05-01

    Campylobacter jejuni is a prevalent cause of bacterial gastroenteritis in humans worldwide. The mechanisms by which C. jejuni survives stomach acidity remain undefined. In the present study, we demonstrated that the C. jejuni ferric uptake regulator (Fur) plays an important role in C. jejuni acid survival and acid-induced cross-protection against oxidative stress. A C. jejuni Δfur mutant was more sensitive to acid than the wild-type strain. Profiling of the acid stimulon of the C. jejuni Δfur mutant allowed us to uncover Fur-regulated genes under acidic conditions. In particular, Fur was found to upregulate genes involved in flagellar and cell envelope biogenesis upon acid stress, and mutants with deletions of these genes were found to be defective in surviving acid stress. Interestingly, prior acid exposure of C. jejuni cross-protected against oxidative stress in a catalase (KatA)- and Fur-dependent manner. Western blotting and reverse transcription-quantitative PCR revealed increased expression of KatA upon acid stress. Electrophoretic mobility shift assays (EMSAs) demonstrated that the binding affinity between Fur and the katA promoter is reduced in vitro under conditions of low pH, rationalizing the higher levels of expression of katA under acidic conditions. Strikingly, the Δfur mutant exhibited reduced virulence in both human epithelial cells and the Galleria mellonella infection model. Altogether, this is the first study showing that, in addition to its role in iron metabolism, Fur is an important regulator of C. jejuni acid responses and this function cross-protects against oxidative stress. Moreover, our results clearly demonstrate Fur's important role in C. jejuni pathogenesis. PMID:26883589

  6. Oxidative Stress Survival in a Clinical Saccharomyces cerevisiae Isolate Is Influenced by a Major Quantitative Trait Nucleotide

    PubMed Central

    Diezmann, Stephanie; Dietrich, Fred S.

    2011-01-01

    One of the major challenges in characterizing eukaryotic genetic diversity is the mapping of phenotypes that are the cumulative effect of multiple alleles. We have investigated tolerance of oxidative stress in the yeast Saccharomyces cerevisiae, a trait showing phenotypic variation in the population. Initial crosses identified that this is a quantitative trait. Microorganisms experience oxidative stress in many environments, including during infection of higher eukaryotes. Natural variation in oxidative stress tolerance is an important aspect of response to oxidative stress exerted by the human immune system and an important trait in microbial pathogens. A clinical isolate of the usually benign yeast S. cerevisiae was found to survive oxidative stress significantly better than the laboratory strain. We investigated the genetic basis of increased peroxide survival by crossing those strains, phenotyping 1500 segregants, and genotyping of high-survival segregants by hybridization of bulk and single segregant DNA to microarrays. This effort has led to the identification of an allele of the transcription factor Rds2 as contributing to stress response. Rds2 has not previously been associated with the survival of oxidative stress. The identification of its role in the oxidative stress response here is an example of a specific trait that appears to be beneficial to Saccharomyces cerevisiae when growing as a pathogen. Understanding the role of this fungal-specific transcription factor in pathogenicity will be important in deciphering how fungi infect and colonize the human host and could eventually lead to a novel drug target. PMID:21515583

  7. Life in a Diverse Oral Community – Strategies for Oxidative Stress Survival

    PubMed Central

    Henry, Leroy G.; Boutrin, Marie-Claire; Aruni, Wilson; Robles, Antonette; Ximinies, Alexia; Fletcher, Hansel M.

    2015-01-01

    Background While the oral cavity harbors more than 680 bacterial species, the interaction and association of selected bacterial species play a role in periodontal diseases. Bacterial species including Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia, a consortium previously designated as the “red complex” is now being expanded to include other new emerging pathogens that are significantly associated with periodontal disease. Highlight In addition to novel mechanisms for oxidative resistance of individual species, community dynamics may lead to an overall strategy for survival in the inflammatory environment of the periodontal pocket. Complex systems controlled by response regulators protect against oxidative and nitrosative stress. Conclusion The combination of these multifaceted strategies would provide a comprehensive defense and support system against the repetitive host immune response to promote microbial persistence and disease. PMID:26744578

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  9. HBx regulates fatty acid oxidation to promote hepatocellular carcinoma survival during metabolic stress

    PubMed Central

    Huang, Shuai; Zhang, Hui-Lu; Qin, Chen-Jie; Zhao, Ling-Hao; Fu, Gong-Bo; Zhou, Xu; Wang, Xian-Ming; Tang, Liang; Wen, Wen; Yang, Wen; Tang, Shan-Hua; Cao, Dan; Guo, Lin-Na; Zeng, Min; Wu, Meng-Chao; Yan, He-Xin; Wang, Hong-Yang

    2016-01-01

    Due to a high rate of nutrient consumption and inadequate vascularization, hepatocellular carcinoma (HCC) cells constantly undergo metabolic stress during tumor development. Hepatitis B virus (HBV) X protein (HBx) has been implicated in the pathogenesis of HBV-induced HCC. In this study, we investigated the functional roles of HBx in HCC adaptation to metabolic stress. Up-regulation of HBx increased the intracellular ATP and NADPH generation, and induced the resistance to glucose deprivation, whereas depletion of HBx via siRNA abolished these effects and conferred HCC cells sensitive to glucose restriction. Though HBx did not affect the glycolysis and oxidative phosphorylation capacity of HCC cells under normal culture conditions, it facilitated fatty acid oxidation (FAO) in the absence of glucose, which maintained NADPH and ATP levels. Further investigation showed that HBx expression, under glucose deprivation, stimulated phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) via a calcium/CaMKK-dependent pathway, which was required for the activation of FAO. Conversely, inhibition of FAO by etomoxir (ETO) restored the sensitivity of HBx-expressing cells to glucose deficiency in vitro and retarded xenograft tumor formation in vivo. Finally, HBx-induced activation of the AMPK and FAO pathways were also observed in xenograft tumors and HBV-associated HCC specimens. Our data suggest that HBx plays a key role in the maintenance of redox and energy homeostasis by activating FAO, which is critical for HCC cell survival under conditions of metabolic stress and might be exploited for therapeutic benefit. PMID:26744319

  10. The C-ETS2-TFEB Axis Promotes Neuron Survival under Oxidative Stress by Regulating Lysosome Activity.

    PubMed

    Ma, Shumin; Fang, Zijun; Luo, Wenwen; Yang, Yunzhi; Wang, Chenyao; Zhang, Qian; Wang, Huafei; Chen, Huaiyong; Chan, Chi Bun; Liu, Zhixue

    2016-01-01

    Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) produced as a result of ageing causes damage to macromolecules and organelles or leads to interference of cell signalling pathways, which in turn results in oxidative stress. Oxidative stress occurs in many neurodegenerative diseases (e.g., Parkinson's disease) and contributes to progressive neuronal loss. In this study, we show that cell apoptosis is induced by oxidative stress and that lysosomes play an important role in cell survival under oxidative stress. As a compensatory response to this stress, lysosomal genes were upregulated via induction of transcription factor EB (TFEB). In addition, localization of TFEB to the nucleus was increased by oxidative stress. We also confirmed that TFEB protects cells from oxidative stress both in vitro and in vivo. Finally, we found that C-ETS2 senses oxidative stress, activates TFEB transcription, and mediates the upregulation of lysosomal genes. Our results demonstrate a mechanistic pathway for inducing lysosomal activity during ageing and neurodegeneration. PMID:27195074

  11. The C-ETS2-TFEB Axis Promotes Neuron Survival under Oxidative Stress by Regulating Lysosome Activity

    PubMed Central

    Fang, Zijun; Luo, Wenwen; Yang, Yunzhi; Wang, Chenyao; Zhang, Qian; Wang, Huafei; Chen, Huaiyong; Chan, Chi bun; Liu, Zhixue

    2016-01-01

    Excessive reactive oxygen species/reactive nitrogen species (ROS/RNS) produced as a result of ageing causes damage to macromolecules and organelles or leads to interference of cell signalling pathways, which in turn results in oxidative stress. Oxidative stress occurs in many neurodegenerative diseases (e.g., Parkinson's disease) and contributes to progressive neuronal loss. In this study, we show that cell apoptosis is induced by oxidative stress and that lysosomes play an important role in cell survival under oxidative stress. As a compensatory response to this stress, lysosomal genes were upregulated via induction of transcription factor EB (TFEB). In addition, localization of TFEB to the nucleus was increased by oxidative stress. We also confirmed that TFEB protects cells from oxidative stress both in vitro and in vivo. Finally, we found that C-ETS2 senses oxidative stress, activates TFEB transcription, and mediates the upregulation of lysosomal genes. Our results demonstrate a mechanistic pathway for inducing lysosomal activity during ageing and neurodegeneration. PMID:27195074

  12. Survival, Reproduction, Avoidance Behavior and Oxidative Stress Biomarkers in the Earthworm Octolasion cyaneum Exposed to Glyphosate.

    PubMed

    Salvio, Carla; Menone, Mirta L; Rafael, Sergio; Iturburu, Fernando G; Manetti, Pablo L

    2016-03-01

    The massive use of glyphosate (GLY) in several countries has increased the interest in investigating its potential adverse effects in non-target organisms. The aim of the present study was to assess the potential effects in survival and reproduction; avoidance behavior and oxidative stress under short-term (48 h) and subchronic exposures (28 days) to GLY in the earthworm Octolasion cyaneum. After 48 h no significant changes in the behavior was observed. In addition, a lower catalase activity at 498 μg GLY kg(-1) dry soil section relative to earthworms from the control section was obtained. After 28 days of exposure inhibition of glutathione S-transferase activity was observed at 535 μg GLY kg(-1) dry soil while no changes in the other endpoints were detected. These results indicate that environmentally relevant concentrations of GLY (up to 996 µg GLY kg(-1) dry soil) did not exert a toxic effect to O. cyaneum. PMID:26754543

  13. Protein Kinase D1 (PKD1) Phosphorylation Promotes Dopaminergic Neuronal Survival during 6-OHDA-Induced Oxidative Stress

    PubMed Central

    Asaithambi, Arunkumar; Ay, Muhammet; Jin, Huajun; Gosh, Anamitra; Anantharam, Vellareddy; Kanthasamy, Arthi; Kanthasamy, Anumantha G.

    2014-01-01

    Oxidative stress is a major pathophysiological mediator of degenerative processes in many neurodegenerative diseases including Parkinson’s disease (PD). Aberrant cell signaling governed by protein phosphorylation has been linked to oxidative damage of dopaminergic neurons in PD. Although several studies have associated activation of certain protein kinases with apoptotic cell death in PD, very little is known about protein kinase regulation of cell survival and protection against oxidative damage and degeneration in dopaminergic neurons. Here, we characterized the PKD1-mediated protective pathway against oxidative damage in cell culture models of PD. Dopaminergic neurotoxicant 6-hydroxy dopamine (6-OHDA) was used to induce oxidative stress in the N27 dopaminergic cell model and in primary mesencephalic neurons. Our results indicated that 6-OHDA induced the PKD1 activation loop (PKD1S744/S748) phosphorylation during early stages of oxidative stress and that PKD1 activation preceded cell death. We also found that 6-OHDA rapidly increased phosphorylation of the C-terminal S916 in PKD1, which is required for PKD1 activation loop (PKD1S744/748) phosphorylation. Interestingly, negative modulation of PKD1 activation by RNAi knockdown or by the pharmacological inhibition of PKD1 by kbNB-14270 augmented 6-OHDA-induced apoptosis, while positive modulation of PKD1 by the overexpression of full length PKD1 (PKD1WT) or constitutively active PKD1 (PKD1S744E/S748E) attenuated 6-OHDA-induced apoptosis, suggesting an anti-apoptotic role for PKD1 during oxidative neuronal injury. Collectively, our results demonstrate that PKD1 signaling plays a cell survival role during early stages of oxidative stress in dopaminergic neurons and therefore, positive modulation of the PKD1-mediated signal transduction pathway can provide a novel neuroprotective strategy against PD. PMID:24806360

  14. Branched-Chain Amino Acid Supplementation Reduces Oxidative Stress and Prolongs Survival in Rats with Advanced Liver Cirrhosis

    PubMed Central

    Mifuji-Moroka, Rumi; Hara, Nagisa; Miyachi, Hirohide; Sugimoto, Ryosuke; Tanaka, Hideaki; Fujita, Naoki; Gabazza, Esteban C.; Takei, Yoshiyuki

    2013-01-01

    Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver. PMID:23936183

  15. Contribution of protein isoaspartate methyl transferase (PIMT) in the survival of Salmonella Typhimurium under oxidative stress and virulence.

    PubMed

    Kumawat, Manoj; Pesingi, Pavan Kumar; Agarwal, Rajesh Kumar; Goswami, Tapas Kumar; Mahawar, Manish

    2016-06-01

    The enteric pathogen Salmonella Typhimurium (ST) survives inside the oxidative environment of phagocytic cells. Phagocyte generated oxidants primarily target proteins and modify amino acids in them. These modifications render the targeted proteins functionally inactive. Conversion of Asp to iso-Asp is one of the several known oxidant mediated amino acids modifications. By repairing iso-Asp to Asp, protein-isoaspartyl methyltransferase (PIMT) maintains the activities of proteins and thus helps in cellular survival under oxidative stress. To elucidate the role of PIMT in ST survival under oxidative stress, we have constructed a pimt gene deletion strain (Δpimt strain) of ST. The Δpimt strain grows normally in various culture media in vitro. However, in comparison to wild type ST, the Δpimt strain is found significantly (p<0.001) more susceptible to H2O2 and hypochlorite (HOCl). Further, the Δpimt mutant strain shows hypersusceptibility (p<0.001) to INF-γ stimulated macrophages. This susceptibility is reversed by pharmacological inhibition of reactive oxygen species (ROS) but not reactive nitrogen species (RNS) production. Further, plasmid based complementation enhances the survival of Δpimt mutant strain against oxidants in vitro and also inside the macrophages. In mice model, the LD50 for wild type ST and mutant Δpimt has been 1.73×10(4) and 1.38×10(5), respectively. Further, the mutant strain shows reduced dissemination to spleen and liver in mice. Following infection with a mixture of wild type ST and the Δpimt mutant (co-infection experiment), we recover significantly (p<0.001) less numbers of mutant bacteria from the spleen and liver of mice. PMID:27156953

  16. GSTP1 Loss Results in Accumulation of Oxidative DNA Base Damage and Promotes Prostate Cancer Cell Survival Following Exposure to Protracted Oxidative Stress

    PubMed Central

    Mian, Omar Y.; Khattab, Mohamed H.; Hedayati, Mohammad; Coulter, Jonathan; Abubaker-Sharif, Budri; Schwaninger, Julie M.; Veeraswamy, Ravi K.; Brooks, James D.; Hopkins, Lisa; Shinohara, Debika Biswal; Cornblatt, Brian; Nelson, William G.; Yegnasubramanian, Srinivasan; DeWeese, Theodore L.

    2016-01-01

    BACKGROUND Epigenetic silencing of glutathione S-transferase π (GSTP1) is a hallmark of transformation from normal prostatic epithelium to adenocarcinoma of the prostate. The functional significance of this loss is incompletely understood. The present study explores the effects of restored GSTP1 expression on glutathione levels, accumulation of oxidative DNA damage, and prostate cancer cell survival following oxidative stress induced by protracted, low dose rate ionizing radiation (LDR). METHODS GSTP1 protein expression was stably restored in LNCaP prostate cancer cells. The effect of GSTP1 restoration on protracted LDR-induced oxidative DNA damage was measured by GC-MS quantitation of modified bases. Reduced and oxidized glutathione levels were measured in control and GSTP1 expressing populations. Clonogenic survival studies of GSTP1-transfected LNCaP cells after exposure to protracted LDR were performed. Global gene expression profiling and pathway analysis were performed. RESULTS GSTP1 expressing cells accumulated less oxidized DNA base damage and exhibited decreased survival compared to control LNCaP-Neo cells following oxidative injury induced by protracted LDR. Restoration of GSTP1 expression resulted in changes in modified glutathione levels that correlated with GSTP1 protein levels in response to protracted LDR-induced oxidative stress. Survival differences were not attributable to depletion of cellular glutathione stores. Gene expression profiling and pathway analysis following GSTP1 restoration suggests this protein plays a key role in regulating prostate cancer cell survival. CONCLUSIONS The ubiquitous epigenetic silencing of GSTP1 in prostate cancer results in enhanced survival and accumulation of potentially promutagenic DNA adducts following exposure of cells to protracted oxidative injury suggesting a protective, anti-neoplastic function of GSTP1. The present work provides mechanistic backing to the tumor suppressor function of GSTP1 and its role in

  17. Survival of the fittest: overcoming oxidative stress at the extremes of Acid, heat and metal.

    PubMed

    Maezato, Yukari; Blum, Paul

    2012-01-01

    The habitat of metal respiring acidothermophilic lithoautotrophs is perhaps the most oxidizing environment yet identified. Geothermal heat, sulfuric acid and transition metals contribute both individually and synergistically under aerobic conditions to create this niche. Sulfuric acid and metals originating from sulfidic ores catalyze oxidative reactions attacking microbial cell surfaces including lipids, proteins and glycosyl groups. Sulfuric acid also promotes hydrocarbon dehydration contributing to the formation of black "burnt" carbon. Oxidative reactions leading to abstraction of electrons is further impacted by heat through an increase in the proportion of reactant molecules with sufficient energy to react. Collectively these factors and particularly those related to metals must be overcome by thermoacidophilic lithoautotrophs in order for them to survive and proliferate. The necessary mechanisms to achieve this goal are largely unknown however mechanistics insights have been gained through genomic studies. This review focuses on the specific role of metals in this extreme environment with an emphasis on resistance mechanisms in Archaea. PMID:25371104

  18. Survival of the Fittest: Overcoming Oxidative Stress at the Extremes of Acid, Heat and Metal

    PubMed Central

    Maezato, Yukari; Blum, Paul

    2012-01-01

    The habitat of metal respiring acidothermophilic lithoautotrophs is perhaps the most oxidizing environment yet identified. Geothermal heat, sulfuric acid and transition metals contribute both individually and synergistically under aerobic conditions to create this niche. Sulfuric acid and metals originating from sulfidic ores catalyze oxidative reactions attacking microbial cell surfaces including lipids, proteins and glycosyl groups. Sulfuric acid also promotes hydrocarbon dehydration contributing to the formation of black “burnt” carbon. Oxidative reactions leading to abstraction of electrons is further impacted by heat through an increase in the proportion of reactant molecules with sufficient energy to react. Collectively these factors and particularly those related to metals must be overcome by thermoacidophilic lithoautotrophs in order for them to survive and proliferate. The necessary mechanisms to achieve this goal are largely unknown however mechanistics insights have been gained through genomic studies. This review focuses on the specific role of metals in this extreme environment with an emphasis on resistance mechanisms in Archaea. PMID:25371104

  19. Formation and Reversibility of BiP Protein Cysteine Oxidation Facilitate Cell Survival during and post Oxidative Stress.

    PubMed

    Wang, Jie; Sevier, Carolyn S

    2016-04-01

    Redox fluctuations within cells can be detrimental to cell function. To gain insight into how cells normally buffer against redox changes to maintain cell function, we have focused on elucidating the signaling pathways that serve to sense and respond to oxidative redox stress within the endoplasmic reticulum (ER) using yeast as a model system. Previously, we have shown that a cysteine in the molecular chaperone BiP, a Hsp70 molecular chaperone within the ER, is susceptible to oxidation by peroxide during ER-derived oxidative stress, forming a sulfenic acid (-SOH) moiety. Here, we demonstrate that this same conserved BiP cysteine is susceptible also to glutathione modification (-SSG). Glutathionylated BiP is detected both as a consequence of enhanced levels of cellular peroxide and also as a by-product of increased levels of oxidized glutathione (GSSG). Similar to sulfenylation, we observe glutathionylation decouples BiP ATPase and peptide binding activities, turning BiP from an ATP-dependent foldase into an ATP-independent holdase. We show glutathionylation enhances cell proliferation during oxidative stress, which we suggest relates to modified BiP's increased ability to limit polypeptide aggregation. We propose the susceptibility of BiP to modification with glutathione may serve also to prevent irreversible oxidation of BiP by peroxide. PMID:26865632

  20. Mycobacterium tuberculosis EsxO (Rv2346c) promotes bacillary survival by inducing oxidative stress mediated genomic instability in macrophages.

    PubMed

    Mohanty, Soumitra; Dal Molin, Michael; Ganguli, Geetanjali; Padhi, Avinash; Jena, Prajna; Selchow, Petra; Sengupta, Srabasti; Meuli, Michael; Sander, Peter; Sonawane, Avinash

    2016-01-01

    Mycobacterium tuberculosis (Mtb) survives inside the macrophages by modulating the host immune responses in its favor. The 6-kDa early secretory antigenic target (ESAT-6; esxA) of Mtb is known as a potent virulence and T-cell antigenic determinant. At least 23 such ESAT-6 family proteins are encoded in the genome of Mtb; however, the function of many of them is still unknown. We herein report that ectopic expression of Mtb Rv2346c (esxO), a member of ESAT-6 family proteins, in non-pathogenic Mycobacterium smegmatis strain (MsmRv2346c) aids host cell invasion and intracellular bacillary persistence. Further mechanistic studies revealed that MsmRv2346c infection abated macrophage immunity by inducing host cell death and genomic instability as evident from the appearance of several DNA damage markers. We further report that the induction of genomic instability in infected cells was due to increase in the hosts oxidative stress responses. MsmRv2346c infection was also found to induce autophagy and modulate the immune function of macrophages. In contrast, blockade of Rv2346c induced oxidative stress by treatment with ROS inhibitor N-acetyl-L-cysteine prevented the host cell death, autophagy induction and genomic instability in infected macrophages. Conversely, MtbΔRv2346c mutant did not show any difference in intracellular survival and oxidative stress responses. We envision that Mtb ESAT-6 family protein Rv2346c dampens antibacterial effector functions namely by inducing oxidative stress mediated genomic instability in infected macrophages, while loss of Rv2346c gene function may be compensated by other redundant ESAT-6 family proteins. Thus EsxO plays an important role in mycobacterial pathogenesis in the context of innate immunity. PMID:26786654

  1. Plant Survival in a Changing Environment: The Role of Nitric Oxide in Plant Responses to Abiotic Stress

    PubMed Central

    Simontacchi, Marcela; Galatro, Andrea; Ramos-Artuso, Facundo; Santa-María, Guillermo E.

    2015-01-01

    Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant’s ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant’s priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signaling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation. PMID:26617619

  2. Plant Survival in a Changing Environment: The Role of Nitric Oxide in Plant Responses to Abiotic Stress.

    PubMed

    Simontacchi, Marcela; Galatro, Andrea; Ramos-Artuso, Facundo; Santa-María, Guillermo E

    2015-01-01

    Nitric oxide in plants may originate endogenously or come from surrounding atmosphere and soil. Interestingly, this gaseous free radical is far from having a constant level and varies greatly among tissues depending on a given plant's ontogeny and environmental fluctuations. Proper plant growth, vegetative development, and reproduction require the integration of plant hormonal activity with the antioxidant network, as well as the maintenance of concentration of reactive oxygen and nitrogen species within a narrow range. Plants are frequently faced with abiotic stress conditions such as low nutrient availability, salinity, drought, high ultraviolet (UV) radiation and extreme temperatures, which can influence developmental processes and lead to growth restriction making adaptive responses the plant's priority. The ability of plants to respond and survive under environmental-stress conditions involves sensing and signaling events where nitric oxide becomes a critical component mediating hormonal actions, interacting with reactive oxygen species, and modulating gene expression and protein activity. This review focuses on the current knowledge of the role of nitric oxide in adaptive plant responses to some specific abiotic stress conditions, particularly low mineral nutrient supply, drought, salinity and high UV-B radiation. PMID:26617619

  3. The impact of oxidative stress on islet transplantation and monitoring the graft survival by non-invasive imaging.

    PubMed

    Ramkumar, K M; Sekar, T V; Bhakkiyalakshmi, E; Foygel, Kira; Rajaguru, P; Berger, F; Paulmurugan, R

    2013-01-01

    Islet transplantation is an attractive strategy to treat severe diabetic conditions in patients suffering from autoimmune derived diabetes, and it has currently been considered a forefront research arena in diabetes. Major aim of islet transplantation is to achieve successful insulin independent disease free survival. The key challenges in transplanted islets are the generation of reactive oxygen species (ROS) and associated oxidative stress, pro-inflammatory cytokine - (TNFα) mediated apoptotic induction, attack by immune cells, and achieving revascularization with minimal hypoxic microenvironment. Free radicals and their derivatives are constantly produced in living systems, but at relatively low level, and in a balanced state. Oxidative stress, which occurs as a result of an imbalance between the intracellular free radicals production and the cellular antioxidant defense mechanisms in the transplanted islets, can lead to cell death. The balance between oxidants and antioxidants in a cell can be easily disturbed by increase in ROS production or reduction in the level of cellular antioxidant defensive substances, which can cause many metabolic complications, including pancreatic β-cell damage. Antioxidants function as blockers of radical processes by eliminating harmful ROS produced during normal cellular metabolism. A complex antioxidant defense mechanism has been developed by nature in cells to protect the cellular homeostasis. This system mainly includes antioxidant enzymes, vitamins and minerals. As transplanted islet survival is crucial for achieving successful therapy, most of these antioxidants can be used as a supplement to scavenge the local ROS thereby improving the survival of transplanted islets. Currently, very few techniques have been routinely used to qualitatively and quantitatively assess the survival and function of islet grafts, especially to confirm the success of treatment, which includes metabolic parameters such as blood glucose, insulin

  4. A eukaryotic-type signalling system of Pseudomonas aeruginosa contributes to oxidative stress resistance, intracellular survival and virulence

    PubMed Central

    2011-01-01

    Background The genome of Pseudomonas aeruginosa contains at least three genes encoding eukaryotic-type Ser/Thr protein kinases, one of which, ppkA, has been implicated in P. aeruginosa virulence. Together with the adjacent pppA phosphatase gene, they belong to the type VI secretion system (H1-T6SS) locus, which is important for bacterial pathogenesis. To determine the biological function of this protein pair, we prepared a pppA-ppkA double mutant and characterised its phenotype and transcriptomic profiles. Results Phenotypic studies revealed that the mutant grew slower than the wild-type strain in minimal media and exhibited reduced secretion of pyoverdine. In addition, the mutant had altered sensitivity to oxidative and hyperosmotic stress conditions. Consequently, mutant cells had an impaired ability to survive in murine macrophages and an attenuated virulence in the plant model of infection. Whole-genome transcriptome analysis revealed that pppA-ppkA deletion affects the expression of oxidative stress-responsive genes, stationary phase σ-factor RpoS-regulated genes, and quorum-sensing regulons. The transcriptome of the pppA-ppkA mutant was also analysed under conditions of oxidative stress and showed an impaired response to the stress, manifested by a weaker induction of stress adaptation genes as well as the genes of the SOS regulon. In addition, expression of either RpoS-regulated genes or quorum-sensing-dependent genes was also affected. Complementation analysis confirmed that the transcription levels of the differentially expressed genes were specifically restored when the pppA and ppkA genes were expressed ectopically. Conclusions Our results suggest that in addition to its crucial role in controlling the activity of P. aeruginosa H1-T6SS at the post-translational level, the PppA-PpkA pair also affects the transcription of stress-responsive genes. Based on these data, it is likely that the reduced virulence of the mutant strain results from an impaired

  5. How radiation kills cells: Survival of Deinococcus radiodurans and Shewanella oneidensis under oxidative stress

    SciTech Connect

    Ghosal, D; Omelchenko, M V.; Gaidamakova, E; Matrosova, V; Vasilenko, A; Venkateswaran, Amudhan; Zhai, M; Kostandarithes, Heather M.; Brim, Hassan; Makarova, Kira S.; Wackett, L. P.; Fredrickson, Jim K.; Daly, Michael J.

    2005-04-01

    The radiation resistant bacterium Deinococcus radiodurans accumulates very high intracellular manganese and relatively low iron levels compared to the dissimilatory metal-reducing bacterium Shewanella oneidensis which is extremely sensitive. For Fe-rich, Mn-poor cells, death at low doses might be caused by the release of Fe(II) from proteins during irradiation, followed by Fe(II)-dependent reduction of hydrogen peroxide produced by metabolism after irradiation. In contrast, Mn(II) ions concentrated in D. radiodurans might serve as antioxidants that reinforce enzymic systems which defend against oxidative stress during recovery. We extend our hypothesis here to include consideration of respiration, tricarboxylic acid cycle activity, peptide transport, and metal reduction, which together with Mn(II) transport represent potential new targets to control cell recovery from radiation injury.

  6. Effects of polymorphisms in alcohol metabolism and oxidative stress genes on survival from head and neck cancer

    PubMed Central

    Hakenewerth, Anne M.; Millikan, Robert C.; Rusyn, Ivan; Herring, Amy H.; Weissler, Mark C.; Funkhouser, William K.; North, Kari E.; Barnholtz-Sloan, Jill S.; Olshan, Andrew F.

    2013-01-01

    Background Heavy alcohol consumption increases risk of developing squamous cell carcinoma of the head and neck (SCCHN). Alcohol metabolism to cytotoxic and mutagenic intermediates acetaldehyde and reactive oxygen species is critical for alcohol-drinking-associated carcinogenesis. We hypothesized that polymorphisms in alcohol metabolism-related and antioxidant genes influence SCCHN survival. Methods Interview and genotyping data (64 polymorphisms in 12 genes) were obtained from 1227 white and African-American cases from the Carolina Head and Neck Cancer Epidemiology study, a population-based case–control study of SCCHN conducted in North Carolina from 2002 to 2006. Vital status, date and cause of death through 2009 were obtained from the National Death Index. Kaplan–Meier log-rank tests and adjusted hazard ratios were calculated to identify alleles associated with survival. Results Most tested SNPs were not associated with survival, with the exception of the minor alleles of rs3813865 and rs8192772 in CYP2E1. These were associated with poorer cancer-specific survival (HRrs3813865, 95%CI = 2.00, 1.33–3.01; HRrs8192772, 95%CI = 1.62, 1.17–2.23). Hazard ratios for 8 additional SNPs in CYP2E1, GPx2, SOD1, and SOD2, though not statistically significant, were suggestive of differences in allele hazards for all-cause and/or cancer death. No consistent associations with survival were found for SNPs in ADH1B, ADH1C, ADH4, ADH7, ALDH2, GPx2, GPx4, and CAT. Conclusions We identified some polymorphisms in alcohol and oxidative stress metabolism genes that influence survival in subjects with SCCHN. Previously unreported associations of SNPs in CYP2E1 warrant further investigation. PMID:23632049

  7. Effects of nonionic and ionic surfactants on survival, oxidative stress, and cholinesterase activity of planarian.

    PubMed

    Li, Mei-Hui

    2008-02-01

    Eight widely used surfactants (cetyltrimethylammonium bromide; CTAB, benzethonium chloride; Hyamine 1622, 4-nonylphenol; NP, octylphenol ethoxylate; Triton X-100, dodecylbenzene sulfonate; LAS, lauryl sulfate; SDS, pentadecafluorooctanoic acid; PFOA, and perfluorooctane sulfonate; PFOS) were selected to examine their acute toxicities and effects on oxidative stress and cholinesterase (ChE) activities in Dugesia japonica. The differences in acute toxicity among eight surfactants to planarians were at least in the range of three orders of magnitudes. The toxicity rank of surfactants according to estimated 48-h LC(50) was SDS>NP>LAS>Hyamine 1622>CTAB>Triton X-100>PFOS>PFOA. The toxicity rank of surfactants according to 96-h LC(50) was as follows: SDS>CTAB>NP>LAS>Hyamine 1622>Triton X-100>PFOS>PFOA. There were significant increases in catalase activities in planarians exposed to LAS at nominal concentrations of 0.5 or 1 mgl(-1) and to PFOS at nominal concentrations of 5 or 10 mgl(-1) after 48-h exposure. Inhibitions of ChE activities were found in planarians exposed to Hyamine 1622 at all concentrations tested, to PFOS at nominal concentration of 10 mgl(-1), to PFOA at nominal concentrations of 50 or 100 mgl(-1) and to NP at nominal concentration of 0.5 mgl(-1). A significant increase in ChE activities was also observed in planarian exposed to Triton X-100 at nominal concentration of 5 mgl(-1). The implication of ChE inhibition by NP, PFOS and PFOA on neurological and behavioral effects in aquatic animals requires further investigation. PMID:17905407

  8. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    PubMed

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales. PMID:25527297

  9. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study

    PubMed Central

    2009-01-01

    Background The purpose of this study was to compare plasma levels of antioxidants and oxidative stress biomarkers in head and neck squamous cell carcinoma (HNSCC) patients with healthy controls. Furthermore, the effect of radiotherapy on these biomarkers and their association with survival in HNSCC patients were investigated. Methods Seventy-eight HNSCC patients and 100 healthy controls were included in this study. Follow-up samples at the end of radiotherapy were obtained in 60 patients. Fifteen antioxidant biomarkers (6 carotenoids, 4 tocopherols, ascorbic acid, total antioxidant capacity, glutathione redox potential, total glutathione and total cysteine) and four oxidative stress biomarkers (total hydroperoxides, γ-glutamyl transpeptidase, 8-isoprostagladin F2α and ratio of oxidized/total ascorbic acid) were measured in plasma samples. Analysis of Covariance was used to compare biomarkers between patients and healthy controls. Kaplan-Meier plots and Cox' proportional hazards models were used to study survival among patients. Results Dietary antioxidants (carotenoids, tocopherols and ascorbic acid), ferric reducing antioxidant power (FRAP) and modified FRAP were lower in HNSCC patients compared to controls and dietary antioxidants decreased during radiotherapy. Total hydroperoxides (d-ROMs), a marker for oxidative stress, were higher in HNSCC patients compared to controls and increased during radiotherapy. Among the biomarkers analyzed, high levels of plasma carotenoids before radiotherapy are associated with a prolonged progression-free survival (hazard rate ratio: 0.42, 95% CI: 0.20-0.91, p = 0.03). Additionally, high relative increase in plasma levels of d-ROMs (hazard rate ratio: 0.31, 95% CI: 0.13-0.76, p = 0.01) and high relative decrease in FRAP (hazard rate ratio: 0.42, 95% CI: 0.17-0.998, p = 0.05) during radiotherapy are also positively associated with survival. Conclusions Biomarkers of antioxidants and oxidative stress are unfavourable in HNSCC

  10. Iron-Superoxide Dismutase Expression in Transgenic Alfalfa Increases Winter Survival without a Detectable Increase in Photosynthetic Oxidative Stress Tolerance1

    PubMed Central

    McKersie, Bryan D.; Murnaghan, Julia; Jones, Kim S.; Bowley, Stephen R.

    2000-01-01

    To determine whether overexpression of Fe-superoxide (SOD) dismutase would increase superoxide-scavenging capacity and thereby improve the winter survival of transgenic alfalfa (Medicago sativa L.) plants, two genotypes were transformed with the vector pEXSOD10, which contains a cDNA for Arabidopsis Fe-SOD with a chloroplast transit peptide and cauliflower mosaic virus 35S promoter. A novel Fe-SOD was detected by native PAGE in both greenhouse- and field-grown transgenic plants, but activity varied among independent transgenic plants. The increased Fe-SOD activity was associated with increased winter survival over 2 years in field trials, but not with oxidative stress tolerance as measured by resistance of leaves to methyl viologen, a superoxide generator. Total shoot dry matter production over 2 harvest years was not associated with Fe-SOD activity. There was no detectable difference in the pattern of primary freezing injury, as shown by vital staining, nor was there additional accumulation of carbohydrates in field-acclimated roots of the transgenic alfalfa plants. We did not detect any difference in growth of one transgenic plant with high Fe-SOD activity compared with a non-transgenic control. Therefore, the improvement in winter survival did not appear to be a consequence of improved oxidative stress tolerance associated with photosynthesis, nor was it a consequence of a change in primary freezing injury. We suggest that Fe-SOD overexpression reduced secondary injury symptoms and thereby enhanced recovery from stresses experienced during winter. PMID:10759538

  11. Proline Mechanisms of Stress Survival

    PubMed Central

    Liang, Xinwen; Zhang, Lu; Natarajan, Sathish Kumar

    2013-01-01

    Abstract Significance: The imino acid proline is utilized by different organisms to offset cellular imbalances caused by environmental stress. The wide use in nature of proline as a stress adaptor molecule indicates that proline has a fundamental biological role in stress response. Understanding the mechanisms by which proline enhances abiotic/biotic stress response will facilitate agricultural crop research and improve human health. Recent Advances: It is now recognized that proline metabolism propels cellular signaling processes that promote cellular apoptosis or survival. Studies have shown that proline metabolism influences signaling pathways by increasing reactive oxygen species (ROS) formation in the mitochondria via the electron transport chain. Enhanced ROS production due to proline metabolism has been implicated in the hypersensitive response in plants, lifespan extension in worms, and apoptosis, tumor suppression, and cell survival in animals. Critical Issues: The ability of proline to influence disparate cellular outcomes may be governed by ROS levels generated in the mitochondria. Defining the threshold at which proline metabolic enzyme expression switches from inducing survival pathways to cellular apoptosis would provide molecular insights into cellular redox regulation by proline. Are ROS the only mediators of proline metabolic signaling or are other factors involved? Future Directions: New evidence suggests that proline biosynthesis enzymes interact with redox proteins such as thioredoxin. An important future pursuit will be to identify other interacting partners of proline metabolic enzymes to uncover novel regulatory and signaling networks of cellular stress response. Antioxid. Redox Signal. 19, 998–1011. PMID:23581681

  12. UDP-glucose pyrophosphorylase Ugp1 is involved in oxidative stress response and long-term survival during stationary phase in Saccharomyces cerevisiae.

    PubMed

    Yi, Dae-Gwan; Huh, Won-Ki

    2015-11-27

    Ugp1, UDP-glucose pyrophosphorylase, plays an important role in carbohydrate metabolism because it provides UDP-glucose that is a pivotal metabolite in several metabolic pathways in Saccharomyces cerevisiae. In this study, we show that a considerable reduction of glycogen and trehalose content in ugp1 knockdown cells is rescued by complementing the expression of Ugp1, indicating that Ugp1 is required for the production of storage carbohydrates. Because of the specific function of trehalose as a stress protectant, Ugp1 expression contributed to oxidative stress response and long-term cell survival during stationary phase. Furthermore, the modulation of Ugp1 level readjusted glycogen and trehalose accumulation in the protein kinase A (PKA)-related gene mutants. The PKA-dependent phenotypes of oxidative stress resistance and long-term cell survival were also alleviated via adjustment of Ugp1 level. Collectively, our data suggest that the regulation of UPG1 influences several PKA-dependent processes by adjusting the levels of various carbohydrates. PMID:26498530

  13. Telomere length is a biomarker of cumulative oxidative stress, biologic age, and an independent predictor of survival and therapeutic treatment requirement associated with smoking behavior.

    PubMed

    Babizhayev, Mark A; Savel'yeva, Ekaterina L; Moskvina, Svetlana N; Yegorov, Yegor E

    2011-11-01

    Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical

  14. Improved survival of very high light and oxidative stress is conferred by spontaneous gain-of-function mutations in Chlamydomonas.

    PubMed

    Förster, Britta; Osmond, C Barry; Pogson, Barry J

    2005-08-15

    Investigations into high light and oxidative stress in photosynthetic organisms have focussed primarily on genetic impairment of different photoprotective functions. There are few reports of "gain-of-function" mutations that provide enhanced resistance to high light and/or oxidative stress without reduced productivity. We have isolated at least four such very high light resistant (VHL(R)) mutations in the green alga, Chlamydomonas reinhardtii, that permit near maximal growth rates at light intensities lethal to wild type. This resistance is not due to an alteration in electron transport rate or quantity and functionality of the two photosystems that could have enhanced photochemical quenching. Nor is it due to reduced excitation pressure by downregulation of the light harvesting antennae or increased nonphotochemical quenching. In fact, photosynthetic activity is unaffected in more than 30 VHL(R) isolates. Instead, the basis of the VHL(R) phenotype is a combination of traits, which appears to be dominated by enhanced capacity to tolerate reactive oxygen species generated by excess light, methylviologen, rose bengal or hydrogen peroxide. This is further evidenced in lower levels of ROS after exposure to very high light in the VHL(R)-S9 mutant. Additionally, the VHL(R) phenotype is associated with increased zeaxanthin accumulation, maintenance of fast synthesis and degradation rates of the D1 protein, and sustained balanced electron flow into and out of PSI under very high light. We conclude that the VHL(R) mutations arose from a selection pressure that favors changes to the regulatory system(s) that coordinates several photoprotective processes amongst which repair of PSII and enhanced detoxification of reactive oxygen species play seminal roles. PMID:16002040

  15. AMPK-mediated increase of glycolysis as an adaptive response to oxidative stress in human cells: implication of the cell survival in mitochondrial diseases.

    PubMed

    Wu, Shi-Bei; Wei, Yau-Huei

    2012-02-01

    We report that the energy metabolism shifts to anaerobic glycolysis as an adaptive response to oxidative stress in the primary cultures of skin fibroblasts from patients with MERRF syndrome. In order to unravel the molecular mechanism involved in the alteration of energy metabolism under oxidative stress, we treated normal human skin fibroblasts (CCD-966SK cells) with sub-lethal doses of H(2)O(2). The results showed that several glycolytic enzymes including hexokinase type II (HK II), lactate dehydrogenase (LDH) and glucose transporter 1 (GLUT1) were up-regulated in H(2)O(2)-treated normal skin fibroblasts. In addition, the glycolytic flux of skin fibroblasts was increased by H(2)O(2) in a dose-dependent manner through the activation of AMP-activated protein kinase (AMPK) and phosphorylation of its downstream target, phosphofructokinase 2 (PFK2). Moreover, we found that the AMPK-mediated increase of glycolytic flux by H(2)O(2) was accompanied by an increase of intracellular NADPH content. By treatment of the cells with glycolysis inhibitors, an AMPK inhibitor or genetic knockdown of AMPK, respectively, the H(2)O(2)-induced increase of NADPH was abrogated leading to the overproduction of intracellular ROS and cell death. Significantly, we showed that phosphorylation levels of AMPK and glycolysis were up-regulated to confer an advantage of survival for MERRF skin fibroblasts. Taken together, our findings suggest that the increased production of NADPH by AMPK-mediated increase of the glycolytic flux contributes to the adaptation of MERRF skin fibroblasts and H(2)O(2)-treated normal skin fibroblasts to oxidative stress. PMID:22001850

  16. In serum veritas—in serum sanitas? Cell non-autonomous aging compromises differentiation and survival of mesenchymal stromal cells via the oxidative stress pathway

    PubMed Central

    Geißler, S; Textor, M; Schmidt-Bleek, K; Klein, O; Thiele, M; Ellinghaus, A; Jacobi, D; Ode, A; Perka, C; Dienelt, A; Klose, J; Kasper, G; Duda, G N; Strube, P

    2013-01-01

    Even tissues capable of complete regeneration, such as bone, show an age-related reduction in their healing capacity. Here, we hypothesized that this decline is primarily due to cell non-autonomous (extrinsic) aging mediated by the systemic environment. We demonstrate that culture of mesenchymal stromal cells (MSCs) in serum from aged Sprague–Dawley rats negatively affects their survival and differentiation ability. Proteome analysis and further cellular investigations strongly suggest that serum from aged animals not only changes expression of proteins related to mitochondria, unfolded protein binding or involved in stress responses, it also significantly enhances intracellular reactive oxygen species production and leads to the accumulation of oxidatively damaged proteins. Conversely, reduction of oxidative stress levels in vitro markedly improved MSC function. These results were validated in an in vivo model of compromised bone healing, which demonstrated significant increase regeneration in aged animals following oral antioxidant administration. These observations indicate the high impact of extrinsic aging on cellular functions and the process of endogenous (bone) regeneration. Thus, addressing the cell environment by, for example, systemic antioxidant treatment is a promising approach to enhance tissue regeneration and to regain cellular function especially in elderly patients. PMID:24357801

  17. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats.

    PubMed

    Marín-Prida, Javier; Pavón-Fuentes, Nancy; Llópiz-Arzuaga, Alexey; Fernández-Massó, Julio R; Delgado-Roche, Liván; Mendoza-Marí, Yssel; Santana, Seydi Pedroso; Cruz-Ramírez, Alieski; Valenzuela-Silva, Carmen; Nazábal-Gálvez, Marcelo; Cintado-Benítez, Alberto; Pardo-Andreu, Gilberto L; Polentarutti, Nadia; Riva, Federica; Pentón-Arias, Eduardo; Pentón-Rol, Giselle

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. PMID:23732081

  18. A Mycobacterial Phosphoribosyltransferase Promotes Bacillary Survival by Inhibiting Oxidative Stress and Autophagy Pathways in Macrophages and Zebrafish*

    PubMed Central

    Mohanty, Soumitra; Jagannathan, Lakshmanan; Ganguli, Geetanjali; Padhi, Avinash; Roy, Debasish; Alaridah, Nader; Saha, Pratip; Nongthomba, Upendra; Godaly, Gabriela; Gopal, Ramesh Kumar; Banerjee, Sulagna; Sonawane, Avinash

    2015-01-01

    Mycobacterium tuberculosis employs various strategies to modulate host immune responses to facilitate its persistence in macrophages. The M. tuberculosis cell wall contains numerous glycoproteins with unknown roles in pathogenesis. Here, by using Concanavalin A and LC-MS analysis, we identified a novel mannosylated glycoprotein phosphoribosyltransferase, encoded by Rv3242c from M. tuberculosis cell walls. Homology modeling, bioinformatic analyses, and an assay of phosphoribosyltransferase activity in Mycobacterium smegmatis expressing recombinant Rv3242c (MsmRv3242c) confirmed the mass spectrometry data. Using Mycobacterium marinum-zebrafish and the surrogate MsmRv3242c infection models, we proved that phosphoribosyltransferase is involved in mycobacterial virulence. Histological and infection assays showed that the M. marinum mimG mutant, an Rv3242c orthologue in a pathogenic M. marinum strain, was strongly attenuated in adult zebrafish and also survived less in macrophages. In contrast, infection with wild type and the complemented ΔmimG:Rv3242c M. marinum strains showed prominent pathological features, such as severe emaciation, skin lesions, hemorrhaging, and more zebrafish death. Similarly, recombinant MsmRv3242c bacteria showed increased invasion in non-phagocytic epithelial cells and longer intracellular survival in macrophages as compared with wild type and vector control M. smegmatis strains. Further mechanistic studies revealed that the Rv3242c- and mimG-mediated enhancement of intramacrophagic survival was due to inhibition of autophagy, reactive oxygen species, and reduced activities of superoxide dismutase and catalase enzymes. Infection with MsmRv3242c also activated the MAPK pathway, NF-κB, and inflammatory cytokines. In summary, we show that a novel mycobacterial mannosylated phosphoribosyltransferase acts as a virulence and immunomodulatory factor, suggesting that it may constitute a novel target for antimycobacterial drugs. PMID:25825498

  19. A mycobacterial phosphoribosyltransferase promotes bacillary survival by inhibiting oxidative stress and autophagy pathways in macrophages and zebrafish.

    PubMed

    Mohanty, Soumitra; Jagannathan, Lakshmanan; Ganguli, Geetanjali; Padhi, Avinash; Roy, Debasish; Alaridah, Nader; Saha, Pratip; Nongthomba, Upendra; Godaly, Gabriela; Gopal, Ramesh Kumar; Banerjee, Sulagna; Sonawane, Avinash

    2015-05-22

    Mycobacterium tuberculosis employs various strategies to modulate host immune responses to facilitate its persistence in macrophages. The M. tuberculosis cell wall contains numerous glycoproteins with unknown roles in pathogenesis. Here, by using Concanavalin A and LC-MS analysis, we identified a novel mannosylated glycoprotein phosphoribosyltransferase, encoded by Rv3242c from M. tuberculosis cell walls. Homology modeling, bioinformatic analyses, and an assay of phosphoribosyltransferase activity in Mycobacterium smegmatis expressing recombinant Rv3242c (MsmRv3242c) confirmed the mass spectrometry data. Using Mycobacterium marinum-zebrafish and the surrogate MsmRv3242c infection models, we proved that phosphoribosyltransferase is involved in mycobacterial virulence. Histological and infection assays showed that the M. marinum mimG mutant, an Rv3242c orthologue in a pathogenic M. marinum strain, was strongly attenuated in adult zebrafish and also survived less in macrophages. In contrast, infection with wild type and the complemented ΔmimG:Rv3242c M. marinum strains showed prominent pathological features, such as severe emaciation, skin lesions, hemorrhaging, and more zebrafish death. Similarly, recombinant MsmRv3242c bacteria showed increased invasion in non-phagocytic epithelial cells and longer intracellular survival in macrophages as compared with wild type and vector control M. smegmatis strains. Further mechanistic studies revealed that the Rv3242c- and mimG-mediated enhancement of intramacrophagic survival was due to inhibition of autophagy, reactive oxygen species, and reduced activities of superoxide dismutase and catalase enzymes. Infection with MsmRv3242c also activated the MAPK pathway, NF-κB, and inflammatory cytokines. In summary, we show that a novel mycobacterial mannosylated phosphoribosyltransferase acts as a virulence and immunomodulatory factor, suggesting that it may constitute a novel target for antimycobacterial drugs. PMID:25825498

  20. Phycocyanobilin promotes PC12 cell survival and modulates immune and inflammatory genes and oxidative stress markers in acute cerebral hypoperfusion in rats

    SciTech Connect

    Marín-Prida, Javier; Riva, Federica; Pentón-Arias, Eduardo

    2013-10-01

    Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24 h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H{sub 2}O{sub 2} and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed. - Highlights: • Phycocyanobilin (PCB) prevents H{sub 2}O{sub 2} and glutamate induced PC12 cell viability loss. • Anterior cortex and striatum are highly vulnerable to cerebral hypoperfusion (CH). • PCB modulates 190 genes associated to inflammation in acute CH. • PCB regulates 19 genes mostly related to a detrimental pro-inflammatory environment. • PCB restores redox and immune balances showing promise as potential stroke therapy.

  1. Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress.

    PubMed Central

    Dougherty, Christopher J; Kubasiak, Lori A; Prentice, Howard; Andreka, Peter; Bishopric, Nanette H; Webster, Keith A

    2002-01-01

    Reperfusion injury occurs when ischaemic tissue is reperfused. It involves the generation and release of reactive oxygen that activates numerous signalling pathways and initiates cell death. Exposure of isolated cardiac myocytes to chronic hypoxia followed by reoxygenation results in the early activation of c-Jun N-terminal kinase (JNK) and death by apoptosis of approx. 30% of the myocytes. Although JNK activation has been described in a number of models of ischaemia/reperfusion, the contribution of JNK activation to cell fate has not been established. Here we report that the activation of JNK by reoxygenation correlates with myocyte survival. Transfection of myocytes with JNK pathway interfering plasmid vectors or infection with adenoviral vectors support the hypothesis that JNK is protective. Transfection or infection with JNK inhibitory mutants increased the rates of apoptosis by almost 2-fold compared with control cultures grown aerobically or subjected to hypoxia and reoxygenation. Caspase 9 activity, measured by LEHD cleavage, increased >3-fold during reoxygenation and this activity was enhanced significantly at all times in cultures infected with dominant negative JNK adenovirus. Hypoxia-reoxygenation mediated a biphasic (2.6- and 2.9-fold) activation of p38 mitogen-activated protein kinase, as well as a small increase of tumour necrosis factor alpha (TNFalpha) secretion, but treatments with the p38 MAPK-specific inhibitor SB203580 or saturating levels of a TNFalpha-1 blocking antibody provided only partial protection against apoptosis. The results suggest that JNK activation is protective and that the pathway is largely independent of p38 MAPK or secreted TNFalpha. PMID:11879182

  2. Staphylococcal response to oxidative stress

    PubMed Central

    Gaupp, Rosmarie; Ledala, Nagender; Somerville, Greg A.

    2012-01-01

    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. PMID:22919625

  3. Oxidative stress in autism.

    PubMed

    Chauhan, Abha; Chauhan, Ved

    2006-08-01

    Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed. PMID:16766163

  4. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress.

    PubMed

    Wang, Yi-Ping; Zhou, Li-Sha; Zhao, Yu-Zheng; Wang, Shi-Wen; Chen, Lei-Lei; Liu, Li-Xia; Ling, Zhi-Qiang; Hu, Fu-Jun; Sun, Yi-Ping; Zhang, Jing-Ye; Yang, Chen; Yang, Yi; Xiong, Yue; Guan, Kun-Liang; Ye, Dan

    2014-06-17

    Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Knockdown of G6PD sensitizes cells to oxidative stress, and re-expression of wild-type G6PD, but not the K403 acetylation mimetic mutant, rescues cells from oxidative injury. Moreover, we show that cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates PPP to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. We also identified KAT9/ELP3 as a potential acetyltransferase of G6PD. Our study uncovers a previously unknown mechanism by which acetylation negatively regulates G6PD activity to maintain cellular NADPH homeostasis during oxidative stress. PMID:24769394

  5. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress#

    PubMed Central

    Wang, Yi-Ping; Zhou, Li-Sha; Zhao, Yu-Zheng; Wang, Shi-Wen; Chen, Lei-Lei; Liu, Li-Xia; Ling, Zhi-Qiang; Hu, Fu-Jun; Sun, Yi-Ping; Zhang, Jing-Ye; Yang, Chen; Yang, Yi; Xiong, Yue; Guan, Kun-Liang; Ye, Dan

    2014-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway (PPP) and plays an essential role in the oxidative stress response by producing NADPH, the main intracellular reductant. G6PD deficiency is the most common human enzyme defect, affecting more than 400 million people worldwide. Here, we show that G6PD is negatively regulated by acetylation on lysine 403 (K403), an evolutionarily conserved residue. The K403 acetylated G6PD is incapable of forming active dimers and displays a complete loss of activity. Knockdown of G6PD sensitizes cells to oxidative stress, and re-expression of wild-type G6PD, but not the K403 acetylation mimetic mutant, rescues cells from oxidative injury. Moreover, we show that cells sense extracellular oxidative stimuli to decrease G6PD acetylation in a SIRT2-dependent manner. The SIRT2-mediated deacetylation and activation of G6PD stimulates PPP to supply cytosolic NADPH to counteract oxidative damage and protect mouse erythrocytes. We also identified KAT9/ELP3 as a potential acetyltransferase of G6PD. Our study uncovers a previously unknown mechanism by which acetylation negatively regulates G6PD activity to maintain cellular NADPH homeostasis during oxidative stress. PMID:24769394

  6. Diversity in Robustness of Lactococcus lactis Strains during Heat Stress, Oxidative Stress, and Spray Drying Stress

    PubMed Central

    Dijkstra, Annereinou R.; Setyawati, Meily C.; Bayjanov, Jumamurat R.; Alkema, Wynand; van Hijum, Sacha A. F. T.; Hugenholtz, Jeroen

    2014-01-01

    In this study we tested 39 Lactococcus lactis strains isolated from diverse habitats for their robustness under heat and oxidative stress, demonstrating high diversity in survival (up to 4 log units). Strains with an L. lactis subsp. lactis phenotype generally displayed more-robust phenotypes than strains with an L. lactis subsp. cremoris phenotype, whereas the habitat from which the strains had been isolated did not appear to influence stress survival. Comparison of the stress survival phenotypes with already available comparative genomic data sets revealed that the absence or presence of specific genes, including genes encoding a GntR family transcriptional regulator, a manganese ABC transporter permease, a cellobiose phosphotransferase system (PTS) component, the FtsY protein, and hypothetical proteins, was associated with heat or oxidative stress survival. Finally, 14 selected strains also displayed diversity in survival after spray drying, ranging from 20% survival for the most robust strains, which appears acceptable for industrial application, to 0.1% survival for the least-tolerant strains. The high and low levels of survival upon spray drying correlated clearly with the combined robustness under heat and oxidative stress. These results demonstrate the relevance of screening culture collections for robustness under heat and oxidative stress on top of the typical screening for acidifying and flavor-forming properties. PMID:24212574

  7. Oxidative Stress and Psychological Disorders

    PubMed Central

    Salim, Samina

    2014-01-01

    Oxidative stress is an imbalance between cellular production of reactive oxygen species and the counteracting antioxidant mechanisms. The brain with its high oxygen consumption and a lipid-rich environment is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have established a link between oxidative stress and psychiatric disorders, the causal relationship between oxidative stress and psychiatric diseases is not fully determined. Another critical aspect that needs much attention and effort is our understanding of the association between cellular oxidative stress and emotional stress. This review examines some of the recent discoveries that link oxidative status with anxiety, depression, schizophrenia and bipolar disorder. A discussion of published results and questions that currently exist in the field regarding a causal relationship between oxidative and emotional stress is also provided. PMID:24669208

  8. Cutaneous oxidative stress.

    PubMed

    Polefka, Thomas G; Meyer, Thomas A; Agin, Patricia P; Bianchini, Robert J

    2012-03-01

    The earliest known microfossil records suggest that microorganisms existed on the earth approximately 3.8 billion years ago. Not only did sunlight drive this evolutionary process, but it also allowed photosynthetic organisms to elaborate oxygen and fundamentally change the earth's atmosphere and subsequent evolution. Paradoxically, however, an atmosphere of 20% oxygen offers aerobic organisms both benefits and some key challenges, particularly, to the external integument. This mini-review summarizes almost 40 years of research and provides a "60 000-foot" perspective on cutaneous oxidative stress. Topics reviewed include the following: What are free radicals and reactive oxygen species? Where do they come from? What is their chemistry? What are their roles and/or impact on the skin? What antioxidant defenses are available to mitigate oxidative stress. PMID:22360336

  9. Oxidative Stress in Malaria

    PubMed Central

    Percário, Sandro; Moreira, Danilo R.; Gomes, Bruno A. Q.; Ferreira, Michelli E. S.; Gonçalves, Ana Carolina M.; Laurindo, Paula S. O. C.; Vilhena, Thyago C.; Dolabela, Maria F.; Green, Michael D.

    2012-01-01

    Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy. PMID:23208374

  10. Oxidative Stress in Myopia

    PubMed Central

    Francisco, Bosch-Morell; Salvador, Mérida; Amparo, Navea

    2015-01-01

    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. PMID:25922643

  11. Oxidative stress by inorganic nanoparticles.

    PubMed

    Tee, Jie Kai; Ong, Choon Nam; Bay, Boon Huat; Ho, Han Kiat; Leong, David Tai

    2016-05-01

    Metallic and metallic oxide nanoparticles (NPs) have been increasingly used for various bio-applications owing to their unique physiochemical properties in terms of conductivity, optical sensitivity, and reactivity. With the extensive usage of NPs, increased human exposure may cause oxidative stress and lead to undesirable health consequences. To date, various endogenous and exogenous sources of oxidants contributing to oxidative stress have been widely reported. Oxidative stress is generally defined as an imbalance between the production of oxidants and the activity of antioxidants, but it is often misrepresented as a single type of cellular stress. At the biological level, NPs can initiate oxidative stress directly or indirectly through various mechanisms, leading to profound effects ranging from the molecular to the disease level. Such effects of oxidative stress have been implicated owing to their small size and high biopersistence. On the other hand, cellular antioxidants help to counteract oxidative stress and protect the cells from further damage. While oxidative stress is commonly known to exert negative biological effects, measured and intentional use of NPs to induce oxidative stress may provide desirable effects to either stimulate cell growth or promote cell death. Hence, NP-induced oxidative stress can be viewed from a wide paradigm. Because oxidative stress is comprised of a wide array of factors, it is also important to use appropriate assays and methods to detect different pro-oxidant and antioxidant species at molecular and disease levels. WIREs Nanomed Nanobiotechnol 2016, 8:414-438. doi: 10.1002/wnan.1374 For further resources related to this article, please visit the WIREs website. PMID:26359790

  12. TolC is important for bacterial survival and oxidative stress response in Salmonella enterica serovar Choleraesuis in an acidic environment.

    PubMed

    Lee, Jen-Jie; Wu, Ying-Chen; Kuo, Chih-Jung; Hsuan, Shih-Ling; Chen, Ter-Hsin

    2016-09-25

    The outer membrane protein TolC, which is one of the key components of several multidrug efflux pumps, is thought to be involved in various independent systems in Enterobacteriaceae. Since the acidic environment of the stomach is an important protection barrier against foodborne pathogen infections in hosts, we evaluated whether TolC played a role in the acid tolerance of Salmonella enterica serovar Choleraesuis. Comparison of the acid tolerance of the tolC mutant and the parental wild-type strain showed that the absence of TolC limits the ability of Salmonella to sustain life under extreme acidic conditions. Additionally, the mutant exhibited morphological changes during growth in an acidic medium, leading to the conflicting results of cell viability measured by spectrophotometry and colony-forming unit counting. Reverse-transcriptional-PCR analysis indicated that acid-related molecules, apparatus, or enzymes and oxidation-induced factors were significantly affected by the acidic environment in the null-tolC mutant. The elongated cellular morphology was restored by adding antioxidants to the culture medium. Furthermore, we found that increased cellular antioxidative activity provides an overlapping protection against acid killing, demonstrating the complexity of the bacterial acid stress response. Our findings reinforce the multifunctional characteristics of TolC in acid tolerance or oxidative stress resistance and support the correlative protection mechanism between oxygen- and acid-mediated stress responses in Salmonella enterica serovar Choleraesuis. PMID:27599929

  13. Glutamate Increases In Vitro Survival and Proliferation and Attenuates Oxidative Stress-Induced Cell Death in Adult Spinal Cord-Derived Neural Stem/Progenitor Cells via Non-NMDA Ionotropic Glutamate Receptors.

    PubMed

    Hachem, Laureen D; Mothe, Andrea J; Tator, Charles H

    2016-08-15

    Traumatic spinal cord injury (SCI) leads to a cascade of secondary chemical insults, including oxidative stress and glutamate excitotoxicity, which damage host neurons and glia. Transplantation of exogenous neural stem/progenitor cells (NSPCs) has shown promise in enhancing regeneration after SCI, although survival of transplanted cells remains poor. Understanding the response of NSPCs to the chemical mediators of secondary injury is essential in finding therapies to enhance survival. We examined the in vitro effects of glutamate and glutamate receptor agonists on adult rat spinal cord-derived NSPCs. NSPCs isolated from the periventricular region of the adult rat spinal cord were exposed to various concentrations of glutamate for 96 h. We found that glutamate treatment (500 μM) for 96 h significantly increased live cell numbers, reduced cell death, and increased proliferation, but did not significantly alter cell phenotype. Concurrent glutamate treatment (500 μM) in the setting of H2O2 exposure (500 μM) for 10 h increased NSPC survival compared to H2O2 exposure alone. The effects of glutamate on NSPCs were blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist GYKI-52466, but not by the N-methyl-D-aspartic acid receptor antagonist MK-801 or DL-AP5, or the mGluR3 antagonist LY-341495. Furthermore, treatment of NSPCs with AMPA, kainic acid, or the kainate receptor-specific agonist (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid mimicked the responses seen with glutamate both alone and in the setting of oxidative stress. These findings offer important insights into potential mechanisms to enhance NSPC survival and implicate a potential role for glutamate in promoting NSPC survival and proliferation after traumatic SCI. PMID:27316370

  14. p-Hydroxyphenylpyruvate, an Intermediate of the Phe/Tyr Catabolism, Improves Mitochondrial Oxidative Metabolism under Stressing Conditions and Prolongs Survival in Rats Subjected to Profound Hemorrhagic Shock

    PubMed Central

    Gefter, Julia V.; Piccoli, Claudia; Cinnella, Gilda; Dambrosio, Michele; Fink, Mitchell P.; Capitanio, Nazzareno

    2014-01-01

    The aim of this study was to test the effect of a small volume administration of p-hydroxyphenylpyruvate (pHPP) in a rat model of profound hemorrhagic shock and to assess a possible metabolic mechanism of action of the compound. The results obtained show that hemorrhaged rats treated with 2–4% of the estimated blood volume of pHPP survived significantly longer (p<0.001) than rats treated with vehicle. In vitro analysis on cultured EA.hy 926 cells demonstrated that pHPP improved cell growth rate and promoted cell survival under stressing conditions. Moreover, pHPP stimulated mitochondria-related respiration under ATP-synthesizing conditions and exhibited antioxidant activity toward mitochondria-generated reactive oxygen species. The compound effects reported in the in vitro and in vivo analyses were obtained in the same millimolar concentration range. These data disclose pHPP as an efficient energetic substrates-supplier to the mitochondrial respiratory chain as well as an antioxidant supporting the view that the compound warrants further evaluation as a therapeutic agent. PMID:24599095

  15. EmrA1 Membrane Fusion Protein of Francisella tularensis LVS is required for Resistance to Oxidative Stress, Intramacrophage Survival and Virulence in Mice

    PubMed Central

    Ma, Zhuo; Banik, Sukalyani; Rane, Harshita; Mora, Vanessa T.; Rabadi, Seham M.; Doyle, Christopher R.; Thanassi, David G.; Bakshi, Chandra Shekhar; Malik, Meenakshi

    2014-01-01

    Francisella tularensis is a Category A Biodefense agent that causes a fatal human disease known as tularemia. The pathogenicity of F. tularensis depends on its ability to persist inside host immune cells primarily by resisting an attack from host-generated reactive oxygen and nitrogen species (ROS/RNS). Based on the ability of F. tularensis to resist high ROS/RNS levels, we have hypothesized that additional unknown factors act in conjunction with known antioxidant defenses to render ROS resistance. By screening a transposon insertion library of F. tularensis LVS in the presence of hydrogen peroxide, we have identified an oxidant sensitive mutant in putative EmrA1 (FTL_0687) secretion protein. The results demonstrate that the emrA1 mutant is highly sensitive to oxidants and several antimicrobial agents, and exhibits diminished intramacrophage growth that can be restored to wild type F. tularensis LVS levels either by transcomplementation, inhibition of ROS generation, or infection in NADPH oxidase deficient (gp91Phox−/−) macrophages. The emrA1 mutant is attenuated for virulence, which is restored by infection in gp91Phox−/− mice. Further, EmrA1 contributes to oxidative stress resistance by affecting secretion of Francisella antioxidant enzymes SodB and KatG. This study exposes unique links between transporter activity and the antioxidant defense mechanisms of F. tularensis. PMID:24397487

  16. Multifactorial Gene Therapy Enhancing the Glutamate Uptake System and Reducing Oxidative Stress Delays Symptom Onset and Prolongs Survival in the SOD1-G93A ALS Mouse Model.

    PubMed

    Benkler, Chen; Barhum, Yael; Ben-Zur, Tali; Offen, Daniel

    2016-01-01

    The 150-year-long search for treatments of amyotrophic lateral sclerosis (ALS) is still fueled by frustration over the shortcomings of available therapeutics. Contributing to the therapeutic limitations might be the targeting of a single aspect of this multifactorial-multisystemic disease. In an attempt to overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding: EAAT2, GDH2, and NRF2, that act synergistically to address the band and width of the effected excito-oxidative axis, reducing extracellular-glutamate and glutamate availability while improving the metabolic state and the anti-oxidant response. This strategy yielded particularly impressive results, as all three genes together but not separately prolonged survival in ALS mice by an average of 19-22 days. This was accompanied by improvement in every parameter evaluated, including body-weight loss, reflex score, neurologic score, and motor performance. We hope to provide a novel strategy to slow down disease progression and alleviate symptoms of patients suffering from ALS. PMID:26691332

  17. BRCA1 and Oxidative Stress

    PubMed Central

    Yi, Yong Weon; Kang, Hyo Jin; Bae, Insoo

    2014-01-01

    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. PMID:24704793

  18. Inhibition of ErbB2 by herceptin reduces viability and survival, induces apoptosis and oxidative stress in Calu-3 cell line.

    PubMed

    Dogan, Irem; Cumaoglu, Ahmet; Aricioglu, Aysel; Ekmekci, Abdullah

    2011-01-01

    Human epidermal growth factor receptor 2 (ErbB2) amplification and overexpression has been seen in many cancer types including non-small cell lung cancer (NSCLC). Thus, ErbB2 is an important target for cancer therapies. Increased ErbB2 expression has been associated with drug resistance in cancer cells. Herceptin is a humanized monoclonal antibody that targets the extracellular domain of ErbB2. In this study, we aimed to block ErbB2 signaling with Herceptin and assess cytotoxicity and effects on apoptosis, oxidative stress, nuclear factor kappa-B (NF-kB), and Survivin expression in Calu-3 cell line. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were used to assess cell viability as a marker of proliferation. Acridine orange/ethidium bromide (AO/EB) staining and caspase 3/7 activity were measured as the markers of apoptosis. The relative expressions of NF-kB-p50 and Survivin mRNAs were evaluated. Activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), and the levels of glutathione (GSH) and reactive oxygen species (ROS) were determined in a time- and dose-dependent manner. Our results show that Herceptin treatment inhibits cell proliferation and activates apoptosis but without effects on Survivin and NF-kB expression in Calu-3 cell line. Intracellular glutathione levels and SOD and CAT activities were decreased in a time- and dose-dependent manner associated with oxidative stress. Also, ROS were increased at 24 h. These results provide evidence that Herceptin can be used as a cytotoxic and apoptotic agent in NSCLC. PMID:20936496

  19. Oxidative stress in Alzheimer disease

    PubMed Central

    Durany, Nuria

    2009-01-01

    Alzheimer disease (AD) is a progressive dementia affecting a large proportion of the aging population. The histopathological changes in AD include neuronal cell death, formation of amyloid plaques and neurofibrillary tangles. There is also evidence that brain tissue in patients with AD is exposed to oxidative stress (e.g., protein oxidation, lipid oxidation, DNA oxidation and glycoxidation) during the course of the disease. Advanced glycation endproducts (AGEs) are present in amyloid plaques in AD, and its extracellular accumulation may be caused by an accelerated oxidation of glycated proteins. AGEs participate in neuronal death causing direct (chemical) and indirect (cellular) free radical production and consequently increase oxidative stress. The development of drugs for the treatment of AD that breaks the vicious cycles of oxidative stress and neurodegeneration offer new opportunities. These approaches include AGE-inhibitors, antioxidants and anti-inflammatory substances, which prevent free radical production. PMID:19372765

  20. DNA fragmentation and oxidative stress compromise sperm motility and survival in late pregnancy exposure to omega-9 fatty acid in rats

    PubMed Central

    Oluwakemi, Oyelowo; Olufeyisipe, Adegoke

    2016-01-01

    Objective(s): The aim of this study was to evaluate the oxidative status and DNA integrity in testes of wistar rat offspring exposed to omega-9 monounsaturated (MUFA) at different times of late organogenesis. Materials and Methods: Sixty female rats were divided into six groups of 10 animals. The first group served as control and received the drug vehicle, olive oil (1 ml/kg/day). The second, third, fourth, fifth and sixth group received 1000 mg/kg of oleic acid on gestation day 15 (D15), 16 (D16), 17 (D17), 18 (D18) and 19 (D19), respectively. Male pups were allowed to attain puberty and thereafter, blood was taken for hormonal analyses. Sperm count and motility were assessed. Testes homogenate was used for the determination of biochemical variables. Testes DNA was also determined. Results: The results showed that sperm count and motility were significantly decreased in the treated groups as compared to the control. There was a marked increase in the malondialdehyde level in rat testes from all of the treated groups as compared to the control (P<0.05). DNA from the testes of rats of D19 had the highest level of fragmentation as compared to the control. Conclusion: Omega-9 MUFA exposure in utero imposes negative effects on sperm variables and increases the level of sperm DNA fragmentation and oxidative stress. PMID:27403258

  1. Oxidant stress in the vasculature.

    PubMed

    Maytin, M; Leopold, J; Loscalzo, J

    1999-09-01

    Vascular disease and vasomotor responses are largely influenced by oxidant stress. Superoxide is generated via the cellular oxidase systems, xanthine oxidase, and NADH/NADPH oxidases. Once formed, superoxides participate in a number of reactions, yielding various free radicals such as hydrogen peroxide, peroxynitrite, oxidized low-density lipoprotein, or hypochlorous acid. Numerous cellular antioxidant systems exist to defend against oxidant stress; glutathione and the enzymes superoxide dismutase and glutathione peroxidase are critical for maintaining the redox balance of the cell. However, the redox state is disrupted by certain vascular diseases. It appears that oxidant stress both promotes and is induced by diseases such as hypertension, atherosclerosis, and restenosis as well as by certain risk factors for coronary artery disease including hyperlipidemia, diabetes, and cigarette smoking. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, namely adverse vessel reactivity, vascular smooth muscle cell proliferation, macrophage adhesion, platelet activation, and lipid peroxidation. PMID:11122705

  2. Oxidative Stress Resistance in Deinococcus radiodurans†

    PubMed Central

    Slade, Dea; Radman, Miroslav

    2011-01-01

    Summary: Deinococcus radiodurans is a robust bacterium best known for its capacity to repair massive DNA damage efficiently and accurately. It is extremely resistant to many DNA-damaging agents, including ionizing radiation and UV radiation (100 to 295 nm), desiccation, and mitomycin C, which induce oxidative damage not only to DNA but also to all cellular macromolecules via the production of reactive oxygen species. The extreme resilience of D. radiodurans to oxidative stress is imparted synergistically by an efficient protection of proteins against oxidative stress and an efficient DNA repair mechanism, enhanced by functional redundancies in both systems. D. radiodurans assets for the prevention of and recovery from oxidative stress are extensively reviewed here. Radiation- and desiccation-resistant bacteria such as D. radiodurans have substantially lower protein oxidation levels than do sensitive bacteria but have similar yields of DNA double-strand breaks. These findings challenge the concept of DNA as the primary target of radiation toxicity while advancing protein damage, and the protection of proteins against oxidative damage, as a new paradigm of radiation toxicity and survival. The protection of DNA repair and other proteins against oxidative damage is imparted by enzymatic and nonenzymatic antioxidant defense systems dominated by divalent manganese complexes. Given that oxidative stress caused by the accumulation of reactive oxygen species is associated with aging and cancer, a comprehensive outlook on D. radiodurans strategies of combating oxidative stress may open new avenues for antiaging and anticancer treatments. The study of the antioxidation protection in D. radiodurans is therefore of considerable potential interest for medicine and public health. PMID:21372322

  3. Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful?

    PubMed Central

    Takaki, Akinobu; Yamamoto, Kazuhide

    2015-01-01

    Oxidative stress is becoming recognized as a key factor in the progression of chronic liver disease (CLD) and hepatocarcinogenesis. The metabolically important liver is a major reservoir of mitochondria that serve as sources of reactive oxygen species, which are apparently responsible for the initiation of necroinflammation. As a result, CLD could be a major inducer of oxidative stress. Chronic hepatitis C is a powerful generator of oxidative stress, causing a high rate of hepatocarcinogenesis among patients with cirrhosis. Non-alcoholic steatohepatitis is also associated with oxidative stress although its hepatocarcinogenic potential is lower than that of chronic hepatitis C. Analyses of serum markers and histological findings have shown that hepatocellular carcinoma correlates with oxidative stress and experimental data indicate that oxidative stress increases the likelihood of developing hepatocarcinogenesis. However, the results of antioxidant therapy have not been favorable. Physiological oxidative stress is a necessary biological response, and thus adequate control of oxidative stress and a balance between oxidative and anti-oxidative responses is important. Several agents including metformin and L-carnitine can reportedly control mechanistic oxidative stress. This study reviews the importance of oxidative stress in hepatocarcinogenesis and of control strategies for the optimal survival of patients with CLD and hepatocellular carcinoma. PMID:25954479

  4. Parkin-Dependent Degradation of the F-Box Protein Fbw7β Promotes Neuronal Survival in Response to Oxidative Stress by Stabilizing Mcl-1

    PubMed Central

    Ekholm-Reed, Susanna; Goldberg, Matthew S.; Schlossmacher, Michael G.

    2013-01-01

    Parkinson's disease (PD) is characterized by progressive loss of midbrain dopaminergic neurons resulting in motor dysfunction. While most PD is sporadic in nature, a significant subset can be linked to either dominant or recessive germ line mutations. PARK2, encoding the ubiquitin ligase parkin, is the most frequently mutated gene in hereditary Parkinson's disease. Here, we present evidence for a neuronal ubiquitin ligase cascade involving parkin and the multisubunit ubiquitin ligase SCFFbw7β. Specifically, parkin targets the SCF substrate adapter Fbw7β for proteasomal degradation. Furthermore, we show that the physiological role of parkin-mediated regulation of Fbw7β levels is the stabilization of the mitochondrial prosurvival factor Mcl-1, an SCFFbw7β target in neurons. We show that neurons depleted of parkin become acutely sensitive to oxidative stress due to an inability to maintain adequate levels of Mcl-1. Therefore, loss of parkin function through biallelic mutation of PARK2 may lead to death of dopaminergic neurons through unregulated SCFFbw7β-mediated ubiquitylation-dependent proteolysis of Mcl-1. PMID:23858059

  5. Oxidative Stress and Insulin Resistance

    PubMed Central

    Park, Kyong; Gross, Myron; Lee, Duk-Hee; Holvoet, Paul; Himes, John H.; Shikany, James M.; Jacobs, David R.

    2009-01-01

    OBJECTIVE Although cumulative evidence suggests that increased oxidative stress may lead to insulin resistance in vivo or in vitro, community-based studies are scarce. This study examined the longitudinal relationships of oxidative stress biomarkers with the development of insulin resistance and whether these relationships were independent of obesity in nondiabetic young adults. RESEARCH DESIGN AND METHODS Biomarkers of oxidative stress (F2-isoprostanes [F2Isop] and oxidized LDL [oxLDL]), insulin resistance (the homeostasis model assessment of insulin resistance [HOMA-IR]), and various fatness measures (BMI, waist circumference, and estimated percent fat) were obtained in a population-based observational study (Coronary Artery Risk Development in Young Adults) and its ancillary study (Young Adult Longitudinal Trends in Antioxidants) during 2000–2006. RESULTS There were substantial increases in estimated mean HOMA-IR over time. OxLDL and F2Isop showed little association with each other. Mean evolving HOMA-IR increased with increasing levels of oxidative stress markers (P < 0.001 for oxLDL and P = 0.06 for F2Isop), measured in 2000–2001. After additional adjustment for adiposity, a positive association between oxLDL and HOMA-IR was strongly evident, whereas the association between F2Isop and HOMA-IR was not. CONCLUSIONS We observed positive associations between each of two oxidative stress markers and insulin resistance. The association with oxidized LDL was independent of obesity, but that with F2Isop was not. PMID:19389821

  6. Inhibition of the oxidative stress response by heat stress in Caenorhabditis elegans.

    PubMed

    Crombie, Timothy A; Tang, Lanlan; Choe, Keith P; Julian, David

    2016-07-15

    It has long been recognized that simultaneous exposure to heat stress and oxidative stress shows a synergistic interaction that reduces organismal fitness, but relatively little is known about the mechanisms underlying this interaction. We investigated the role of molecular stress responses in driving this synergistic interaction using the nematode Caenorhabditis elegans To induce oxidative stress, we used the pro-oxidant compounds acrylamide, paraquat and juglone. As expected, we found that heat stress and oxidative stress interact synergistically to reduce survival. Compared with exposure to each stressor alone, during simultaneous sublethal exposure to heat stress and oxidative stress the normal induction of key oxidative-stress response (OxSR) genes was generally inhibited, whereas the induction of key heat-shock response (HSR) genes was not. Genetically activating the SKN-1-dependent OxSR increased a marker for protein aggregation and decreased whole-worm survival during heat stress alone, with the latter being independent of HSF-1. In contrast, compared with wild-type worms, inactivating the HSR by HSF-1 knockdown, which would be expected to decrease basal heat shock protein expression, increased survival during oxidative stress alone. Taken together, these data suggest that, in C. elegans, the HSR and OxSR cannot be simultaneously activated to the same extent that each can be activated during a single stressor exposure. We conclude that the observed synergistic reduction in survival during combined exposure to heat stress and oxidative stress is due, at least in part, to inhibition of the OxSR during activation of the HSR. PMID:27207646

  7. [Heme metabolism and oxidative stress].

    PubMed

    Kaliman, P A; Barannik, T B

    2001-01-01

    The role of heme metabolism in oxidative stress development and defense reactions formation in mammals under different stress factors are discussed in the article. Heme metabolism is considered as the totality of synthesis, degradation, transport and exchange processes of exogenous heme and heme liberated from erythrocyte hemoglobin under erythrocyte aging and hemolysis. The literature data presented display normal heme metabolism including mammals heme-binding proteins and intracellular free heme pool and heme metabolism alterations under oxidative stress development. The main attention is focused to the prooxidant action of heme, the interaction of heme transport and lipid exchange, and to the heme metabolism key enzymes (delta-aminolevulinate synthase and heme oxygenase), serum heme-binding protein hemopexin and intracellular heme-binding proteins participating in metabolism adaptation under the action of factors, which cause oxidative stress. PMID:11599427

  8. Oxidative Stress Markers in Sputum

    PubMed Central

    Antus, Balazs

    2016-01-01

    Although oxidative stress is thought to play a pivotal role in the pathogenesis of inflammatory airway diseases, its assessment in clinical practice remains elusive. In recent years, it has been conceptualized that oxidative stress markers in sputum should be employed to monitor oxidative processes in patients with asthma, chronic obstructive pulmonary disease (COPD), or cystic fibrosis (CF). In this review, the use of sputum-based oxidative markers was explored and potential clinical applications were considered. Among lipid peroxidation-derived products, 8-isoprostane and malondialdehyde have been the most frequently investigated, while nitrosothiols and nitrotyrosine may serve as markers of nitrosative stress. Several studies have showed higher levels of these products in patients with asthma, COPD, or CF compared to healthy subjects. Marker concentrations could be further increased during exacerbations and decreased along with recovery of these diseases. Measurement of oxidized guanine species and antioxidant enzymes in the sputum could be other approaches for assessing oxidative stress in pulmonary patients. Collectively, even though there are promising findings in this field, further clinical studies using more established detection techniques are needed to clearly show the benefit of these measurements in the follow-up of patients with inflammatory airway diseases. PMID:26885248

  9. Phagocytes and oxidative stress.

    PubMed

    Babior, B M

    2000-07-01

    Neutrophils and other phagocytes manufacture O(2)(-) (superoxide) by the one-electron reduction of oxygen at the expense of NADPH. Most of the O(2)(-) reacts with itself to form H(2)O(2) (hydrogen peroxide). From these agents a large number of highly reactive microbicidal oxidants are formed, including HOCl (hypochlorous acid), which is produced by the myeloperoxidase-catalyzed oxidation of Cl(-) by H(2)O(2); OH(*) (hydroxyl radical), produced by the reduction of H(2)O(2) by Fe(++) or Cu(+); ONOO(-) (peroxynitrite), formed by the reaction between O(2)(-) and NO(*); and many others. These reactive oxidants are manufactured for the purpose of killing invading microorganisms, but they also inflict damage on nearby tissues, and are thought to be of pathogenic significance in a large number of diseases. Included among these are emphysema, acute respiratory distress syndrome, atherosclerosis, reperfusion injury, malignancy and rheumatoid arthritis. PMID:10936476

  10. Oxidative Stress in Atopic Dermatitis

    PubMed Central

    Ji, Hongxiu; Li, Xiao-Kang

    2016-01-01

    Atopic dermatitis (AD) is a chronic pruritic skin disorder affecting many people especially young children. It is a disease caused by the combination of genetic predisposition, immune dysregulation, and skin barrier defect. In recent years, emerging evidence suggests oxidative stress may play an important role in many skin diseases and skin aging, possibly including AD. In this review, we give an update on scientific progress linking oxidative stress to AD and discuss future treatment strategies for better disease control and improved quality of life for AD patients. PMID:27006746

  11. Ethanol and oxidative stress.

    PubMed

    Sun, A Y; Ingelman-Sundberg, M; Neve, E; Matsumoto, H; Nishitani, Y; Minowa, Y; Fukui, Y; Bailey, S M; Patel, V B; Cunningham, C C; Zima, T; Fialova, L; Mikulikova, L; Popov, P; Malbohan, I; Janebova, M; Nespor, K; Sun, G Y

    2001-05-01

    This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The chair was Albert Y. Sun. The presentations were (1) Ethanol-inducible cytochrome P-4502E1 in alcoholic liver disease, by Magnus Ingelman-Sundberg and Etienne Neve; (2) Regulation of NF-kappaB by ethanol, by H. Matsumoto, Y. Nishitani, Y. Minowa, and Y. Fukui; (3) Chronic ethanol consumption increases concentration of oxidized proteins in rat liver, by Shannon M. Bailey, Vinood B. Patel, and Carol C. Cunningham; (4) Antiphospholipids antibodies and oxidized modified low-density lipoprotein in chronic alcoholic patients, by Tomas Zima, Lenka Fialova, Ludmila Mikulikova, Ptr Popov, Ivan Malbohan, Marta Janebova, and Karel Nespor; and (5) Amelioration of ethanol-induced damage by polyphenols, by Albert Y. Sun and Grace Y. Sun. PMID:11391077

  12. Hemoglobin oxidative stress

    NASA Astrophysics Data System (ADS)

    Croci, S.; Ortalli, I.; Pedrazzi, G.; Passeri, G.; Piccolo, P.

    2000-07-01

    Venous blood obtained from healthy donors and from patients suffering from breast cancer have been treated with acetylphenylhydrazine (APH) for different time. Mössbauer spectra of the packed red cells have been recorded and compared. The largest difference occurs after 50 min of treatment with APH where the patient samples show a broad spectral pattern indicating an advanced hemoglobin oxidation. These results may have some relevance in early cancer diagnosis.

  13. TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis

    PubMed Central

    Arimoto-Matsuzaki, Kyoko; Saito, Haruo; Takekawa, Mutsuhiro

    2016-01-01

    Cytoplasmic stress granules (SGs) are multimolecular aggregates of stalled translation pre-initiation complexes that prevent the accumulation of misfolded proteins, and that are formed in response to certain types of stress including ER stress. SG formation contributes to cell survival not only by suppressing translation but also by sequestering some apoptosis regulatory factors. Because cells can be exposed to various stresses simultaneously in vivo, the regulation of SG assembly under multiple stress conditions is important but unknown. Here we report that reactive oxygen species (ROS) such as H2O2 oxidize the SG-nucleating protein TIA1, thereby inhibiting SG assembly. Thus, when cells are confronted with a SG-inducing stress such as ER stress caused by protein misfolding, together with ROS-induced oxidative stress, they cannot form SGs, resulting in the promotion of apoptosis. We demonstrate that the suppression of SG formation by oxidative stress may underlie the neuronal cell death seen in neurodegenerative diseases. PMID:26738979

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

    SciTech Connect

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

    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.

  15. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

    Li, Jie; O, Wuliji; Li, Wei; Jiang, Zhi-Gang; Ghanbari, Hossein A.

    2013-01-01

    Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs. PMID:24351827

  16. Space flight and oxidative stress.

    PubMed

    Stein, T P

    2002-10-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress. PMID:12361781

  17. Space flight and oxidative stress

    NASA Technical Reports Server (NTRS)

    Stein, T. P.

    2002-01-01

    Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.

  18. Oxidative stress and alopecia areata

    PubMed Central

    Prie, BE; Voiculescu, VM; Ionescu-Bozdog, OB; Petrutescu, B; Iosif, L; Gaman, LE; Clatici, VG; Stoian, I; Giurcaneanu, C

    2015-01-01

    Alopecia areata (AA) is an inflammatory and autoimmune disease presenting with non-scarring hair loss. The aethiopathogenesis of alopecia areata is unclear and many factors including autoimmunity, genetic predisposition, emotional and environmental stress are thought to play important roles in its development. Antioxidant/ oxidant balance perturbation is a common feature in autoimmune, emotional and environmental stress. Therefore, our paper discusses the implications of oxidative stress in alopecia areata. Abbreviations: AA = alopecia areata, ROS = reactive oxygen species, H2O2 = hydrogen peroxide, TBARS = thiobarbituric acid rective substances, MDA = malondialdehyde, TBARS = thiobarbituric acid-reactive substances, SOD = superoxide dismutase, CAT = catalase, GSH-Px = glutathione peroxidase, PON1 = paraoxonase 1, HO-1 = hemoxigenase 1, TrxR = thioredoxin reductase, GSH = glutathione PMID:26361510

  19. Marine carotenoids and oxidative stress.

    PubMed

    Riccioni, Graziano

    2012-01-01

    Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease. PMID:22363224

  20. Marine Carotenoids and Oxidative Stress

    PubMed Central

    Riccioni, Graziano

    2012-01-01

    Oxidative stress induced by reactive oxygen species plays an important role in the etiology of many diseases. Dietary phytochemical products, such as bioactive food components and marine carotenoids (asthaxantin, lutein, β-carotene, fucoxanthin), have shown an antioxidant effect in reducing oxidative markers stress. Scientific evidence supports the beneficial role of phytochemicals in the prevention of some chronic diseases. Many carotenoids with high antioxidant properties have shown a reduction in disease risk both in epidemiological studies and supplementation human trials. However, controlled clinical trials and dietary intervention studies using well-defined subjects population have not provided clear evidence of these substances in the prevention of diseases. The most important aspects of this special issue will cover the synthesis, biological activities, and clinical applications of marine carotenoids, with particular attention to recent evidence regarding anti-oxidant and anti-inflammatory properties in the prevention of cardiovascular disease. PMID:22363224

  1. [Statins and oxidative stress].

    PubMed

    Filip-Ciubotaru, Florina; Foia, Liliana; Manciuc, Carmen

    2009-01-01

    Statins, as inhibitors of the first regulatory enzyme in cholesterol biosynthesis --HMG-CoA reductase--have a special impact in medical practice. Given their therapeutic efficacy, statins are believed to be the strongest class of agents in the treatment of cardiovascular disorders. Moreover, besides decreasing total cholesterol and C-LDL levels, numerous fundamental and clinical researches suggest that statins also have an antiinflammatory effect. Inflammation is closely related to the production of oxygen-derived reactive species (ROS). The antioxidant effects of statins associated with their ability to block the formation and/or action of ROS may add up their therapeutic efficacy. Within this context, the present paper presents data in literature related to the effect of statins on the expression and activity of NAD(P)H oxidase, activity of the enzymes involved in the antioxidative defence (SOD, GPx, catalase, paraoxonase), and their ability to act as free radical scavengers and oxidized-LDL inhibitors. By their antioxidant properties statins may decrease the atherogenic potential of lipoproteins. PMID:21495335

  2. Hypoxia, Oxidative Stress and Fat.

    PubMed

    Netzer, Nikolaus; Gatterer, Hannes; Faulhaber, Martin; Burtscher, Martin; Pramsohler, Stephan; Pesta, Dominik

    2015-01-01

    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. PMID:26061760

  3. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    NASA Technical Reports Server (NTRS)

    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.

  4. Oxidative stress and adrenocortical insufficiency

    PubMed Central

    Prasad, R; Kowalczyk, J C; Meimaridou, E; Storr, H L; Metherell, L A

    2014-01-01

    Maintenance of redox balance is essential for normal cellular functions. Any perturbation in this balance due to increased reactive oxygen species (ROS) leads to oxidative stress and may lead to cell dysfunction/damage/death. Mitochondria are responsible for the majority of cellular ROS production secondary to electron leakage as a consequence of respiration. Furthermore, electron leakage by the cytochrome P450 enzymes may render steroidogenic tissues acutely vulnerable to redox imbalance. The adrenal cortex, in particular, is well supplied with both enzymatic (glutathione peroxidases and peroxiredoxins) and non-enzymatic (vitamins A, C and E) antioxidants to cope with this increased production of ROS due to steroidogenesis. Nonetheless oxidative stress is implicated in several potentially lethal adrenal disorders including X-linked adrenoleukodystrophy, triple A syndrome and most recently familial glucocorticoid deficiency. The finding of mutations in antioxidant defence genes in the latter two conditions highlights how disturbances in redox homeostasis may have an effect on adrenal steroidogenesis. PMID:24623797

  5. Oxidative stress in prostate cancer.

    PubMed

    Khandrika, Lakshmipathi; Kumar, Binod; Koul, Sweaty; Maroni, Paul; Koul, Hari K

    2009-09-18

    As prostate cancer and aberrant changes in reactive oxygen species (ROS) become more common with aging, ROS signaling may play an important role in the development and progression of this malignancy. Increased ROS, otherwise known as oxidative stress, is a result of either increased ROS generation or a loss of antioxidant defense mechanisms. Oxidative stress is associated with several pathological conditions including inflammation and infection. ROS are products of normal cellular metabolism and play vital roles in stimulation of signaling pathways in response to changing intra- and extracellular environmental conditions. Chronic increases in ROS over time are known to induce somatic mutations and neoplastic transformation. In this review we summarize the causes for increased ROS generation and its potential role in etiology and progression of prostate cancer. PMID:19185987

  6. Oxidative Stress and Major Depression

    PubMed Central

    Verma, Akhilesh Kumar; Srivastava, Mona; Srivastava, Ragini

    2014-01-01

    Background: Major causative factor for major depression is inflammation, autoimmune tissue damage and prolonged psychological stress, which leads to oxidative stress. The aim of this study was to know the association of free radicals and antioxidant status in subjects suffering from major depression. Materials and Methods: Sixty patients diagnosed as a case of unipolar depression as per DSM IV, fulfilling the inclusion and exclusion criteria were compared with 40 healthy age and sex matched controls. The sera of both the groups were collected taking aseptic precautions and were evaluated for the markers of oxidative stress and for the antioxidants. The age group of the sample and the controls was between 18-60 y, both males and females were equally represented in the groups. Results: A significantly high level of malondialdehyde (MDA) was found in the patients with major depression (1.95 ± 1.04 mmol/L) as compared to healthy controls (0.366 ± 0.175 mmol/L) (p < 0.0001). The serum level of nitrite was found to be lower in cases (23.18 ± 12.08 μmol/L) in comparison to controls (26.18 ± 8.68 μmol/L) (p = 0.1789). Similarly the serum level of ascorbic acid and superoxide dismutase (SOD) were significantly below as compared to healthy controls (all p < 0.0001). Ceruloplasmin levels were also depressed in cases (p = 0.3943). Conclusion: The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression. PMID:25653939

  7. Bridges between mitochondrial oxidative stress, ER stress and mTOR signaling in pancreatic β cells.

    PubMed

    Wang, Jing; Yang, Xin; Zhang, Jingjing

    2016-08-01

    Pancreatic β cell dysfunction, i.e., failure to provide insulin in concentrations sufficient to control blood sugar, is central to the etiology of all types of diabetes. Current evidence implicates mitochondrial oxidative stress and endoplasmic reticulum (ER) stress in pancreatic β cell loss and impaired insulin secretion. Oxidative and ER stress are interconnected so that misfolded proteins induce reactive oxygen species (ROS) production; likewise, oxidative stress disturbs the ER redox state thereby disrupting correct disulfide bond formation and proper protein folding. mTOR signaling regulates many metabolic processes including protein synthesis, cell growth, survival and proliferation. Oxidative stress inhibits mTORC1, which is considered an important suppressor of mitochondrial oxidative stress in β cells, and ultimately, controls cell survival. The interplay between ER stress and mTORC1 is complicated, since the unfolded protein response (UPR) activation can occur upstream or downstream of mTORC1. Persistent activation of mTORC1 initiates protein synthesis and UPR activation, while in the later phase induces ER stress. Chronic activation of ER stress inhibits Akt/mTORC1 pathway, while under particular settings, acute activation of UPR activates Akt-mTOR signaling. Thus, modulating mitochondrial oxidative stress and ER stress via mTOR signaling may be an approach that will effectively suppress obesity- or glucolipotoxicity-induced metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM). In this review, we focus on the regulations between mTOR signaling and mitochondrial oxidative or ER stress in pancreatic β cells. PMID:27185188

  8. Role of sulfiredoxin in systemic diseases influenced by oxidative stress

    PubMed Central

    Ramesh, Asha; Varghese, Sheeja S.; Doraiswamy, Jayakumar; Malaiappan, Sankari

    2014-01-01

    Sulfiredoxin is a recently discovered member of the oxidoreductases family which plays a crucial role in thiol homoeostasis when under oxidative stress. A myriad of systemic disorders have oxidative stress and reactive oxygen species as the key components in their etiopathogenesis. Recent studies have evaluated the role of this enzyme in oxidative stress mediated diseases such as atherosclerosis, chronic obstructive pulmonary disease and a wide array of carcinomas. Its action is responsible for the normal functioning of cells under oxidative stress and the promotion of cell survival in cancerous cells. This review will highlight the cumulative effects of sulfiredoxin in various systemic disorders with a strong emphasis on its target activity and the factors influencing its expression in such conditions. PMID:25460739

  9. Management of multicellular senescence and oxidative stress

    PubMed Central

    Haines, David D; Juhasz, Bela; Tosaki, Arpad

    2013-01-01

    Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of ageing is recognized as a consequence of oxidative damage. This leads to hyperactivity of cell growth pathways, prominently including mTOR (mammalian target of rapamycin), that contribute to a build-up in cells of toxic aggregates such as progerin (a mutant nuclear cytoskeletal protein), lipofuscin and other cellular debris, triggering formation of senescent cellular phenotypes, which interact destructively with surrounding tissue. Indeed, senescent cell ablation dramatically inhibits physical deterioration in progeroid (age-accelerated) mice. This review explores ways in which oxidative stress creates ageing-associated cellular damage and triggers induction of the cell death/survival programs’ apoptosis, necrosis, autophagy and ‘necroapoptophagy’. The concept of ‘necroapoptophagy’ is presented here as a strategy for varying tissue oxidative stress intensity in ways that induce differential activation of death versus survival programs, resulting in enhanced and sustained representation of healthy functional cells. These strategies are discussed in the context of specialized mesenchymal stromal cells with the potential to synergize with telocytes in stabilizing engrafted progenitor cells, thereby extending periods of healthy life. Information and concepts are summarized in a hypothetical approach to suppressing whole-organism senescence, with methods drawn from emerging understandings of ageing, gained from Cnidarians (jellyfish, corals and anemones) that undergo a

  10. Management of multicellular senescence and oxidative stress.

    PubMed

    Haines, David D; Juhasz, Bela; Tosaki, Arpad

    2013-08-01

    Progressively sophisticated understanding of cellular and molecular processes that contribute to age-related physical deterioration is being gained from ongoing research into cancer, chronic inflammatory syndromes and other serious disorders that increase with age. Particularly valuable insight has resulted from characterization of how senescent cells affect the tissues in which they form in ways that decrease an organism's overall viability. Increasingly, the underlying pathophysiology of ageing is recognized as a consequence of oxidative damage. This leads to hyperactivity of cell growth pathways, prominently including mTOR (mammalian target of rapamycin), that contribute to a build-up in cells of toxic aggregates such as progerin (a mutant nuclear cytoskeletal protein), lipofuscin and other cellular debris, triggering formation of senescent cellular phenotypes, which interact destructively with surrounding tissue. Indeed, senescent cell ablation dramatically inhibits physical deterioration in progeroid (age-accelerated) mice. This review explores ways in which oxidative stress creates ageing-associated cellular damage and triggers induction of the cell death/survival programs' apoptosis, necrosis, autophagy and 'necroapoptophagy'. The concept of 'necroapoptophagy' is presented here as a strategy for varying tissue oxidative stress intensity in ways that induce differential activation of death versus survival programs, resulting in enhanced and sustained representation of healthy functional cells. These strategies are discussed in the context of specialized mesenchymal stromal cells with the potential to synergize with telocytes in stabilizing engrafted progenitor cells, thereby extending periods of healthy life. Information and concepts are summarized in a hypothetical approach to suppressing whole-organism senescence, with methods drawn from emerging understandings of ageing, gained from Cnidarians (jellyfish, corals and anemones) that undergo a unique form of

  11. Developmental and Evolutionary History Affect Survival in Stressful Environments

    PubMed Central

    Hopkins, Gareth R.; Brodie, Edmund D.; French, Susannah S.

    2014-01-01

    The world is increasingly impacted by a variety of stressors that have the potential to differentially influence life history stages of organisms. Organisms have evolved to cope with some stressors, while with others they have little capacity. It is thus important to understand the effects of both developmental and evolutionary history on survival in stressful environments. We present evidence of the effects of both developmental and evolutionary history on survival of a freshwater vertebrate, the rough-skinned newt (Taricha granulosa) in an osmotically stressful environment. We compared the survival of larvae in either NaCl or MgCl2 that were exposed to salinity either as larvae only or as embryos as well. Embryonic exposure to salinity led to greater mortality of newt larvae than larval exposure alone, and this reduced survival probability was strongly linked to the carry-over effect of stunted embryonic growth in salts. Larval survival was also dependent on the type of salt (NaCl or MgCl2) the larvae were exposed to, and was lowest in MgCl2, a widely-used chemical deicer that, unlike NaCl, amphibian larvae do not have an evolutionary history of regulating at high levels. Both developmental and evolutionary history are critical factors in determining survival in this stressful environment, a pattern that may have widespread implications for the survival of animals increasingly impacted by substances with which they have little evolutionary history. PMID:24748021

  12. Oxidative Stress in Neurodegenerative Diseases.

    PubMed

    Niedzielska, Ewa; Smaga, Irena; Gawlik, Maciej; Moniczewski, Andrzej; Stankowicz, Piotr; Pera, Joanna; Filip, Małgorzata

    2016-08-01

    The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD), are far from being fully explained. Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders. Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies. In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction. PMID:26198567

  13. Oxidative Stress in Cardiovascular Disease

    PubMed Central

    Csányi, Gábor; Miller, Francis J.

    2014-01-01

    In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS)-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine. PMID:24722571

  14. Oxidative stress in cardiovascular disease.

    PubMed

    Csányi, Gábor; Miller, Francis J

    2014-01-01

    In the special issue "Oxidative Stress in Cardiovascular Disease" authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS)-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine. PMID:24722571

  15. Oxidative stress in inherited mitochondrial diseases.

    PubMed

    Hayashi, Genki; Cortopassi, Gino

    2015-11-01

    Mitochondria are a source of reactive oxygen species (ROS). Mitochondrial diseases are the result of inherited defects in mitochondrially expressed genes. One potential pathomechanism for mitochondrial disease is oxidative stress. Oxidative stress can occur as the result of increased ROS production or decreased ROS protection. The role of oxidative stress in the five most common inherited mitochondrial diseases, Friedreich ataxia, LHON, MELAS, MERRF, and Leigh syndrome (LS), is discussed. Published reports of oxidative stress involvement in the pathomechanisms of these five mitochondrial diseases are reviewed. The strongest evidence for an oxidative stress pathomechanism among the five diseases was for Friedreich ataxia. In addition, a meta-analysis was carried out to provide an unbiased evaluation of the role of oxidative stress in the five diseases, by searching for "oxidative stress" citation count frequency for each disease. Of the five most common mitochondrial diseases, the strongest support for oxidative stress is for Friedreich ataxia (6.42%), followed by LHON (2.45%), MELAS (2.18%), MERRF (1.71%), and LS (1.03%). The increased frequency of oxidative stress citations was significant relative to the mean of the total pool of five diseases (p<0.01) and the mean of the four non-Friedreich diseases (p<0.0001). Thus there is support for oxidative stress in all five most common mitochondrial diseases, but the strongest, significant support is for Friedreich ataxia. PMID:26073122

  16. Oxidative stress in oral diseases.

    PubMed

    Kesarwala, A H; Krishna, M C; Mitchell, J B

    2016-01-01

    Oxidative species, including reactive oxygen species (ROS), are components of normal cellular metabolism and are required for intracellular processes as varied as proliferation, signal transduction, and apoptosis. In the situation of chronic oxidative stress, however, ROS contribute to various pathophysiologies and are involved in multiple stages of carcinogenesis. In head and neck cancers specifically, many common risk factors contribute to carcinogenesis via ROS-based mechanisms, including tobacco, areca quid, alcohol, and viruses. Given their widespread influence on the process of carcinogenesis, ROS and their related pathways are attractive targets for intervention. The effects of radiation therapy, a central component of treatment for nearly all head and neck cancers, can also be altered via interfering with oxidative pathways. These pathways are also relevant to the development of many benign oral diseases. In this review, we outline how ROS contribute to pathophysiology with a focus toward head and neck cancers and benign oral diseases, describing potential targets and pathways for intervention that exploit the role of oxidative species in these pathologic processes. PMID:25417961

  17. Analysis of Oxidative Stress in Zebrafish Embryos

    PubMed Central

    Mugoni, Vera; Camporeale, Annalisa; Santoro, Massimo M.

    2014-01-01

    High levels of reactive oxygen species (ROS) may cause a change of cellular redox state towards oxidative stress condition. This situation causes oxidation of molecules (lipid, DNA, protein) and leads to cell death. Oxidative stress also impacts the progression of several pathological conditions such as diabetes, retinopathies, neurodegeneration, and cancer. Thus, it is important to define tools to investigate oxidative stress conditions not only at the level of single cells but also in the context of whole organisms. Here, we consider the zebrafish embryo as a useful in vivo system to perform such studies and present a protocol to measure in vivo oxidative stress. Taking advantage of fluorescent ROS probes and zebrafish transgenic fluorescent lines, we develop two different methods to measure oxidative stress in vivo: i) a “whole embryo ROS-detection method” for qualitative measurement of oxidative stress and ii) a “single-cell ROS detection method” for quantitative measurements of oxidative stress. Herein, we demonstrate the efficacy of these procedures by increasing oxidative stress in tissues by oxidant agents and physiological or genetic methods. This protocol is amenable for forward genetic screens and it will help address cause-effect relationships of ROS in animal models of oxidative stress-related pathologies such as neurological disorders and cancer. PMID:25046434

  18. Etiologies of sperm oxidative stress

    PubMed Central

    Sabeti, Parvin; Pourmasumi, Soheila; Rahiminia, Tahereh; Akyash, Fatemeh; Talebi, Ali Reza

    2016-01-01

    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. PMID:27351024

  19. Etiologies of sperm oxidative stress.

    PubMed

    Sabeti, Parvin; Pourmasumi, Soheila; Rahiminia, Tahereh; Akyash, Fatemeh; Talebi, Ali Reza

    2016-04-01

    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. PMID:27351024

  20. Peroxisomal metabolism and oxidative stress.

    PubMed

    Nordgren, Marcus; Fransen, Marc

    2014-03-01

    Peroxisomes are ubiquitous and multifunctional organelles that are primarily known for their role in cellular lipid metabolism. As many peroxisomal enzymes catalyze redox reactions as part of their normal function, these organelles are also increasingly recognized as potential regulators of oxidative stress-related signaling pathways. This in turn suggests that peroxisome dysfunction is not only associated with rare inborn errors of peroxisomal metabolism, but also with more common age-related diseases such as neurodegeneration, type 2 diabetes, and cancer. This review intends to provide a comprehensive picture of the complex role of mammalian peroxisomes in cellular redox metabolism. We highlight how peroxisomal metabolism may contribute to the bioavailability of important mediators of oxidative stress, with particular emphasis on reactive oxygen species. In addition, we review the biological properties of peroxisome-derived signaling messengers and discuss how these molecules may mediate various biological responses. Furthermore, we explore the emerging concepts that peroxisomes and mitochondria share an intricate redox-sensitive relationship and cooperate in cell fate decisions. This is particularly relevant to the observed demise of peroxisome function which accompanies cellular senescence, organismal aging, and age-related diseases. PMID:23933092

  1. Inflammation, Oxidative Stress, and Obesity

    PubMed Central

    Fernández-Sánchez, Alba; Madrigal-Santillán, Eduardo; Bautista, Mirandeli; Esquivel-Soto, Jaime; Morales-González, Ángel; Esquivel-Chirino, Cesar; Durante-Montiel, Irene; Sánchez-Rivera, Graciela; Valadez-Vega, Carmen; Morales-González, José A.

    2011-01-01

    Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease. PMID:21686173

  2. Oxidative Stress in Cystinosis Patients

    PubMed Central

    Vaisbich, Maria Helena; Pache de Faria Guimaraes, Luciana; Shimizu, Maria Heloisa Mazzola; Seguro, Antonio Carlos

    2011-01-01

    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 < 0.0001). We detected no significant correlation between plasma TBARS levels and renal function. 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. PMID:22470381

  3. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    PubMed Central

    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

  4. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy.

    PubMed

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

    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

  5. Glycogen: A must have storage to survive stressful emergencies.

    PubMed

    Possik, Elite; Pause, Arnim

    2016-01-01

    Mechanisms of adaptation to acute changes in osmolarity are fundamental for life. When exposed to hyperosmotic stress, cells and organisms utilize conserved strategies to prevent water loss and maintain cellular integrity and viability. The production of glycerol is a common strategy utilized by the nematode Caenorhabditis elegans (C. elegans) and many other organisms to survive hyperosmotic stress. Specifically, the transcriptional upregulation of glycerol-3-phosphate dehydrogenase, a rate-limiting enzyme in the production of glycerol, has been previously implicated in many model organisms. However, what fuels this massive and rapid production of glycerol upon hyperosmotic stress has not been clearly elucidated. We have recently discovered an AMPK-dependent pathway that mediates hyperosmotic stress resistance in C. elegans. Specifically, we demonstrated that the chronic activation of AMPK leads to glycogen accumulation, which under hyperosmotic stress exposure, is rapidly degraded to mediate glycerol production. Importantly, we demonstrate that this strategy is utilized by flcn-1 mutant C. elegans nematodes in an AMPK-dependent manner. FLCN-1 is the worm homolog of the human renal tumor suppressor Folliculin (FLCN) responsible for the Birt-Hogg-Dubé neoplastic syndrome. Here, we comment on the dual role for glycogen in stress resistance: it serves as an energy store and a fuel for osmolyte production. We further discuss the potential utilization of this mechanism by organisms in general and by human cancer cells in order to survive harsh environmental conditions and notably hyperosmotic stress. PMID:27383221

  6. Oxidative stress and life histories: unresolved issues and current needs.

    PubMed

    Speakman, John R; Blount, Jonathan D; Bronikowski, Anne M; Buffenstein, Rochelle; Isaksson, Caroline; Kirkwood, Tom B L; Monaghan, Pat; Ozanne, Susan E; Beaulieu, Michaël; Briga, Michael; Carr, Sarah K; Christensen, Louise L; Cochemé, Helena M; Cram, Dominic L; Dantzer, Ben; Harper, Jim M; Jurk, Diana; King, Annette; Noguera, Jose C; Salin, Karine; Sild, Elin; Simons, Mirre J P; Smith, Shona; Stier, Antoine; Tobler, Michael; Vitikainen, Emma; Peaker, Malcolm; Selman, Colin

    2015-12-01

    Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting

  7. Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress.

    PubMed

    Schiavone, Stefania; Colaianna, Marilena; Curtis, Logos

    2015-01-01

    Stress is an inevitable part of human life and it is experienced even before birth. Stress to some extent could be considered normal and even necessary for the survival and the regular psychological development during childhood or adolescence. However, exposure to prolonged stress could become harmful and strongly impact mental health increasing the risk of developing psychiatric disorders. Recent studies have attempted to clarify how the human central nervous system (CNS) reacts to early life stress, focusing mainly on neurobiological modifications. Oxidative stress, defined as a disequilibrium between the oxidant generation and the antioxidant response, has been recently described as a candidate for most of the observed modifications. In this review, we will discuss how prolonged stressful events during childhood or adolescence (such as early maternal separation, parental divorce, physical violence, sexual or psychological abuses, or exposure to war events) can lead to increased oxidative stress in the CNS and enhance the risk to develop psychiatric diseases such as anxiety, depression, drug abuse or psychosis. Defining the sources of oxidative stress following exposure to early life stress might open new beneficial insights in therapeutic approaches to these mental disorders. PMID:25564385

  8. Induction of Oxidative Stress in Kidney

    PubMed Central

    Ozbek, Emin

    2012-01-01

    Oxidative stress has a critical role in the pathophysiology of several kidney diseases, and many complications of these diseases are mediated by oxidative stress, oxidative stress-related mediators, and inflammation. Several systemic diseases such as hypertension, diabetes mellitus, and hypercholesterolemia; infection; antibiotics, chemotherapeutics, and radiocontrast agents; and environmental toxins, occupational chemicals, radiation, smoking, as well as alcohol consumption induce oxidative stress in kidney. We searched the literature using PubMed, MEDLINE, and Google scholar with “oxidative stress, reactive oxygen species, oxygen free radicals, kidney, renal injury, nephropathy, nephrotoxicity, and induction”. The literature search included only articles written in English language. Letters or case reports were excluded. Scientific relevance, for clinical studies target populations, and study design, for basic science studies full coverage of main topics, are eligibility criteria for articles used in this paper. PMID:22577546

  9. Primary and secondary oxidative stress in Bacillus.

    PubMed

    Mols, Maarten; Abee, Tjakko

    2011-06-01

    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 minireview highlights novel insights in the primary oxidative stress response caused by oxidizing compounds including hydrogen peroxide and the secondary oxidative stress responses apparent upon exposure to a range of agents and conditions leading to environmental stresses such as antibiotics, heat and acid. Insights in the pathways and damaging radicals involved have been compiled based among others on transcriptome studies, network analyses and fluorescence techniques for detection of ROS at single cell level. Exploitation of the current knowledge for the control of spoilage and pathogenic bacteria is discussed. PMID:21352461

  10. Survival of microbial isolates from clouds toward simulated atmospheric stress factors

    NASA Astrophysics Data System (ADS)

    Joly, Muriel; Amato, Pierre; Sancelme, Martine; Vinatier, Virginie; Abrantes, Magali; Deguillaume, Laurent; Delort, Anne-Marie

    2015-09-01

    In the atmosphere, airborne microbial cells are exposed to conditions that are thought to affect their survival. Here, we investigated the survival of 5 microorganisms among the most represented in the cultivable community of clouds (4 bacteria affiliated to Pseudomonas, Sphingomonas and Arthrobacter and 1 yeast of Dioszegia) after exposition to different atmospheric factors generally considered stressful for cells: artificial solar light (10 h), oxidant (hydrogen peroxide: 0-1 mM for 90 min), osmotic shocks (0.1-2.5 M NaCl) and freeze-thaw cycles (6 cycles of 5 °C/-40 °C). Each condition was applied separately to cell suspensions, and survival rates were examined by culture. Survival was highly strain and stress dependent, with no relationship with pigmentation or ice nucleation activity. In all strains, solar light had no or mitigated influence, and exposition to H2O2 at the concentration measured in cloud water only slightly impacted viability (>70% of the cells survived). The strain Sphingomonas sp. was particularly impacted by osmotic shocks while repeated freeze-thaw was particularly damaging for Arthrobacter and Pseudomonas species. Overall, our results tend to indicate that in the atmosphere, the most stringent selection factors on living organisms are probably freeze-thaw and condensation/evaporation (osmotic shocks) cycles, whereas the impacts of oxidants and of solar light are limited.

  11. Role of oxidative stress and nitric oxide in atherothrombosis

    PubMed Central

    Lubos, Edith; Handy, Diane E.; Loscalzo, Joseph

    2008-01-01

    During the last decade basic and clinical research has highlighted the central role of reactive oxygen species (ROS) in cardiovascular disease. Enhanced production or attenuated degradation of ROS leads to oxidative stress, a process that affects endothelial and vascular function, and contributes to vascular disease. Nitric oxide (NO), a product of the normal endothelium, is a principal determinant of normal endothelial and vascular function. In states of inflammation, NO production by the vasculature increases considerably and, in conjunction with other ROS, contributes to oxidative stress. This review examines the role of oxidative stress and NO in mechanisms of endothelial and vascular dysfunction with an emphasis on atherothrombosis. PMID:18508590

  12. Oxidative and nitrative stress in neurodegeneration.

    PubMed

    Cobb, Catherine A; Cole, Marsha P

    2015-12-01

    Aerobes require oxygen for metabolism and normal free radical formation. As a result, maintaining the redox homeostasis is essential for brain cell survival due to their high metabolic energy requirement to sustain electrochemical gradients, neurotransmitter release, and membrane lipid stability. Further, brain antioxidant levels are limited compared to other organs and less able to compensate for reactive oxygen and nitrogen species (ROS/RNS) generation which contribute oxidative/nitrative stress (OS/NS). Antioxidant treatments such as vitamin E, minocycline, and resveratrol mediate neuroprotection by prolonging the incidence of or reversing OS and NS conditions. Redox imbalance occurs when the antioxidant capacity is overwhelmed, consequently leading to activation of alternate pathways that remain quiescent under normal conditions. If OS/NS fails to lead to adaptation, tissue damage and injury ensue, resulting in cell death and/or disease. The progression of OS/NS-mediated neurodegeneration along with contributions from microglial activation, dopamine metabolism, and diabetes comprise a detailed interconnected pathway. This review proposes a significant role for OS/NS and more specifically, lipid peroxidation (LPO) and other lipid modifications, by triggering microglial activation to elicit a neuroinflammatory state potentiated by diabetes or abnormal dopamine metabolism. Subsequently, sustained stress in the neuroinflammatory state overwhelms cellular defenses and prompts neurotoxicity resulting in the onset or amplification of brain damage. PMID:26024962

  13. Influence of Oxidative Stress on Stored Platelets

    PubMed Central

    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. 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. PMID:26949396

  14. Clinical Relevance of Biomarkers of Oxidative Stress

    PubMed Central

    Frijhoff, Jeroen; Winyard, Paul G.; Zarkovic, Neven; Davies, Sean S.; Stocker, Roland; Cheng, David; Knight, Annie R.; Taylor, Emma Louise; Oettrich, Jeannette; Ruskovska, Tatjana; Gasparovic, Ana Cipak; Cuadrado, Antonio; Weber, Daniela; Poulsen, Henrik Enghusen; Grune, Tilman; Schmidt, Harald H.H.W.

    2015-01-01

    Abstract 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. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Future Directions: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 23, 1144–1170. PMID:26415143

  15. Oxidative Stress, Lens Gap Junctions, and Cataracts

    PubMed Central

    Beyer, Eric C.

    2009-01-01

    Abstract The eye lens is constantly subjected to oxidative stress from radiation and other sources. The lens has several mechanisms to protect its components from oxidative stress and to maintain its redox state, including enzymatic pathways and high concentrations of ascorbate and reduced glutathione. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities or cataracts. Maintenance of transparency and homeostasis of the avascular lens depend on an extensive network of gap junctions. Communication through gap junction channels allows intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are also subject to the effects of oxidative stress. These observations suggest that oxidative stress-induced damage to connexins (and consequent altered intercellular communication) may contribute to cataract formation. Antioxid. Redox Signal. 11, 339–353. PMID:18831679

  16. Oxidative Stress Related Diseases in Newborns

    PubMed Central

    Aykac, Kubra

    2016-01-01

    We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229

  17. Oxidative Stress Related Diseases in Newborns.

    PubMed

    Ozsurekci, Yasemin; Aykac, Kubra

    2016-01-01

    We review oxidative stress-related newborn disease and the mechanism of oxidative damage. In addition, we outline diagnostic and therapeutic strategies and future directions. Many reports have defined oxidative stress as an imbalance between an enhanced reactive oxygen/nitrogen species and the lack of protective ability of antioxidants. From that point of view, free radical-induced damage caused by oxidative stress seems to be a probable contributing factor to the pathogenesis of many newborn diseases, such as respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and retinopathy of prematurity. We share the hope that the new understanding of the concept of oxidative stress and its relation to newborn diseases that has been made possible by new diagnostic techniques will throw light on the treatment of those diseases. PMID:27403229

  18. Mitochondrial Oxidative Stress in Temporal Lobe Epilepsy

    PubMed Central

    Waldbaum, Simon; Patel, Manisha

    2011-01-01

    Mitochondrial oxidative stress and dysfunction are contributing factors to various neurological disorders. Recently, there has been increasing evidence supporting the association between mitochondrial oxidative stress and epilepsy. Although certain inherited epilepsies are associated with mitochondrial dysfunction, little is known about its role in acquired epilepsies such as temporal lobe epilepsy. Mitochondrial oxidative stress and dysfunction are emerging as key factors that not only result from seizures, but may also contribute to epileptogenesis. The occurrence of epilepsy increases with age, and mitochondrial oxidative stress is a leading mechanism of aging and age-related degenerative disease, suggesting a further involvement of mitochondrial dysfunction in seizure generation. Mitochondria have critical cellular functions that effect neuronal excitability including production of adenosine triphosphate (ATP), fatty acid oxidation, control of apoptosis and necrosis, regulation of amino acid cycling, neurotransmitter biosynthesis, and regulation of cytosolic Ca2+ homeostasis. Mitochondria are the primary site of reactive oxygen species (ROS) production making them uniquely vulnerable to oxidative stress and damage which can further affect cellular macromolecule function, the ability of the electron transport chain to produce ATP, antioxidant defenses, mitochondrial DNA stability, and synaptic glutamate homeostasis. Oxidative damage to one or more of these cellular targets may affect neuronal excitability and increase seizure susceptibility. The specific targeting of mitochondrial oxidative stress, dysfunction, and bioenergetics with pharmacological and non-pharmacological treatments may be a novel avenue for attenuating epileptogenesis and seizure initiation. PMID:19850449

  19. Autophagy is activated for cell survival after endoplasmic reticulum stress.

    PubMed

    Ogata, Maiko; Hino, Shin-ichiro; Saito, Atsushi; Morikawa, Keisuke; Kondo, Shinichi; Kanemoto, Soshi; Murakami, Tomohiko; Taniguchi, Manabu; Tanii, Ichiro; Yoshinaga, Kazuya; Shiosaka, Sadao; Hammarback, James A; Urano, Fumihiko; Imaizumi, Kazunori

    2006-12-01

    Eukaryotic cells deal with accumulation of unfolded proteins in the endoplasmic reticulum (ER) by the unfolded protein response, involving the induction of molecular chaperones, translational attenuation, and ER-associated degradation, to prevent cell death. Here, we found that the autophagy system is activated as a novel signaling pathway in response to ER stress. Treatment of SK-N-SH neuroblastoma cells with ER stressors markedly induced the formation of autophagosomes, which were recognized at the ultrastructural level. The formation of green fluorescent protein (GFP)-LC3-labeled structures (GFP-LC3 "dots"), representing autophagosomes, was extensively induced in cells exposed to ER stress with conversion from LC3-I to LC3-II. In IRE1-deficient cells or cells treated with c-Jun N-terminal kinase (JNK) inhibitor, the autophagy induced by ER stress was inhibited, indicating that the IRE1-JNK pathway is required for autophagy activation after ER stress. In contrast, PERK-deficient cells and ATF6 knockdown cells showed that autophagy was induced after ER stress in a manner similar to the wild-type cells. Disturbance of autophagy rendered cells vulnerable to ER stress, suggesting that autophagy plays important roles in cell survival after ER stress. PMID:17030611

  20. Lung transplantation: does oxidative stress contribute to the development of bronchiolitis obliterans syndrome?

    PubMed

    Madill, Janet; Aghdassi, Ellie; Arendt, Bianca; Hartman-Craven, Brenda; Gutierrez, Carlos; Chow, Chung-Wai; Allard, Johane

    2009-04-01

    Lung transplantation is the ultimate treatment of end-stage lung disease. After transplantation, the 1-year survival rate is 80%. However, 5-year survival rates drop to 50% due to bronchiolitis obliterans syndrome (BOS). Ischemia/reperfusion injury, infections, and acute rejection are major risk factors contributing to the development of BOS. These risk factors are also associated with increased oxidative stress. Oxidative stress is a condition whereby prooxidants overwhelm the antioxidant defense system and may contribute to the pathogenesis of BOS by inducing more tissue injury and inflammation. This article reviews the current state of knowledge on oxidative stress in lung transplantation and BOS. PMID:19298941

  1. Oxidative stress and oxidative damage in chemical carcinogenesis

    SciTech Connect

    Klaunig, James E. Wang Zemin; Pu Xinzhu; Zhou Shaoyu

    2011-07-15

    Reactive oxygen species (ROS) are induced through a variety of endogenous and exogenous sources. Overwhelming of antioxidant and DNA repair mechanisms in the cell by ROS may result in oxidative stress and oxidative damage to the cell. This resulting oxidative stress can damage critical cellular macromolecules and/or modulate gene expression pathways. Cancer induction by chemical and physical agents involves a multi-step process. This process includes multiple molecular and cellular events to transform a normal cell to a malignant neoplastic cell. Oxidative damage resulting from ROS generation can participate in all stages of the cancer process. An association of ROS generation and human cancer induction has been shown. It appears that oxidative stress may both cause as well as modify the cancer process. Recently association between polymorphisms in oxidative DNA repair genes and antioxidant genes (single nucleotide polymorphisms) and human cancer susceptibility has been shown.

  2. Nrf2 protects mitochondrial decay by oxidative stress.

    PubMed

    Strom, Joshua; Xu, Beibei; Tian, Xiuqing; Chen, Qin M

    2016-01-01

    Sublethal levels of oxidative stress are commonly associated with various pathophysiological conditions. Cardiomyocytes have the highest content of mitochondria among all cell types, allowing the study of mitochondria in cells surviving oxidative stress and address whether nuclear factor-erythroid-derived 2-related factor 2 (Nrf2) can reverse these changes. Mitochondria normally exist in elaborated networks, which were replaced by predominately individual punctuate mitochondria 24 h after exposure to a nonlethal dose of H2O2. Electron microscopy revealed that cells surviving H2O2 show swelling of mitochondria with disorganized cristae and areas of condensation. Measurements of functional mitochondria showed a H2O2 dose-dependent decrease over a course of 5 d. At the protein and mRNA levels, cells surviving H2O2 treatment show a reduction of mitochondrial components, cytochrome c, and cytochrome b. Nrf2 overexpression prevented H2O2 from inducing mitochondria morphologic changes and reduction of cytochrome b/c. Although Nrf2 is known as a transcription factor regulating antioxidant and detoxification genes, Nrf2 overexpression did not significantly reduce the level of protein oxidation. Instead, Nrf2 was found to associate with the outer mitochondrial membrane. Mitochondria prepared from the myocardium of Nrf2 knockout mice are more sensitive to permeability transition. Our data suggest that Nrf2 protects mitochondria from oxidant injury likely through direct interaction with mitochondria. PMID:26340923

  3. Are metallothioneins equally good biomarkers of metal and oxidative stress?

    PubMed

    Figueira, Etelvina; Branco, Diana; Antunes, Sara C; Gonçalves, Fernando; Freitas, Rosa

    2012-10-01

    Several researchers investigated the induction of metallothioneins (MTs) in the presence of metals, namely Cadmium (Cd). Fewer studies observed the induction of MTs due to oxidizing agents, and literature comparing the sensitivity of MTs to different stressors is even more scarce or even nonexistent. The role of MTs in metal and oxidative stress and thus their use as a stress biomarker, remains to be clearly elucidated. To better understand the role of MTs as a biomarker in Cerastoderma edule, a bivalve widely used as bioindicator, a laboratory assay was conducted aiming to assess the sensitivity of MTs to metal and oxidative stressors. For this purpose, Cd was used to induce metal stress, whereas hydrogen peroxide (H2O2), being an oxidizing compound, was used to impose oxidative stress. Results showed that induction of MTs occurred at very different levels in metal and oxidative stress. In the presence of the oxidizing agent (H2O2), MTs only increased significantly when the degree of oxidative stress was very high, and mortality rates were higher than 50 percent. On the contrary, C. edule survived to all Cd concentrations used and significant MTs increases, compared to the control, were observed in all Cd exposures. The present work also revealed that the number of ions and the metal bound to MTs varied with the exposure conditions. In the absence of disturbance, MTs bound most (60-70 percent) of the essential metals (Zn and Cu) in solution. In stressful situations, such as the exposure to Cd and H2O2, MTs did not bind to Cu and bound less to Zn. When organisms were exposed to Cd, the total number of ions bound per MT molecule did not change, compared to control. However the sort of ions bound per MT molecule differed; part of the Zn and all Cu ions where displaced by Cd ions. For organisms exposed to H2O2, each MT molecule bound less than half of the ions compared to control and Cd conditions, which indicates a partial oxidation of thiol groups in the cysteine

  4. Contrasting extremes in water-related stresses determine species survival

    NASA Astrophysics Data System (ADS)

    Bartholomeus, R. P.; Witte, J. P. M.; van Bodegom, P. M.; van Dam, J. C.; Aerts, R.

    2012-04-01

    In temperate climates, soil moisture, in concert with nutrient availability and soil acidity, is the most important environmental filter in determining local plant species composition, as it determines the availability of both oxygen and water to plant roots. These resources are indispensable for meeting the physiological demands of plants. Especially the occurrence of both excessive dry and wet moisture conditions at a particular site has strong implications for the survival of species, because plants need traits that allow them to respond to such counteracting conditions. However, adapting to one stress may go at the cost of the other, i.e. there exists a trade-off in the tolerance for wet conditions and the tolerance for dry conditions. Until now, both large-scale (global) and plot-scale effects of soil moisture conditions on plant species composition have mostly been investigated through indirect environmental measures, which do not include the key soil physical and plant physiological processes in the soil-plant-atmosphere system. Moreover, researchers only determined effects of one of the water-related stresses, i.e. either oxygen or drought stress. In order to quantify both oxygen and drought stress with causal measures, we focused on interacting meteorological, soil physical, microbial, and plant physiological processes in the soil-plant-atmosphere system. We simulated these plant stresses with a novel, process-based approach, incorporating in detail the interacting processes in the soil-plant-atmosphere interface. High variability and extremes in resource availability can be highly detrimental to plant species ('you can only die once'). We show that co-occurrence of oxygen and drought stress reduces the percentage of specialists within a vegetation plot. The percentage of non-specialists within a vegetation plot, however, decreases significantly with increasing stress as long as only one of the stresses prevails, but increases significantly with an

  5. An update on oxidative stress-mediated organ pathophysiology.

    PubMed

    Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

    2013-12-01

    Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. PMID:24084033

  6. p66Shc, oxidative stress and aging

    PubMed Central

    Pinton, Paolo; Rizzuto, Rosario

    2009-01-01

    The 66 KDa isoform of Shc and its signalling properties have attracted in the past years major interest in aging research. Here, we summarize p66Shc functions and outline a specific signalling route leading to mitochondrial import, that accounts for its pro-apoptotic activity upon oxidative stress. This model, that could explain the alterations of mitochondrial Ca2+ homeostasis observed after oxidative stress, highlights novel pharmacological targets in age-related disorders. PMID:18235239

  7. Surviving in the cold: yeast mutants with extended hibernating lifespan are oxidant sensitive

    PubMed Central

    Postma, Lucie; Lehrach, Hans; Ralser, Markus

    2009-01-01

    Metabolic activity generates oxidizing molecules throughout life, but it is still debated if the resulting damage of macromolecules is a causality, or consequence, of the aging process. This problem demands for studying growth- and longevity phenotypes separately. Here, we assayed a complete collection of haploid Saccharomyces cerevisiae knock-out strains for their capacity to endure long periods at low metabolic rates. Deletion of 93 genes, predominantly factors of primary metabolism, allowed yeast to survive for more than 58 months in the cold. The majority of these deletion strains were not resistant against oxidants or reductants, but many were hypersensitive. Hence, survival at low metabolic rates has limiting genetic components, and correlates with stress resistance inversely. Indeed, maintaining the energy consuming anti-oxidative machinery seems to be disadvantageous under coldroom conditions. PMID:20157578

  8. Muscle aging and oxidative stress in wild-caught shrews.

    PubMed

    Hindle, Allyson G; Lawler, John M; Campbell, Kevin L; Horning, Markus

    2010-04-01

    Red-toothed shrews (Soricidae, subfamily Soricinae) are an intriguing model system to examine the free-radical theory of aging in wild mammals, given their short (<18months) lifespan and high mass-specific metabolic rates. As muscle performance underlies both foraging ability and predator avoidance, any age-related decline should be detrimental to fitness and survival. Muscle samples of water shrews (Sorex palustris) and sympatrically distributed short-tailed shrews (Blarina brevicauda) were therefore assessed for oxidative stress markers, protective antioxidant enzymes and apoptosis. Activity levels of catalase and glutathione peroxidase increased with age in both species. Similarly, Cu,Zn-superoxide dismutase isoform content was elevated significantly in older animals of both species (increases of 60% in the water shrew, 25% in the short-tailed shrew). Only one oxidative stress marker (lipid peroxidation) was age-elevated; the others were stable or declined (4-hydroxynonenal adducts and dihydroethidium oxidation). Glutathione peroxidase activity was significantly higher in the short-tailed shrew, while catalase activity was 2x higher in water shrews. Oxidative stress indicators were on average higher in short-tailed shrews. Apoptosis occurred in <1% of myocytes examined, and did not increase with age. Within the constraints of the sample size we found evidence of protection against elevated oxidative stress in wild-caught shrews. PMID:20109576

  9. Muscle Aging and Oxidative Stress in Wild-Caught Shrews

    PubMed Central

    Hindle, Allyson G.; Lawler, John M.; Campbell, Kevin L.; Horning, Markus

    2010-01-01

    Red-toothed shrews (Soricidae, subfamily Soricinae) are an intriguing model system to examine the free radical theory of aging in wild mammals, given their short (<18 month) lifespan and high mass-specific metabolic rates. As muscle performance underlies both foraging ability and predator avoidance, any age-related decline should be detrimental to fitness and survival. Muscle samples of water shrews (Sorex palustris) and sympatrically distributed short-tailed shrews (Blarina brevicauda) were therefore assessed for oxidative stress markers, protective antioxidant enzymes and apoptosis. Activity levels of catalase and glutathione peroxidase increased with age in both species. Similarly, Cu,Zn-superoxide dismutase isoform content was elevated significantly in older animals of both species (increases of 60% in the water shrew, 25% in the short-tailed shrew). Only one oxidative stress marker (lipid peroxidation) was age-elevated; the others were stable or declined (4-hydroxynonenal adducts and dihydroethidium oxidation). Glutathione peroxidase activity was significantly higher in the short-tailed shrew, while catalase activity was 2× higher in water shrews. Oxidative stress indicators were on average higher in short-tailed shrews. Apoptosis occurred in <1% of myocytes examined, and did not increase with age. Within the constraints of the sample size we found evidence of protection against elevated oxidative stress in wild-caught shrews. PMID:20109576

  10. Thioredoxin-1 Increases Survival in Sepsis by Inflammatory Response Through Suppressing Endoplasmic Reticulum Stress.

    PubMed

    Chen, Guobing; Li, Xiang; Huang, Mengbing; Li, Mei; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

    2016-07-01

    Sepsis is the main cause of death in critically ill patients, pathogenesis of which is still unclear. The nuclear factor κB (NF-κB) inflammatory signal pathway mediated by endoplasmic reticulum stress is involved in sepsis. Thioredoxin-1 (Trx-1) is an important protein of regulating oxidative stress. It plays a crucial role in the anti-oxidation, anti-apoptosis, and anti-inflammation. However, the role and the mechanism of Trx-1 in sepsis have not been extensively studied. In the present study, we showed that the survival was longer in sepsis induced by cecal ligation and puncture in Trx-1 overexpression transgenic (Tg) mice compared with wild-type mice. Wet/dry lung weight ratio was decreased in Trx-1 Tg mice. The levels of TNF-α and IL-1β in plasma and lung tissue were inhibited in Tg mice. The expressions of glucose-regulated protein 78, inositol-requiring enzyme 1α (IRE1α), tumor necrosis factor receptor-associated factor 2, C/EBP homologous protein, NF-κB, and inhibitors of NF-κBα were increased in lung tissue. More importantly, the overexpression of Trx-1 in transgenic mice suppressed NF-κB inflammatory signal pathway by inhibiting the activation of molecules involved in ER stress. Our results suggest that Trx-1 may play protective role in extending survival in sepsis by regulating inflammatory response through suppressing ER stress. PMID:27299588

  11. Oxidative Stress in Caenorhabditis elegans: Protective Effects of Spartin

    PubMed Central

    Truong, Timothy; Karlinski, Zachary A.; O’Hara, Christopher; Cabe, Maleen; Kim, Hongkyun; Bakowska, Joanna C.

    2015-01-01

    Troyer syndrome is caused by a mutation in the SPG20 gene, which results in complete loss of expression of the protein spartin. We generated a genetic model of Troyer syndrome in worms to explore the locomotor consequences of a null mutation of the Caenorhabditis elegans SPG20 orthologue, F57B10.9, also known as spg-20. Spg-20 mutants showed decreased length, crawling speed, and thrashing frequency, and had a shorter lifespan than wild-type animals. These results suggest an age-dependent decline in motor function in mutant animals. The drug paraquat was used to induce oxidative stress for 4 days in the animals. We measured survival rate and examined locomotion by measuring crawling speed and thrashing frequency. After 4 days of paraquat exposure, 77% of wild-type animals survived, but only 38% of spg-20 mutant animals survived. Conversely, animals overexpressing spg-20 had a survival rate of 95%. We also tested lifespan after a 1 hour exposure to sodium azide. After a 24 hour recovery period, 87% of wild type animals survived, 57% of spg-20 mutant animals survived, and 82% of animals overexpressing spg-20 survived. In the behavioral assays, spg-20 mutant animals showed a significant decrease in both crawling speed and thrashing frequency compared with wild-type animals. Importantly, the locomotor phenotype for both crawling and thrashing was rescued in animals overexpressing spg-20. The animals overexpressing spg-20 had crawling speeds and thrashing frequencies similar to those of wild-type animals. These data suggest that the protein F57B10.9/SPG-20 might have a protective role against oxidative stress. PMID:26114733

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

    PubMed Central

    Chaudhari, Namrata; Talwar, Priti; Parimisetty, Avinash; Lefebvre d’Hellencourt, Christian; Ravanan, Palaniyandi

    2014-01-01

    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 disturbs 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 have 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. PMID:25120434

  13. Specioside ameliorates oxidative stress and promotes longevity in Caenorhabditis elegans.

    PubMed

    Asthana, Jyotsna; Yadav, A K; Pant, Aakanksha; Pandey, Swapnil; Gupta, M M; Pandey, Rakesh

    2015-03-01

    Specioside (6-O-coumaroylcatalpol) is an iridoid glucoside which possesses multifunctional activities viz. analgesic, antidyspeptic, astringent, liver stimulating and wound healing properties. The present study for the first time delineates stress alleviating and lifespan prolonging action of specioside (SPC), isolated from Stereospermum suaveolens in the free living, multicellular nematode model Caenorhabditis elegans. A strong correlation between lifespan extension and stress modulation in adult worms was established in a dose dependent manner. The dietary intake of this phytomolecule elevated juglone induced oxidative and heat induced thermal stress tolerance in C. elegans. On evaluation, it was found that 25 μM dose of SPC significantly extended lifespan by 15.47% (P≤0.0001) with reduction in stress level. Furthermore, SPC enhanced mean survival in mev-1 mutant suggesting its oxidative stress reducing potential. Furthermore, SPC augmented stress modulatory enzymes superoxide dismutase (SOD) and catalase (CAT) level in C. elegans. Altogether, these findings broaden current perspectives concerning stress alleviating potentials of SPC and have implications in development of therapeutics for curing age related disorders. PMID:25619942

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

    PubMed Central

    Rahal, Anu; Kumar, Amit; Singh, Vivek; Yadav, Brijesh

    2014-01-01

    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. PMID:24587990

  15. Oxidative Stress in Aging Human Skin

    PubMed Central

    Rinnerthaler, Mark; Bischof, Johannes; Streubel, Maria Karolin; Trost, Andrea; Richter, Klaus

    2015-01-01

    Oxidative stress in skin plays a major role in the aging process. This is true for intrinsic aging and even more for extrinsic aging. Although the results are quite different in dermis and epidermis, extrinsic aging is driven to a large extent by oxidative stress caused by UV irradiation. In this review the overall effects of oxidative stress are discussed as well as the sources of ROS including the mitochondrial ETC, peroxisomal and ER localized proteins, the Fenton reaction, and such enzymes as cyclooxygenases, lipoxygenases, xanthine oxidases, and NADPH oxidases. Furthermore, the defense mechanisms against oxidative stress ranging from enzymes like superoxide dismutases, catalases, peroxiredoxins, and GSH peroxidases to organic compounds such as L-ascorbate, α-tocopherol, beta-carotene, uric acid, CoQ10, and glutathione are described in more detail. In addition the oxidative stress induced modifications caused to proteins, lipids and DNA are discussed. Finally age-related changes of the skin are also a topic of this review. They include a disruption of the epidermal calcium gradient in old skin with an accompanying change in the composition of the cornified envelope. This modified cornified envelope also leads to an altered anti-oxidative capacity and a reduced barrier function of the epidermis. PMID:25906193

  16. Calcineurin Targets Involved in Stress Survival and Fungal Virulence.

    PubMed

    Park, Hee-Soo; Chow, Eve W L; Fu, Ci; Soderblom, Erik J; Moseley, M Arthur; Heitman, Joseph; Cardenas, Maria E

    2016-09-01

    Calcineurin governs stress survival, sexual differentiation, and virulence of the human fungal pathogen Cryptococcus neoformans. Calcineurin is activated by increased Ca2+ levels caused by stress, and transduces signals by dephosphorylating protein substrates. Herein, we identified and characterized calcineurin substrates in C. neoformans by employing phosphoproteomic TiO2 enrichment and quantitative mass spectrometry. The identified targets include the transactivator Crz1 as well as novel substrates whose functions are linked to P-bodies/stress granules (PBs/SGs) and mRNA translation and decay, such as Pbp1 and Puf4. We show that Crz1 is a bona fide calcineurin substrate, and Crz1 localization and transcriptional activity are controlled by calcineurin. We previously demonstrated that thermal and other stresses trigger calcineurin localization to PBs/SGs. Several calcineurin targets localized to PBs/SGs, including Puf4 and Pbp1, contribute to stress resistance and virulence individually or in conjunction with Crz1. Moreover, Pbp1 is also required for sexual development. Genetic epistasis analysis revealed that Crz1 and the novel targets Lhp1, Puf4, and Pbp1 function in a branched calcineurin pathway that orchestrates stress survival and virulence. These findings support a model whereby calcineurin controls stress and virulence, at the transcriptional level via Crz1, and post-transcriptionally by localizing to PBs/SGs and acting on targets involved in mRNA metabolism. The calcineurin targets identified in this study share little overlap with known calcineurin substrates, with the exception of Crz1. In particular, the mRNA binding proteins and PBs/SGs residents comprise a cohort of novel calcineurin targets that have not been previously linked to calcineurin in mammals or in Saccharomyces cerevisiae. This study suggests either extensive evolutionary rewiring of the calcineurin pathway, or alternatively that these novel calcineurin targets have yet to be characterized

  17. Oxidative Stress in Placenta: Health and Diseases.

    PubMed

    Wu, Fan; Tian, Fu-Ju; Lin, Yi

    2015-01-01

    During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. PMID:26693479

  18. Oxidative Stress in Placenta: Health and Diseases

    PubMed Central

    Wu, Fan; Tian, Fu-Ju; Lin, Yi

    2015-01-01

    During pregnancy, development of the placenta is interrelated with the oxygen concentration. Embryo development takes place in a low oxygen environment until the beginning of the second trimester when large amounts of oxygen are conveyed to meet the growth requirements. High metabolism and oxidative stress are common in the placenta. Reactive oxidative species sometimes harm placental development, but they are also reported to regulate gene transcription and downstream activities such as trophoblast proliferation, invasion, and angiogenesis. Autophagy and apoptosis are two crucial, interconnected processes in the placenta that are often influenced by oxidative stress. The proper interactions between them play an important role in placental homeostasis. However, an imbalance between the protective and destructive mechanisms of autophagy and apoptosis seems to be linked with pregnancy-related disorders such as miscarriage, preeclampsia, and intrauterine growth restriction. Thus, potential therapies to hold oxidative stress in leash, promote placentation, and avoid unwanted apoptosis are discussed. PMID:26693479

  19. Oxidative stress in developmental brain disorders.

    PubMed

    Hayashi, Masaharu; Miyata, Rie; Tanuma, Naoyuki

    2012-01-01

    In order to examine the involvement of oxidative stress in developmental brain disorders, we have performed immunohistochemistry in autopsy brains and enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid and urines of patients. Here, we review our data on the hereditary DNA repair disorders, congenital metabolic errors and childhood-onset neurodegenerative disorders. First, in our studies on hereditary DNA repair disorders, increased oxidative DNA damage and lipid peroxidation were carried out in the degeneration of basal ganglia, intracerebral calcification and cerebellar degeneration in patients with xeroderma pigmentosum, Cockayne syndrome and ataxia-telangiectasia-like disorder, respectively. Next, congenital metabolic errors, apoptosis due to lipid peroxidation seemed to cause neuronal damage in neuronal ceroid-lipofuscinosis. Oxidative stress of DNA combined with reduced expression of antioxidant enzymes occurred in the lesion of the cerebral cortex in mucopolysaccharidoses and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. In childhood-onset neurodegenerative disorders, increased oxidative DNA damage and lipid peroxidation may lead to motor neuron death in spinal muscular atrophy like in amyotrophic lateral sclerosis. In patients with dentatorubral-pallidoluysian atrophy, a triplet repeat disease, deposition of oxidative products of nucleosides and reduced expression of antioxidant enzymes were found in the lenticular nucleus. In contrast, the involvement of oxidative stress is not definite in patients with Lafora disease. Rett syndrome patients showed changes of oxidative stress markers and antioxidant power in urines, although the changes may be related to systemic complications. PMID:22411250

  20. NRF2 Regulates PINK1 Expression under Oxidative Stress Conditions

    PubMed Central

    Murata, Hitoshi; Takamatsu, Hitoshi; Liu, Sulai; Kataoka, Ken; Huh, Nam-ho; Sakaguchi, Masakiyo

    2015-01-01

    Mutations of the PTEN-induced putative kinase 1 (PINK1) gene are a cause of autosomal recessive forms of Parkinson’s disease. Recent studies have revealed that PINK1 is an essential factor for controlling mitochondrial quality, and that it protects cells from oxidative stresses. Although there has been considerable progress in the elucidation of various aspects of PINK1 protein regulation such as activation, stability and degradation, the transcriptional regulation of PINK1 mRNA under stress conditions remains unclear. In this study, we found that nuclear factor (erythroid-derived 2)-like 2 (NRF2), an antioxidant transcription factor, regulates PINK1 expression under oxidative stress conditions. Damaged mitochondria arising from stress conditions induced NRF2-dependent transcription of the PINK1 gene through production of reactive oxygen species (ROS). Either an ROS scavenger or forced expression of KEAP1, a potent inhibitory partner to NRF2, restricted PINK1 expression induced by activated NRF2. Transcriptionally up-regulated PINK1 diminished oxidative stress-associated cell death. The results indicate that PINK1 expression is positively regulated by NRF2 and that the NRF2-PINK1 signaling axis is deeply involved in cell survival. PMID:26555609

  1. Sustained stress response after oxidative stress in trabecular meshwork cells

    PubMed Central

    Li, Guorong; Luna, Coralia; Liton, Paloma B.; Navarro, Iris; Epstein, David L.

    2007-01-01

    Purpose To investigate the mechanisms by which chronic oxidative stress may lead to a sustained stress response similar to that previously observed in the trabecular meshwork (TM) of glaucoma donors. Methods Porcine TM cells were treated with 200 μM H2O2 twice a day for four days and were allowed to recover for three additional days. After the treatment, TM cells were analyzed for generation of intracellular reactive oxygen species (iROS), mitochondrial potential, activation of NF-κB, and the expression of inflammatory markers IL-1α, IL-6, IL-8, and ELAM-1. Potential sources of iROS were evaluated using inhibitors for nitric oxide, nitric oxide synthetase, cyclooxygenase, xanthine oxidase, NADPH oxidase, mitochondrial ROS, and PKC. The role of NF-κB activation in the induction of inflammatory markers was evaluated using the inhibitors Lactacystin and BAY11–7082. Results Chronic oxidative stress simulated by H2O2 exposure of porcine TM cells resulted in the sustained production of iROS by the mitochondria. Inhibition of mitochondrial iROS had a significant inhibitory effect on the activation of NF-κB and the induction of IL-1α, IL-6, IL-8, and ELAM-1 triggered by chronic oxidative stress. Inhibition of NF-κB partially prevented the induction of IL-1α, IL-8, and ELAM-1, but not IL-6. Conclusions Chronic oxidative stress in TM cells induced iROS production in mitochondria. This increase in iROS may contribute to the pathogenesis of the TM in glaucoma by inducing the expression of inflammatory mediators previously observed in glaucoma donors as well as the levels of oxidative damage in the tissue. PMID:18199969

  2. Cocoa Phenolic Extract Protects Pancreatic Beta Cells against Oxidative Stress

    PubMed Central

    Martín, María Ángeles; Ramos, Sonia; Cordero-Herrero, Isabel; Bravo, Laura; Goya, Luis

    2013-01-01

    Diabetes mellitus is associated with reductions in glutathione, supporting the critical role of oxidative stress in its pathogenesis. Antioxidant food components such as flavonoids have a protective role against oxidative stress-induced degenerative and age-related diseases. Flavonoids constitute an important part of the human diet; they can be found in most plant foods, including green tea, grapes or cocoa and possess multiple biological activities. This study investigates the chemo-protective effect of a cocoa phenolic extract (CPE) containing mainly flavonoids against oxidative stress induced by tert-butylhydroperoxide (t-BOOH) on Ins-1E pancreatic beta cells. Cell viability and oxidative status were evaluated. Ins-1E cells treatment with 5–20 μg/mL CPE for 20 h evoked no cell damage and did not alter ROS production. Addition of 50 μM t-BOOH for 2 h increased ROS and carbonyl groups content and decreased reduced glutathione level. Pre-treatment of cells with CPE significantly prevented the t-BOOH-induced ROS and carbonyl groups and returned antioxidant defences to adequate levels. Thus, Ins-1E cells treated with CPE showed a remarkable recovery of cell viability damaged by t-BOOH, indicating that integrity of surviving machineries in the CPE-treated cells was notably protected against the oxidative insult. PMID:23912326

  3. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    PubMed Central

    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. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    PubMed Central

    Kayama, Yosuke; Raaz, Uwe; Jagger, Ann; Adam, Matti; Schellinger, Isabel N.; Sakamoto, Masaya; Suzuki, Hirofumi; Toyama, Kensuke; Spin, Joshua M.; Tsao, Philip S.

    2015-01-01

    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. PMID:26512646

  5. The impact of oxidative stress on hair.

    PubMed

    Trüeb, R M

    2015-12-01

    Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to detoxify the reactive intermediates or to repair the resulting damage. Reactive oxygen species or free radicals are highly reactive molecules that can directly damage lipids, proteins, and DNA. They are generated by a multitude of endogenous and environmental challenges, while the body possesses endogenous defense mechanisms. With age, production of free radicals increases, while the endogenous defense mechanisms decrease. This imbalance leads to progressive damage of cellular structures, presumably resulting in the aging phenotype. While the role of oxidative stress has been widely discussed in skin aging, little focus has been placed on its impact on hair condition. Moreover, most literature on age-related hair changes focuses on alopecia, but it is equally important that the hair fibers that emerge from the scalp exhibit significant age-related changes that have equal impact on the overall cosmetic properties of hair. Sources of oxidative stress with impact on the pre-emerging fiber include: oxidative metabolism, smoking, UVR, and inflammation from microbial, pollutant, or irritant origins. Sources of oxidative stress with impact on the post-emerging fiber include: UVR (enhanced by copper), chemical insults, and oxidized scalp lipids. The role of the dermatologist is recognition and treatment of pre- and post-emerging factors for lifetime scalp and hair health. PMID:26574302

  6. Oxidative Stress and Programmed Cell Death in Yeast

    PubMed Central

    Farrugia, Gianluca; Balzan, Rena

    2012-01-01

    Yeasts, such as Saccharomyces cerevisiae, have long served as useful models for the study of oxidative stress, an event associated with cell death and severe human pathologies. This review will discuss oxidative stress in yeast, in terms of sources of reactive oxygen species (ROS), their molecular targets, and the metabolic responses elicited by cellular ROS accumulation. Responses of yeast to accumulated ROS include upregulation of antioxidants mediated by complex transcriptional changes, activation of pro-survival pathways such as mitophagy, and programmed cell death (PCD) which, apart from apoptosis, includes pathways such as autophagy and necrosis, a form of cell death long considered accidental and uncoordinated. The role of ROS in yeast aging will also be discussed. PMID:22737670

  7. The Pseudomonas aeruginosa universal stress protein PA4352 is essential for surviving anaerobic energy stress.

    PubMed

    Boes, Nelli; Schreiber, Kerstin; Härtig, Elisabeth; Jaensch, Lothar; Schobert, Max

    2006-09-01

    During infection of the cystic fibrosis (CF) lung, Pseudomonas aeruginosa microcolonies are embedded in the anaerobic CF mucus. This anaerobic environment seems to contribute to the formation of more robust P. aeruginosa biofilms and to an increased antibiotic tolerance and therefore promotes persistent infection. This study characterizes the P. aeruginosa protein PA4352, which is important for survival under anaerobic energy stress conditions. PA4352 belongs to the universal stress protein (Usp) superfamily and harbors two Usp domains in tandem. In Escherichia coli, Usp-type stress proteins are involved in survival during aerobic growth arrest and under various other stresses. A P. aeruginosa PA4352 knockout mutant was tested for survival under several stress conditions. We found a decrease in viability of this mutant compared to the P. aeruginosa wild type during anaerobic energy starvation caused by the missing electron acceptors oxygen and nitrate. Consistent with this phenotype under anaerobic conditions, the PA4352 knockout mutant was also highly sensitive to carbonyl cyanide m-chlorophenylhydrazone, the chemical uncoupler of the electron transport chain. Primer extension experiments identified two promoters upstream of the PA4352 gene. One promoter is activated in response to oxygen limitation by the oxygen-sensing regulatory protein Anr. The center of a putative Anr binding site was identified 41.5 bp upstream of the transcriptional start site. The second promoter is active only in the stationary phase, however, independently of RpoS, RelA, or quorum sensing. This is the second P. aeruginosa Usp-type stress protein that we have identified as important for survival under anaerobic conditions, which resembles the environment during persistent infection. PMID:16952944

  8. Oxidative stress, mitochondrial damage and neurodegenerative diseases

    PubMed Central

    Guo, Chunyan; Sun, Li; Chen, Xueping; Zhang, Danshen

    2013-01-01

    Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2+ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative eases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases. PMID:25206509

  9. Drug-Induced Oxidative Stress and Toxicity

    PubMed Central

    Deavall, Damian G.; Martin, Elizabeth A.; Horner, Judith M.; Roberts, Ruth

    2012-01-01

    Reactive oxygen species (ROS) are a byproduct of normal metabolism and have roles in cell signaling and homeostasis. Species include oxygen radicals and reactive nonradicals. Mechanisms exist that regulate cellular levels of ROS, as their reactive nature may otherwise cause damage to key cellular components including DNA, protein, and lipid. When the cellular antioxidant capacity is exceeded, oxidative stress can result. Pleiotropic deleterious effects of oxidative stress are observed in numerous disease states and are also implicated in a variety of drug-induced toxicities. In this paper, we examine the nature of ROS-induced damage on key cellular targets of oxidative stress. We also review evidence implicating ROS in clinically relevant, drug-related side effects including doxorubicin-induced cardiac damage, azidothymidine-induced myopathy, and cisplatin-induced ototoxicity. PMID:22919381

  10. An Exposure to the Oxidized DNA Enhances Both Instability of Genome and Survival in Cancer Cells

    PubMed Central

    Kostyuk, Svetlana V.; Konkova, Marina S.; Ershova, Elizaveta S.; Alekseeva, Anna J.; Smirnova, Tatiana D.; Stukalov, Sergey V.; Kozhina, Ekaterina A.; Shilova, Nadezda V.; Zolotukhina, Tatiana V.; Markova, Zhanna G.; Izhevskaya, Vera L.; Baranova, Ancha; Veiko, Natalia N.

    2013-01-01

    Background Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response. Principal Findings Here we show that oxidized extracellular DNA stimulates the survival of MCF-7 tumor cells. Importantly, in cells exposed to oxidized DNA, the suppression of cell death is accompanied by an increase in the markers of genome instability. Short-term exposure to oxidized DNA results in both single- and double strand DNA breaks. Longer treatments evoke a compensatory response that leads to a decrease in the levels of chromatin fragmentations across cell populations. Exposure to oxidized DNA leads to a decrease in the activity of NRF2 and an increase in the activity of NF-kB and STAT3. A model that describes the role of oxidized DNA released from apoptotic cells in tumor biology is proposed. Conclusions/Significance Survival of cells with an unstable genome may substantially augment progression of malignancy. Further studies of the effects of extracellular DNA on malignant and normal cells are warranted. PMID:24147001

  11. Embryonic exposure to corticosterone modifies the juvenile stress response, oxidative stress and telomere length

    PubMed Central

    Haussmann, Mark F.; Longenecker, Andrew S.; Marchetto, Nicole M.; Juliano, Steven A.; Bowden, Rachel M.

    2012-01-01

    Early embryonic exposure to maternal glucocorticoids can broadly impact physiology and behaviour across phylogenetically diverse taxa. The transfer of maternal glucocorticoids to offspring may be an inevitable cost associated with poor environmental conditions, or serve as a maternal effect that alters offspring phenotype in preparation for a stressful environment. Regardless, maternal glucocorticoids are likely to have both costs and benefits that are paid and collected over different developmental time periods. We manipulated yolk corticosterone (cort) in domestic chickens (Gallus domesticus) to examine the potential impacts of embryonic exposure to maternal stress on the juvenile stress response and cellular ageing. Here, we report that juveniles exposed to experimentally increased cort in ovo had a protracted decline in cort during the recovery phase of the stress response. All birds, regardless of treatment group, shifted to oxidative stress during an acute stress response. In addition, embryonic exposure to cort resulted in higher levels of reactive oxygen metabolites and an over-representation of short telomeres compared with the control birds. In many species, individuals with higher levels of oxidative stress and shorter telomeres have the poorest survival prospects. Given this, long-term costs of glucocorticoid-induced phenotypes may include accelerated ageing and increased mortality. PMID:22072607

  12. Oxidative stress and antioxidant strategies in dermatology.

    PubMed

    Baek, Jinok; Lee, Min-Geol

    2016-07-01

    Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology. PMID:26020527

  13. Oxidative Stress in Schizophrenia: An Integrated Approach

    PubMed Central

    Bitanihirwe, Byron K.Y.; Woo, Tsung-Ung W.

    2010-01-01

    Oxidative stress has been suggested to contribute to the pathophysiology of schizophrenia. In particular, oxidative damage to lipids, proteins, and DNA as observed in schizophrenia is known to impair cell viability and function, which may subsequently account for the deteriorating course of the illness. Currently available evidence points towards an alteration in the activities of enzymatic and nonenzymatic antioxidant systems in schizophrenia. In fact, experimental models have demonstrated that oxidative stress induces behavioural and molecular anomalies strikingly similar to those observed in schizophrenia. These findings suggest that oxidative stress is intimately linked to a variety of pathophysiological processes, such as inflammation, oligodendrocyte abnormalities, mitochondrial dysfunction, hypoactive N-methyl-D-aspartate receptors and the impairment of fast-spiking gamma-aminobutyric acid interneurons.[bkyb1] Such self-sustaining mechanisms may progressively worsen producing the functional and structural consequences associated with schizophrenia. Recent clinical studies have shown antioxidant treatment to be effective in ameliorating schizophrenic symptoms. Hence, identifying viable therapeutic strategies to tackle oxidative stress and the resulting physiological disturbances provide an exciting opportunity for the treatment and ultimately prevention of schizophrenia. PMID:20974172

  14. Potential Modulation of Sirtuins by Oxidative Stress

    PubMed Central

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

    Sirtuins are a conserved family of NAD-dependent protein deacylases. Initially proposed as histone deacetylases, it is now known that they act on a variety of proteins including transcription factors and metabolic enzymes, having a key role in the regulation of cellular homeostasis. Seven isoforms are identified in mammals (SIRT1–7), all of them sharing a conserved catalytic core and showing differential subcellular localization and activities. Oxidative stress can affect the activity of sirtuins at different levels: expression, posttranslational modifications, protein-protein interactions, and NAD levels. Mild oxidative stress induces the expression of sirtuins as a compensatory mechanism, while harsh or prolonged oxidant conditions result in dysfunctional modified sirtuins more prone to degradation by the proteasome. Oxidative posttranslational modifications have been identified in vitro and in vivo, in particular cysteine oxidation and tyrosine nitration. In addition, oxidative stress can alter the interaction with other proteins, like SIRT1 with its protein inhibitor DBC1 resulting in a net increase of deacetylase activity. In the same way, manipulation of cellular NAD levels by pharmacological inhibition of other NAD-consuming enzymes results in activation of SIRT1 and protection against obesity-related pathologies. Nevertheless, further research is needed to establish the molecular mechanisms of redox regulation of sirtuins to further design adequate pharmacological interventions. PMID:26788256

  15. Potential Modulation of Sirtuins by Oxidative Stress.

    PubMed

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

    Sirtuins are a conserved family of NAD-dependent protein deacylases. Initially proposed as histone deacetylases, it is now known that they act on a variety of proteins including transcription factors and metabolic enzymes, having a key role in the regulation of cellular homeostasis. Seven isoforms are identified in mammals (SIRT1-7), all of them sharing a conserved catalytic core and showing differential subcellular localization and activities. Oxidative stress can affect the activity of sirtuins at different levels: expression, posttranslational modifications, protein-protein interactions, and NAD levels. Mild oxidative stress induces the expression of sirtuins as a compensatory mechanism, while harsh or prolonged oxidant conditions result in dysfunctional modified sirtuins more prone to degradation by the proteasome. Oxidative posttranslational modifications have been identified in vitro and in vivo, in particular cysteine oxidation and tyrosine nitration. In addition, oxidative stress can alter the interaction with other proteins, like SIRT1 with its protein inhibitor DBC1 resulting in a net increase of deacetylase activity. In the same way, manipulation of cellular NAD levels by pharmacological inhibition of other NAD-consuming enzymes results in activation of SIRT1 and protection against obesity-related pathologies. Nevertheless, further research is needed to establish the molecular mechanisms of redox regulation of sirtuins to further design adequate pharmacological interventions. PMID:26788256

  16. Mitochondrial oxidative stress promotes atrial fibrillation

    PubMed Central

    Xie, Wenjun; Santulli, Gaetano; Reiken, Steven R.; Yuan, Qi; Osborne, Brent W.; Chen, Bi-Xing; Marks, Andrew R.

    2015-01-01

    Oxidative stress has been suggested to play a role in the pathogenesis of atrial fibrillation (AF). Indeed, the prevalence of AF increases with age as does oxidative stress. However, the mechanisms linking redox state to AF are not well understood. In this study we identify a link between oxidative stress and aberrant intracellular Ca2+ release via the type 2 ryanodine receptor (RyR2) that promotes AF. We show that RyR2 are oxidized in the atria of patients with chronic AF compared with individuals in sinus rhythm. To dissect the molecular mechanism linking RyR2 oxidation to AF we used two murine models harboring RyR2 mutations that cause intracellular Ca2+ leak. Mice with intracellular Ca2+ leak exhibited increased atrial RyR2 oxidation, mitochondrial dysfunction, reactive oxygen species (ROS) production and AF susceptibility. Both genetic inhibition of mitochondrial ROS production and pharmacological treatment of RyR2 leakage prevented AF. Collectively, our results indicate that alterations of RyR2 and mitochondrial ROS generation form a vicious cycle in the development of AF. Targeting this previously unrecognized mechanism could be useful in developing effective interventions to prevent and treat AF. PMID:26169582

  17. Oxidative Stress and the Homeodynamics of Iron Metabolism

    PubMed Central

    Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

    Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress. PMID:25970586

  18. Oxidative stress, NADPH oxidases, and arteries.

    PubMed

    Sun, Qi-An; Runge, Marschall S; Madamanchi, Nageswara R

    2016-05-10

    Atherosclerosis and its major complications - myocardial infarction and stroke - remain major causes of death and disability in the United States and world-wide. Indeed, with dramatic increases in obesity and diabetes mellitus, the prevalence and public health impact of cardiovascular diseases (CVD) will likely remain high. Major advances have been made in development of new therapies to reduce the incidence of atherosclerosis and CVD, in particular for treatment of hypercholesterolemia and hypertension. Oxidative stress is the common mechanistic link for many CVD risk factors. However, only recently have the tools existed to study the interface between oxidative stress and CVD in animal models. The most important source of reactive oxygen species (and hence oxidative stress) in vascular cells are the multiple forms of enzymes nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Recently published and emerging studies now clearly establish that: 1) NADPH oxidases are of critical importance in atherosclerosis and hypertension in animal models; 2) given the tissue-specific expression of key components of NADPH oxidase, it may be possible to target vascular oxidative stress for prevention of CVD. PMID:25649240

  19. Oxidative Stress Control by Apicomplexan Parasites

    PubMed Central

    Izui, Natália M.; Schettert, Isolmar; Liebau, Eva

    2015-01-01

    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. PMID:25722976

  20. Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response.

    PubMed

    Busch, Andrea W U; Montgomery, Beronda L

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

  1. Interdependence of tetrapyrrole metabolism, the generation of oxidative stress and the mitigative oxidative stress response

    PubMed Central

    Busch, Andrea W.U.; Montgomery, Beronda L.

    2015-01-01

    Tetrapyrroles are involved in light harvesting and light perception, electron-transfer reactions, and as co-factors for key enzymes and sensory proteins. Under conditions in which cells exhibit stress-induced imbalances of photosynthetic reactions, or light absorption exceeds the ability of the cell to use photoexcitation energy in synthesis reactions, redox imbalance can occur in photosynthetic cells. Such conditions can lead to the generation of reactive oxygen species (ROS) associated with alterations in tetrapyrrole homeostasis. ROS accumulation can result in cellular damage and detrimental effects on organismal fitness, or ROS molecules can serve as signals to induce a protective or damage-mitigating oxidative stress signaling response in cells. Induced oxidative stress responses include tetrapyrrole-dependent and -independent mechanisms for mitigating ROS generation and/or accumulation. Thus, tetrapyrroles can be contributors to oxidative stress, but are also essential in the oxidative stress response to protect cells by contributing to detoxification of ROS. In this review, we highlight the interconnection and interdependence of tetrapyrrole metabolism with the occurrence of oxidative stress and protective oxidative stress signaling responses in photosynthetic organisms. PMID:25618582

  2. Thiol specific oxidative stress response in Mycobacteria.

    PubMed

    Dosanjh, Nirpjit S; Rawat, Mamta; Chung, Ji-Hae; Av-Gay, Yossef

    2005-08-01

    The cellular response of mycobacteria to thiol specific oxidative stress was studied in Mycobacterium bovis BCG cultures. Two-dimensional gel electrophoresis revealed that upon diamide treatment at least 60 proteins were upregulated. Fourteen of these proteins were identified by MALDI-MS; four proteins, AhpC, Tpx, GroEL2, and GroEL1 are functionally related to oxidative stress response; eight proteins, LeuC, LeuD, Rv0224c, Rv3029c, AsnB, Rv2971, PheA and HisH are classified as part of the bacterial intermediary metabolism and respiration pathways; protein EchA14 belong to lipid metabolism, and NrdE, belongs to the mycobacterial information pathway category. Reverse transcription followed by quantitative real time PCR in response to diamide stress demonstrated that protein expression is directly proportional to the corresponding gene transcription. PMID:16006064

  3. Protein Quality Control Under Oxidative Stress Conditions

    PubMed Central

    Dahl, Jan-Ulrik; Gray, Michael J.; Jakob, Ursula

    2015-01-01

    Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the E. coli protein RidA, and the mammalian protein α2-macroglobin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and of how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation. PMID:25698115

  4. Protein quality control under oxidative stress conditions.

    PubMed

    Dahl, Jan-Ulrik; Gray, Michael J; Jakob, Ursula

    2015-04-10

    Accumulation of reactive oxygen and chlorine species (RO/CS) is generally regarded to be a toxic and highly undesirable event, which serves as contributing factor in aging and many age-related diseases. However, it is also put to excellent use during host defense, when high levels of RO/CS are produced to kill invading microorganisms and regulate bacterial colonization. Biochemical and cell biological studies of how bacteria and other microorganisms deal with RO/CS have now provided important new insights into the physiological consequences of oxidative stress, the major targets that need protection, and the cellular strategies employed by organisms to mitigate the damage. This review examines the redox-regulated mechanisms by which cells maintain a functional proteome during oxidative stress. We will discuss the well-characterized redox-regulated chaperone Hsp33, and we will review recent discoveries demonstrating that oxidative stress-specific activation of chaperone function is a much more widespread phenomenon than previously anticipated. New members of this group include the cytosolic ATPase Get3 in yeast, the Escherichia coli protein RidA, and the mammalian protein α2-macroglobulin. We will conclude our review with recent evidence showing that inorganic polyphosphate (polyP), whose accumulation significantly increases bacterial oxidative stress resistance, works by a protein-like chaperone mechanism. Understanding the relationship between oxidative and proteotoxic stresses will improve our understanding of both host-microbe interactions and how mammalian cells combat the damaging side effects of uncontrolled RO/CS production, a hallmark of inflammation. PMID:25698115

  5. Differential oxidative stress responses in castor semilooper, Achaea janata.

    PubMed

    Pavani, Ayinampudi; Chaitanya, R K; Chauhan, Vinod K; Dasgupta, Anwesha; Dutta-Gupta, Aparna

    2015-11-01

    Balance between reactive oxygen species (ROS) and the antioxidant (AO) defense mechanisms is vital for organism survival. Insects serve as an ideal model to elucidate oxidative stress responses as they are prone to different kinds of stress during their life cycle. The present study demonstrates the modulation of AO enzyme gene expression in the insect pest, Achaea janata (castor semilooper), when subjected to different oxidative stress stimuli. Antioxidant enzymes' (catalase (Cat), superoxide dismutase (Sod), glutathione-S-transferase (GST) and glutathione peroxidase (Gpx)) partial coding sequences were cloned and characterized from larval whole body. Tissue expression studies reveal a unique pattern of AO genes in the larval tissues with maximum expression in the gut and fat body. Ontogeny profile depicts differential expression pattern through the larval developmental stages for each AO gene studied. Using quantitative RT-PCR, the expression pattern of these genes was monitored during sugar-induced (d-galactose feeding), infection-induced (Gram positive, Gram negative and non-pathogenic bacteria) and pesticide-induced oxidative stress (Bt Cry toxin). d-Galactose feeding differentially modulates the expression of AO genes in the larval gut and fat body. Immune challenge with Escherichia coli induces robust upregulation of AO genes when compared to Bacillus coagulans and Bacillus cereus in the larval fat body and gut. Cry toxin feeding predominantly induced GST upregulation in the gut. The current study suggests that though there are multiple ways of generation of oxidative stress in the insect, the organism tailors its response by insult- and tissue-specific recruitment of the antioxidant players and their differential regulation for each inducer. PMID:26455997

  6. Inflammatory and oxidative stress in rotavirus infection

    PubMed Central

    Guerrero, Carlos A; Acosta, Orlando

    2016-01-01

    Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines. PMID:27175349

  7. Inflammatory and oxidative stress in rotavirus infection.

    PubMed

    Guerrero, Carlos A; Acosta, Orlando

    2016-05-12

    Rotaviruses are the single leading cause of life-threatening diarrhea affecting children under 5 years of age. Rotavirus entry into the host cell seems to occur by sequential interactions between virion proteins and various cell surface molecules. The entry mechanisms seem to involve the contribution of cellular molecules having binding, chaperoning and oxido-reducing activities. It appears to be that the receptor usage and tropism of rotaviruses is determined by the species, cell line and rotavirus strain. Rotaviruses have evolved functions which can antagonize the host innate immune response, whereas are able to induce endoplasmic reticulum (ER) stress, oxidative stress and inflammatory signaling. A networking between ER stress, inflammation and oxidative stress is suggested, in which release of calcium from the ER increases the generation of mitochondrial reactive oxygen species (ROS) leading to toxic accumulation of ROS within ER and mitochondria. Sustained ER stress potentially stimulates inflammatory response through unfolded protein response pathways. However, the detailed characterization of the molecular mechanisms underpinning these rotavirus-induced stressful conditions is still lacking. The signaling events triggered by host recognition of virus-associated molecular patterns offers an opportunity for the development of novel therapeutic strategies aimed at interfering with rotavirus infection. The use of N-acetylcysteine, non-steroidal anti-inflammatory drugs and PPARγ agonists to inhibit rotavirus infection opens a new way for treating the rotavirus-induced diarrhea and complementing vaccines. PMID:27175349

  8. Cofactor binding protects flavodoxin against oxidative stress.

    PubMed

    Lindhoud, Simon; van den Berg, Willy A M; van den Heuvel, Robert H H; Heck, Albert J R; van Mierlo, Carlo P M; van Berkel, Willem J H

    2012-01-01

    In organisms, various protective mechanisms against oxidative damaging of proteins exist. Here, we show that cofactor binding is among these mechanisms, because flavin mononucleotide (FMN) protects Azotobacter vinelandii flavodoxin against hydrogen peroxide-induced oxidation. We identify an oxidation sensitive cysteine residue in a functionally important loop close to the cofactor, i.e., Cys69. Oxidative stress causes dimerization of apoflavodoxin (i.e., flavodoxin without cofactor), and leads to consecutive formation of sulfinate and sulfonate states of Cys69. Use of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) reveals that Cys69 modification to a sulfenic acid is a transient intermediate during oxidation. Dithiothreitol converts sulfenic acid and disulfide into thiols, whereas the sulfinate and sulfonate forms of Cys69 are irreversible with respect to this reagent. A variable fraction of Cys69 in freshly isolated flavodoxin is in the sulfenic acid state, but neither oxidation to sulfinic and sulfonic acid nor formation of intermolecular disulfides is observed under oxidising conditions. Furthermore, flavodoxin does not react appreciably with NBD-Cl. Besides its primary role as redox-active moiety, binding of flavin leads to considerably improved stability against protein unfolding and to strong protection against irreversible oxidation and other covalent thiol modifications. Thus, cofactors can protect proteins against oxidation and modification. PMID:22829943

  9. Oxidative stress and proteasome inhibitors in multiple myeloma.

    PubMed

    Lipchick, Brittany C; Fink, Emily E; Nikiforov, Mikhail A

    2016-03-01

    Multiple myeloma is a form of plasma cell neoplasm that accounts for approximately 10% of all hematological malignancies. Recently, several novel drugs have been discovered that almost doubled the overall survival of multiple myeloma patients. One of these drugs, the first-in-class proteasome inhibitor bortezomib (Velcade) has demonstrated remarkable response rates in multiple myeloma patients, and yet, currently this disease remains incurable. The major factor undermining the success of multiple myeloma treatment is a rapidly emerging resistance to the available therapy. Thus, the development of stand-alone or adjuvant anti-myeloma agents becomes of paramount importance. Overproduction of intracellular reactive oxygen species (ROS) often accompanies malignant transformation due to oncogene activation and/or enhanced metabolism in tumor cells. As a result, these cells possess higher levels of ROS and lower levels of antioxidant molecules compared to their normal counterparts. Unbalanced production of ROS leads to oxidative stress which, if left unchecked, could be toxic for the cell. In multiple myeloma cells where high rates of immunoglobulin synthesis is an additional factor contributing to overproduction of ROS, further induction of oxidative stress can be an effective strategy to cope with this disease. Here we will review the available data on the role of oxidative stress in the cytotoxicity of proteasome inhibitors and the use of ROS-inducing compounds as anti-myeloma agents. PMID:26827824

  10. Oxidative stress induced carbonylation in human plasma.

    PubMed

    Madian, Ashraf G; Diaz-Maldonado, Naomi; Gao, Qiang; Regnier, Fred E

    2011-10-19

    The focus of this study was on the assessment of technology that might be of clinical utility in identification, quantification, characterization of carbonylation in human plasma proteins. Carbonylation is widely associated with oxidative stress diseases. Breast cancer patient samples were chosen as a stress positive case based on the fact that oxidative stress has been reported to be elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that breast cancer patients in this study were indeed experiencing significant oxidative stress. Carbonyl groups in proteins from freshly drawn blood were derivatized with biotin hydrazide after which the samples were dialyzed and the biotinylated proteins subsequently selected, digested and labeled with iTRAQ™ heavy isotope coding reagent(s). Four hundred sixty proteins were identified and quantified, 95 of which changed 1.5 fold or more in concentration. Beyond confirming the utility of the analytical method, association of protein carbonylation was examined as well. Nearly one fourth of the selected proteins were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by unbiased knowledge assembly methods indicated the most likely disease associated with the proteins was breast neoplasm. Pathway analysis showed the proteins which changed in carbonylation were strongly associated with Brca1, the breast cancer type-1 susceptibility protein. Pathway analysis indicated the major molecular functions of these proteins are defense, immunity and nucleic acid binding. PMID:21856457

  11. Oxidative stress induced carbonylation in human plasma

    PubMed Central

    Madian, Ashraf G.; Diaz-Maldonado, Naomi; Gao, Qiang; Regnier, Fred E.

    2011-01-01

    The focus of this study was on the assessment of technology that might be of clinical utility in identification, quantification, characterization of carbonylation in human plasma proteins. Carbonylation is widely associated with oxidative stress diseases. Breast cancer patient samples were chosen as a stress positive case based on the fact that oxidative stress has been reported to be elevated in this disease. Measurements of 8-isoprostane in plasma confirmed that breast cancer patients in this study were indeed experiencing significant oxidative stress. Carbonyl groups in proteins from freshly drawn blood were derivatized with biotin hydrazide after which the samples were dialyzed and the biotinylated proteins subsequently selected, digested and labeled with iTRAQ™ heavy isotope coding reagent(s). Four hundred sixty proteins were identified and quantified, 95 of which changed 1.5 fold or more in concentration. Beyond confirming the utility of the analytical method, association of protein carbonylation was examined as well. Nearly one fourth of the selected proteins were of cytoplasmic, nuclear, or membrane origin. Analysis of the data by unbiased knowledge assembly methods indicated the most likely disease associated with the proteins was breast neoplasm. Pathway analysis showed the proteins which changed in carbonylation were strongly associated with Brca1, the breast cancer type-1 susceptibility protein. Pathway analysis indicated the major molecular functions of these proteins are defense, immunity and nucleic acid binding. PMID:21856457

  12. Measuring oxidative stress resistance of Caenorhabditis elegans in 96-well microtiter plates.

    PubMed

    Possik, Elite; Pause, Arnim

    2015-01-01

    Oxidative stress, which is the result of an imbalance between production and detoxification of reactive oxygen species, is a major contributor to chronic human disorders, including cardiovascular and neurodegenerative diseases, diabetes, aging, and cancer. Therefore, it is important to study oxidative stress not only in cell systems but also using whole organisms. C. elegans is an attractive model organism to study the genetics of oxidative stress signal transduction pathways, which are highly evolutionarily conserved. Here, we provide a protocol to measure oxidative stress resistance in C. elegans in liquid. Briefly, ROS-inducing reagents such as paraquat (PQ) and H2O2 are dissolved in M9 buffer, and solutions are aliquoted in the wells of a 96 well microtiter plate. Synchronized L4/young adult C. elegans animals are transferred to the wells (5-8 animals/well) and survival is measured every hour until most worms are dead. When performing an oxidative stress resistance assay using a low concentration of stressors in plates, aging might influence the behavior of animals upon oxidative stress, which could lead to an incorrect interpretation of the data. However, in the assay described herein, this problem is unlikely to occur since only L4/young adult animals are being used. Moreover, this protocol is inexpensive and results are obtained in one day, which renders this technique attractive for genetic screens. Overall, this will help to understand oxidative stress signal transduction pathways, which could be translated into better characterization of oxidative stress-associated human disorders. PMID:25993260

  13. Higher in vitro resistance to oxidative stress in extra-pair offspring.

    PubMed

    Losdat, S; Helfenstein, F; Saladin, V; Richner, H

    2011-11-01

    Oxidative stress is considered to act as a universal physiological constraint in life-history evolution of animals. This should be of interest for extra-pair paternity behaviour, and we tested here the prediction that offspring arising from extra-pair matings of female great tits show higher resistance to oxidative stress than within-pair offspring. Resistance to oxidative stress, measured as the whole blood resistance to a controlled free-radical attack, was significantly higher for extra-pair offspring as predicted although these were not heavier or in better body condition than within-pair offspring. Since resistance to oxidative stress has been suggested to enhance survival and reproductive rates, extra-pair offspring with superior resistance to oxidative stress, be it through maternal effects or paternal inheritance, may achieve higher fitness and thus provide significant indirect fitness benefits to their mothers. In addition, because oxidative stress affects colour signals and sperm traits, females may also gain fitness benefits by producing sons that are more attractive (sexy-sons hypothesis) and have sperm of superior quality (sexy-sperm hypothesis). Heritability of resistance to oxidative stress as well as maternal effects may both act as proximate mechanisms for the observed result. Disentangling these two mechanisms would require an experimental approach. Future long-term studies should also aim at experimentally testing whether higher resistance to oxidative stress of EP nestlings indeed translates into fitness benefits to females. PMID:21899636

  14. Folliculin Regulates Ampk-Dependent Autophagy and Metabolic Stress Survival

    PubMed Central

    Nouët, Yann; Yan, Ming; Gingras, Marie-Claude; Schmeisser, Kathrin; Panaite, Lorena; Dupuy, Fanny; Kharitidi, Dmitri; Chotard, Laëtitia; Jones, Russell G.; Hall, David H.; Pause, Arnim

    2014-01-01

    Dysregulation of AMPK signaling has been implicated in many human diseases, which emphasizes the importance of characterizing AMPK regulators. The tumor suppressor FLCN, responsible for the Birt-Hogg Dubé renal neoplasia syndrome (BHD), is an AMPK-binding partner but the genetic and functional links between FLCN and AMPK have not been established. Strikingly, the majority of naturally occurring FLCN mutations predisposing to BHD are predicted to produce truncated proteins unable to bind AMPK, pointing to the critical role of this interaction in the tumor suppression mechanism. Here, we demonstrate that FLCN is an evolutionarily conserved negative regulator of AMPK. Using Caenorhabditis elegans and mammalian cells, we show that loss of FLCN results in constitutive activation of AMPK which induces autophagy, inhibits apoptosis, improves cellular bioenergetics, and confers resistance to energy-depleting stresses including oxidative stress, heat, anoxia, and serum deprivation. We further show that AMPK activation conferred by FLCN loss is independent of the cellular energy state suggesting that FLCN controls the AMPK energy sensing ability. Together, our data suggest that FLCN is an evolutionarily conserved regulator of AMPK signaling that may act as a tumor suppressor by negatively regulating AMPK function. PMID:24763318

  15. Oxidative stress and mitochondrial dysfunction in fibromyalgia.

    PubMed

    Cordero, Mario D; de Miguel, Manuel; Carmona-López, Inés; Bonal, Pablo; Campa, Francisco; Moreno-Fernández, Ana María

    2010-01-01

    Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and pathophysiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM. Furthermore, it is controversial the role of mitochondria in the oxidant imbalance documented in FM. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with FM. To this respect, Coenzyme Q10 (CoQ10) deficiency, an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant, alters mitochondria function and mitochondrial respiratory complexes organization and leading to increased ROS generation. Recently have been showed CoQ10 deficiency in blood mononuclear cells in FM patients, so if the hypothesis that mitochondrial dysfunction is the origin of oxidative stress in FM patients is demonstrated, could help to understand the complex pathophysiology of this disorder and may lead to development of new therapeutic strategies for prevention and treatment of this disease. PMID:20424583

  16. Selected oxidative stress markers in gynecological laparoscopy

    PubMed Central

    Koźlik, Jacek; Przybyłowska, Joanna; Mikrut, Kinga; Zwoliński, Jacek; Piątek, Jacek; Sobczak, Paweł

    2014-01-01

    Introduction The surgical stress response after laparoscopy is smaller when compared with open surgery, and it is expected that after minimally invasive surgery the possible development of oxidative stress will be less severe. Aim To evaluate markers of pro-oxidant activity – levels of lipid peroxides and malondialdehyde – and activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase in the perioperative period in patients undergoing gynecological laparoscopy and to determine whether the duration of laparoscopy can affect these changes. Material and methods The study included 64 patients, divided into two groups: group 1 with duration of laparoscopy up to 20 min, and group 2 with duration of the operation over 40 min. Blood samples were collected before anesthesia, 5 min after release of pneumoperitoneum, and 10 h after surgery. Results A statistically significant increase in the levels of lipid peroxides and malondialdehyde in samples collected after surgery was found in comparison with values obtained before surgery. Also statistically significant differences existed between groups of patients with different duration of surgery. Superoxide dismutase and glutathione peroxidase activity values were significantly decreased. They were also significantly different between the two groups with different duration of surgery. Conclusions In our study, levels of the markers of pro-oxidant activity increased and levels of the markers of antioxidant enzymes decreased, suggesting development of oxidative stress. The duration of laparoscopic procedures affects the severity of the presented changes. PMID:25960799

  17. Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

    PubMed Central

    Consales, Claudia; Merla, Caterina; Marino, Carmela; Benassi, Barbara

    2012-01-01

    Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system. PMID:22991514

  18. Airway oxidative stress in chronic cough

    PubMed Central

    2013-01-01

    Background The mechanisms of chronic cough are unclear. Many reactive oxygen species affect airway sensory C-fibres which are capable to induce cough. Several chronic lung diseases are characterised by cough and oxidative stress. In asthma, an association between the cough severity and airway oxidative stress has been demonstrated. The present study was conducted to investigate whether airway oxidative stress is associated with chronic cough in subjects without chronic lung diseases. Methods Exhaled breath condensate samples were obtained in 43 non-smoking patients with chronic cough and 15 healthy subjects. Exclusion criteria included a doctor’s diagnosis of any lung disorders and any abnormality in lung x-ray. The concentration of 8-isoprostane was measured. In addition, the patients filled in Leicester Cough Questionnaire and underwent hypertonic saline cough provocation test, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, and histamine airway challenge. In a subgroup of patients the measurements were repeated during 12 weeks’ treatment with inhaled budesonide, 800 ug/day. Results The 8-isoprostane concentrations were higher in the cough patients than in the healthy subjects (24.6 ± 1.2 pg/ml vs. 10.1 ± 1.7 pg/ml, p = 0.045). The 8-isoprostane concentration was associated with the Leicester Cough Questionnaire total score (p = 0.044) but not with the cough sensitivity to saline or other tests. Budesonide treatment did not affect the 8-isoprostane concentrations. Conclusions Chronic cough seems to be associated with airway oxidative stress in subjects with chronic cough but without chronic lung diseases. This finding may help to develop novel antitussive drugs. Trial registration The study was registered in ClinicalTrials.gov database (KUH5801112), identifier NCT00859274. PMID:24294924

  19. Oxidative stress and immunotoxicity induced by graphene oxide in zebrafish.

    PubMed

    Chen, Minjie; Yin, Junfa; Liang, Yong; Yuan, Shaopeng; Wang, Fengbang; Song, Maoyong; Wang, Hailin

    2016-05-01

    Graphene oxide (GO) has been extensively explored as a promising nanomaterial for applications in biology because of its unique properties. Therefore, systematic investigation of GO toxicity is essential to determine its fate in the environment and potential adverse effects. In this study, acute toxicity, oxidative stress and immunotoxicity of GO were investigated in zebrafish. No obvious acute toxicity was observed when zebrafish were exposed to 1, 5, 10 or 50mg/L GO for 14 days. However, a number of cellular alterations were detected by histological analysis of the liver and intestine, including vacuolation, loose arrangement of cells, histolysis and disintegration of cell boundaries. As evidence for oxidative stress, malondialdehyde levels and superoxide dismutase and catalase activities were increased and glutathione content was decreased in the liver after treatment with GO. GO treatment induced an immune response in zebrafish, as demonstrated by increased expression of tumor necrosis factor α, interleukin-1 β, and interleukin-6 in the spleen. Our findings demonstrated that GO administration in an aquatic system can cause oxidative stress and immune toxicity in adult zebrafish. To our knowledge, this is the first report of immune toxicity of GO in zebrafish. PMID:26921726

  20. Reproduction is not costly in terms of oxidative stress.

    PubMed

    Ołdakowski, Łukasz; Wasiluk, Aleksandra; Sadowska, Edyta T; Koteja, Paweł; Taylor, Jan R E

    2015-12-01

    One of the core assumptions of life-history theory is the negative trade-off between current and future reproduction. Investment in current reproduction is expected to decrease future reproductive success or survival, but the physiological mechanisms underlying these costs are still obscure. To test for a role of oxidative stress, we measured oxidative damage to lipids and proteins in liver, heart, kidneys and muscles, as well as the level of antioxidants (total glutathione and catalase), in breeding and non-breeding bank voles. We used females from lines selected for high aerobic metabolism and non-selected control lines and manipulated their reproductive investment by decreasing or increasing litter size. Unlike in most previous studies, the females reared four consecutive litters (the maximum possible during a breeding season). Contrary to predictions, oxidative damage in reproducing females was decreased or not changed, and did not differ between the selected and control lines. Oxidative damage to lipids and proteins in the liver was lower in females that weaned enlarged litters than in non-breeding ones, and was intermediate in those with reduced litters. Oxidative damage to proteins in the heart also tended to be lower in breeding females than in non-breeding ones. A negative relationship between the level of oxidative damage and activity of catalase in kidneys indicated a protective action of antioxidants. In conclusion, our study falsified the hypothesis that oxidative stress is a part of the proximate physiological mechanism underlying the fundamental life-history trade-off between current and future reproduction. PMID:26519508

  1. Oxidative Stress and Air Pollution Exposure

    PubMed Central

    Lodovici, Maura; Bigagli, Elisabetta

    2011-01-01

    Air pollution is associated with increased cardiovascular and pulmonary morbidity and mortality. The mechanisms of air pollution-induced health effects involve oxidative stress and inflammation. As a matter of fact, particulate matter (PM), especially fine (PM2.5, PM < 2.5 μm) and ultrafine (PM0.1, PM < 0.1 μm) particles, ozone, nitrogen oxides, and transition metals, are potent oxidants or able to generate reactive oxygen species (ROS). Oxidative stress can trigger redox-sensitive pathways that lead to different biological processes such as inflammation and cell death. However, it does appear that the susceptibility of target organ to oxidative injury also depends upon its ability to upregulate protective scavenging systems. As vehicular traffic is known to importantly contribute to PM exposure, its intensity and quality must be strongly relevant determinants of the qualitative characteristics of PM spread in the atmosphere. Change in the composition of this PM is likely to modify its health impact. PMID:21860622

  2. Oxidative Stress and Periodontal Disease in Obesity

    PubMed Central

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

    2016-01-01

    Abstract 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

  3. Oxidative Stress and Periodontal Disease in Obesity.

    PubMed

    Dursun, Erhan; Akaln, 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

  4. Impact of oxidative and osmotic stresses on Candida albicans biofilm formation.

    PubMed

    Pemmaraju, Suma C; Padmapriya, Kumar; Pruthi, Parul A; Prasad, R; Pruthi, Vikas

    2016-09-01

    Candida albicans possesses an ability to grow under different host-driven stress conditions by developing robust protective mechanisms. In this investigation the focus was on the impact of osmotic (2M NaCl) and oxidative (5 mM H2O2) stress conditions during C. albicans biofilm formation. Oxidative stress enhanced extracellular DNA secretion into the biofilm matrix, increased the chitin level, and reduced virulence factors, namely phospholipase and proteinase activity, while osmotic stress mainly increased extracellular proteinase and decreased phospholipase activity. Fourier transform infrared and nuclear magnetic resonance spectroscopy analysis of mannan isolated from the C. albicans biofilm cell wall revealed a decrease in mannan content and reduced β-linked mannose moieties under stress conditions. The results demonstrate that C. albicans adapts to oxidative and osmotic stress conditions by inducing biofilm formation with a rich exopolymeric matrix, modulating virulence factors as well as the cell wall composition for its survival in different host niches. PMID:27472386

  5. ALS and Oxidative Stress: The Neurovascular Scenario

    PubMed Central

    Thakur, Keshav; Gupta, Pawan Kumar

    2013-01-01

    Oxidative stress and angiogenic factors have been placed as the prime focus of scientific investigations after an establishment of link between vascular endothelial growth factor promoter (VEGF), hypoxia, and amyotrophic lateral sclerosis (ALS) pathogenesis. Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter and mutant superoxide dismutase 1 (SOD1) which are characterised by atrophy and muscle weakness resulted in phenotype resembling human ALS in mice. This results in lower motor neurodegeneration thus establishing an important link between motor neuron degeneration, vasculature, and angiogenic molecules. In this review, we have presented human, animal, and in vitro studies which suggest that molecules like VEGF have a therapeutic, diagnostic, and prognostic potential in ALS. Involvement of vascular growth factors and hypoxia response elements also highlights the converging role of oxidative stress and neurovascular network for understanding and treatment of various neurodegenerative disorders like ALS. PMID:24367722

  6. Oxidative stress and Parkinson’s disease

    PubMed Central

    Blesa, Javier; Trigo-Damas, Ines; Quiroga-Varela, Anna; Jackson-Lewis, Vernice R.

    2015-01-01

    Parkinson disease (PD) is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra pars compacta 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 PD. Environmental factors, such as neurotoxins, pesticides, insecticides, dopamine (DA) itself, and genetic mutations in PD-associated 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. PMID:26217195

  7. Oxidative stress in coronary artery bypass surgery

    PubMed Central

    Dias, Amaury Edgardo Mont’Serrat Ávila Souza; Melnikov, Petr; Cônsolo, Lourdes Zélia Zanoni

    2015-01-01

    Objective The aim of this prospective study was to assess the dynamics of oxidative stress during coronary artery bypass surgery with cardiopulmonary bypass. Methods Sixteen patients undergoing coronary artery bypass grafting were enrolled. Blood samples were collected from the systemic circulation during anesthesia induction (radial artery - A1), the systemic venous return (B1 and B2) four minutes after removal of the aortic cross-clamping, of the coronary sinus (CS1 and CS2) four minutes after removal of the aortic cross-clamping and the systemic circulation four minutes after completion of cardiopulmonary bypass (radial artery - A2). The marker of oxidative stress, malondialdehyde, was measured using spectrophotometry. Results The mean values of malondialdehyde were (ng/dl): A1 (265.1), B1 (490.0), CS1 (527.0), B2 (599.6), CS2 (685.0) and A2 (527.2). Comparisons between A1/B1, A1/CS1, A1/B2, A1/CS2, A1/A2 were significant, with ascending values (P<0.05). Comparisons between the measurements of the coronary sinus and venous reservoir after the two moments of reperfusion (B1/B2 and CS1/CS2) were higher when CS2 (P<0.05). Despite higher values ​​after the end of cardiopulmonary bypass (A2), when compared to samples of anesthesia (A1), those show a downward trend when compared to the samples of the second moment of reperfusion (CS2) (P<0.05). Conclusion The measurement of malondialdehyde shows that coronary artery bypass grafting with cardiopulmonary bypass is accompanied by increase of free radicals and this trend gradually decreases after its completion. Aortic clamping exacerbates oxidative stress but has sharper decline after reperfusion when compared to systemic metabolism. The behavior of thiobarbituric acid species indicates that oxidative stress is an inevitable pathophysiological component. PMID:27163415

  8. Oxidative Stress and Nitric Oxide in Autism Spectrum Disorder and Other Neuropsychiatric Disorders.

    PubMed

    Yui, Kunio; Kawasaki, Yohei; Yamada, Hiroshi; Ogawa, Shintaro

    2016-01-01

    The etiology of autism spectrum disorder (ASD) remains unclear; however, the toxic environmental exposure to oxidative stress has been suggested to play an important role in its pathogenesis. A loss of balance between oxidative stress and antioxidant capacity produces an excess of reactive nitrogen species (RNS) such as nitric oxide (NO). Polyunsaturated fatty acids (PUFAs), particularly arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, are closely related to NO and NO synthase. In the pathophysiology of ASD, NO is related to the activity of primary PUFAs. NO modulates short- and long-term synaptic plasticity and plays essential roles in the regulation of a wide range of physiological processes including neurotransmission. NO affects the function of reactive oxygen species (ROS) in the local cellular milieu, in which biological antioxidants are present. NO plays a double role in the organism showing both neuroprotective and neurotoxic effects. Redox imbalance leads to the activation of the neurotoxic pathway, suggesting crossroads for the neurotoxic or neuroprotective effects of NO. Furthermore, the dual role of NO could depend on the adaptive functions of the antioxidant capacity and oxidative stress-related ROS/RNS as the disease progresses. Increased concentrations of arachidonic acid promote neuronal survival, and the dysregulation of the NO system plays an important role in the pathophysiology of bipolar disorder and recurrent depressive disorders. Therefore, the NO system could provide useful drug targets for these diseases. NO and NO donors also show therapeutic potential for Alzheimer's disease and schizophrenia with refractory symptoms and cognitive dysfunction. PMID:27071787

  9. Lamins as mediators of oxidative stress

    SciTech Connect

    Sieprath, Tom; Darwiche, Rabih; De Vos, Winnok H.

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer The nuclear lamina defines structural and functional properties of the cell nucleus. Black-Right-Pointing-Pointer Lamina dysfunction leads to a broad spectrum of laminopathies. Black-Right-Pointing-Pointer Recent data is reviewed connecting laminopathies to oxidative stress. Black-Right-Pointing-Pointer A framework is proposed to explain interactions between lamins and oxidative stress. -- Abstract: The nuclear lamina defines both structural and functional properties of the eukaryotic cell nucleus. Mutations in the LMNA gene, encoding A-type lamins, lead to a broad spectrum of diseases termed laminopathies. While different hypotheses have been postulated to explain disease development, there is still no unified view on the mechanistic basis of laminopathies. Recent observations indicate that laminopathies are often accompanied by altered levels of reactive oxygen species and a higher susceptibility to oxidative stress at the cellular level. In this review, we highlight the role of reactive oxygen species for cell function and disease development in the context of laminopathies and present a framework of non-exclusive mechanisms to explain the reciprocal interactions between a dysfunctional lamina and altered redox homeostasis.

  10. Chrononutrition against Oxidative Stress in Aging

    PubMed Central

    Garrido, M.; Terrón, M. P.; Rodríguez, A. B.

    2013-01-01

    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. PMID:23861994

  11. Asthmatic cough and airway oxidative stress.

    PubMed

    Koskela, Heikki O; Purokivi, Minna K; Nieminen, Riina M; Moilanen, Eeva

    2012-05-31

    The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma. PMID:22546340

  12. Renal oxidative stress, oxygenation, and hypertension.

    PubMed

    Palm, Fredrik; Nordquist, Lina

    2011-11-01

    Hypertension is closely associated with progressive kidney dysfunction, manifested as glomerulosclerosis, interstitial fibrosis, proteinuria, and eventually declining glomerular filtration. The postulated mechanism for development of glomerulosclerosis is barotrauma caused by increased capillary pressure, but the reason for development of interstitial fibrosis and the subsequently reduced kidney function is less clear. However, it has been hypothesized that tissue hypoxia induces fibrogenesis and progressive renal failure. This is very interesting, since recent reports highlight several different mechanisms resulting in altered oxygen handling and availability in the hypertensive kidney. Such mechanisms include decreased renal blood flow due to increased vascular tone induced by ANG II that limits oxygen delivery and increases oxidative stress, resulting in increased mitochondrial oxygen usage, increased oxygen usage for tubular electrolyte transport, and shunting of oxygen from arterial to venous blood in preglomerular vessels. It has been shown in several studies that interventions to prevent oxidative stress and to restore kidney tissue oxygenation prevent progression of kidney dysfunction. Furthermore, inhibition of ANG II activity, by either blocking ANG II type 1 receptors or angiotensin-converting enzyme, or by preventing oxidative stress by administration of antioxidants also results in improved blood pressure control. Therefore, it seems likely that tissue hypoxia in the hypertensive kidney contributes to progression of kidney damage, and perhaps also persistence the high blood pressure. PMID:21832206

  13. Oxidative Stress in Patients With Acne Vulgaris

    PubMed Central

    Arican, Ozer; Belge Kurutas, Ergul; Sasmaz, Sezai

    2005-01-01

    Acne vulgaris is one of the common dermatological diseases and its pathogenesis is multifactorial. In this study, we aim to determine the effects of oxidative stress in acne vulgaris. Forty-three consecutive acne patients and 46 controls were enrolled. The parameters of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood of cases were measured spectrophotometrically. The values compared with control group, the relation between the severity and distribution of acne, and the correlation of each enzyme level were researched. CAT and G6PD levels in patients were found to be statistically decreased, and SOD and MDA levels were found to be statistically increased (P < .001). However, any statistical difference and correlation could not be found between the severity and distribution of lesions and the mean levels of enzymes. In addition, we found that each enzyme is correlated with one another. Our findings show that oxidative stress exists in the acne patients. It will be useful to apply at least one antioxidant featured drug along with the combined acne treatment. PMID:16489259

  14. Adrenergic signaling and oxidative stress: a role for sirtuins?

    PubMed Central

    Corbi, Graziamaria; Conti, Valeria; Russomanno, Giusy; Longobardi, Giancarlo; Furgi, Giuseppe; Filippelli, Amelia; Ferrara, Nicola

    2013-01-01

    The adrenergic system plays a central role in stress signaling and stress is often associated with increased production of ROS. However, ROS overproduction generates oxidative stress, that occurs in response to several stressors. β-adrenergic signaling is markedly attenuated in conditions such as heart failure, with downregulation and desensitization of the receptors and their uncoupling from adenylyl cyclase. Transgenic activation of β2-adrenoceptor leads to elevation of NADPH oxidase activity, with greater ROS production and p38MAPK phosphorylation. Inhibition of NADPH oxidase or ROS significantly reduced the p38MAPK signaling cascade. Chronic β2-adrenoceptor activation is associated with greater cardiac dilatation and dysfunction, augmented pro-inflammatory and profibrotic signaling, while antioxidant treatment protected hearts against these abnormalities, indicating ROS production to be central to the detrimental signaling of β2-adrenoceptors. It has been demonstrated that sirtuins are involved in modulating the cellular stress response directly by deacetylation of some factors. Sirt1 increases cellular stress resistance, by an increased insulin sensitivity, a decreased circulating free fatty acids and insulin-like growth factor (IGF-1), an increased activity of AMPK, increased activity of PGC-1a, and increased mitochondrial number. Sirt1 acts by involving signaling molecules such P-I-3-kinase-Akt, MAPK and p38-MAPK-β. βAR stimulation antagonizes the protective effect of the AKT pathway through inhibiting induction of Hif-1α and Sirt1 genes, key elements in cell survival. More studies are needed to better clarify the involvement of sirtuins in the β-adrenergic response and, overall, to better define the mechanisms by which tools such as exercise training are able to counteract the oxidative stress, by both activation of sirtuins and inhibition of GRK2 in many cardiovascular conditions and can be used to prevent or treat diseases such as heart failure

  15. Role of oxidative stress in Alzheimer's disease

    PubMed Central

    HUANG, WEN-JUAN; ZHANG, XIA; CHEN, WEI-WEI

    2016-01-01

    Alzheimer's disease (AD) is the most common cause of disability in individuals aged >65 years worldwide. AD is characterized by the abnormal deposition of amyloid β (Aβ) peptide, and intracellular accumulation of neurofibrillary tangles of hyperphosphorylated τ protein and dementia. The neurotoxic oligomer Aβ peptide, which is the neuropathological diagnostic criterion of the disease, together with τ protein, are mediators of the neurodegeneration that is among the main causative factors. However, these phenomena are mainly initiated and enhanced by oxidative stress, a process referring to an imbalance between antioxidants and oxidants in favour of oxidants. This imbalance can occur as a result of increased free radicals or a decrease in antioxidant defense, free radicals being a species that contains one or more unpaired electrons in its outer shell. The major source of potent free radicals is the reduction of molecular oxygen in water, that initially yields the superoxide radical, which produces hydrogen peroxide by the addition of an electron. The reduction of hydrogen peroxide produces highly reactive hydroxyl radicals, termed reactive oxygen species (ROS) that can react with lipids, proteins, nucleic acids, and other molecules and may also alter their structures and functions. Thus, tissues and organs, particularly the brain, a vulnerable organ, are affected by ROS due to its composition. The brain is largely composed of easily oxidizable lipids while featuring a high oxygen consumption rate. The current review examined the role of oxidative stress in AD. PMID:27123241

  16. Ferritin and the response to oxidative stress.

    PubMed Central

    Orino, K; Lehman, L; Tsuji, Y; Ayaki, H; Torti, S V; Torti, F M

    2001-01-01

    Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reactive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron levels. Chief among these is the sequestration of iron in ferritin. Ferritin is a 24 subunit protein composed of two subunit types, termed H and L. The ferritin H subunit has a potent ferroxidase activity that catalyses the oxidation of ferrous iron, whereas ferritin L plays a role in iron nucleation and protein stability. In the present study we report that increased synthesis of both subunits of ferritin occurs in HeLa cells exposed to oxidative stress. An increase in the activity of iron responsive element binding proteins in response to oxidative stress was also observed. However, this activation was transient, allowing ferritin protein induction to subsequently proceed. To assess whether ferritin induction reduced the accumulation of ROS, and to test the relative contribution of ferritin H and L subunits in this process, we prepared stable transfectants that overexpressed either ferritin H or ferritin L cDNA under control of a tetracycline-responsive promoter. We observed that overexpression of either ferritin H or ferritin L reduced the accumulation of ROS in response to oxidant challenge. PMID:11415455

  17. Oxidative stress, activity behaviour and body mass in captive parrots.

    PubMed

    Larcombe, S D; Tregaskes, C A; Coffey, J; Stevenson, A E; Alexander, L G; Arnold, K E

    2015-01-01

    Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melopsittacus undulatus) maintained in typical pet cages and on ad libitum food varied in oxidative profile, behaviour and body mass. Importantly, as with many birds held in captivity, they did not have enough space to engage in extensive free flight. Four types of oxidative damage, single-stranded DNA breaks (low-pH comet assay), alkali-labile sites in DNA (high-pH comet assay), sensitivity of DNA to ROS (H2O2-treated comet assay) and malondialdehyde (a byproduct of lipid peroxidation), were uncorrelated with each other and with plasma concentrations of dietary antioxidants. Without strenuous exercise over 28 days in a relatively small cage, more naturally 'active' individuals had more single-stranded DNA breaks than sedentary birds. High body mass at the start or end of the experiment, coupled with substantial mass gain, were all associated with raised sensitivity of DNA to ROS. Thus, high body mass in these captive birds was associated with oxidative damage. These birds were not lacking dietary antioxidants, because final body mass was positively related to plasma levels of retinol, zeaxanthin and α-tocopherol. Individuals varied widely in activity levels, feeding behaviour, mass gain and oxidative profile despite standardized living conditions. DNA damage is often associated with poor immunocompetence, low fertility and faster ageing. Thus, we have candidate mechanisms for the limited lifespan and fecundity common to many birds kept for conservation purposes. PMID:27293729

  18. Oxidative stress, activity behaviour and body mass in captive parrots

    PubMed Central

    Larcombe, S. D.; Tregaskes, C. A.; Coffey, J.; Stevenson, A. E.; Alexander, L. G.; Arnold, K. E.

    2015-01-01

    Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melopsittacus undulatus) maintained in typical pet cages and on ad libitum food varied in oxidative profile, behaviour and body mass. Importantly, as with many birds held in captivity, they did not have enough space to engage in extensive free flight. Four types of oxidative damage, single-stranded DNA breaks (low-pH comet assay), alkali-labile sites in DNA (high-pH comet assay), sensitivity of DNA to ROS (H2O2-treated comet assay) and malondialdehyde (a byproduct of lipid peroxidation), were uncorrelated with each other and with plasma concentrations of dietary antioxidants. Without strenuous exercise over 28 days in a relatively small cage, more naturally ‘active’ individuals had more single-stranded DNA breaks than sedentary birds. High body mass at the start or end of the experiment, coupled with substantial mass gain, were all associated with raised sensitivity of DNA to ROS. Thus, high body mass in these captive birds was associated with oxidative damage. These birds were not lacking dietary antioxidants, because final body mass was positively related to plasma levels of retinol, zeaxanthin and α-tocopherol. Individuals varied widely in activity levels, feeding behaviour, mass gain and oxidative profile despite standardized living conditions. DNA damage is often associated with poor immunocompetence, low fertility and faster ageing. Thus, we have candidate mechanisms for the limited lifespan and fecundity common to many birds kept for conservation purposes. PMID

  19. The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress

    PubMed Central

    Krupkova, Olga; Handa, Junichi; Hlavna, Marian; Klasen, Juergen; Ospelt, Caroline; Ferguson, Stephen John; Wuertz-Kozak, Karin

    2016-01-01

    Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2 (total n = 36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associated β-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associated β-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration. PMID:27119009

  20. Nitric oxide, stomatal closure, and abiotic stress.

    PubMed

    Neill, Steven; Barros, Raimundo; Bright, Jo; Desikan, Radhika; Hancock, John; Harrison, Judith; Morris, Peter; Ribeiro, Dimas; Wilson, Ian

    2008-01-01

    Various data indicate that nitric oxide (NO) is an endogenous signal in plants that mediates responses to several stimuli. Experimental evidence in support of such signalling roles for NO has been obtained via the application of NO, usually in the form of NO donors, via the measurement of endogenous NO, and through the manipulation of endogenous NO content by chemical and genetic means. Stomatal closure, initiated by abscisic acid (ABA), is effected through a complex symphony of intracellular signalling in which NO appears to be one component. Exogenous NO induces stomatal closure, ABA triggers NO generation, removal of NO by scavengers inhibits stomatal closure in response to ABA, and ABA-induced stomatal closure is reduced in mutants that are impaired in NO generation. The data indicate that ABA-induced guard cell NO generation requires both nitric oxide synthase-like activity and, in Arabidopsis, the NIA1 isoform of nitrate reductase (NR). NO stimulates mitogen-activated protein kinase (MAPK) activity and cGMP production. Both these NO-stimulated events are required for ABA-induced stomatal closure. ABA also stimulates the generation of H2O2 in guard cells, and pharmacological and genetic data demonstrate that NO accumulation in these cells is dependent on such production. Recent data have extended this model to maize mesophyll cells where the induction of antioxidant defences by water stress and ABA required the generation of H2O2 and NO and the activation of a MAPK. Published data suggest that drought and salinity induce NO generation which activates cellular processes that afford some protection against the oxidative stress associated with these conditions. Exogenous NO can also protect cells against oxidative stress. Thus, the data suggest an emerging model of stress responses in which ABA has several ameliorative functions. These include the rapid induction of stomatal closure to reduce transpirational water loss and the activation of antioxidant defences

  1. Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum Group II CF-1.

    PubMed

    Ferrer, Alonso; Rivera, Javier; Zapata, Claudia; Norambuena, Javiera; Sandoval, Álvaro; Chávez, Renato; Orellana, Omar; Levicán, Gloria

    2016-01-01

    Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species (ROS). Cobalamin (vitamin B12) is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular ROSs and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective. PMID:27242761

  2. Cobalamin Protection against Oxidative Stress in the Acidophilic Iron-oxidizing Bacterium Leptospirillum Group II CF-1

    PubMed Central

    Ferrer, Alonso; Rivera, Javier; Zapata, Claudia; Norambuena, Javiera; Sandoval, Álvaro; Chávez, Renato; Orellana, Omar; Levicán, Gloria

    2016-01-01

    Members of the genus Leptospirillum are aerobic iron-oxidizing bacteria belonging to the phylum Nitrospira. They are important members of microbial communities that catalyze the biomining of sulfidic ores, thereby solubilizing metal ions. These microorganisms live under extremely acidic and metal-loaded environments and thus must tolerate high concentrations of reactive oxygen species (ROS). Cobalamin (vitamin B12) is a cobalt-containing tetrapyrrole cofactor involved in intramolecular rearrangement reactions and has recently been suggested to be an intracellular antioxidant. In this work, we investigated the effect of the exogenous addition of cobalamin on oxidative stress parameters in Leptospirillum group II strain CF-1. Our results revealed that the external supplementation of cobalamin reduces the levels of intracellular ROSs and the damage to biomolecules, and also stimulates the growth and survival of cells exposed to oxidative stress exerted by ferric ion, hydrogen peroxide, chromate and diamide. Furthermore, exposure of strain CF-1 to oxidative stress elicitors resulted in the transcriptional activation of the cbiA gene encoding CbiA of the cobalamin biosynthetic pathway. Altogether, these data suggest that cobalamin plays an important role in redox protection of Leptospirillum strain CF-1, supporting survival of this microorganism under extremely oxidative environmental conditions. Understanding the mechanisms underlying the protective effect of cobalamin against oxidative stress may help to develop strategies to make biomining processes more effective. PMID:27242761

  3. Melanocytes as instigators and victims of oxidative stress.

    PubMed

    Denat, Laurence; Kadekaro, Ana L; Marrot, Laurent; Leachman, Sancy A; Abdel-Malek, Zalfa A

    2014-06-01

    Epidermal melanocytes are particularly vulnerable to oxidative stress owing to the pro-oxidant state generated during melanin synthesis, and to the intrinsic antioxidant defenses that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help counteract oxidative stress, the role of oxidative stress in melanoma initiation and progression and in melanocyte death in vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo treatment. PMID:24573173

  4. Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging?

    PubMed Central

    Salmon, Adam B.; Richardson, Arlan; Pérez, Viviana I.

    2010-01-01

    The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is lifespan, i.e., does altering oxidative stress/damage change lifespan? Mice with genetic manipulations in the antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in lifespan. However, when these transgenic/knockout mice are tested using models that develop various types of age-related pathology, they show alterations in progression and/or severity of pathology as predicted by the oxidative stress theory; increased oxidative stress accelerates pathology and reduced oxidative stress retards pathology. These contradictory observations might mean a) oxidative stress plays a very limited, if any, role in aging but a major role in healthspan; and/or b) the role that oxidative stress plays in aging depends on environment. In environments with minimal stress, as expected under optimal husbandry, oxidative damage plays little role in aging. However, under chronic stress, including pathological phenotypes that diminish optimal health, oxidative stress/damage plays a major role in aging. Under these conditions, enhanced antioxidant defenses exert an “anti-aging” action, leading to changes in lifespan, age-related pathology, and physiological function as predicted by the oxidative stress theory of aging. PMID:20036736

  5. Microbial oxidative stress response: Novel insights from environmental facultative anaerobic bacteria.

    PubMed

    Fu, Huihui; Yuan, Jie; Gao, Haichun

    2015-10-15

    Facultative bacteria can grow under either oxic or anoxic conditions. While oxygen provides substantial advantages in energy yield by respiration, it can become life-threatening because of reactive oxygen species that derive from the molecule naturally. Thus, to survive and thrive in a given niche, these bacteria have to constantly regulate physiological processes to make maximum benefits from oxygen respiration while restraining oxidative stress. Molecular mechanisms and physiological consequences of oxidative stress have been under extensive investigation for decades, mostly on research model Escherichia coli, from which our understanding of bacterial oxidative stress response is largely derived. Nevertheless, given that bacteria live in enormously diverse environments, to cope with oxidative stress different strategies are conceivably developed. PMID:26319291

  6. Trade-offs between survival, longevity, and reproduction, and variation of survival tolerance in Mediterranean Bemisia tabaci after temperature stress.

    PubMed

    Lü, Zhi-Chuang; Wang, Yan-Min; Zhu, Shao-Guang; Yu, Hao; Guo, Jian-Ying; Wan, Fang-Hao

    2014-01-01

    The invasive Mediterranean Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) has emerged as one of the most common agricultural pests in the world. In the present study, we examined the cross-tolerance, fitness costs, and benefits of thermal tolerance and the variation in the responses of life history traits after heat-shock selection. The results showed that survival and longevity of Mediterranean B. tabaci were decreased significantly after direct or cross temperature stress and that the number of eggs per female was not reduced significantly. Furthermore, heat-shock selection dramatically increased the survival of Mediterranean B. tabaci within two generations, and it did not significantly affect the egg number per female within five generations. These results indicated that there was a trade-off between survival, longevity, and reproduction in Mediterranean B. tabaci after temperature stress. The improvement in reproduction was costly in terms of decreased survival and longevity, and there was a fitness consequence to temperature stress. In addition, heat tolerance in Mediterranean B. tabaci increased substantially after selection by heat shock, indicating a considerable variation for survival tolerance in this species. This information could help us better understand the thermal biology of Mediterranean B. tabaci within the context of climate change. PMID:25368068

  7. Cryopreservation affects ROS-induced oxidative stress and antioxidant response in Arabidopsis seedlings

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant recovery status after cryopreservation by vitrification had a negative relationship to the oxidative stress induced by reactive oxygen species (ROS). Arabidopsis thaliana seedlings germinated for 48-h or 72-h with different cryopreservation survival tolerances were examined at five steps of a ...

  8. Oxidative stress, thyroid dysfunction & Down syndrome

    PubMed Central

    Campos, Carlos; Casado, Ángela

    2015-01-01

    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 (H2O2). ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS. PMID:26354208

  9. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    PubMed Central

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio

    2014-01-01

    Abstract Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both transcriptional and post-translational events. This cross talk, in turn, regulates the structural integrity of cardiomyocytes, promotes proteostasis, and reduces inflammation, events critical to disease pathogenesis. Critical Issues: Dysregulation of either autophagy or redox state has been implicated in many cardiovascular diseases. Cardiomyocytes are rich in mitochondria, which make them particularly sensitive to oxidative damage. Maintenance of mitochondrial homeostasis and elimination of defective mitochondria are each critical to the maintenance of redox homeostasis. Future Directions: The complex interplay between autophagy and oxidative stress underlies a wide range of physiological and pathological events and its elucidation holds promise of potential clinical applicability. Antioxid. Redox Signal. 20, 507–518. PMID:23641894

  10. Oxidative stress in haemodialysis--intradialytic changes.

    PubMed

    Srinivasa Rao, P V; Dakshinamurty, K V; Saibaba, K S; Raghavan, M S; Vijayabhaskar, M; Sreekrishna, V; Ambekar, J G; Jayaseelan, L

    2001-01-01

    Oxidative stress is likely to be involved in the development of complications due to haemodialysis. Though there is evidence for production of oxygen free radicals during haemodialysis, reports on net oxidative imbalance due to a single dialysis session are conflicting. Hence, a time-course analysis of changes in lipid peroxides (LPO) along with antioxidant enzymes and vitamins was carried out. Hourly changes in LPO and antioxidants were studied during a first-use cuprophan membrane and acetate dialysis in 20 patients on regular haemodialysis treatment. Data were corrected for haemoconcentration and standardised to measure the rate of change before statistical evaluation using analysis of variance for repeated measures. The results of the study showed a net oxidative stress due to a single dialysis session in the form of increased plasma and erythrocyte lipid peroxidation, decrease in plasma vitamin E, slight increase in plasma superoxide dismutase and erythrocyte glutathione peroxidase and no change in plasma glutathione peroxidase. erythrocyte superoxide dismutase and plasma vitamin A levels. The oxygen radical production was found to be maximum in the first hour of dialysis. PMID:11778848

  11. Blood oxidative stress markers after ultramarathon swimming.

    PubMed

    Kabasakalis, Athanasios; Kyparos, Antonios; Tsalis, Georgios; Loupos, Dimitrios; Pavlidou, Anastasia; Kouretas, Dimitrios

    2011-03-01

    Data on redox balance in response to marathon swimming are lacking, whereas findings from studies using other types of ultraendurance exercise are controversial. The aim of the present study was to investigate the effect of ultramarathon swimming on selective blood oxidative stress markers. Five well-trained male swimmers aged 28.8 (6.0) years participated in the study. Blood samples were obtained before and after the ultramarathon swimming, for full blood count analysis and determination of protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and total antioxidant capacity (TAC). The swimmers swam 19.4 (3.4) hours, covering 50.5 (15.0) km. Hematocrit and erythrocyte count, and leukocyte, neutrophil and monocyte counts were significantly elevated after swimming, whereas protein carbonyls, TBARS and TAC did not significantly change. The findings of the present study indicate that well-trained swimmers were able to regulate a redox homeostasis during ultra-long duration swimming. It is also postulated that the relatively low intensity of marathon swimming may not be a sufficient stimulus to induce oxidative stress in well-trained swimmers. The fact that low-intensity long-duration exercise protocols are not associated with oxidative damage is useful knowledge for coaches and athletes in scheduling the content of the training sessions that preceded and followed these exercise protocols. PMID:20613649

  12. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress.

    PubMed

    Zaugg, Kathrin; Yao, Yi; Reilly, Patrick T; Kannan, Karuppiah; Kiarash, Reza; Mason, Jacqueline; Huang, Ping; Sawyer, Suzanne K; Fuerth, Benjamin; Faubert, Brandon; Kalliomäki, Tuula; Elia, Andrew; Luo, Xunyi; Nadeem, Vincent; Bungard, David; Yalavarthi, Sireesha; Growney, Joseph D; Wakeham, Andrew; Moolani, Yasmin; Silvester, Jennifer; Ten, Annick You; Bakker, Walbert; Tsuchihara, Katsuya; Berger, Shelley L; Hill, Richard P; Jones, Russell G; Tsao, Ming; Robinson, Murray O; Thompson, Craig B; Pan, Guohua; Mak, Tak W

    2011-05-15

    Tumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKα. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors. PMID:21576264

  13. Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress

    PubMed Central

    Zaugg, Kathrin; Yao, Yi; Reilly, Patrick T.; Kannan, Karuppiah; Kiarash, Reza; Mason, Jacqueline; Huang, Ping; Sawyer, Suzanne K.; Fuerth, Benjamin; Faubert, Brandon; Kalliomäki, Tuula; Elia, Andrew; Luo, Xunyi; Nadeem, Vincent; Bungard, David; Yalavarthi, Sireesha; Growney, Joseph D.; Wakeham, Andrew; Moolani, Yasmin; Silvester, Jennifer; Ten, Annick You; Bakker, Walbert; Tsuchihara, Katsuya; Berger, Shelley L.; Hill, Richard P.; Jones, Russell G.; Tsao, Ming; Robinson, Murray O.; Thompson, Craig B.; Pan, Guohua; Mak, Tak W.

    2011-01-01

    Tumor cells gain a survival/growth advantage by adapting their metabolism to respond to environmental stress, a process known as metabolic transformation. The best-known aspect of metabolic transformation is the Warburg effect, whereby cancer cells up-regulate glycolysis under aerobic conditions. However, other mechanisms mediating metabolic transformation remain undefined. Here we report that carnitine palmitoyltransferase 1C (CPT1C), a brain-specific metabolic enzyme, may participate in metabolic transformation. CPT1C expression correlates inversely with mammalian target of rapamycin (mTOR) pathway activation, contributes to rapamycin resistance in murine primary tumors, and is frequently up-regulated in human lung tumors. Tumor cells constitutively expressing CPT1C show increased fatty acid (FA) oxidation, ATP production, and resistance to glucose deprivation or hypoxia. Conversely, cancer cells lacking CPT1C produce less ATP and are more sensitive to metabolic stress. CPT1C depletion via siRNA suppresses xenograft tumor growth and metformin responsiveness in vivo. CPT1C can be induced by hypoxia or glucose deprivation and is regulated by AMPKα. Cpt1c-deficient murine embryonic stem (ES) cells show sensitivity to hypoxia and glucose deprivation and altered FA homeostasis. Our results indicate that cells can use a novel mechanism involving CPT1C and FA metabolism to protect against metabolic stress. CPT1C may thus be a new therapeutic target for the treatment of hypoxic tumors. PMID:21576264

  14. Oxidative stress-mediated HMGB1 biology

    PubMed Central

    Yu, Yan; Tang, Daolin; Kang, Rui

    2015-01-01

    High mobility group box 1 (HMGB1) is a widely-expressed and highly-abundant protein that acts as an extracellular signal upon active secretion by immune cells or passive release by dead, dying, and injured cells. Both intracellular and extracellular HMGB1 play pivotal roles in regulation of the cellular response to stress. Targeting the translocation, release, and activity of HMGB1 can limit inflammation and reduce tissue damage during infection and sterile inflammation. Although the mechanisms contributing to HMGB1 biology are still under investigation, it appears that oxidative stress is a central regulator of HMGB1's translocation, release, and activity in inflammation and cell death (e.g., necrosis, apoptosis, autophagic cell death, pyroptosis, and NETosis). Thus, targeting HMGB1 with antioxidant compounds may be an attractive therapeutic strategy for inflammation-associated diseases such as sepsis, ischemia and reperfusion injury, arthritis, diabetes, and cancer. PMID:25904867

  15. Effect of single or combined climatic and hygienic stress in four layer lines: 2. Endocrine and oxidative stress responses.

    PubMed

    Star, L; Decuypere, E; Parmentier, H K; Kemp, B

    2008-06-01

    Effects of long-term climatic stress (heat exposure), short-term hygienic stress [lipopolysaccharide (LPS)], or combined exposure to these stressors on endocrine and oxidative stress parameters of 4 layer lines (B1, WA, WB, and WF) were investigated. The lines were earlier characterized for natural humoral immune competence and survival rate. Eighty hens per line were randomly divided over 2 identical climate chambers and exposed to constant high temperature (32 degrees C) or a control temperature (21 degrees C) for 23 d. Half of the hens housed in each chamber were i.v. injected with LPS at d 1 after the start of the heat stress period. The effect of heat, LPS, or combined exposure on plasma levels of corticosterone, 3,5,3'-triiodothyronine (T(3)), glucose, uric acid (UA), and TBA reacting substances (TBARS) were investigated. Except for UA, there were no interactions between heat stress and LPS administration. Heat stress enhanced levels of corticosterone, glucose, and TBARS, whereas levels of T(3) and UA were decreased. The T(3) levels, however, were enhanced by LPS administration, whereas levels of UA were decreased. Administration of LPS had no effect on levels of corticosterone and TBARS. Because both stressors caused a reduction in feed intake, it is assumed that changes in most of the plasma levels of the endocrine and oxidative stress parameters are related with the reduction in feed intake. Neither natural humoral immune competence nor survival rate, for which the lines have been characterized, was indicative for the endocrine and oxidative stress responses to different stressors. The present data suggest that hens were able to cope with single or combined heat stress and LPS administration and that heat stress and LPS administration acted like 2 independent stressors. Furthermore, the 4 layer lines differed in response patterns and response levels; line WB was physiologically most sensitive to environmental changes. PMID:18492989

  16. Oxidative stress in prostate hyperplasia and carcinogenesis.

    PubMed

    Udensi, Udensi K; Tchounwou, Paul B

    2016-01-01

    Prostatic hyperplasia (PH) is a common urologic disease that affects mostly elderly men. PH can be classified as benign prostatic hyperplasia (BPH), or prostate cancer (PCa) based on its severity. Oxidative stress (OS) is known to influence the activities of inflammatory mediators and other cellular processes involved in the initiation, promotion and progression of human neoplasms including prostate cancer. Scientific evidence also suggests that micronutrient supplementation may restore the antioxidant status and hence improve the clinical outcomes for patients with BPH and PCa. This review highlights the recent studies on prostate hyperplasia and carcinogenesis, and examines the role of OS on the molecular pathology of prostate cancer progression and treatment. PMID:27609145

  17. Regulation of Synaptic nlg-1/Neuroligin Abundance by the skn-1/Nrf Stress Response Pathway Protects against Oxidative Stress

    PubMed Central

    Staab, Trisha A.; Egrafov, Oleg; Knowles, James A.; Sieburth, Derek

    2014-01-01

    The Nrf family of transcription factors mediates adaptive responses to stress and longevity, but the identities of the crucial Nrf targets, and the tissues in which they function in multicellular organisms to promote survival, are not known. Here, we use whole transcriptome RNA sequencing to identify 810 genes whose expression is controlled by the SKN-1/Nrf2 negative regulator WDR-23 in the nervous system of Caenorhabditis elegans. Among the genes identified is the synaptic cell adhesion molecule nlg-1/neuroligin. We find that the synaptic abundance of NLG-1 protein increases following pharmacological treatments that generate oxidative stress or by the genetic activation of skn-1. Increasing nlg-1 dosage correlates with increased survival in response to oxidative stress, whereas genetic inactivation of nlg-1 reduces survival and impairs skn-1-mediated stress resistance. We identify a canonical SKN-1 binding site in the nlg-1 promoter that binds to SKN-1 in vitro and is necessary for SKN-1 and toxin-mediated increases in nlg-1 expression in vivo. Together, our results suggest that SKN-1 activation in the nervous system can confer protection to organisms in response to stress by directly regulating nlg-1/neuroligin expression. PMID:24453991

  18. ZNF32 protects against oxidative stress-induced apoptosis by modulating C1QBP transcription

    PubMed Central

    Li, Yanyan; Wei, Yuyan; Gong, Di; Gao, Junping; Zhang, Jie; Tan, Weiwei; Wen, Tianfu; Zhang, Le; Huang, Lugang; Xiang, Rong; Lin, Ping; Wei, Yuquan

    2015-01-01

    Reactive oxygen species (ROS)-driven oxidative stress has been recognized as a critical inducer of cancer cell death in response to therapeutic agents. Our previous studies have demonstrated that zinc finger protein (ZNF)32 is key to cell survival upon oxidant stimulation. However, the mechanisms by which ZNF32 mediates cell death remain unclear. Here, we show that at moderate levels of ROS, Sp1 directly binds to two GC boxes within the ZNF32 promoter to activate ZNF32 transcription. Alternatively, at cytotoxic ROS concentrations, ZNF32 expression is repressed due to decreased binding activity of Sp1. ZNF32 overexpression maintains mitochondrial membrane potential and enhances the antioxidant capacity of cells to detoxify ROS, and these effects promote cell survival upon pro-oxidant agent treatment. Alternatively, ZNF32-deficient cells are more sensitive and vulnerable to oxidative stress-induced cell injury. Mechanistically, we demonstrate that complement 1q-binding protein (C1QBP) is a direct target gene of ZNF32 that inactivates the p38 MAPK pathway, thereby exerting the protective effects of ZNF32 on oxidative stress-induced apoptosis. Taken together, our findings indicate a novel mechanism by which the Sp1-ZNF32-C1QBP axis protects against oxidative stress and implicate a promising strategy that ZNF32 inhibition combined with pro-oxidant anticancer agents for hepatocellular carcinoma treatment. PMID:26497555

  19. Nitric Oxide, Oxidative Stress and Inflammation in Pulmonary Arterial Hypertension

    PubMed Central

    Crosswhite, Patrick; Sun, Zhongjie

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by a persistent elevation of pulmonary artery pressure accompanied by right ventricular hypertrophy (RVH). The current treatment for pulmonary hypertension is limited and only provides symptomatic relief due to unknown etiology and pathogenesis of the disease. Both vasoconstriction and structural remodeling (enhanced proliferation of VSMC) of the pulmonary arteries contribute to the progressive course of PAH, irrespective of different underlying causes. The exact molecular mechanism of PAH, however, is not fully understood. The purpose of this review is to provide recent advances in the mechanistic investigation of PAH. Specifically, this review focuses on nitric oxide (NO), oxidative stress and inflammation and how these factors contribute to the development and progression of PAH. This review also discusses recent and potential therapeutic advancements for the treatment of PAH. PMID:20051913

  20. Air pollution and circulating biomarkers of oxidative stress

    PubMed Central

    Staimer, Norbert; Vaziri, Nosratola D.

    2013-01-01

    Chemical components of air pollutant exposures that induce oxidative stress and subsequent inflammation may be partly responsible for associations of cardiovascular morbidity and mortality with airborne particulate matter and combustion-related pollutant gasses. However, epidemiologic evidence regarding this is limited. An exposure-assessment approach is to measure the oxidative potential of particle mixtures because it is likely that hundreds of correlated chemicals are involved in overall effects of air pollution on health. Oxidative potential likely depends on particle composition and size distribution, especially ultrafine particle concentration, and on transition metals and certain semivolatile and volatile organic chemicals. For health effects, measuring systemic oxidative stress in the blood is one feasible approach, but there is no universal biomarker of oxidative stress and there are many potential target molecules (lipids, proteins, DNA, nitric oxide, etc.), which may be more or less suitable for specific study goals. Concurrent with the measurement of oxidative stress, it is important to measure gene and/or protein expression of endogenous antioxidant enzymes because they can modify relations between oxidative stress biomarkers and air pollutants. Conversely, the expression and activities of these enzymes are modified by oxidative stress. This interplay will likely determine the observed effects of air pollutants on systemic inflammatory and thrombotic mediators and related clinical outcomes. Studies are needed to assess the reliability and validity of oxidative stress biomarkers, evaluate differences in associations between oxidative stress biomarkers and various pollutant measurements (mass, chemical components, and oxidative potential), and evaluate impacts of antioxidant responses on these relations. PMID:23626660

  1. Melamine Induces Oxidative Stress in Mouse Ovary

    PubMed Central

    Dai, Xiao-Xin; Duan, Xing; Cui, Xiang-Shun; Kim, Nam-Hyung; Xiong, Bo; Sun, Shao-Chen

    2015-01-01

    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 glutathi-one 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. PMID:26545251

  2. Mitophagy in TGEV infection counteracts oxidative stress and apoptosis.

    PubMed

    Zhu, Liqi; Mou, Chunxiao; Yang, Xing; Lin, Jian; Yang, Qian

    2016-05-10

    The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection. PMID:27027356

  3. Increased Oxidative Stress as a Selective Anticancer Therapy

    PubMed Central

    Liu, Jiahui; Wang, Zhichong

    2015-01-01

    Reactive oxygen species (ROS) are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs) in cancer stem cells (CSCs), resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment. PMID:26273420

  4. Oxidative stress induction by nanoparticles in THP-1 cells with 4-HNE production: stress biomarker or oxidative stress signalling molecule?

    PubMed

    Foucaud, L; Goulaouic, S; Bennasroune, A; Laval-Gilly, P; Brown, D; Stone, V; Falla, J

    2010-09-01

    The aim of this study was to investigate whether carbon black (CB) nanoparticles might induce toxicity to monocytic cells in vitro via an oxidative stress mechanism involving formation of the lipid peroxidation product 4-hydroxynonenal (4-HNE) and the subsequent role of 4-HNE in inducing further cytotoxic effects. ROS production in cells by CB nanoparticles was shown by the oxidation of DCFH after a short time exposure. These particles induced the formation of 4-HNE-protein adducts and significant modification of glutathione content corresponding to an increase of oxidized glutathione form (GSSG) and a decrease of total glutathione (GSX) content. These results attest to an oxidative stress induced by the carbon black nanoparticles, although no induction of HO-1 protein expression was detected. Concerning the effects of a direct exposure to 4-HNE, our results showed that 4-HNE is not cytotoxic for concentrations lower than 12.5 microM. By contrast, it provokes a very high cytotoxicity for concentrations above 25 microM. An induction of HO-1 expression was observed from concentrations above 5 microM of 4-HNE. Finally, glutathione content decreased significantly from 5 microM of 4-HNE but no modification was observed under this concentration. The discrepancy between effects of carbon black nanoparticles and 4-HNE on the intracellular markers of oxidative stress suggests that 4-HNE is not directly implied in the signalling of oxidative toxicity of nanoparticles but is an effective biomarker of oxidative effects of nanoparticles. PMID:20638469

  5. Oxidative Stress in Genetic Mouse Models of Parkinson's Disease

    PubMed Central

    Varçin, Mustafa; Bentea, Eduard; Michotte, Yvette; Sarre, Sophie

    2012-01-01

    There is extensive evidence in Parkinson's disease of a link between oxidative stress and some of the monogenically inherited Parkinson's disease-associated genes. This paper focuses on the importance of this link and potential impact on neuronal function. Basic mechanisms of oxidative stress, the cellular antioxidant machinery, and the main sources of cellular oxidative stress are reviewed. Moreover, attention is given to the complex interaction between oxidative stress and other prominent pathogenic pathways in Parkinson's disease, such as mitochondrial dysfunction and neuroinflammation. Furthermore, an overview of the existing genetic mouse models of Parkinson's disease is given and the evidence of oxidative stress in these models highlighted. Taken into consideration the importance of ageing and environmental factors as a risk for developing Parkinson's disease, gene-environment interactions in genetically engineered mouse models of Parkinson's disease are also discussed, highlighting the role of oxidative damage in the interplay between genetic makeup, environmental stress, and ageing in Parkinson's disease. PMID:22829959

  6. Going retro: Oxidative stress biomarkers in modern redox biology.

    PubMed

    Margaritelis, N V; Cobley, J N; Paschalis, V; Veskoukis, A S; Theodorou, A A; Kyparos, A; Nikolaidis, M G

    2016-09-01

    The field of redox biology is inherently intertwined with oxidative stress biomarkers. Oxidative stress biomarkers have been utilized for many different objectives. Our analysis indicates that oxidative stress biomarkers have several salient applications: (1) diagnosing oxidative stress, (2) pinpointing likely redox components in a physiological or pathological process and (3) estimating the severity, progression and/or regression of a disease. On the contrary, oxidative stress biomarkers do not report on redox signaling. Alternative approaches to gain more mechanistic insights are: (1) measuring molecules that are integrated in pathways linking redox biochemistry with physiology, (2) using the exomarker approach and (3) exploiting -omics techniques. More sophisticated approaches and large trials are needed to establish oxidative stress biomarkers in the clinical setting. PMID:26855421

  7. A Nucleocytoplasmic Shuttling Protein in Oxidative Stress Tolerance

    SciTech Connect

    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.

  8. Chasing great paths of Helmut Sies "Oxidative Stress".

    PubMed

    Majima, Hideyuki J; Indo, Hiroko P; Nakanishi, Ikuo; Suenaga, Shigeaki; Matsumoto, Ken-Ichiro; Matsui, Hirofumi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Yen, Hsiu-Chuan; Hawkins, Clare L; Davies, Michael J; Ozawa, Toshihiko; St Clair, Daret K

    2016-04-01

    Prof. Dr. Helmut Sies is a pioneer of "Oxidative Stress", and has published over 18 papers with the name of "Oxidative Stress" in the title. He has been Editor-in-Chief of the journal "Archives of Biochemistry and Biophysics" for many years, and is a former Editor-in-Chief of the journal "Free Radical Research". He has clarified our understanding of the causes of chronic developing diseases, and has studied antioxidant factors. In this article, importance of "Oxidative Stress" and our mitochondrial oxidative stress studies; roles of mitochondrial ROS, effects of vitamin E and its homologues in oxidative stress-related diseases, effects of antioxidants in vivo and in vitro, and a mitochondrial superoxide theory for oxidative stress diseases and aging are introduced, and some of our interactions with Helmut are described, congratulating and appreciating his great path. PMID:27095216

  9. Diabetes and the Brain: Oxidative Stress, Inflammation, and Autophagy

    PubMed Central

    Muriach, María; Flores-Bellver, Miguel; Romero, Francisco J.; Barcia, Jorge M.

    2014-01-01

    Diabetes mellitus is a common metabolic disorder associated with chronic complications including a state of mild to moderate cognitive impairment, in particular psychomotor slowing and reduced mental flexibility, not attributable to other causes, and shares many symptoms that are best described as accelerated brain ageing. A common theory for aging and for the pathogenesis of this cerebral dysfunctioning in diabetes relates cell death to oxidative stress in strong association to inflammation, and in fact nuclear factor κB (NFκB), a master regulator of inflammation and also a sensor of oxidative stress, has a strategic position at the crossroad between oxidative stress and inflammation. Moreover, metabolic inflammation is, in turn, related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect. In parallel, blockade of autophagy can relate to proinflammatory signaling via oxidative stress pathway and NFκB-mediated inflammation. PMID:25215171

  10. Oxidative stress in psoriasis and potential therapeutic use of antioxidants.

    PubMed

    Lin, Xiran; Huang, Tian

    2016-06-01

    The pathophysiology of psoriasis is complex and dynamic. Recently, the involvement of oxidative stress in the pathogenesis of psoriasis has been proposed. Oxidative stress is an imbalance between oxidants and antioxidants in favor of the oxidants, leading to a disruption of redox signaling and control and/or molecular damage. In this article, the published studies on the role of oxidative stress in psoriasis pathogenesis are reviewed, focusing on the impacts of oxidative stress on dendritic cells, T lymphocytes, and keratinocytes, on angiogenesis and on inflammatory signaling (mitogen-activated protein kinase, nuclear factor-κB, and Janus kinase/signal transducer and activator of transcription). As there is compelling evidence that oxidative stress is involved in the pathogenesis of psoriasis, the possibility of using this information to develop novel strategies for treatment of patients with psoriasis is of considerable interest. In this article, we also review the published studies on treating psoriasis with antioxidants and drugs with antioxidant activity. PMID:27098416

  11. Combined neonicotinoid pesticide and parasite stress alter honeybee queens’ physiology and survival

    PubMed Central

    Dussaubat, Claudia; Maisonnasse, Alban; Crauser, Didier; Tchamitchian, Sylvie; Bonnet, Marc; Cousin, Marianne; Kretzschmar, André; Brunet, Jean-Luc; Le Conte, Yves

    2016-01-01

    Honeybee colony survival strongly relies on the queen to overcome worker losses exposed to combined stressors like pesticides and parasites. Queen’s capacity to withstand these stressors is however very little known. The effects of the common neonicotinoid pesticide imidacloprid in a chronic and sublethal exposure together with the wide distributed parasite Nosema ceranae have therefore been investigated on queen’s physiology and survivorship in laboratory and field conditions. Early physiological changes were observed on queens, particularly the increase of enzyme activities (catalase [CAT] and glutathione-S-transferase [GST] in the heads) related to protective responses to xenobiotics and oxidative stress against pesticide and parasite alone or combined. Stressors also alter the activity of two other enzymes (carboxylesterase alpha [CaE α] and carboxylesterase para [CaE p] in the midguts) involved in metabolic and detoxification functions. Furthermore, single and combined effects of pesticide and parasite decrease survivorship of queens introduced into mating hives for three months. Because colony demographic regulation relies on queen’s fertility, the compromise of its physiology and life can seriously menace colony survival under pressure of combined stressors. PMID:27578396

  12. Combined neonicotinoid pesticide and parasite stress alter honeybee queens' physiology and survival.

    PubMed

    Dussaubat, Claudia; Maisonnasse, Alban; Crauser, Didier; Tchamitchian, Sylvie; Bonnet, Marc; Cousin, Marianne; Kretzschmar, André; Brunet, Jean-Luc; Le Conte, Yves

    2016-01-01

    Honeybee colony survival strongly relies on the queen to overcome worker losses exposed to combined stressors like pesticides and parasites. Queen's capacity to withstand these stressors is however very little known. The effects of the common neonicotinoid pesticide imidacloprid in a chronic and sublethal exposure together with the wide distributed parasite Nosema ceranae have therefore been investigated on queen's physiology and survivorship in laboratory and field conditions. Early physiological changes were observed on queens, particularly the increase of enzyme activities (catalase [CAT] and glutathione-S-transferase [GST] in the heads) related to protective responses to xenobiotics and oxidative stress against pesticide and parasite alone or combined. Stressors also alter the activity of two other enzymes (carboxylesterase alpha [CaE α] and carboxylesterase para [CaE p] in the midguts) involved in metabolic and detoxification functions. Furthermore, single and combined effects of pesticide and parasite decrease survivorship of queens introduced into mating hives for three months. Because colony demographic regulation relies on queen's fertility, the compromise of its physiology and life can seriously menace colony survival under pressure of combined stressors. PMID:27578396

  13. FurA contributes to the oxidative stress response regulation of Mycobacterium avium ssp. paratuberculosis

    PubMed Central

    Eckelt, Elke; Meißner, Thorsten; Meens, Jochen; Laarmann, Kristin; Nerlich, Andreas; Jarek, Michael; Weiss, Siegfried; Gerlach, Gerald-F.; Goethe, Ralph

    2015-01-01

    The ferric uptake regulator A (FurA) is known to be involved in iron homeostasis and stress response in many bacteria. In mycobacteria the precise role of FurA is still unclear. In the presented study, we addressed the functional role of FurA in the ruminant pathogen Mycobacterium avium ssp. paratuberculosis (MAP) by construction of a furA deletion strain (MAPΔfurA). RNA deep sequencing revealed that the FurA regulon consists of repressed and activated genes associated to stress response or intracellular survival. Not a single gene related to metal homeostasis was affected by furA deletion. A decisive role of FurA during intracellular survival in macrophages was shown by significantly enhanced survival of MAPΔfurA compared to the wildtype, indicating that a principal task of mycobacterial FurA is oxidative stress response regulation in macrophages. This resistance was not associated with altered survival of mice after long term infection with MAP. Our results demonstrate for the first time, that mycobacterial FurA is not involved in the regulation of iron homeostasis. However, they provide strong evidence that FurA contributes to intracellular survival as an oxidative stress sensing regulator. PMID:25705205

  14. Differential Trafficking of Oxidized LDL and Oxidized LDL Immune Complexes in Macrophages: Impact on Oxidative Stress

    PubMed Central

    Al Gadban, Mohammed M.; Smith, Kent J.; Soodavar, Farzan; Piansay, Christabelle; Chassereau, Charlyne; Twal, Waleed O.; Klein, Richard L.; Virella, Gabriel; Lopes-Virella, Maria F.; Hammad, Samar M.

    2010-01-01

    Background 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 FCγ receptor I (FCγ RI). This study examined differences in intracellular trafficking of lipid and apolipoprotein moieties of oxLDL and oxLDL-IC and the impact on oxidative stress. Methodology/Findings 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. Conclusions/Significance 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

  15. Oxidative stress modulates theophylline effects on steroid responsiveness.

    PubMed

    Marwick, John A; Wallis, Gillian; Meja, Koremu; Kuster, Bernhard; Bouwmeester, Tewis; Chakravarty, Probir; Fletcher, Danielle; Whittaker, Paul A; Barnes, Peter J; Ito, Kazuhiro; Adcock, Ian M; Kirkham, Paul A

    2008-12-19

    Oxidative stress is a central factor in many chronic inflammatory diseases such as severe asthma and chronic obstructive pulmonary disease (COPD). Oxidative stress reduces the anti-inflammatory corticosteroid action and may therefore contribute to the relative corticosteroid insensitivity seen in these diseases. Low concentrations of theophylline can restore the anti-inflammatory action of corticosteroids in oxidant exposed cells, however the mechanism remains unknown. Here, we demonstrate that a low concentration of theophylline restores corticosteroid repression of pro-inflammatory mediator release and histone acetylation in oxidant exposed cells. Global gene expression analysis shows that theophylline regulates distinct pathways in naïve and oxidant exposed cells and reverses oxidant mediated modulated of pathways. Furthermore, quantitative chemoproteomics revealed that theophylline has few high affinity targets in naive cells but an elevated affinity in oxidant stressed cells. In conclusion, oxidative stress alters theophylline binding profile and gene expression which may result in restoration of corticosteroid function. PMID:18951874

  16. Oxidative Stress and Heat-Shock Responses in Desulfovibrio vulgaris by Genome-Wide Transcriptomic Analysis

    SciTech Connect

    Zhang, Weiwen; Culley, David E.; Hogan, Mike; Vitiritti, Luigi; Brockman, Fred J.

    2006-05-30

    Abstract Sulfate-reducing bacteria, like Desulfovibrio vulgaris have developed a set of reactions allowing them to survive in environments. To obtain further knowledge of the protecting mechanisms employed in D. vulgaris against the oxidative stress and heat shock, we performed a genome-wide transcriptomic analysis to determine the cellular responses to both stimuli. The results showed that 130 genes were responsive to oxidative stress, while 427 genes responsive to heat-shock, respectively. Functional analyses suggested that the genes regulated were involved in a variety of cellular functions. Metabolic analysis showed that amino acid biosynthetic pathways were induced by both oxidative stress and heat shock treatments, while fatty acid metabolism, purine and cofactor biosynthesis were induced by heat shock only. Rubrerythrin gene (rbR) were upregulated by the oxidative stress, suggesting its important role in the oxidative resistance, whereas the expression of rubredoxin oxidoreductase (rbO), superoxide ismutase (sodB) and catalase (katA) genes were not subjected to regulation by oxidative stress in D. vulgaris. In addition, the results showed that thioredoxin reductase (trxB) was responsive to oxidative stress, suggesting the thiol-specific redox system might be involved in oxidative protection in D. vulgaris. Comparison of cellular responses to oxidative stress and heat-shock allowed the identification of 66 genes that showed a similar drastic response to both environmental stimuli, implying that they might be part of the general stress response (GSR) network in D. vulgaris, which was further supported by the finding of a conserved motif upstream these common-responsive genes.

  17. Effects of oxidative stress on erythrocyte deformability

    NASA Astrophysics Data System (ADS)

    Bayer, Rainer; Wasser, Gerd

    1996-05-01

    Hemolysis as a consequence of open heart surgery is well investigated and explained by the oxidative and/or mechanical stress produced, e.g. by the heart lung machine. In Europe O3 is widely used by physicians, dedicated to alternative medicine. They apply O3 mostly by means of the Major Autohematotherapy (MAH, a process of removing 50 - 100 ml of blood, adding O3 gas to it and returning it to the patient's body). No controlled studies on the efficacy of O3 are available so far, but several anecdotal cases appear to confirm that MAH improves microcirculation, possibly due to increased RBC flexibility. Most methods established to estimate RBC deformability are hard to standardize and include high error of measurement. For our present investigation we used the method of laser diffraction in combination with image analysis. The variation coefficient of the measurement is less than 1%. Previous investigations of our group have shown, that mechanical stress decreases deformability, already at rather low levels of mechanical stress which do not include hemolysis. On the other hand exposure to O2, H2O2 or O3 does not alter the deformability of RBC and--except O3--does not induce considerably hemolysis. However this only holds true if deformability (shear rates 36/s - 2620/s) is determined in isotonic solutions. In hypertonic solutions O3 decreases RBC deformability, but improves it in hypotonic solutions. The results indicate that peroxidative stress dehydrates RBC and reduces their size. To explain the positive effect of O3 on the mechanical fragility of RBC we tentatively assume, that the reduction of RBC size facilitates the feed through small pore filters. In consequence, the size reduction in combination with undisturbed deformability at iso-osmolarity may have a beneficial effect on microcirculation.

  18. Female Adult Mouse Cardiomyocytes Are Protected Against Oxidative Stress

    PubMed Central

    Wang, Fangfei; He, Quan; Sun, Ying; Dai, Xiangguo; Yang, Xiao-Ping

    2010-01-01

    Premenopausal women have less cardiovascular disease and lower cardiovascular morbidity and mortality than men the same age. Our previous studies showed that female mice have lower mortality and better preserved cardiac function after myocardial infarction. However, the precise cellular and molecular mechanisms responsible for such a sex difference are not well established. Using cultured adult mouse cardiomyocytes (ACMs), we tested the hypothesis that the survival advantage of females stems from activated estrogen receptors (ER) and Akt survival signaling pathways. ACMs were isolated from male and female C57BL/6J mice and treated with hydrogen peroxide (H2O2, 100 μM) for 30 min. Cell survival was indicated by rod ratio (rod shaped cells/total cells) and cell death by lactate dehydrogenase (LDH) release and positive staining of Annexin-V (AV+, a marker for apoptosis) and propidium iodide (PI+, a marker for necrosis). In response to H2O2, female ACMs exhibited a higher rod ratio, lower LDH release and fewer AV+ and PI+ cells compared to males. Phospho-Akt was greater in females both at baseline and after H2O2 stimulation. The downstream molecule of Akt, phosphor-GSK-3β (inactivation), was also higher while caspase-3 activity was lower in females in response to H2O2. Bcl-2 did not differ between genders. ERα was the dominant isoform in females, whereas ERβ was low but similar in both genders. Our findings demonstrate that female ACMs have a greater survival advantage when challenged with oxidative stress-induced cell death. This may be attributable to activation of Akt and inhibition of GSK-3β and caspase-3 through an ERα-mediated mechanism. PMID:20212261

  19. Immune Response in a Wild Bird Is Predicted by Oxidative Status, but Does Not Cause Oxidative Stress

    PubMed Central

    Cram, Dominic L.; Blount, Jonathan D.; York, Jennifer E.; Young, Andrew J.

    2015-01-01

    The immune system provides vital protection against pathogens, but extensive evidence suggests that mounting immune responses can entail survival and fecundity costs. The physiological mechanisms that underpin these costs remain poorly understood, despite their potentially important role in shaping life-histories. Recent studies involving laboratory models highlight the possibility that oxidative stress could mediate these costs, as immune-activation can increase the production of reactive oxygen species leading to oxidative stress. However, this hypothesis has rarely been tested in free-ranging wild populations, where natural oxidative statuses and compensatory strategies may moderate immune responses and their impacts on oxidative status. Furthermore, the possibility that individuals scale their immune responses according to their oxidative status, conceivably to mitigate such costs, remains virtually unexplored. Here, we experimentally investigate the effects of a phytohaemagglutinin (PHA) immune-challenge on oxidative status in wild male and female white-browed sparrow weavers, Plocepasser mahali. We also establish whether baseline oxidative status prior to challenge predicts the scale of the immune responses. Contrary to previous work on captive animals, our findings suggest that PHA-induced immune-activation does not elicit oxidative stress. Compared with controls (n = 25 birds), PHA-injected birds (n = 27 birds) showed no evidence of a differential change in markers of oxidative damage or enzymatic and non-enzymatic antioxidant protection 24 hours after challenge. We did, however, find that the activity of a key antioxidant enzyme (superoxide dismutase, SOD) prior to immune-activation predicted the scale of the resulting swelling: birds with stronger initial SOD activity subsequently produced smaller swellings. Our findings (i) suggest that wild birds can mount immune responses without suffering from systemic oxidative stress, and (ii) lend support to

  20. SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells

    PubMed Central

    Khan, Reas S.; Fonseca-Kelly, Zoe; Callinan, Catherine; Zuo, Ling; Sachdeva, Mira M.; Shindler, Kenneth S.

    2012-01-01

    Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC) loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators reduce oxidative stress and promote mitochondrial function in neuronal cells. Oxidative stress, marked by reactive oxygen species (ROS) accumulation, was induced in RGC-5 cells by serum deprivation, or addition of doxorubicin or hydrogen peroxide, and resulted in significant cell loss. SIRT1 activators resveratrol (RSV) and SRTAW04 reduced ROS levels and promoted cell survival in RGC-5 cells as well as primary RGC cultures. Effects were blocked by SIRT1 siRNA. SIRT1 activators also increased expression of succinate dehydrogenase (SDH), a mitochondrial enzyme, and promoted deacetylation of PGC-1α, a co-enzyme involved in mitochondrial function. Results show SIRT1 activators prevent cell loss by reducing oxidative stress and promoting mitochondrial function in a neuronal cell line. Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress. PMID:23293585

  1. Lung cancer: what are the links with oxidative stress, physical activity and nutrition.

    PubMed

    Filaire, Edith; Dupuis, Carmen; Galvaing, Géraud; Aubreton, Sylvie; Laurent, Hélène; Richard, Ruddy; Filaire, Marc

    2013-12-01

    Oxidative stress appears to play an essential role as a secondary messenger in the normal regulation of a variety of physiological processes, such as apoptosis, survival, and proliferative signaling pathways. Oxidative stress also plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer. Among cancers, lung cancer is the leading cause of cancer in the Western world. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating oxidative stress. It can be subdivided into two broad categories, small cell lung cancer and non-small-cell lung cancer, the latter is the most common type. Distinct measures of primary and secondary prevention have been investigated to reduce the risk of morbidity and mortality caused by lung cancer. Among them, it seems that physical activity and nutrition have some beneficial effects. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress. Micronutrient supplementation seems to have a positive impact in lung surgery, particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and nutrition. PMID:24161719

  2. Requirement for human Mps1/TTK in oxidative DNA damage repair and cell survival through MDM2 phosphorylation

    PubMed Central

    Yu, Zheng-Cheng; Huang, Yi-Fu; Shieh, Sheau-Yann

    2016-01-01

    Human Mps1 (hMps1) is a protein kinase essential for mitotic checkpoints and the DNA damage response. Here, we present new evidence that hMps1 also participates in the repair of oxidative DNA lesions and cell survival through the MDM2-H2B axis. In response to oxidative stress, hMps1 phosphorylates MDM2, which in turn promotes histone H2B ubiquitination and chromatin decompaction. These events facilitate oxidative DNA damage repair and ATR-CHK1, but not ATM-CHK2 signaling. Depletion of hMps1 or MDM2 compromised H2B ubiquitination, DNA repair and cell survival. The impairment could be rescued by re-expression of WT but not the phospho-deficient MDM2 mutant, supporting the involvement of hMps1-dependent MDM2 phosphorylation in the oxidative stress response. In line with these findings, localization of RPA and base excision repair proteins to damage foci also requires MDM2 and hMps1. Significantly, like MDM2, hMps1 is upregulated in human sarcoma, suggesting high hMps1 and MDM2 expression may be beneficial for tumors constantly challenged by an oxidative micro-environment. Our study therefore identified an hMps1-MDM2-H2B signaling axis that likely plays a relevant role in tumor progression. PMID:26531827

  3. Requirement for human Mps1/TTK in oxidative DNA damage repair and cell survival through MDM2 phosphorylation.

    PubMed

    Yu, Zheng-Cheng; Huang, Yi-Fu; Shieh, Sheau-Yann

    2016-02-18

    Human Mps1 (hMps1) is a protein kinase essential for mitotic checkpoints and the DNA damage response. Here, we present new evidence that hMps1 also participates in the repair of oxidative DNA lesions and cell survival through the MDM2-H2B axis. In response to oxidative stress, hMps1 phosphorylates MDM2, which in turn promotes histone H2B ubiquitination and chromatin decompaction. These events facilitate oxidative DNA damage repair and ATR-CHK1, but not ATM-CHK2 signaling. Depletion of hMps1 or MDM2 compromised H2B ubiquitination, DNA repair and cell survival. The impairment could be rescued by re-expression of WT but not the phospho-deficient MDM2 mutant, supporting the involvement of hMps1-dependent MDM2 phosphorylation in the oxidative stress response. In line with these findings, localization of RPA and base excision repair proteins to damage foci also requires MDM2 and hMps1. Significantly, like MDM2, hMps1 is upregulated in human sarcoma, suggesting high hMps1 and MDM2 expression may be beneficial for tumors constantly challenged by an oxidative micro-environment. Our study therefore identified an hMps1-MDM2-H2B signaling axis that likely plays a relevant role in tumor progression. PMID:26531827

  4. The Oxygen Paradox, oxidative stress, and ageing.

    PubMed

    Davies, Kelvin J A

    2016-04-01

    Professor Helmut Sies is being lauded in this special issue of Archives of Biochemistry & Biophysics, on the occasion of his retirement as Editor-in-Chief. There is no doubt that Helmut has exerted an enormously positive influence on this journal, the fields of Biochemistry & Biophysics in general, and the areas of free radical and redox biology & medicine in particular. Helmut Sies' many discoveries about peroxide metabolism, glutathione, glutathione peroxidases, singlet oxygen, carotenoids in general and lycopene in particular, and flavonoids, fill the pages of his more than 600 publications. In addition, he will forever be remembered for coining the term 'oxidative stress' that is so widely used (and sometimes abused) by most of his colleagues. PMID:27095211

  5. Amyloids, Melanins and Oxidative Stress in Melanomagenesis

    PubMed Central

    Liu-Smith, Feng; Poe, Carrie; Farmer, Patrick J.; Meyskens, Frank L.

    2015-01-01

    Melanoma has traditionally been viewed as an ultra-violet (UV) radiation induced malignancy. While UV is a common inducing factor, other endogenous stresses such as metal ion accumulation or the melanin pigment itself, may provide alternative pathways to melanoma progression. Eumelanosomes within melanoma often exhibit disrupted membranes and fragmented pigment which may be due to alterations in their amyloid-based striatial matrix. The melanosomal amyloid can itself be toxic, especially in combination with reactive oxygen species (ROS) and reactive nitrogen species (RNS) generated by endogenous NADPH oxidase (NOX) and nitric oxide synthase (NOS) enzymes; a toxic mix that may initiate melanomagenesis. Further understanding of the loss of the melanosomal organization, the behavior of the exposed melanin, and the induction of ROS/RNS in melanomas may provide critical insights into this deadly disease. PMID:25271672

  6. Thyroid Hormones, Oxidative Stress, and Inflammation.

    PubMed

    Mancini, Antonio; Di Segni, Chantal; Raimondo, Sebastiano; Olivieri, Giulio; Silvestrini, Andrea; Meucci, Elisabetta; Currò, Diego

    2016-01-01

    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases. PMID:27051079

  7. Oxidative stress in normal and diabetic rats.

    PubMed

    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 (p<0.001) greater than the control levels. The diabetic animals presented an amount of vitamin E far greater (p<0.0001) than the controls, as was also the case for the vitaminE/polyunsaturated fatty acid (PUFA) and vitaminE/linoleic acid (C18:2) 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. PMID:10523056

  8. Glutamate neurotoxicity, oxidative stress and mitochondria.

    PubMed

    Atlante, A; Calissano, P; Bobba, A; Giannattasio, S; Marra, E; Passarella, S

    2001-05-18

    The excitatory neurotransmitter glutamate plays a major role in determining certain neurological disorders. This situation, referred to as 'glutamate neurotoxicity' (GNT), is characterized by an increasing damage of cell components, including mitochondria, leading to cell death. In the death process, reactive oxygen species (ROS) are generated. The present study describes the state of art in the field of GNT with a special emphasis on the oxidative stress and mitochondria. In particular, we report how ROS are generated and how they affect mitochondrial function in GNT. The relationship between ROS generation and cytochrome c release is described in detail, with the released cytochrome c playing a role in the cell defense mechanism against neurotoxicity. PMID:11376653

  9. Thyroid Hormones, Oxidative Stress, and Inflammation

    PubMed Central

    Raimondo, Sebastiano; Olivieri, Giulio; Meucci, Elisabetta; Currò, Diego

    2016-01-01

    Inflammation and oxidative stress (OS) are closely related processes, as well exemplified in obesity and cardiovascular diseases. OS is also related to hormonal derangement in a reciprocal way. Among the various hormonal influences that operate on the antioxidant balance, thyroid hormones play particularly important roles, since both hyperthyroidism and hypothyroidism have been shown to be associated with OS in animals and humans. In this context, the nonthyroidal illness syndrome (NTIS) that typically manifests as reduced conversion of thyroxine (T4) to triiodothyronine (T3) in different acute and chronic systemic conditions is still a debated topic. The pathophysiological mechanisms of this syndrome are reviewed, together with the roles of deiodinases, the enzymes responsible for the conversion of T4 to T3, in both physiological and pathological situations. The presence of OS indexes in NTIS supports the hypothesis that it represents a condition of hypothyroidism at the tissue level and not only an adaptive mechanism to diseases. PMID:27051079

  10. Traumatic stress, oxidative stress and posttraumatic stress disorder: neurodegeneration and the accelerated-aging hypothesis

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

    Posttraumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and then identify mechanisms by which PTSD might promote OXS and accelerated aging. We review studies on OXS-related genes and the role that they may play in moderating the effects of PTSD on neural integrity and conclude with a discussion of directions for future research on antioxidant treatments and biomarkers of accelerated aging in PTSD. PMID:25245500