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Sample records for cellular oxidative stress

  1. Activation of the hypothalamic-pituitary-adrenal stress axis induces cellular oxidative stress

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    Jereme G. Spiers

    2015-01-01

    Full Text Available Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA axis induce activity in the cellular reduction-oxidation (redox system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure.

  2. Enhanced transfection by antioxidative polymeric gene carrier that reduces polyplex-mediated cellular oxidative stress.

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    Lee, Min Sang; Kim, Nak Won; Lee, Kyuri; Kim, Hongtae; Jeong, Ji Hoon

    2013-06-01

    To test the hypothesis in which polyplex-induced oxidative stress may affect overall transfection efficiency, an antioxidative transfection system minimizing cellular oxidative stress was designed for enhanced transfection. An amphiphilic copolymer (PEI-PLGA) was synthesized and used as a micelle-type gene carrier containing hydrophobic antioxidant, α-tocopherol. Cellular oxidative stress and the change of mitochondrial membrane potential after transfection was measured by using a fluorescent probe (H₂DCFDA) and lipophilic cationic probe (JC-1), respectively. Transfection efficiency was determined by measuring a reporter gene (luciferase) expression level. The initial transfection study with conventional PEI/plasmid DNA polyplex showed significant generation of reactive oxygen species (ROS). The PEI-PLGA copolymer successfully carried out the simultaneous delivery of α-tocopherol and plasmid DNA (PEI-PLGA/Toco/pDNA polyplex) into cells, resulting in a significant reduction in cellular ROS generation after transfection and helped to maintain the mitochondrial membrane potential (ΔΨ). In addition, the transfection efficiency was dramatically increased using the antioxidative transfection system. This work showed that oxidative stress would be one of the important factors that should be considered in designing non-viral gene carriers and suggested a possible way to reduce the carrier-mediated oxidative stress, which consequently leads to enhanced transfection.

  3. Cellular and exosome mediated molecular defense mechanism in bovine granulosa cells exposed to oxidative stress.

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    Mohammed Saeed-Zidane

    Full Text Available Various environmental insults including diseases, heat and oxidative stress could lead to abnormal growth, functions and apoptosis in granulosa cells during ovarian follicle growth and oocyte maturation. Despite the fact that cells exposed to oxidative stress are responding transcriptionally, the potential release of transcripts associated with oxidative stress response into extracellular space through exosomes is not yet determined. Therefore, here we aimed to investigate the effect of oxidative stress in bovine granulosa cells in vitro on the cellular and exosome mediated defense mechanisms. Bovine granulosa cells were aspirated from ovarian follicles and cultured in DMEM/F-12 Ham culture medium supplemented with 10% exosome-depleted fetal bovine serum. In the first experiment sub-confluent cells were treated with 5 μM H2O2 for 40 min to induce oxidative stress. Thereafter, cells were subjected to ROS and mitochondrial staining, cell proliferation and cell cycle assays. Furthermore, gene and protein expression analysis were performed in H2O2-challenged versus control group 24 hr post-treatment using qRT-PCR and immune blotting or immunocytochemistry assay, respectively. Moreover, exosomes were isolated from spent media using ultracentrifugation procedure, and subsequently used for RNA isolation and qRT-PCR. In the second experiment, exosomes released by granulosa cells under oxidative stress (StressExo or those released by granulosa cells without oxidative stress (NormalExo were co-incubated with bovine granulosa cells in vitro to proof the potential horizontal transfer of defense molecules from exosomes to granulosa cells and investigate any phenotype changes. Exposure of bovine granulosa cells to H2O2 induced the accumulation of ROS, reduced mitochondrial activity, increased expression of Nrf2 and its downstream antioxidant genes (both mRNA and protein, altered the cell cycle transitions and induced cellular apoptosis. Granulosa cells

  4. Unraveling the cellular response to oxidative stress in the endoplasmic reticulum

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    Hansen, Henning Gram

    , disulfide bonds are predominantly generated by the two isoforms of the ER oxidoreductin-1 (Ero1) family: Ero1α and Ero1β. Both enzymes oxidize the active-site cysteines in protein disulfide isomerases (PDIs), which in turn introduce disulfide bonds into newly synthesized proteins. Ero1 is re......-oxidized by molecular oxygen and this step generates hydrogen peroxide: a reactive oxygen species. Intramolecular disulfide bonds tightly regulate the oxidase activity of Ero1α. Whereas the regulatory mechanisms that regulate Ero1α activity are well understood, the overall cellular response to oxidative stress....... Interestingly, depletion of GPx8 in cells induced expression of an antioxidant response marker only in the presence of Ero1. These findings imply that GPx8 is an important scavenger of Ero1-generated hydrogen peroxide, and thus provides a critical function in negotiating oxidative stress originating from...

  5. Various cellular stress components change as the rat ages: An insight into the putative overall age-related cellular stress network.

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    Cueno, Marni E; Imai, Kenichi

    2018-02-01

    Cellular stress is mainly comprised of oxidative, nitrosative, and endoplasmic reticulum stresses and has long been correlated to the ageing process. Surprisingly, the age-related difference among the various components in each independent stress pathway and the possible significance of these components in relation to the overall cellular stress network remain to be clearly elucidated. In this study, we obtained blood from ageing rats upon reaching 20-, 40-, and 72-wk.-old. Subsequently, we measured representative cellular stress-linked biomolecules (H 2 O 2 , glutathione reductase, heme, NADPH, NADP, nitric oxide, GADD153) and cell signals [substance P (SP), free fatty acid, calcium, NF-κB] in either or both blood serum and cytosol. Subsequently, network analysis of the overall cellular stress network was performed. Our results show that there are changes affecting stress-linked biomolecules and cell signals as the rat ages. Additionally, based on our network analysis data, we postulate that NADPH, H 2 O 2 , GADD153, and SP are the key components and the interactions between these components are central to the overall age-related cellular stress network in the rat blood. Thus, we propose that the main pathway affecting the overall age-related cellular stress network in the rat blood would entail NADPH-related oxidative stress (involving H 2 O 2 ) triggering GADD153 activation leading to SP induction which in-turn affects other cell signals. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Antioxidant responses and cellular adjustments to oxidative stress.

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    Espinosa-Diez, Cristina; Miguel, Verónica; Mennerich, Daniela; Kietzmann, Thomas; Sánchez-Pérez, Patricia; Cadenas, Susana; Lamas, Santiago

    2015-12-01

    Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases. Copyright © 2015. Published by Elsevier B.V.

  7. Deficiency of methionine sulfoxide reductase A causes cellular dysfunction and mitochondrial damage in cardiac myocytes under physical and oxidative stresses

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    Nan, Changlong; Li, Yuejin; Jean-Charles, Pierre-Yves; Chen, Guozhen; Kreymerman, Alexander; Prentice, Howard; Weissbach, Herbert; Huang, Xupei

    2010-01-01

    Research highlights: → Deficiency of MsrA in the heart renders myocardial cells more sensitive to oxidative stress. → Mitochondrial damage happens in the heart lacking MsrA. → More protein oxidation in myocardial cells lacking MsrA. → MsrA protects the heart against oxidative stress. -- Abstract: Methionine sulfoxide reductase A (MsrA) is an enzyme that reverses oxidation of methionine in proteins. Using a MsrA gene knockout (MsrA -/- ) mouse model, we have investigated the role of MsrA in the heart. Our data indicate that cellular contractility and cardiac function are not significantly changed in MsrA -/- mice if the hearts are not stressed. However, the cellular contractility, when stressed using a higher stimulation frequency (2 Hz), is significantly reduced in MsrA -/- cardiac myocytes. MsrA -/- cardiac myocytes also show a significant decrease in contractility after oxidative stress using H 2 O 2 . Corresponding changes in Ca 2+ transients are observed in MsrA -/- cardiomyocytes treated with 2 Hz stimulation or with H 2 O 2 . Electron microscope analyses reveal a dramatic morphological change of mitochondria in MsrA -/- mouse hearts. Further biochemical measurements indicate that protein oxidation levels in MsrA -/- mouse hearts are significantly higher than those in wild type controls. Our study demonstrates that the lack of MsrA in cardiac myocytes reduces myocardial cell's capability against stress stimulations resulting in a cellular dysfunction in the heart.

  8. Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

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    Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

    2016-02-01

    In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

  9. Oxidative stress

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    Stevanović Jelka

    2012-01-01

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

  10. Happily (never after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence

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    Annika Höhn

    2017-04-01

    Full Text Available Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.

  11. Staphylococcal response to oxidative stress

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    Rosmarie eGaupp

    2012-03-01

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

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

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    Lushchak, Volodymyr I

    2014-12-05

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

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

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    Silvia Angori

    2017-05-01

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

  14. Environmentally persistent free radicals amplify ultrafine particle mediated cellular oxidative stress and cytotoxicity

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    Balakrishna Shrilatha

    2009-04-01

    Full Text Available Abstract Background Combustion generated particulate matter is deposited in the respiratory tract and pose a hazard to the lungs through their potential to cause oxidative stress and inflammation. We have previously shown that combustion of fuels and chlorinated hydrocarbons produce semiquinone-type radicals that are stabilized on particle surfaces (i.e. environmentally persistent free radicals; EPFRs. Because the composition and properties of actual combustion-generated particles are complex, heterogeneous in origin, and vary from day-to-day, we have chosen to use surrogate particle systems. In particular, we have chosen to use the radical of 2-monochlorophenol (MCP230 as the EPFR because we have previously shown that it forms a EPFR on Cu(IIO surfaces and catalyzes formation of PCDD/F. To understand the physicochemical properties responsible for the adverse pulmonary effects of combustion by-products, we have exposed human bronchial epithelial cells (BEAS-2B to MCP230 or the CuO/silica substrate. Our general hypothesis was that the EPFR-containing particle would have greater toxicity than the substrate species. Results Exposure of BEAS-2B cells to our combustion generated particle systems significantly increased reactive oxygen species (ROS generation and decreased cellular antioxidants resulting in cell death. Resveratrol treatment reversed the decline in cellular glutathione (GSH, glutathione peroxidase (GPx, and superoxide dismutase (SOD levels for both types of combustion-generated particle systems. Conclusion The enhanced cytotoxicity upon exposure to MCP230 correlated with its ability to generate more cellular oxidative stress and concurrently reduce the antioxidant defenses of the epithelial cells (i.e. reduced GSH, SOD activity, and GPx. The EPFRs in MCP230 also seem to be of greater biological concern due to their ability to induce lipid peroxidation. These results are consistent with the oxidizing nature of the CuO/silica ultrafine

  15. Functional characterization of novel genotypes and cellular oxidative stress studies in propionic acidemia.

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    Gallego-Villar, Lorena; Pérez-Cerdá, Celia; Pérez, Belén; Abia, David; Ugarte, Magdalena; Richard, Eva; Desviat, Lourdes R

    2013-09-01

    Propionic acidemia (PA), caused by a deficiency of the mitochondrial biotin dependent enzyme propionyl-CoA carboxylase (PCC) is one of the most frequent organic acidurias in humans. PA is caused by mutations in either the PCCA or PCCB genes encoding the α- and β-subunits of the PCC enzyme which are assembled as an α6β6 dodecamer. In this study we have investigated the molecular basis of the defect in ten fibroblast samples from PA patients. Using homology modeling with the recently solved crystal structure of the PCC holoenzyme and a eukaryotic expression system we have analyzed the structural and functional effect of novel point mutations, also revealing a novel splice defect by minigene analysis. In addition, we have investigated the contribution of oxidative stress to cellular damage measuring reactive oxygen species (ROS) levels and apoptosis parameters in patient fibroblasts, as recent studies point to a secondary mitochondrial dysfunction as pathophysiological mechanism in this disorder. The results show an increase in intracellular ROS content compared to controls, correlating with the activation of the JNK and p38 signaling pathways. Highest ROS levels were present in cells harboring functionally null mutations, including one severe missense mutation. This work provides molecular insight into the pathogenicity of PA variants and indicates that oxidative stress may be a major contributing factor to the cellular damage, supporting the proposal of antioxidant strategies as novel supplementary therapy in this rare disease.

  16. Oxidatively generated DNA/RNA damage in psychological stress states

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    Jørgensen, Anders

    2013-01-01

    age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8...... between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased......Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several...

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

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    Katie Richardson

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

  18. Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

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    Lai, H.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yeh, Y.C. [Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan (China); Wang, L.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Ting, C.T.; Lee, W.L. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Lee, H.W. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, K.Y. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan (China); Wu, A. [College of Biological Science, University of California, Davis (United States); Su, C.S. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Liu, T.J., E-mail: trliu@vghtc.gov.tw [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

    2011-12-15

    Background: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. Methods: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1 {mu}M), propofol (1 {mu}M), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. Results: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-{delta} was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. Conclusions: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application. -- Highlights: Black-Right-Pointing-Pointer We evaluate how propofol prevents doxorubicin-induced toxicity in cardiomyocytes. Black-Right-Pointing-Pointer Propofol reduces doxorubicin-imposed nitrative and oxidative stress. Black-Right-Pointing-Pointer Propofol suppresses mitochondrion-, p53- and PKC-related apoptotic signaling. Black-Right-Pointing-Pointer Propofol ameliorates apoptosis and

  19. Protective effect of gallic acid and Syzygium cumini extract against oxidative stress-induced cellular injury in human lymphocytes.

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    De Bona, Karine Santos; Bonfanti, Gabriela; Bitencourt, Paula Eliete Rodrigues; da Silva, Thainan Paz; Borges, Raphaela Maleski; Boligon, Aline; Pigatto, Aline; Athayde, Margareth Lynde; Moretto, Maria Beatriz

    2016-01-01

    Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2'-azobis-2-amidinopropane dihydrochloride (AAPH). Lymphocytes were incubated with ASc (100 and 500 µg/ml) and gallic acid (50 and 200 µM) at 37 °C for 30 min followed by incubation with AAPH (1 mM) at 37 °C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects.

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

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    Metro, D; Muraca, U; Manasseri, L

    2006-01-01

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

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

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    Jaya Kumar

    2017-09-01

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

  2. Accelerated aging in schizophrenia patients: the potential role of oxidative stress.

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    Okusaga, Olaoluwa O

    2014-08-01

    Several lines of evidence suggest that schizophrenia, a severe mental illness characterized by delusions, hallucinations and thought disorder is associated with accelerated aging. The free radical (oxidative stress) theory of aging assumes that aging occurs as a result of damage to cell constituents and connective tissues by free radicals arising from oxygen-associated reactions. Schizophrenia has been associated with oxidative stress and chronic inflammation, both of which also appear to reciprocally induce each other in a positive feedback manner. The buildup of damaged macromolecules due to increased oxidative stress and failure of protein repair and maintenance systems is an indicator of aging both at the cellular and organismal level. When compared with age-matched healthy controls, schizophrenia patients have higher levels of markers of oxidative cellular damage such as protein carbonyls, products of lipid peroxidation and DNA hydroxylation. Potential confounders such as antipsychotic medication, smoking, socio-economic status and unhealthy lifestyle make it impossible to solely attribute the earlier onset of aging-related changes or oxidative stress to having a diagnosis of schizophrenia. Regardless of whether oxidative stress can be attributed solely to a diagnosis of schizophrenia or whether it is due to other factors associated with schizophrenia, the available evidence is in support of increased oxidative stress-induced cellular damage of macromolecules which may play a role in the phenomenon of accelerated aging presumed to be associated with schizophrenia.

  3. Oxidative stress in ageing of hair.

    Science.gov (United States)

    Trüeb, Ralph M

    2009-01-01

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

  4. Oxidative stress signaling to chromatin in health and disease

    KAUST Repository

    Kreuz, Sarah

    2016-06-20

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

  5. Neuronal cellular responses to extremely low frequency electromagnetic field exposure: implications regarding oxidative stress and neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Marcella Reale

    Full Text Available Neurodegenerative diseases comprise both hereditary and sporadic conditions characterized by an identifying progressive nervous system dysfunction and distinctive neuopathophysiology. The majority are of non-familial etiology and hence environmental factors and lifestyle play key roles in their pathogenesis. The extensive use of and ever increasing worldwide demand for electricity has stimulated societal and scientific interest on the environmental exposure to low frequency electromagnetic fields (EMFs on human health. Epidemiological studies suggest a positive association between 50/60-Hz power transmission fields and leukemia or lymphoma development. Consequent to the association between EMFs and induction of oxidative stress, concerns relating to development of neurodegenerative diseases, such as Alzheimer disease (AD, have been voiced as the brain consumes the greatest fraction of oxygen and is particularly vulnerable to oxidative stress. Exposure to extremely low frequency (ELF-EMFs are reported to alter animal behavior and modulate biological variables, including gene expression, regulation of cell survival, promotion of cellular differentiation, and changes in cerebral blood flow in aged AD transgenic mice. Alterations in inflammatory responses have also been reported, but how these actions impact human health remains unknown. We hence evaluated the effects of an electromagnetic wave (magnetic field intensity 1 mT; frequency, 50-Hz on a well-characterized immortalized neuronal cell model, human SH-SY5Y cells. ELF-EMF exposure elevated the expession of NOS and O2(-, which were countered by compensatory changes in antioxidant catylase (CAT activity and enzymatic kinetic parameters related to CYP-450 and CAT activity. Actions of ELF-EMFs on cytokine gene expression were additionally evaluated and found rapidly modified. Confronted with co-exposure to H2O2-induced oxidative stress, ELF-EMF proved not as well counteracted and resulted in a

  6. Periodontitis and increase in circulating oxidative stress

    Directory of Open Access Journals (Sweden)

    Takaaki Tomofuji

    2009-05-01

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

  7. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

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

  8. Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Shvedova, Anna A., E-mail: ats1@cdc.gov [Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, University of Rome “Tor Vergata”, Rome (Italy); Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV, University of Rome “Tor Vergata”, Rome (Italy); Pietroiusti, Antonio [Department of Biopathology, University of Rome “Tor Vergata”, Rome (Italy); Fadeel, Bengt [Division of Molecular Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm (Sweden); Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA (United States); Kagan, Valerian E. [Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA (United States)

    2012-06-01

    Nanotechnologies are emerging as highly promising technologies in many sectors in the society. However, the increasing use of engineered nanomaterials also raises concerns about inadvertent exposure to these materials and the potential for adverse effects on human health and the environment. Despite several years of intensive investigations, a common paradigm for the understanding of nanoparticle-induced toxicity remains to be firmly established. Here, the so-called oxidative stress paradigm is scrutinized. Does oxidative stress represent a secondary event resulting inevitably from disruption of biochemical processes and the demise of the cell, or a specific, non-random event that plays a role in the induction of cellular damage e.g. apoptosis? The answer to this question will have important ramifications for the development of strategies for mitigation of adverse effects of nanoparticles. Recent examples of global lipidomics studies of nanoparticle-induced tissue damage are discussed along with proteomics and transcriptomics approaches to achieve a comprehensive understanding of the complex and interrelated molecular changes in cells and tissues exposed to nanoparticles. We also discuss instances of non-oxidative stress-mediated cellular damage resulting from direct physical interference of nanomaterials with cellular structures. -- Highlights: ► CNT induced non-random oxidative stress associated with apoptosis. ► Non-oxidative mechanisms for cellular toxicity of carbon nanotubes. ► Biodegradation of CNT by cells of innate immune system. ► “Omics”-based biomarkers of CNT exposures.

  9. Mechanisms of carbon nanotube-induced toxicity: Focus on oxidative stress

    International Nuclear Information System (INIS)

    Shvedova, Anna A.; Pietroiusti, Antonio; Fadeel, Bengt; Kagan, Valerian E.

    2012-01-01

    Nanotechnologies are emerging as highly promising technologies in many sectors in the society. However, the increasing use of engineered nanomaterials also raises concerns about inadvertent exposure to these materials and the potential for adverse effects on human health and the environment. Despite several years of intensive investigations, a common paradigm for the understanding of nanoparticle-induced toxicity remains to be firmly established. Here, the so-called oxidative stress paradigm is scrutinized. Does oxidative stress represent a secondary event resulting inevitably from disruption of biochemical processes and the demise of the cell, or a specific, non-random event that plays a role in the induction of cellular damage e.g. apoptosis? The answer to this question will have important ramifications for the development of strategies for mitigation of adverse effects of nanoparticles. Recent examples of global lipidomics studies of nanoparticle-induced tissue damage are discussed along with proteomics and transcriptomics approaches to achieve a comprehensive understanding of the complex and interrelated molecular changes in cells and tissues exposed to nanoparticles. We also discuss instances of non-oxidative stress-mediated cellular damage resulting from direct physical interference of nanomaterials with cellular structures. -- Highlights: ► CNT induced non-random oxidative stress associated with apoptosis. ► Non-oxidative mechanisms for cellular toxicity of carbon nanotubes. ► Biodegradation of CNT by cells of innate immune system. ► “Omics”-based biomarkers of CNT exposures.

  10. Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

    Science.gov (United States)

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-01-01

    The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

  11. Yeast aquaporin regulation by 4-hydroxynonenal is implicated in oxidative stress response.

    Science.gov (United States)

    Rodrigues, Claudia; Tartaro Bujak, Ivana; Mihaljević, Branka; Soveral, Graça; Cipak Gasparovic, Ana

    2017-05-01

    Reactive oxygen species, especially hydrogen peroxide (H 2 O 2 ), contribute to functional molecular impairment and cellular damage, but also are necessary in normal cellular metabolism, and in low doses play stimulatory role in cell proliferation and stress resistance. In parallel, reactive aldehydes such as 4-hydroxynonenal (HNE), are lipid peroxidation breakdown products which also contribute to regulation of numerous cellular processes. Recently, channeling of H 2 O 2 by some mammalian aquaporin isoforms has been reported and suggested to contribute to aquaporin involvement in cancer malignancies, although the mechanism by which these membrane water channels are implicated in oxidative stress is not clear. In this study, two yeast models with increased levels of membrane polyunsaturated fatty acids (PUFAs) and aquaporin AQY1 overexpression, respectively, were used to evaluate their interplay in cell's oxidative status. In particular, the aim of the study was to investigate if HNE accumulation could affect aquaporin function with an outcome in oxidative stress response. The data showed that induction of aquaporin expression by PUFAs results in increased water permeability in yeast membranes and that AQY1 activity is impaired by HNE. Moreover, AQY1 expression increases cellular sensitivity to oxidative stress by facilitating H 2 O 2 influx. On the other hand, AQY1 expression has no influence on the cellular antioxidant GSH levels and catalase activity. These results strongly suggest that aquaporins are important players in oxidative stress response and could contribute to regulation of cellular processes by regulation of H 2 O 2 influx. © 2017 IUBMB Life, 69(5):355-362, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  12. 1,4-Naphthoquinones: From Oxidative Damage to Cellular and Inter-Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Lars-Oliver Klotz

    2014-09-01

    Full Text Available Naphthoquinones may cause oxidative stress in exposed cells and, therefore, affect redox signaling. Here, contributions of redox cycling and alkylating properties of quinones (both natural and synthetic, such as plumbagin, juglone, lawsone, menadione, methoxy-naphthoquinones, and others to cellular and inter-cellular signaling processes are discussed: (i naphthoquinone-induced Nrf2-dependent modulation of gene expression and its potentially beneficial outcome; (ii the modulation of receptor tyrosine kinases, such as the epidermal growth factor receptor by naphthoquinones, resulting in altered gap junctional intercellular communication. Generation of reactive oxygen species and modulation of redox signaling are properties of naphthoquinones that render them interesting leads for the development of novel compounds of potential use in various therapeutic settings.

  13. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2017-06-18

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

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

    Directory of Open Access Journals (Sweden)

    Namrata eChaudhari

    2014-07-01

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

  16. The Role of Oxidative Stress in Aging and Dementia

    Directory of Open Access Journals (Sweden)

    Joana Teixeira

    2014-12-01

    Full Text Available Introduction: Biologic aging is a process, and oxidative stress theory, which is one of the most accepted biological theories for aging, states that oxidative stress causes cumulative damage to mitochondrial DNA resulting in cellular senescence. Dementia is a neurodegenerative disorder whose major risk factor is aging. Although the exact neuronal lesion mechanisms underlying neurodegenerative disorders, including dementia, are not yet known, most recent studies suggest oxidative stress and mitochondrial dynamics’ role in the process.Objective: Literature review on the role of oxidative stress’ role in aging and dementia.Methods: Literature review of selected arti-cles and books deemed relevant by the authors, supplemented by Medline/Pubmed database search using combinations of the following key-words: “oxidative stress”, “de-mentia”, “aging” and “pathogenesis”, published between 1950 and 2013. References of the selected articles and books were also considered.Results: In the last five years new research has been undertaken that enlightens the relation between oxidative stress and aging. One of the considered hypotheses states that during aging, the homeostatic regulation of biogenesis, dynamics and autophagic turnover of mitochondria disturbs their functioning, resulting in cellular senescence. Consequently, the oxidative burden may reach a critical threshold above which apoptosis is triggered, leading to irreversible mitochondrial derangement and cellular death. Although the exact neuronal lesion mechanisms underlying dementias are not known, multiple studies have consistently found increased oxidative damage in brain of patients with Alzheimer disease and recent data suggests involvement of mitochondrial dynamics in dementia processes, such as in aging.Conclusions: Most recent studies suggest the role of oxidative stress and mitochondrial dynamics’ in aging and dementia, either directly or

  17. Roles of the tyrosine isomers meta-tyrosine and ortho-tyrosine in oxidative stress.

    Science.gov (United States)

    Ipson, Brett R; Fisher, Alfred L

    2016-05-01

    The damage to cellular components by reactive oxygen species, termed oxidative stress, both increases with age and likely contributes to age-related diseases including Alzheimer's disease, atherosclerosis, diabetes, and cataract formation. In the setting of oxidative stress, hydroxyl radicals can oxidize the benzyl ring of the amino acid phenylalanine, which then produces the abnormal tyrosine isomers meta-tyrosine or ortho-tyrosine. While elevations in m-tyrosine and o-tyrosine concentrations have been used as a biological marker of oxidative stress, there is emerging evidence from bacterial, plant, and mammalian studies demonstrating that these isomers, particularly m-tyrosine, directly produce adverse effects to cells and tissues. These new findings suggest that the abnormal tyrosine isomers could in fact represent mediators of the effects of oxidative stress. Consequently the accumulation of m- and o-tyrosine may disrupt cellular homeostasis and contribute to disease pathogenesis, and as result, effective defenses against oxidative stress can encompass not only the elimination of reactive oxygen species but also the metabolism and ultimately the removal of the abnormal tyrosine isomers from the cellular amino acid pool. Future research in this area is needed to clarify the biologic mechanisms by which the tyrosine isomers damage cells and disrupt the function of tissues and organs and to identify the metabolic pathways involved in removing the accumulated isomers after exposure to oxidative stress. Published by Elsevier B.V.

  18. Biological markers of oxidative stress: Applications to cardiovascular research and practice

    Directory of Open Access Journals (Sweden)

    Edwin Ho

    2013-01-01

    Full Text Available Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an “integrator” of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are “functionally silent”. Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment.

  19. Ebselen alters cellular oxidative status and induces endoplasmic reticulum stress in rat hippocampal astrocytes.

    Science.gov (United States)

    Santofimia-Castaño, Patricia; Izquierdo-Alvarez, Alicia; de la Casa-Resino, Irene; Martinez-Ruiz, Antonio; Perez-Lopez, Marcos; Portilla, Juan C; Salido, Gines M; Gonzalez, Antonio

    2016-05-16

    Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti-inflammatory effects. Because of its properties, it may be protective against injury to the nervous tissue. However, evidence suggests that its glutathione peroxidase activity could underlie certain deleterious actions on cell physiology. In this study we have analyzed the effect of ebselen on rat hippocampal astrocytes in culture. Cellular oxidative status, cytosolic free-Ca(2+) concentration ([Ca(2+)]c), setting of endoplasmic reticulum stress and phosphorylation of glial fibrillary acidic protein and major mitogen-activated protein kinases were analyzed. Our results show that ebselen induced a concentration-dependent increase in the generation of reactive oxygen species in the mitochondria. We observed a concentration-dependent increase in global cysteine oxidation and in the level of malondialdehyde in the presence of ebselen. We also detected increases in catalase, glutathione S-transferase and glutathione reductase activity. Ebselen also evoked a concentration-dependent increase in [Ca(2+)]c. Moreover, we observed a concentration-dependent increase in the phosphorylation of the unfolded protein response markers, eukaryotic translation initiation factor 2α and X-box binding protein 1. Finally, ebselen also induced an increase in the phosphorylation of glial fibrillary acidic protein, SAPK/JNK, p38 MAPK and p44/42 MAPK. Our results provide strong evidence that implicate endoplasmic reticulum stress and activation of crucial mitogen-activated protein kinases in an oxidative damage of cells in the presence of ebselen. The compound thus might exert deleterious actions on astrocyte physiology that could compromise their function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Oxidative stress in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Shyamal K Goswami

    2015-01-01

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

  1. From Oxidative Stress Damage to Pathways, Networks, and Autophagy via MicroRNAs

    Directory of Open Access Journals (Sweden)

    Nikolai Engedal

    2018-01-01

    Full Text Available Oxidative stress can alter the expression level of many microRNAs (miRNAs, but how these changes are integrated and related to oxidative stress responses is poorly understood. In this article, we addressed this question by using in silico tools. We reviewed the literature for miRNAs whose expression is altered upon oxidative stress damage and used them in combination with various databases and software to predict common gene targets of oxidative stress-modulated miRNAs and affected pathways. Furthermore, we identified miRNAs that simultaneously target the predicted oxidative stress-modulated miRNA gene targets. This generated a list of novel candidate miRNAs potentially involved in oxidative stress responses. By literature search and grouping of pathways and cellular responses, we could classify these candidate miRNAs and their targets into a larger scheme related to oxidative stress responses. To further exemplify the potential of our approach in free radical research, we used our explorative tools in combination with ingenuity pathway analysis to successfully identify new candidate miRNAs involved in the ubiquitination process, a master regulator of cellular responses to oxidative stress and proteostasis. Lastly, we demonstrate that our approach may also be useful to identify novel candidate connections between oxidative stress-related miRNAs and autophagy. In summary, our results indicate novel and important aspects with regard to the integrated biological roles of oxidative stress-modulated miRNAs and demonstrate how this type of in silico approach can be useful as a starting point to generate hypotheses and guide further research on the interrelation between miRNA-based gene regulation, oxidative stress signaling pathways, and autophagy.

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

    DEFF Research Database (Denmark)

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

    2018-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Liang-Jun Yan

    2014-01-01

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

  4. Redox Role of Lactobacillus casei Shirota Against the Cellular Damage Induced by 2,2′-Azobis (2-Amidinopropane Dihydrochloride-Induced Oxidative and Inflammatory Stress in Enterocytes-Like Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Alberto Finamore

    2018-05-01

    Full Text Available In western societies where most of the day is spent in the postprandial state, the existence of oxidative and inflammatory stress conditions makes postprandial stress an important factor involved in the development of cardiovascular risk factors. A large body of evidence have been accumulated on the anti-inflammatory effects of probiotics, but no information is available on the mechanisms through which intestinal microbiota modulates redox unbalance associated with inflammatory stress. Here, we aimed to investigate the ability of Lactobacillus casei Shirota (LS to induce an antioxidant response to counteract oxidative and inflammatory stress in an in vitro model of enterocytes. Our results show that pretreatment of enterocytes with LS prevents membrane barrier disruption and cellular reactive oxygen species (ROS accumulation inside the cells, modulates the expression of the gastro-intestinal glutathione peroxidase (GPX2 antioxidant enzyme, and reduces p65 phosphorylation, supporting the involvement of the Nfr2 and nuclear factor kappa B pathways in the activation of antioxidant cellular defenses by probiotics. These results suggest, for the first time, a redox mechanism by LS in protecting intestinal cells from AAPH-induced oxidative and inflammatory stress.

  5. Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention

    KAUST Repository

    Olivieri, S.; Conti, A.; Iannaccone, S.; Cannistraci, C. V.; Campanella, A.; Barbariga, M.; Codazzi, F.; Pelizzoni, I.; Magnani, G.; Pesca, M.; Franciotta, D.; Cappa, S. F.; Alessio, M.

    2011-01-01

    Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative

  6. Clinical Perspective of Oxidative Stress in Sporadic ALS

    Science.gov (United States)

    D’Amico, Emanuele; Factor-Litvak, Pam; Santella, Regina M.; Mitsumoto, Hiroshi

    2013-01-01

    Sporadic amyotrophic lateral sclerosis (sALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/anti-oxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine, are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly support the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis. PMID:23797033

  7. Role of Free Radicals, Oxidative Stress and Xenobiotics in Carcinogenesis by Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Dibyajyoti Saha

    2014-09-01

    Full Text Available Carcinogenesis by many small molecular weight chemicals involves either a direct action of the chemical on cellular DNA or metabolism of the parent chemical to an active or ultimate form, which can than react with cellular DNA to produce a permanent chemical change in a DNA structure. A free radical is an atom or molecule that has one or more unpaired electron(s. These are highly reactive species capable of wide spread, indiscriminate oxidation and per oxidation of proteins, lipids and DNA which can lead to significant cellular damage and even tissue and/or organ failure. . Oxidative stress is a leading cause to damage cells by oxidation. The rate at which oxidative damage is induced (input and the rate at which it is efficiently repaired and removed (output. Xenobiotics are a compound that is foreign to the body. Xenobiotics can produce a variety of biological effects, including pharmacologic responses, toxicity, genes, immunologic reactions and cancer. Oxidative stress is a leading cause to damage cells by oxidation. The rate at which oxidative damage is induced (input and the rate at which it is efficiently repaired and removed (output. This communication highlights the role of carcinogens as environmental pollutants with the possible mechanism of free radicals, oxidative stress and xenobiotics.

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

    Science.gov (United States)

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

    2013-09-01

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

  9. Enhanced tolerance against early and late apoptotic oxidative stress in mammalian neurons through nicotinamidase and sirtuin mediated pathways.

    Science.gov (United States)

    Chong, Zhao Zhong; Maiese, Kenneth

    2008-08-01

    Focus upon therapeutic strategies that intersect between pathways that govern cellular metabolism and cellular survival may offer the greatest impact for the treatment of a number of neurodegenerative and metabolic disorders, such as diabetes mellitus. In this regard, we investigated the role of a Drosophila nicotinamidase (DN) in mammalian SH-SY5Y neuronal cells during oxidative stress. We demonstrate that during free radical exposure to nitric oxide generators DN neuronal expression significantly increased cell survival and blocked cellular membrane injury. Furthermore, DN neuronal expression prevented both apoptotic late DNA degradation and early phosphatidylserine exposure that may serve to modulate inflammatory cell activation in vivo. Nicotinamidase activity that limited nicotinamide cellular concentrations appeared to be necessary for DN neuroprotection, since application of progressive nicotinamide concentrations could abrogate the benefits of DN expression during oxidative stress. Pathways that involved sirtuin activation and SIRT1 were suggested to be vital, at least in part, for DN to confer protection through a series of studies. First, application of resveratrol increased cell survival during oxidative stress either alone or in conjunction with the expression of DN to a similar degree, suggesting that DN may rely upon SIRT1 activation to foster neuronal protection. Second, the overexpression of either SIRT1 or DN in neurons prevented apoptotic injury specifically in neurons expressing these proteins during oxidative stress, advancing the premise that DN and SIRT1 may employ similar pathways for neuronal protection. Third, inhibition of sirtuin activity with sirtinol was detrimental to neuronal survival during oxidative stress and prevented neuronal protection during overexpression of DN or SIRT1, further supporting that SIRT1 activity may be necessary for DN neuroprotection during oxidative stress. Implementation of further work to elucidate the

  10. Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Gunawan, Cindy, E-mail: c.gunawan@unsw.edu.au [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia); Sirimanoonphan, Aunchisa [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia); Teoh, Wey Yang [Clean Energy and Nanotechnology (CLEAN) Laboratory, School of Energy and Environment, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region (Hong Kong); Marquis, Christopher P., E-mail: c.marquis@unsw.edu.au [School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW (Australia); Amal, Rose [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia)

    2013-09-15

    Highlights: • Uptake of TiO{sub 2} solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO{sub 2} exhibit benign effect on cell proliferation. • Uptake of ZnO solids and leached zinc by C. reinhardtii inhibit the alga growth. • No cellular oxidative stress is detected with submicron and nano ZnO exposure. • The toxicity of particles is not necessarily mediated by cellular oxidative stress. -- Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO{sub 2} and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO{sub 2} exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO{sub 2} stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO{sub 2} exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO{sub 2}/L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50 ≥ 0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials.

  11. Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Gunawan, Cindy; Sirimanoonphan, Aunchisa; Teoh, Wey Yang; Marquis, Christopher P.; Amal, Rose

    2013-01-01

    Highlights: • Uptake of TiO 2 solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO 2 exhibit benign effect on cell proliferation. • Uptake of ZnO solids and leached zinc by C. reinhardtii inhibit the alga growth. • No cellular oxidative stress is detected with submicron and nano ZnO exposure. • The toxicity of particles is not necessarily mediated by cellular oxidative stress. -- Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO 2 and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO 2 exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO 2 stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO 2 exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO 2 /L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50 ≥ 0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials

  12. Toward an understanding of mechanism of aging-induced oxidative stress in human mesenchymal stem cells.

    Science.gov (United States)

    Benameur, Laila; Charif, Naceur; Li, Yueying; Stoltz, Jean-François; de Isla, Natalia

    2015-01-01

    Under physiological conditions, there is a production of limited range of free radicals. However, when the cellular antioxidant defence systems, overwhelm and fail to reverse back the free radicals to their normal basal levels, there is a creation of a condition of redox disequilibrium termed "oxidative stress", which is implicated in a very wide spectrum of genetic, metabolic, and cellular responses. The excess of free radicals can, cause unfavourable molecular alterations to biomolecules through oxidation of lipids, proteins, RNA and DNA, that can in turn lead to mutagenesis, carcinogenesis, and aging. Mesenchymal stem cells (MSCs) have been proven to be a promising source of cells for regenerative medicine, and to be useful in the treatment of pathologies in which tissue damage is linked to oxidative stress. Moreover, MSCs appeared to efficiently manage oxidative stress and to be more resistant to oxidative insult than normal somatic cells, making them an interesting and testable model for the role of oxidative stress in the aging process. In addition, aging is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Also, there is an obvious link between intracellular reactive oxygen species levels and cellular senescence. To date, few studies have investigated the promotion of aging by oxidative stress on human MSCs, and the mechanism by which oxidative stress induce stem cell aging is poorly understood. In this context, the aim of this review is to gain insight the current knowledge about the molecular mechanisms of aging-induced oxidative stress in human MSCs.

  13. Oxidative potential of particulate matter 2.5 as predictive indicator of cellular stress

    International Nuclear Information System (INIS)

    Crobeddu, Bélinda; Aragao-Santiago, Leticia; Bui, Linh-Chi; Boland, Sonja; Baeza Squiban, Armelle

    2017-01-01

    Particulate air pollution being recognized to be responsible for short and long term health effects, regulations for particulate matter with an aerodynamic diameter less than 2.5 (PM 2.5 ) are more and more restrictive. PM 2.5 regulation is based on mass without taking into account PM 2.5 composition that drives toxicity. Measurement of the oxidative potential (OP) of PM could be an additional PM indicator that would encompass the PM components involved in oxidative stress, the main mechanism of PM toxicity. We compared different methods to evaluate the intrinsic oxidative potential of PM 2.5 sampled in Paris and their ability to reflect the oxidative and inflammatory response in bronchial epithelial cells used as relevant target organ cells. The dithiothreitol depletion assay, the antioxidant (ascorbic acid and glutathione) depletion assay (OP AO ), the plasmid scission assay and the dichlorofluorescein (DCFH) oxidation assay used to characterize the OP of PM 2.5 (10–100 μg/mL) provided positive results of different magnitude with all the PM 2.5 samples used with significant correlation with different metals such as Cu and Zn as well as total polyaromatic hydrocarbons and the soluble organic fraction. The OP AO assay showed the best correlation with the production of intracellular reactive oxygen species by NCI-H292 cell line assessed by DCFH oxidation and with the expression of anti-oxidant genes (superoxide dismutase 2, heme-oxygenase-1) as well as the proinflammatory response (Interleukin 6) when exposed from 1 to 10 μg/cm 2 . The OP AO assay appears as the most prone to predict the biological effect driven by PM 2.5 and related to oxidative stress. - Highlights: • 5 Acellular assays were used to compare the intrinsic oxidative potential (OP) of PM. • The amount of ROS generation in bronchial cells is particle dependent. • Particles induce the expression of anti-oxidant and proinflammatory genes. • Biological effects correlates with OP assay

  14. Toxicological and pharmacological concerns on oxidative stress and related diseases

    Energy Technology Data Exchange (ETDEWEB)

    Saeidnia, Soodabeh [Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411 (Iran, Islamic Republic of); College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon (Canada); Abdollahi, Mohammad, E-mail: Mohammad@TUMS.Ac.Ir [Department of Toxicology and Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 1417614411 (Iran, Islamic Republic of)

    2013-12-15

    Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD.

  15. Toxicological and pharmacological concerns on oxidative stress and related diseases

    International Nuclear Information System (INIS)

    Saeidnia, Soodabeh; Abdollahi, Mohammad

    2013-01-01

    Although reactive oxygen species (ROS) such as superoxide, hydrogen peroxide and hydroxyl radical are generated as the natural byproduct of normal oxygen metabolism, they can create oxidative damage via interaction with bio-molecules. The role of oxidative stress as a remarkable upstream part is frequently reported in the signaling cascade of inflammation as well as chemo attractant production. Even though hydrogen peroxide can control cell signaling and stimulate cell proliferation at low levels, in higher concentrations it can initiate apoptosis and in very high levels may create necrosis. So far, the role of ROS in cellular damage and death is well documented with implicating in a broad range of degenerative alterations e.g. carcinogenesis, aging and other oxidative stress related diseases (OSRDs). Reversely, it is cleared that antioxidants are potentially able to suppress (at least in part) the immune system and to enhance the normal cellular protective responses to tissue damage. In this review, we aimed to provide insights on diverse OSRDs, which are correlated with the concept of oxidative stress as well as its cellular effects that can be inhibited by antioxidants. Resveratrol, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, nebivolol and carvedilol, pentaerythritol tetranitrate, mitochondria-targeted antioxidants, and plant-derived drugs (alone or combined) are the potential medicines that can be used to control OSRD

  16. Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine

    International Nuclear Information System (INIS)

    Velsor, Leonard W.; Kovacevic, Miro; Goldstein, Mark; Leitner, Heather M.; Lewis, William; Day, Brian J.

    2004-01-01

    The toxicity of nucleoside reverse transcriptase inhibitors (NRTIs) is linked to altered mitochondrial DNA (mtDNA) replication and subsequent disruption of cellular energetics. This manifests clinically as elevated concentrations of lactate in plasma. The mechanism(s) underlying how the changes in mtDNA replication lead to lactic acidosis remains unclear. It is hypothesized that mitochondrial oxidative stress links the changes in mtDNA replication to mitochondrial dysfunction and ensuing NRTIs toxicity. To test this hypothesis, changes in mitochondrial function, mtDNA amplification efficiency, and oxidative stress were assessed in HepG2-cultured human hepatoblasts treated with the NRTI stavudine (2',3'-didehydro-2',3'-deoxythymidine or d4T) for 48 h. d4T produced significant mitochondrial dysfunction with a 1.5-fold increase in cellular lactate to pyruvate ratios. In addition, d4T caused a dose-dependent decrease in mtDNA amplification and a correlative increase in abundance of markers of mitochondrial oxidative stress. Manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, MnTBAP, a catalytic antioxidant, ameliorated or reversed d4T-induced changes in cell injury, energetics, mtDNA amplification, and mitochondrial oxidative stress. In conclusion, d4T treatment elevates mitochondrial reactive oxygen species (ROS), enhances mitochondrial oxidative stress, and contributes mechanistically to NRTI-induced toxicity. These deleterious events may be potentiated in acquired immunodeficiency syndrome (AIDS) by human immunodeficiency virus (HIV) infection itself, coinfection (e.g., viral hepatitis), aging, substance, and alcohol use

  17. Oxidative stress induced pulmonary endothelial cell proliferation is ...

    African Journals Online (AJOL)

    Cellular hyper-proliferation, endothelial dysfunction and oxidative stress are hallmarks of the pathobiology of pulmonary hypertension. Indeed, pulmonary endothelial cells proliferation is susceptible to redox state modulation. Some studies suggest that superoxide stimulates endothelial cell proliferation while others have ...

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

    Science.gov (United States)

    Collins, John A.; Wood, Scott T.; Nelson, Kimberly J.; Rowe, Meredith A.; Carlson, Cathy S.; Chubinskaya, Susan; Poole, Leslie B.; Furdui, Cristina M.; Loeser, Richard F.

    2016-01-01

    Oxidative stress-mediated post-translational modifications of redox-sensitive proteins are postulated as a key mechanism underlying age-related cellular dysfunction and disease progression. Peroxiredoxins (PRX) are critical intracellular antioxidants that also regulate redox signaling events. Age-related osteoarthritis is a common form of arthritis that has been associated with mitochondrial dysfunction and oxidative stress. The objective of this study was to determine the effect of aging and oxidative stress on chondrocyte intracellular signaling, with a specific focus on oxidation of cytosolic PRX2 and mitochondrial PRX3. Menadione was used as a model to induce cellular oxidative stress. Compared with chondrocytes isolated from young adult humans, chondrocytes from older adults exhibited higher levels of PRX1–3 hyperoxidation basally and under conditions of oxidative stress. Peroxiredoxin hyperoxidation was associated with inhibition of pro-survival Akt signaling and stimulation of pro-death p38 signaling. These changes were prevented in cultured human chondrocytes by adenoviral expression of catalase targeted to the mitochondria (MCAT) and in cartilage explants from MCAT transgenic mice. Peroxiredoxin hyperoxidation was observed in situ in human cartilage sections from older adults and in osteoarthritic cartilage. MCAT transgenic mice exhibited less age-related osteoarthritis. These findings demonstrate that age-related oxidative stress can disrupt normal physiological signaling and contribute to osteoarthritis and suggest peroxiredoxin hyperoxidation as a potential mechanism. PMID:26797130

  19. Oxidative stress induces senescence in human mesenchymal stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Brandl, Anita [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Meyer, Matthias; Bechmann, Volker [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Nerlich, Michael [Department of Anesthesiology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany); Angele, Peter, E-mail: Peter.Angele@klinik.uni-regensburg.de [Department of Trauma Surgery, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93042 Regensburg (Germany)

    2011-07-01

    Mesenchymal stem cells (MSCs) contribute to tissue repair in vivo and form an attractive cell source for tissue engineering. Their regenerative potential is impaired by cellular senescence. The effects of oxidative stress on MSCs are still unknown. Our studies were to investigate into the proliferation potential, cytological features and the telomere linked stress response system of MSCs, subject to acute or prolonged oxidant challenge with hydrogen peroxide. Telomere length was measured using the telomere restriction fragment assay, gene expression was determined by rtPCR. Sub-lethal doses of oxidative stress reduced proliferation rates and induced senescent-morphological features and senescence-associated {beta}-galactosidase positivity. Prolonged low dose treatment with hydrogen peroxide had no effects on cell proliferation or morphology. Sub-lethal and prolonged low doses of oxidative stress considerably accelerated telomere attrition. Following acute oxidant insult p21 was up-regulated prior to returning to initial levels. TRF1 was significantly reduced, TRF2 showed a slight up-regulation. SIRT1 and XRCC5 were up-regulated after oxidant insult and expression levels increased in aging cells. Compared to fibroblasts and chondrocytes, MSCs showed an increased tolerance to oxidative stress regarding proliferation, telomere biology and gene expression with an impaired stress tolerance in aged cells.

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

    Science.gov (United States)

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

    2011-10-01

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

  1. Oxidative Stress Induces Senescence in Cultured RPE Cells.

    Science.gov (United States)

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

    2016-01-01

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

  2. Oxidative stress induced by cerium oxide nanoparticles in cultured BEAS-2B cells

    International Nuclear Information System (INIS)

    Park, Eun-Jung; Choi, Jinhee; Park, Young-Kwon; Park, Kwangsik

    2008-01-01

    Cerium oxide nanoparticles of different sizes (15, 25, 30, 45 nm) were prepared by the supercritical synthesis method, and cytotoxicity was evaluated using cultured human lung epithelial cells (BEAS-2B). Exposure of the cultured cells to nanoparticles (5, 10, 20, 40 μg/ml) led to cell death, ROS increase, GSH decrease, and the inductions of oxidative stress-related genes such as heme oxygenase-1, catalase, glutathione S-transferase, and thioredoxin reductase. The increased ROS by cerium oxide nanoparticles triggered the activation of cytosolic caspase-3 and chromatin condensation, which means that cerium oxide nanoparticles exert cytotoxicity by an apoptotic process. Uptake of the nanoparticles to the cultured cells was also tested. It was observed that cerium oxide nanoparticles penetrated into the cytoplasm and located in the peri-region of the nucleus as aggregated particles, which may induce the direct interaction between nanoparticles and cellular molecules to cause adverse cellular responses

  3. E-cigarette aerosols induce lower oxidative stress in vitro when compared to tobacco smoke.

    Science.gov (United States)

    Taylor, Mark; Carr, Tony; Oke, Oluwatobiloba; Jaunky, Tomasz; Breheny, Damien; Lowe, Frazer; Gaça, Marianna

    2016-07-01

    Tobacco smoking is a risk factor for various diseases. The underlying cellular mechanisms are not fully characterized, but include oxidative stress, apoptosis, and necrosis. Electronic-cigarettes (e-cigarettes) have emerged as an alternative to and a possible means to reduce harm from tobacco smoking. E-cigarette vapor contains significantly lower levels of toxicants than cigarette smoke, but standardized methods to assess cellular responses to exposure are not well established. We investigated whether an in vitro model of the airway epithelium (human bronchial epithelial cells) and commercially available assays could differentiate cellular stress responses to aqueous aerosol extracts (AqE) generated from cigarette smoke and e-cigarette aerosols. After exposure to AqE concentrations of 0.063-0.500 puffs/mL, we measured the intracellular glutathione ratio (GSH:GSSG), intracellular generation of oxidant species, and activation of the nuclear factor erythroid-related factor 2 (Nrf2)-controlled antioxidant response elements (ARE) to characterize oxidative stress. Apoptotic and necrotic responses were characterized by increases in caspase 3/7 activity and reductions in viable cell protease activities. Concentration-dependent responses indicative of oxidative stress were obtained for all endpoints following exposure to cigarette smoke AqE: intracellular generation of oxidant species increased by up to 83%, GSH:GSSG reduced by 98.6% and transcriptional activation of ARE increased by up to 335%. Caspase 3/7 activity was increased by up to 37% and the viable cell population declined by up to 76%. No cellular stress responses were detected following exposure to e-cigarette AqE. The methods used were suitably sensitive to be employed for comparative studies of tobacco and nicotine products.

  4. Oxidative Stress and the Homeodynamics of Iron Metabolism

    Science.gov (United States)

    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

  5. Global transcriptomic profiling demonstrates induction of oxidative stress and of compensatory cellular stress responses in brown trout exposed to glyphosate and Roundup.

    Science.gov (United States)

    Uren Webster, Tamsyn M; Santos, Eduarda M

    2015-01-31

    Glyphosate, the active ingredient in Roundup formulations, is the most widely used herbicide worldwide, and as a result contaminates surface waters and has been detected in food residues, drinking water and human urine, raising concerns for potential environmental and human health impacts. Research has shown that glyphosate and Roundup can induce a broad range of biological effects in exposed organisms, particularly via generation of oxidative stress. However, there has been no comprehensive investigation of the global molecular mechanisms of toxicity of glyphosate and Roundup for any species. We aimed to characterise and compare the global mechanisms of toxicity of glyphosate and Roundup in the liver of brown trout (Salmo trutta), an ecologically and economically important vertebrate species, using RNA-seq on an Illumina HiSeq 2500 platform. To do this, we exposed juvenile female brown trout to 0, 0.01, 0.5 and 10 mg/L of glyphosate and Roundup (glyphosate acid equivalent) for 14 days, and sequenced 6 replicate liver samples from each treatment. We assembled the brown trout transcriptome using an optimised de novo approach, and subsequent differential expression analysis identified a total of 1020 differentially-regulated transcripts across all treatments. These included transcripts encoding components of the antioxidant system, a number of stress-response proteins and pro-apoptotic signalling molecules. Functional analysis also revealed over-representation of pathways involved in regulating of cell-proliferation and turnover, and up-regulation of energy metabolism and other metabolic processes. These transcriptional changes are consistent with generation of oxidative stress and the widespread induction of compensatory cellular stress response pathways. The mechanisms of toxicity identified were similar across both glyphosate and Roundup treatments, including for environmentally relevant concentrations. The significant alterations in transcript expression observed

  6. Apolipoprotein J/Clusterin is a novel structural component of human erythrocytes and a biomarker of cellular stress and senescence.

    Directory of Open Access Journals (Sweden)

    Marianna H Antonelou

    Full Text Available BACKGROUND: Secretory Apolipoprotein J/Clusterin (sCLU is a ubiquitously expressed chaperone that has been functionally implicated in several pathological conditions of increased oxidative injury, including aging. Nevertheless, the biological role of sCLU in red blood cells (RBCs remained largely unknown. In the current study we identified sCLU as a component of human RBCs and we undertook a detailed analysis of its cellular topology. Moreover, we studied the erythrocytic membrane sCLU content during organismal aging, in conditions of increased organismal stress and accelerated RBCs senescence, as well as during physiological in vivo cellular senescence. METHODOLOGY/PRINCIPAL FINDINGS: By using a combination of molecular, biochemical and high resolution microscopical methods we found that sCLU is a novel structural component of RBCs extra- and intracellular plasma membrane and cytosol. We observed that the RBCs membrane-associated sCLU decreases during organismal aging or exposure to acute stress (e.g. smoking, in patients with congenital hemolytic anemia, as well as during RBCs in vivo senescence. In all cases, sCLU reduction paralleled the expression of typical cellular senescence, redox imbalance and erythrophagocytosis markers which are also indicative of the senescence- and oxidative stress-mediated RBCs membrane vesiculation. CONCLUSIONS/SIGNIFICANCE: We propose that sCLU at the mature RBCs is not a silent remnant of the erythroid precursors, but an active component being functionally implicated in the signalling mechanisms of cellular senescence and oxidative stress-responses in both healthy and diseased organism. The reduced sCLU protein levels in the RBCs membrane following cell exposure to various endogenous or exogenous stressors closely correlates to the levels of cellular senescence and redox imbalance markers, suggesting the usefulness of sCLU as a sensitive biomarker of senescence and cellular stress.

  7. ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

    International Nuclear Information System (INIS)

    Pi Jingbo; Zhang Qiang; Fu Jingqi; Woods, Courtney G.; Hou Yongyong; Corkey, Barbara E.; Collins, Sheila; Andersen, Melvin E.

    2010-01-01

    This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H 2 O 2 , act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

  8. Evidence for an association between increased oxidative stress and derangement of FOXO1 signaling in tumorigenesis of a cellular angiofibroma with monoallelic 13q14: a case report.

    Science.gov (United States)

    Arakaki, Kazunari; Chinen, Katsuya; Kamiya, Masuzo; Tanabe, Yasuka; Tawata, Natsumi; Ikehara, Fukino; Uehara, Karina; Shimabukuro, Hiroichi; Kinjo, Takao

    2014-01-01

    Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in the stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.

  9. Oxidative stress biomarkers in Oreochromis niloticus as early ...

    African Journals Online (AJOL)

    2018-04-10

    Apr 10, 2018 ... stress biomarkers and sub-cellular components are the most commonly used ..... metal ions usually occur in low concentrations in the aquatic environment and ..... injured cells from a reduced to an oxidized state (Gul et al.,. 2004). ... ions through their gills, impaired respiration may result from chronic and ...

  10. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, Shanghai, China 201203 (China)

    2017-04-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD

  11. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A.; Ke, Zun-ji; Luo, Jia

    2017-01-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. - Highlights: • Thiamine deficiency (TD) causes death of human neurons in culture. • TD induces both endoplasmic reticulum (ER) stress and oxidative stress. • Alleviating ER stress and oxidative stress reduces TD

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

    Science.gov (United States)

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

    2017-10-01

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

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

    Science.gov (United States)

    Kumar, Amit; Ratan, Rajiv R

    2016-10-01

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

  14. The Drosophila carbonyl reductase sniffer prevents oxidative stress-induced neurodegeneration.

    Science.gov (United States)

    Botella, Jose A; Ulschmid, Julia K; Gruenewald, Christoph; Moehle, Christoph; Kretzschmar, Doris; Becker, Katja; Schneuwly, Stephan

    2004-05-04

    A growing body of evidence suggests that oxidative stress is a common underlying mechanism in the pathogenesis of neurodegenerative disorders such as Alzheimer's, Huntington's, Creutzfeld-Jakob and Parkinson's diseases. Despite the increasing number of reports finding a causal relation between oxidative stress and neurodegeneration, little is known about the genetic elements that confer protection against the deleterious effects of oxidation in neurons. We have isolated and characterized the Drosophila melanogaster gene sniffer, whose function is essential for preventing age-related neurodegeneration. In addition, we demonstrate that oxidative stress is a direct cause of neurodegeneration in the Drosophila central nervous system and that reduction of sniffer activity leads to neuronal cell death. The overexpression of the gene confers neuronal protection against oxygen-induced apoptosis, increases resistance of flies to experimental normobaric hyperoxia, and improves general locomotor fitness. Sniffer belongs to the family of short-chain dehydrogenase/reductase (SDR) enzymes and exhibits carbonyl reductase activity. This is the first in vivo evidence of the direct and important implication of this enzyme as a neuroprotective agent in the cellular defense mechanisms against oxidative stress.

  15. The partial pressure of oxygen affects biomarkers of oxidative stress in cultured rainbow trout (Oncorhynchus mykiss) hepatocytes.

    Science.gov (United States)

    Finne, E F; Olsvik, P A; Berntssen, M H G; Hylland, K; Tollefsen, K E

    2008-09-01

    Oxidative stress, the imbalance between production of reactive oxygen species and the cellular detoxification of these reactive compounds, is believed to be involved in the pathology of various diseases. Several biomarkers for oxidative stress have been proposed to serve as tools in toxicological and ecotoxicological research. Not only may exposure to various pro-oxidants create conditions of cellular oxidative stress, but hyperoxic conditions may also increase the production of reactive oxygen species. The objective of the current study was to determine the extent to which differences in oxygen partial pressure would affect biomarkers of oxidative stress in a primary culture of hepatocytes from rainbow trout (Oncorhynchus mykiss). Membrane integrity, metabolic activity, levels of total and oxidized glutathione (tGSH/GSSG) was determined, as well as mRNA expression levels of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), gamma-glutamyl-cystein synthetase (GCS) and thioredoxin (TRX). The results show that different biomarkers of oxidative stress are affected when the cell culture is exposed to atmospheric oxygen, and that changes such as increased GSSG content and induction of GSSG-R and GSH-Px can be reduced by culturing the cells under lower oxygen tension. Oxygen tension may thus influence results of in vitro based cell research and is particularly important when assessing parameters in the antioxidant defence system. Further research is needed to establish the magnitude of this effect in different cellular systems.

  16. Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Allison L Weber

    Full Text Available Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress.We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67-79% and 56-66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis.We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease.

  17. Oxidative Stress and Programmed Cell Death in Yeast

    International Nuclear Information System (INIS)

    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.

  18. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Osredkar Joško

    2012-05-01

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

  19. Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

    Science.gov (United States)

    Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

    2013-01-01

    Abstract Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful. Antioxid. Redox Signal. 19, 192–208 PMID:23198849

  20. Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Xueqi; Huang, Shengbin; Yu, Qing [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States); State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yu, Haiyang [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041 (China); Yan, Shirley ShiDu, E-mail: shidu@ku.edu [Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas, Lawrence, KS, 66047 (United States)

    2015-12-25

    Osteoblast dysfunction, induced by oxidative stress, plays a critical role in the pathophysiology of osteoporosis. However, the underlying mechanisms remain unclarified. Imbalance of mitochondrial dynamics has been closely linked to oxidative stress. Here, we reveal an unexplored role of dynamic related protein 1(Drp1), the major regulator in mitochondrial fission, in the oxidative stress-induced osteoblast injury model. We demonstrate that levels of phosphorylation and expression of Drp1 significantly increased under oxidative stress. Blockade of Drp1, through pharmaceutical inhibitor or gene knockdown, significantly protected against H{sub 2}O{sub 2}-induced osteoblast dysfunction, as shown by increased cell viability, improved cellular alkaline phosphatase (ALP) activity and mineralization and restored mitochondrial function. The protective effects of blocking Drp1 in H{sub 2}O{sub 2}-induced osteoblast dysfunction were evidenced by increased mitochondrial function and suppressed production of reactive oxygen species (ROS). These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the pathology of osteoporosis, indicating that the Drp1 pathway may be targetable for the development of new therapeutic approaches in the prevention and the treatment of osteoporosis. - Highlights: • Oxidative stress is an early pathological event in osteoporosis. • Imbalance of mitochondrial dynamics are linked to oxidative stress in osteoporosis. • The role of the Drp1-dependent mitochondrial pathway in osteoporosis.

  1. Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a Key Initiator for the Development of Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Valentin Bragin

    2010-01-01

    Full Text Available Mitochondrial dysfunction may be a principal underlying event in aging, including age-associated brain degeneration. Mitochondria provide energy for basic metabolic processes. Their decay with age impairs cellular metabolism and leads to a decline of cellular function. Alzheimer disease (AD and cerebrovascular accidents (CVAs are two leading causes of age-related dementia. Increasing evidence strongly supports the theory that oxidative stress, largely due to reactive oxygen species (ROS, induces mitochondrial damage, which arises from chronic hypoperfusion and is primarily responsible for the pathogenesis that underlies both disease processes. Mitochondrial membrane potential, respiratory control ratios and cellular oxygen consumption decline with age and correlate with increased oxidant production. The sustained hypoperfusion and oxidative stress in brain tissues can stimulate the expression of nitric oxide synthases (NOSs and brain endothelium probably increase the accumulation of oxidative stress products, which therefore contributes to blood brain barrier (BBB breakdown and brain parenchymal cell damage. Determining the mechanisms behind these imbalances may provide crucial information in the development of new, more effective therapies for stroke and AD patients in the near future.

  2. Thiamine Deficiency and Neurodegeneration: the Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy.

    Science.gov (United States)

    Liu, Dexiang; Ke, Zunji; Luo, Jia

    2017-09-01

    Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Thiamine metabolites may serve as promising biomarkers for neurodegenerative diseases, and thiamine supplementations exhibit therapeutic potential for patients of some neurodegenerative diseases. Experimental TD has been used to model aging-related neurodegenerative diseases. However, to date, the cellular and molecular mechanisms underlying TD-induced neurodegeneration are not clear. Recent research evidence indicates that TD causes oxidative stress, endoplasmic reticulum (ER) stress, and autophagy in the brain, which are known to contribute to the pathogenesis of various neurodegenerative diseases. In this review, we discuss the role of oxidative stress, ER stress, and autophagy in TD-mediated neurodegeneration. We propose that it is the interplay of oxidative stress, ER stress, and autophagy that contributes to TD-mediated neurodegeneration.

  3. Involvement of inositol biosynthesis and nitric oxide in the mediation of UV-B induced oxidative stress

    Directory of Open Access Journals (Sweden)

    Dmytro I Lytvyn

    2016-04-01

    Full Text Available The involvement of NO-signaling in ultraviolet B (UV-B induced oxidative stress in plants is an open question. Inositol biosynthesis contributes to numerous cellular functions, including the regulation of plants tolerance to stress. This work reveals the involvement of inositol-3-phosphate synthase 1 (IPS1, a key enzyme for biosynthesis of myo-inositol and its derivatives, in the response to NO-dependent oxidative stress in Arabidopsis. Homozygous mutants deficient for IPS1 (atips1 and wild-type plants were transformed with a reduction-oxidation-sensitive green fluorescent protein 2 (grx1-rogfp2 and used for the dynamic measurement of UV-B-induced and SNP (sodium nitroprusside-mediated oxidative stresses by confocal microscopy. atips1 mutants displayed greater tissue-specific resistance to the action of UV-B than the wild type. SNP can act both as an oxidant or repairer depending on the applied concentration, but mutant plants were more tolerant than the wild type to nitrosative effects of high concentration of SNP. Additionally, pretreatment with low concentrations of SNP (10, 100 μM before UV-B irradiation resulted in a tissue-specific protective effect that was enhanced in atips1. We conclude that the interplay between nitric oxide and inositol signaling can be involved in the mediation of UV-B-initiated oxidative stress in the plant cell.

  4. Non-invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognitive Functions

    Science.gov (United States)

    2017-05-14

    the impact of oxidative stress on brain function, but also enable development of reliable screening tools for cognitive performance of individuals in...of Brain Oxidative Stress and its Correlation with Cognitive Functions Date 04/20/2017 PI information: Dr. Pravat K. Mandal,Ph.D Professor...relationship between the brain oxidative status and stress at a cellular, physiological as well as a psychological level. These stressors, in turn, have

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

    Science.gov (United States)

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

    2018-01-01

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

  6. Oxidative Stress in Human Atherothrombosis: Sources, Markers and Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Jose Luis Martin-Ventura

    2017-11-01

    Full Text Available Atherothrombosis remains one of the main causes of morbidity and mortality worldwide. The underlying pathology is a chronic pathological vascular remodeling of the arterial wall involving several pathways, including oxidative stress. Cellular and animal studies have provided compelling evidence of the direct role of oxidative stress in atherothrombosis, but such a relationship is not clearly established in humans and, to date, clinical trials on the possible beneficial effects of antioxidant therapy have provided equivocal results. Nicotinamide adenine dinucleotide phosphate (NADPH oxidase is one of the main sources of reactive oxygen species (ROS in human atherothrombosis. Moreover, leukocyte-derived myeloperoxidase (MPO and red blood cell-derived iron could be involved in the oxidative modification of lipids/lipoproteins (LDL/HDL in the arterial wall. Interestingly, oxidized lipoproteins, and antioxidants, have been analyzed as potential markers of oxidative stress in the plasma of patients with atherothrombosis. In this review, we will revise sources of ROS, focusing on NADPH oxidase, but also on MPO and iron. We will also discuss the impact of these oxidative systems on LDL and HDL, as well as the value of these modified lipoproteins as circulating markers of oxidative stress in atherothrombosis. We will finish by reviewing some antioxidant systems and compounds as therapeutic strategies to prevent pathological vascular remodeling.

  7. Nitric Oxide Synthase and Cyclooxygenase Pathways: A Complex Interplay in Cellular Signaling.

    Science.gov (United States)

    Sorokin, Andrey

    2016-01-01

    The cellular reaction to external challenges is a tightly regulated process consisting of integrated processes mediated by a variety of signaling molecules, generated as a result of modulation of corresponding biosynthetic systems. Both, nitric oxide synthase (NOS) and cyclooxygenase (COX) systems, consist of constitutive forms (NOS1, NOS3 and COX-1), which are mostly involved in housekeeping tasks, and inducible forms (NOS2 and COX-2), which shape the cellular response to stress and variety of bioactive agents. The complex interplay between NOS and COX pathways can be observed at least at three levels. Firstly, products of NOS and Cox systems can mediate the regulation and the expression of inducible forms (NOS2 and COX-2) in response of similar and dissimilar stimulus. Secondly, the reciprocal modulation of cyclooxygenase activity by nitric oxide and NOS activity by prostaglandins at the posttranslational level has been shown to occur. Mechanisms by which nitric oxide can modulate prostaglandin synthesis include direct S-nitrosylation of COX and inactivation of prostaglandin I synthase by peroxynitrite, product of superoxide reaction with nitric oxide. Prostaglandins, conversely, can promote an increased association of dynein light chain (DLC) (also known as protein inhibitor of neuronal nitric oxide synthase) with NOS1, thereby reducing its activity. The third level of interplay is provided by intracellular crosstalk of signaling pathways stimulated by products of NOS and COX which contributes significantly to the complexity of cellular signaling. Since modulation of COX and NOS pathways was shown to be principally involved in a variety of pathological conditions, the dissection of their complex relationship is needed for better understanding of possible therapeutic strategies. This review focuses on implications of interplay between NOS and COX for cellular function and signal integration.

  8. Mechanism of oxidative stress involved in the toxicity of ZnO nanoparticles against eukaryotic cells

    Directory of Open Access Journals (Sweden)

    M. Saliani

    2016-01-01

    Full Text Available ZnO NPs (zinc oxide nanoparticles has generated significant scientific interest as a novel antibacterial and anticancer agent. Since oxidative stress is a critical determinant of ZnO NPs-induced damage, it is necessary to characterize their underlying mode of action. Different structural and physicochemical properties of ZnO NPs such as particle surface, size, shape, crystal structure, chemical position, and presence of metals can lead to changes in biological activities including ROS (reactive oxygen species production. However, there are some inconsistencies in the literature on the relation between the physicochemical features of ZnO NPs and their plausible oxidative stress mechanism. Herein, the possible oxidative stress mechanism of ZnO NPs was reviewed. This is worthy of further detailed evaluations in order to improve our understanding of vital NPs characteristics governing their toxicity. Therefore, this study focuses on the different reported oxidative stress paradigms induced by ZnO NPs including ROS generated by NPs, oxidative stress due to the NPs-cell interaction, and role of the particle dissolution in the oxidative damage. Also, this study tries to characterize and understand the multiple pathways involved in oxidative stress induced by ZnO NPs. Knowledge about different cellular signaling cascades stimulated by ZnO NPs lead to the better interpretation of the toxic influences induced by the cellular and acellular parameters. Regarding the potential benefits of toxic effects of ZnO NPs, in-depth evaluation of their toxicity mechanism and various effects of these nanoparticles would facilitate their implementation for biomedical applications.

  9. Exercise and oxidative stress: potential effects of antioxidant dietary strategies in sports.

    Science.gov (United States)

    Pingitore, Alessandro; Lima, Giuseppina Pace Pereira; Mastorci, Francesca; Quinones, Alfredo; Iervasi, Giorgio; Vassalle, Cristina

    2015-01-01

    Free radicals are produced during aerobic cellular metabolism and have key roles as regulatory mediators in signaling processes. Oxidative stress reflects an imbalance between production of reactive oxygen species and an adequate antioxidant defense. This adverse condition may lead to cellular and tissue damage of components, and is involved in different physiopathological states, including aging, exercise, inflammatory, cardiovascular and neurodegenerative diseases, and cancer. In particular, the relationship between exercise and oxidative stress is extremely complex, depending on the mode, intensity, and duration of exercise. Regular moderate training appears beneficial for oxidative stress and health. Conversely, acute exercise leads to increased oxidative stress, although this same stimulus is necessary to allow an up-regulation in endogenous antioxidant defenses (hormesis). Supporting endogenous defenses with additional oral antioxidant supplementation may represent a suitable noninvasive tool for preventing or reducing oxidative stress during training. However, excess of exogenous antioxidants may have detrimental effects on health and performance. Whole foods, rather than capsules, contain antioxidants in natural ratios and proportions, which may act in synergy to optimize the antioxidant effect. Thus, an adequate intake of vitamins and minerals through a varied and balanced diet remains the best approach to maintain an optimal antioxidant status. Antioxidant supplementation may be warranted in particular conditions, when athletes are exposed to high oxidative stress or fail to meet dietary antioxidant requirements. Aim of this review is to discuss the evidence on the relationship between exercise and oxidative stress, and the potential effects of dietary strategies in athletes. The differences between diet and exogenous supplementation as well as available tools to estimate effectiveness of antioxidant intake are also reported. Finally, we advocate the need

  10. Limitations in Using Chemical Oxidative Potential to Understand Oxidative Stress from Particulate Matter

    Science.gov (United States)

    Chan, A. W. H.; Wang, S.; Wang, X.; Kohl, L.; Chow, C. W.

    2017-12-01

    Particulate matter (PM) in the atmosphere is known to cause adverse cardiorespiratory health effects. It has been suggested that the ability of PM to generate oxidative stress leads to a proinflammatory response. In this work, we study the biological relevance of using a chemical oxidative potential (OP) assay to evaluate proinflammatory response in airway epithelial cells. Here we study the OPs of laboratory secondary organic aerosol (SOA) and metal mixtures, ambient PM from India, ash from the 2016 Alberta wildfires, and diesel exhaust particles. We use SOA derived from naphthalene and from monoterpenes as model systems for SOA. We measure OP using the dithiothreitol (DTT) assay, and cytosolic reactive oxygen species (ROS) production in BEAS-2B cell culture was measured using CellROX assay. We found that both SOA and copper show high OPs individually, but the OP of the combined SOA/copper mixture, which is more atmospherically relevant, was lower than either of the individual OPs. The reduced activity is attributed to chelation between metals and organic compounds using proton nuclear magnetic resonance. There is reasonable association between DTT activity and cellular ROS production within each particle type, but weak association across different particle types, suggesting that particle composition plays an important role in distinguishing between antioxidant consumption and ROS production. Our results highlight that while oxidative potential is a useful metric of PM's ability to generate oxidative stress, the chemical composition and cellular environment should be considered in understanding health impacts of PM.

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

    Science.gov (United States)

    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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Association of oxidative stress with the pathophysiology of depresion and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Lačković Maja

    2013-01-01

    Full Text Available The production of free radicals in an organism is under the control of various antioxidant mechanisms. If their production overcomes the capacity of antioxidant protection, oxidative stress occurs which is capable of damaging different cellular structures and biomolecules, leading to various diseases. The importance of oxidative stress was proven in many psychiatric diseases among which are depression and bipolar disorder. Different studies show the significant improvement of clinical presentation when antioxidant substances are administered, suggesting that redox imbalance can influence their symptoms appearance and severity. In addition, oxidative stress is intercrossed with the different comorbidities that appear among depressive and bipolar patients. Beside the clinical presentation, oxidative stress influences the chronicity of depression, which was demonstrated in patients with recurrent depressive disorder. Better understanding of oxidant/antioxidant imbalance and its role in the pathophysiology of depression and bipolar disorder could be useful for the development of a novel therapeutic approach to the management of these diseases.

  13. Symbiosis-induced adaptation to oxidative stress.

    Science.gov (United States)

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

    2005-01-01

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

  14. Oxidative stress and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Javier eBlesa

    2015-07-01

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

  15. Oxidative Stress Evaluation in Patients Treated with Orthodontic Self-ligating Multibracket Appliances: An in Vivo Case-Control Study.

    Science.gov (United States)

    Portelli, Marco; Militi, Angela; Cervino, Gabriele; Lauritano, Floriana; Sambataro, Sergio; Mainardi, Alberto; Nucera, Riccardo

    2017-01-01

    Oxidative stress is a pathologic event induced by a prevalence of oxidant agents on the antioxidant ones, with a consequent alteration of oxide-reducing balance. Freeradicals produce damages both in cellular and extra-cellular components; phospholipid membranes, proteins, mitochondrial and nuclear DNA, are the target of the oxidative stress, that can finally cause cellular death due to apoptosis. Orthodontic appliances such as brackets, wires, resins and soldering have some components that can be considered as potential allergen, carcinogenic, cytotoxic and gene mutation factors. The primary aim of this research is to evaluate oxidative stress in the saliva of patients treated with multibracket self-ligating vestibular orthodontic appliances; the secondary purpose is to investigate the influence of orthodontic multibracket therapy on oral hygiene and the consequent effect on oxidative stress. Salivary specimens has been collected in a sample of 23 patients were enrolled (12 Female, 11 Male) between 12 and 16 years of age (mean age 14.2). For each patient has been collected a salivary specimen at the following time points; before orthodontic bonding (T1), five weeks (T2) and ten weeks (T3) after orthodontic appliance bonding. Samples has been analysed with a photometer due to SAT Test (Salivary Antioxidant Test). Data obtained show a mean of 2971 mEq/l of anti-oxidant agents before orthodontic treatment, and after five weeks from the bonding the mean was decreased to 2909 mEq/l, instead at ten weeks was increased to 3332 mEq/l. Repeated measures ANOVA did not reveal statistically significant differences between the time points ( P = 0.1697). The study did not reveal any correlation between the level of dental hygiene and that of oxidative stress (Pearson Correlation Coefficient R = 0). Orthodontic treatment with multibrackets vestibular metallic appliance seems to be not able to affect oxidative stress during the first ten weeks of therapy.

  16. Oxidative stress suppresses the cellular bioenergetic effect of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway

    International Nuclear Information System (INIS)

    Módis, Katalin; Asimakopoulou, Antonia; Coletta, Ciro; Papapetropoulos, Andreas; Szabo, Csaba

    2013-01-01

    Highlights: •Oxidative stress impairs 3-MST-derived H 2 S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H 2 S in hepatocytes. •This has implications for the pathophysiology of diseases with oxidative stress. -- Abstract: Recent data show that lower concentrations of hydrogen sulfide (H 2 S), as well as endogenous, intramitochondrial production of H 2 S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H 2 S pathway in vitro. Hydrogen peroxide (H 2 O 2 , 100–500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H 2 O 2 (50–500 μM) caused a concentration-dependent decrease in production of H 2 S from 3-MP. In cultured murine hepatoma cells H 2 O 2 , (3–100 μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100–300 nM) was completely abolished by pre-treatment of the cells with H 2 O 2 (50 μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H 2 S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging

  17. Vitamin B12 deficiency results in severe oxidative stress, leading to memory retention impairment in Caenorhabditis elegans.

    Science.gov (United States)

    Bito, Tomohiro; Misaki, Taihei; Yabuta, Yukinori; Ishikawa, Takahiro; Kawano, Tsuyoshi; Watanabe, Fumio

    2017-04-01

    Oxidative stress is implicated in various human diseases and conditions, such as a neurodegeneration, which is the major symptom of vitamin B 12 deficiency, although the underlying disease mechanisms associated with vitamin B 12 deficiency are poorly understood. Vitamin B 12 deficiency was found to significantly increase cellular H 2 O 2 and NO content in Caenorhabditis elegans and significantly decrease low molecular antioxidant [reduced glutathione (GSH) and L-ascorbic acid] levels and antioxidant enzyme (superoxide dismutase and catalase) activities, indicating that vitamin B 12 deficiency induces severe oxidative stress leading to oxidative damage of various cellular components in worms. An NaCl chemotaxis associative learning assay indicated that vitamin B 12 deficiency did not affect learning ability but impaired memory retention ability, which decreased to approximately 58% of the control value. When worms were treated with 1mmol/L GSH, L-ascorbic acid, or vitamin E for three generations during vitamin B 12 deficiency, cellular malondialdehyde content as an index of oxidative stress decreased to the control level, but the impairment of memory retention ability was not completely reversed (up to approximately 50%). These results suggest that memory retention impairment formed during vitamin B 12 deficiency is partially attributable to oxidative stress. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Oxidative Stress: A Pathogenic Mechanism for Niemann-Pick Type C Disease

    Directory of Open Access Journals (Sweden)

    Mary Carmen Vázquez

    2012-01-01

    Full Text Available Niemann-Pick type C (NPC disease is a neurovisceral atypical lipid storage disorder involving the accumulation of cholesterol and other lipids in the late endocytic pathway. The pathogenic mechanism that links the accumulation of intracellular cholesterol with cell death in NPC disease in both the CNS and the liver is currently unknown. Oxidative stress has been observed in the livers and brains of NPC mice and in different NPC cellular models. Moreover, there is evidence of an elevation of oxidative stress markers in the serumof NPC patients. Recent evidence strongly suggests that mitochondrial dysfunction plays an important role in NPC pathogenesis and that mitochondria could be a significant source of oxidative stress in this disease. In this context, the accumulation of vitamin E in the late endosomal/lysosomal compartments in NPC could lead to a potential decrease of its bioavailability and could be another possible cause of oxidative damage. Another possible source of reactive species in NPC is the diminished activity of different antioxidant enzymes. Moreover, because NPC is mainly caused by the accumulation of free cholesterol, oxidized cholesterol derivatives produced by oxidative stress may contribute to the pathogenesis of the disease.

  19. Apoptosis and telomeres shortening related to HIV-1 induced oxidative stress in an astrocytoma cell line

    Directory of Open Access Journals (Sweden)

    Mollace Vincenzo

    2009-05-01

    Full Text Available Abstract Background Oxidative stress plays a key role in the neuropathogenesis of Human Immunodeficiency Virus-1 (HIV-1 infection causing apoptosis of astroglia cells and neurons. Recent data have shown that oxidative stress is also responsible for the acceleration of human fibroblast telomere shortening in vitro. In the present study we analyzed the potential relations occurring between free radicals formation and telomere length during HIV-1 mediated astroglial death. Results To this end, U373 human astrocytoma cells have been directly exposed to X4-using HIV-1IIIB strain, for 1, 3 or 5 days and treated (where requested with N-acetylcysteine (NAC, a cysteine donor involved in the synthesis of glutathione (GSH, a cellular antioxidant and apoptosis has been evaluated by FACS analysis. Quantitative-FISH (Q-FISH has been employed for studying the telomere length while intracellular reduced/oxidized glutathione (GSH/GSSG ratio has been determined by High-Performance Liquid Chromatography (HPLC. Incubation of U373 with HIV-1IIIB led to significant induction of cellular apoptosis that was reduced in the presence of 1 mM NAC. Moreover, NAC improved the GSH/GSSG, a sensitive indicator of oxidative stress, that significantly decreased after HIV-1IIIB exposure in U373. Analysis of telomere length in HIV-1 exposed U373 showed a statistically significant telomere shortening, that was completely reverted in NAC-treated U373. Conclusion Our results support the role of HIV-1-mediated oxidative stress in astrocytic death and the importance of antioxidant compounds in preventing these cellular damages. Moreover, these data indicate that the telomere structure, target for oxidative damage, could be the key sensor of cell apoptosis induced by oxidative stress after HIV infection.

  20. Comparison of the protective effects of seven selected herbs against oxidative stress

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    Lee-Wen Chang

    2015-07-01

    Full Text Available Objective: To compare the protective effects of the water extracts of seven herbs, including Solanum indicum L., Mallotus repandus (Wild Muell-Arg. (MRM, Bombax malabarica DC (BMDC, Tadehagi triquetrum (L. Ohashi (TTLO, Clinacanthus nutans (Burm f. Lindau, Salvia plebeia R. Br (SPRB, Ixeris chinensis Mak (ICM, against tert-butylhydroperoxide (t-BHP-induced oxidative stress in Clone 9 cells. Methods: To evaluate the antioxidant properties of water extracts from seven herbs, reducing ability, metal-chelating activity and radical-scavenging activity such as 2,2′-azino-bis(3- ethylbenzothiazoline-6-sulphonic acid radical cation and 1,1-diphenyl-2-picrylhydrazyl (DPPH were determined. In cellular systems, t-BHP was used as a model oxidant to induce oxidative stress. 2′,7′-Dichlorofluorescin diacetate and chloromethylfluorescein-diacetate were used as fluorescence probe to determine reactive oxygen species generation and glutathione level in t-BHP-induced Clone 9 cells, respectively. In addition, total tannins, total anthocyanins, total polyphenolics and flavonoids were determined. Results: According to the data obtained from the trolox equivalent antioxidant capacity method, DPPH radical scavenging assay and reducing ability determination, MRM, SPRB, and BMDC showed relatively high antioxidant properties while TTLO and ICM were in the middle and Solanum indicum and Clinacanthus nutans had relatively low activity. In cellular model systems, SPRB, BMDC, and TTLO showed higher protective effects against t-BHP-induced oxidative stress. BMDC, ICM, and TTLO displayed higher inhibitory effects on reactive oxygen species generation in t-BHP-induced Clone 9 cells. In addition, SPRB, MRM, and BMDC showed significantly positive modulated glutathione levels. Tannins, anthocyanins, flavonoids and polyphenolics were present in the herbs, which may in part contribute to regulating the oxidative stress. Conclusions: These results indicated that the seven

  1. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    Dubner, D.; Perez, M.R. Del; Michelin, S.C.; Gisone, P.A.

    1997-01-01

    The mechanisms of radiation induced cellular death constitute an objective of research ever since the first biological effects of radiation were first observed. The explosion of information produced in the last 20 years calls for a careful analysis due to the apparent contradictory data related to the cellular system studied and the range of doses used. This review focuses on the role of the active oxygen species, in particular the nitric oxides, in its relevance as potential mediator of radiation induced cellular death

  2. Bactericidal Antibiotics Do Not Appear To Cause Oxidative Stress in Listeria monocytogenes

    DEFF Research Database (Denmark)

    Feld, Louise; Knudsen, Gitte Maegaard; Gram, Lone

    2012-01-01

    Oxidative stress can be an important contributor to the lethal effect of bactericidal antibiotics in some bacteria, such as Escherichia coli and Staphylococcus aureus. Thus, despite the different target-specific actions of bactericidal antibiotics, they have a common mechanism leading to bacterial...... to cause oxidative stress in L. monocytogenes and propose that this is caused by its noncyclic tricarboxylic acid (TCA) pathway. Hence, in this noncyclic metabolism, there is a decoupling between the antibiotic-mediated cellular requirement for NADH and the induction of TCA enzyme activity, which...

  3. Are plant endogenous factors like ethylene modulators of the early oxidative stress induced by mercury?

    Directory of Open Access Journals (Sweden)

    M Belén eMontero-Palmero

    2014-08-01

    Full Text Available The induction of oxidative stress is one of the quickest symptoms appearing in plants subjected to metal stress. A transcriptional analysis of the early responses of alfalfa (Medicago sativa seedlings to mercury (Hg; 3 µM for 3, 6 and 24 h showed that up-regulation of genes responding to ethylene were up-regulated, a phytohormone known to mediate in the cellular redox homeostasis. In this mini-review we have compared these quick responses with two other concurrent transcriptomic analysis in Barrel medic (Medicago truncatula and barley (Hordeum vulgare under Hg stress. Besides ethylene, ABA and jasmonate related genes were up-regulated, all of them are endogenous factors known to intervene in oxidative stress responses. The information obtained may target future work to understand the cellular mechanisms triggered by Hg, enabling biotechnological approaches to diminish Hg-induced phytotoxicity.

  4. Oxidative Stress in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Varsha Shukla

    2011-01-01

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

  5. Thiamine deficiency induces endoplasmic reticulum stress and oxidative stress in human neurons derived from induced pluripotent stem cells.

    Science.gov (United States)

    Wang, Xin; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Luo, Jia

    2017-04-01

    Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear. The progress in this line of research is hindered due to the lack of appropriate in vitro models. The neurons derived for the human induced pluripotent stem cells (hiPSCs) provide a relevant and powerful tool for the research in pharmaceutical and environmental neurotoxicity. In this study, we for the first time used human induced pluripotent stem cells (hiPSCs)-derived neurons (iCell neurons) to investigate the mechanisms of TD-induced neurodegeneration. We showed that TD caused a concentration- and duration-dependent death of iCell neurons. TD induced ER stress which was evident by the increase in ER stress markers, such as GRP78, XBP-1, CHOP, ATF-6, phosphorylated eIF2α, and cleaved caspase-12. TD also triggered oxidative stress which was shown by the increase in the expression 2,4-dinitrophenyl (DNP) and 4-hydroxynonenal (HNE). ER stress inhibitors (STF-083010 and salubrinal) and antioxidant N-acetyl cysteine (NAC) were effective in alleviating TD-induced death of iCell neurons, supporting the involvement of ER stress and oxidative stress. It establishes that the iCell neurons are a novel tool to investigate cellular and molecular mechanisms for TD-induced neurodegeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein.

    Science.gov (United States)

    Fitzgerald, Kerry D; Semler, Bert L

    2013-09-01

    Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Poliovirus infection induces the co-localization of cellular protein SRp20 with TIA-1, a cytoplasmic stress granule protein

    Science.gov (United States)

    Fitzgerald, Kerry D.; Semler, Bert L.

    2013-01-01

    Different types of environmental stress cause mammalian cells to form cytoplasmic foci, termed stress granules, which contain mRNPs that are translationally silenced. These foci are transient and dynamic, and contain components of the cellular translation machinery as well as certain mRNAs and RNA binding proteins. Stress granules are known to be induced by conditions such as hypoxia, nutrient deprivation, and oxidative stress, and a number of cellular factors have been identified that are commonly associated with these foci. More recently it was discovered that poliovirus infection also induces the formation of stress granules, although these cytoplasmic foci appear to be somewhat compositionally unique. Work described here examined the punctate pattern of SRp20 (a host cell mRNA splicing protein) localization in the cytoplasm of poliovirus-infected cells, demonstrating the partial co-localization of SRp20 with the stress granule marker protein TIA-1. We determined that SRp20 does not co-localize with TIA-1, however, under conditions of oxidative stress, indicating that the close association of these two proteins during poliovirus infection is not representative of a general response to cellular stress. We confirmed that the expression of a dominant negative version of TIA-1 (TIA-1-PRD) results in the dissociation of stress granules. Finally, we demonstrated that expression of wild type TIA-1 or dominant negative TIA-1-PRD in cells during poliovirus infection does not dramatically affect viral translation. Taken together, these studies provide a new example of the unique cytoplasmic foci that form during poliovirus infection. PMID:23830997

  8. Oxidative Stress in Dog with Heart Failure: The Role of Dietary Fatty Acids and Antioxidants

    Directory of Open Access Journals (Sweden)

    Emmanuelle Sagols

    2011-01-01

    Full Text Available In dogs with heart failure, cell oxygenation and cellular metabolism do not work properly, leading to the production of a large amount of free radicals. In the organism, these free radicals are responsible of major cellular damages: this is oxidative stress. However, a suitable food intake plays an important role in limiting this phenomenon: on the one hand, the presence of essential fatty acids in the composition of membranes decreases sensitivity of cells to free radicals and constitutes a first protection against the oxidative stress; on the other hand, coenzyme Q10, vitamin E, and polyphenols are antioxidant molecules which can help cells to neutralize these free radicals.

  9. Beyond Diabetes: Does Obesity-Induced Oxidative Stress Drive the Aging Process?

    Directory of Open Access Journals (Sweden)

    Adam B. Salmon

    2016-07-01

    Full Text Available Despite numerous correlative data, a causative role for oxidative stress in mammalian longevity has remained elusive. However, there is strong evidence that increased oxidative stress is associated with exacerbation of many diseases and pathologies that are also strongly related to advanced age. Obesity, or increased fat accumulation, is one of the most common chronic conditions worldwide and is associated with not only metabolic dysfunction but also increased levels of oxidative stress in vivo. Moreover, obesity is also associated with significantly increased risks of cardiovascular disease, neurological decline and cancer among many other diseases as well as a significantly increased risk of mortality. In this review, we investigate the possible interpretation that the increased incidence of these diseases in obesity may be due to chronic oxidative stress mediating segmental acceleration of the aging process. Understanding how obesity can alter cellular physiology beyond that directly related to metabolic function could open new therapeutic areas of approach to extend the period of healthy aging among people of all body composition.

  10. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    International Nuclear Information System (INIS)

    Rashid, Kahkashan; Sil, Parames C.

    2015-01-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  11. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  12. Oxidative stress suppresses the cellular bioenergetic effect of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway

    Energy Technology Data Exchange (ETDEWEB)

    Módis, Katalin [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Asimakopoulou, Antonia [Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras (Greece); Coletta, Ciro [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Papapetropoulos, Andreas [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States); Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras (Greece); Szabo, Csaba, E-mail: szabocsaba@aol.com [Department of Anesthesiology, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, TX (United States)

    2013-04-19

    Highlights: •Oxidative stress impairs 3-MST-derived H{sub 2}S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H{sub 2}S in hepatocytes. •This has implications for the pathophysiology of diseases with oxidative stress. -- Abstract: Recent data show that lower concentrations of hydrogen sulfide (H{sub 2}S), as well as endogenous, intramitochondrial production of H{sub 2}S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H{sub 2}S pathway in vitro. Hydrogen peroxide (H{sub 2}O{sub 2}, 100–500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H{sub 2}O{sub 2} (50–500 μM) caused a concentration-dependent decrease in production of H{sub 2}S from 3-MP. In cultured murine hepatoma cells H{sub 2}O{sub 2}, (3–100 μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100–300 nM) was completely abolished by pre-treatment of the cells with H{sub 2}O{sub 2} (50 μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H{sub 2}S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging.

  13. Updates of the role of oxidative stress in the pathogenesis of ovarian cancer.

    Science.gov (United States)

    Saed, Ghassan M; Diamond, Michael P; Fletcher, Nicole M

    2017-06-01

    Clinical and epidemiological investigations have provided evidence supporting the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS), collectively known as oxidative stress, in the etiology of cancer. Exogenous factors such as chronic inflammation, infection and hypoxia are major sources of cellular oxidative stress. Specifically, oxidative stress plays an important role in the pathogenesis, neoangiogenesis, and dissemination of local or distant ovarian cancer, as it is known to induce phenotypic modifications of tumor cells by cross talk between tumor cells and the surrounding stroma. Subsequently, the biological significance of the relationship between oxidative stress markers and various stages of epithelial ovarian cancer highlights potential therapeutic interventions as well as provides urgently needed early detection biomarkers. In the light of our scientific research and the most recent experimental and clinical observations, this review provides the reader with up to date most relevant findings on the role of oxidative stress in the pathogenesis of ovarian cancer and the possible therapeutic implications. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Petroselinum Crispum is Effective in Reducing Stress-Induced Gastric Oxidative Damage

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    Ayşin Akıncı

    2017-02-01

    Full Text Available Background: Oxidative stress has been shown to play a principal role in the pathogenesis of stress-induced gastric injury. Parsley (Petroselinum crispum contains many antioxidants such as flavanoids, carotenoids and ascorbic acid. Aims: In this study, the histopathological and biochemical results of nutrition with a parsley-rich diet in terms of eliminating stress-induced oxidative gastric injury were evaluated. Study Design: Animal experimentation. Methods: Forty male Wistar albino rats were divided into five groups: control, stress, stress + standard diet, stress + parsley-added diet and stress + lansoprazole (LPZ groups. Subjects were exposed to 72 hours of fasting and later immobilized and exposed to the cold at +4 degrees for 8 hours to create a severe stress condition. Samples from the animals’ stomachs were arranged for microscopic and biochemical examinations. Results: Gastric mucosal injury was obvious in rats exposed to stress. The histopathologic damage score of the stress group (7.00±0.57 was higher than that of the control group (1.50±0.22 (p<0.05. Significant differences in histopathologic damage score were found between the stress and stress + parsley-added diet groups (p<0.05, the stress and stress + standard diet groups (p<0.05, and the stress and stress + LPZ groups (p<0.05. The mean tissue malondialdehyde levels of the stress + parsley-added group and the stress + LPZ group were lower than that of the stress group (p<0.05. Parsley supported the cellular antioxidant system by increasing the mean tissue glutathione level (53.31±9.50 and superoxide dismutase (15.18±1.05 and catalase (16.68±2.29 activities. Conclusion: Oral administration of parsley is effective in reducing stress-induced gastric injury by supporting the cellular antioxidant defence system

  15. Cardiovascular Complications of Sleep Apnea: Role of Oxidative Stress

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    Mohammad Badran

    2014-01-01

    Full Text Available Obstructive sleep apnea (OSA occurs in 2% of middle-aged women and 4% of middle-aged men with a higher prevalence among obese subjects. This condition is considered as an independent risk factor for cerebrovascular and cardiovascular diseases. One of the major pathophysiological characteristics of OSA is intermittent hypoxia. Hypoxia can lead to oxidative stress and overproduction of reactive oxygen species, which can lead to endothelial dysfunction, a hallmark of atherosclerosis. Many animal models, such as the rodent model of intermittent hypoxia, mimic obstructive sleep apnea in human patients and allow more in-depth investigation of biological and cellular mechanisms of this condition. This review discusses the role of oxidative stress in cardiovascular disease resulting from OSA in humans and animal models.

  16. Effects of intracellular chelatable iron and oxidative stress on transcription of classical cellular glutathione peroxidase gene in murine erythroleukemia cells

    International Nuclear Information System (INIS)

    Fuchs, O.

    1997-01-01

    The effect of intracellular chelatable iron levels and of oxidative stress on nuclear classical cellular glutathione peroxidase (GSHPx-1) RNA nascent chain elongation (run-on transcription) and on the stability of cytoplasmic GSHPx-1 mRNA was investigated in murine erythroleukemia (MEL) cells. The amount in the intracellular low molecular mass iron pool was changed by incubation of MEL cells transformed by Friend virus with iron donors or iron chelators. Transcription in vitro in isolated nuclei from treated cells showed that the treatment with chelators (desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone) decrease the rate of nuclear GSHPx-1 RNA nascent chain elongation in both un-induced and with 5 mmol hexamethylenebisacetamide to erythroid differentiation induced MEL cells. Iron donors (diferric transferrin,, Fe-PIH or their combination) and t-butyl hydroperoxide (t-BuOOH) had the opposite effect on GSHPx-1 gene transcription in run-on experiments. On the other hand, 50 μmol DFO or 2.5 μmol t-BuOOH did not change the stability of cytoplasmic GSHPx-1 mRNA in both un-induced and induced MEL cells treated with 5 μmol actinomycin D and with or without these agents for 9 h. These findings indicate that iron and oxidative stress play their role at the transcriptional level of GSHPx-1 gene expression. (author)

  17. The peroxisomal import receptor PEX5 functions as a stress sensor, retaining catalase in the cytosol in times of oxidative stress.

    Science.gov (United States)

    Walton, Paul A; Brees, Chantal; Lismont, Celien; Apanasets, Oksana; Fransen, Marc

    2017-10-01

    Accumulating evidence indicates that peroxisome functioning, catalase localization, and cellular oxidative balance are intimately interconnected. Nevertheless, it remains largely unclear why modest increases in the cellular redox state especially interfere with the subcellular localization of catalase, the most abundant peroxisomal antioxidant enzyme. This study aimed at gaining more insight into this phenomenon. Therefore, we first established a simple and powerful approach to study peroxisomal protein import and protein-protein interactions in living cells in response to changes in redox state. By employing this approach, we confirm and extend previous observations that Cys-11 of human PEX5, the shuttling import receptor for peroxisomal matrix proteins containing a C-terminal peroxisomal targeting signal (PTS1), functions as a redox switch that modulates the protein's activity in response to intracellular oxidative stress. In addition, we show that oxidative stress affects the import of catalase, a non-canonical PTS1-containing protein, more than the import of a reporter protein containing a canonical PTS1. Furthermore, we demonstrate that changes in the local redox state do not affect PEX5-substrate binding and that human PEX5 does not oligomerize in cellulo, not even when the cells are exposed to oxidative stress. Finally, we present evidence that catalase retained in the cytosol can protect against H 2 O 2 -mediated redox changes in a manner that peroxisomally targeted catalase does not. Together, these findings lend credit to the idea that inefficient catalase import, when coupled with the role of PEX5 as a redox-regulated import receptor, constitutes a cellular defense mechanism to combat oxidative insults of extra-peroxisomal origin. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

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    Iwai Ohbayashi

    2018-01-01

    Full Text Available The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

  19. Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses.

    Science.gov (United States)

    Ohbayashi, Iwai; Sugiyama, Munetaka

    2017-01-01

    The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized pathway of this stress response involves p53 and MDM2 as key players. p53 is a crucial transcription factor that functions in response to not only nucleolar stress but also other cellular stresses such as DNA damage stress. These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin ligase targeting p53, in various ways, which leads to p53-dependent activation of a set of genes. In plants, genetic impairments of ribosome biogenesis factors or ribosome components have been shown to cause characteristic phenotypes, including a narrow and pointed leaf shape, implying a common signaling pathway connecting ribosomal perturbations and certain aspects of growth and development. Unlike animals, however, plants have neither p53 nor MDM2 family proteins. Then the question arises whether plant cells have a nucleolar stress response pathway. In recent years, it has been reported that several members of the plant-specific transcription factor family NAC play critical roles in the pathways responsive to various cellular stresses. In this mini review, we outline the plant cellular stress response pathways involving NAC transcription factors with reference to the p53-MDM2-dependent pathways of animal cells, and discuss the possible involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress response in plants.

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

    Science.gov (United States)

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

    2018-04-01

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

  1. Nitric oxide in the stress axis.

    Science.gov (United States)

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

    1998-10-01

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

  2. Reductive Stress in Inflammation-Associated Diseases and the Pro-Oxidant Effect of Antioxidant Agents

    Directory of Open Access Journals (Sweden)

    Israel Pérez-Torres

    2017-10-01

    Full Text Available Abstract: Reductive stress (RS is the counterpart oxidative stress (OS, and can occur in response to conditions that shift the redox balance of important biological redox couples, such as the NAD+/NADH, NADP+/NADPH, and GSH/GSSG, to a more reducing state. Overexpression of antioxidant enzymatic systems leads to excess reducing equivalents that can deplete reactive oxidative species, driving the cells to RS. A feedback regulation is established in which chronic RS induces OS, which in turn, stimulates again RS. Excess reducing equivalents may regulate cellular signaling pathways, modify transcriptional activity, induce alterations in the formation of disulfide bonds in proteins, reduce mitochondrial function, decrease cellular metabolism, and thus, contribute to the development of some diseases in which NF-κB, a redox-sensitive transcription factor, participates. Here, we described the diseases in which an inflammatory condition is associated to RS, and where delayed folding, disordered transport, failed oxidation, and aggregation are found. Some of these diseases are aggregation protein cardiomyopathy, hypertrophic cardiomyopathy, muscular dystrophy, pulmonary hypertension, rheumatoid arthritis, Alzheimer’s disease, and metabolic syndrome, among others. Moreover, chronic consumption of antioxidant supplements, such as vitamins and/or flavonoids, may have pro-oxidant effects that may alter the redox cellular equilibrium and contribute to RS, even diminishing life expectancy.

  3. Oxidative stress reduces levels of dysbindin-1A via its PEST domain.

    Science.gov (United States)

    Yap, Mei-Yi Alicia; Lo, Yew-Long; Talbot, Konrad; Ong, Wei-Yi

    2014-12-01

    Oxidative stress resulting from the generation of reactive oxygen species has been proposed as an etiological factor in schizophrenia. The present study tests the hypothesis that oxidative stress can affect levels of dysbindin-1A, encoded by Dtnbp1, a genetic risk factor for schizophrenia, via its PEST domain. In vitro studies on SH-SY5Y cells indicate that oxidative stress triggers proteasomal degradation of dysbindin-1A, and that this requires interactions with its PEST domain, which may be a TRIM32 target. We specifically found (a) that oxidative stress induced in SH-SY5Y cells by 500 µM hydrogen peroxide reduced levels of full-length dysbindin-1, but did not reduce levels of that protein lacking its PEST domain and (b) that levels of full-length dysbindin-1, but not dysbindin-1 lacking its PEST domain, were higher in cells treated with the proteasome inhibitor MG132. Oxidative stress thus emerges as the first known cellular factor regulating dysbindin-1 isoforms with PEST domains. These findings are consistent with the previously noted fact that phosphorylation of PEST domains often marks proteins for proteasomal degradation, and raises the possibility that treatments reducing oxidative stress in the brain, especially during development, may lower schizophrenia risk. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster.

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    Katherine W Jordan

    Full Text Available Reactive oxygen species (ROS are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host defense mechanisms. However, an imbalance of ROS induces oxidative stress and cellular death and is associated with human disease, including age-related locomotor impairment. To identify genes affecting sensitivity and resistance to ROS-induced locomotor decline, we assessed locomotion of aged flies of the sequenced, wild-derived lines from the Drosophila melanogaster Genetics Reference Panel on standard medium and following chronic exposure to medium supplemented with 3 mM menadione sodium bisulfite (MSB. We found substantial genetic variation in sensitivity to oxidative stress with respect to locomotor phenotypes. We performed genome-wide association analyses to identify candidate genes associated with variation in sensitivity to ROS-induced decline in locomotor performance, and confirmed the effects for 13 of 16 mutations tested in these candidate genes. Candidate genes associated with variation in sensitivity to MSB-induced oxidative stress form networks of genes involved in neural development, immunity, and signal transduction. Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease.

  5. Does oxidative stress shorten telomeres?

    NARCIS (Netherlands)

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

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

  6. Oxidative Stress and Ageing: The Influence of Environmental Pollution, Sunlight and Diet on Skin

    Directory of Open Access Journals (Sweden)

    Khimara Naidoo

    2017-01-01

    Full Text Available Skin ageing is a complex process that is determined by both intrinsic and extrinsic factors, which leads to a progressive loss of structure and function. There is extensive evidence indicating that oxidative stress induced by reactive oxygen species plays an important role in the process of human skin ageing. Mitochondria are the major source of cellular oxidative stress and are widely implicated in cutaneous ageing. Extrinsic skin ageing is driven to a large extent by environmental factors and external stressors such as ultraviolet radiation (UVR, pollution and lifestyle factors which have been shown to stimulate the production of reactive oxygen species and generate oxidative stress. The oxidative damage from these exogenous sources can impair skin structure and function, leading to the phenotypic features of extrinsic skin ageing. The following review highlights the current evidence surrounding the role of mitochondria and oxidative stress in the ageing process and the influence of environmental factors such as ultraviolet radiation, pollution and diet on skin ageing.

  7. Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

    Science.gov (United States)

    Torres, Samantha M.; Schreurs, Ann-Sofie; Truong, Tiffany A.; Tahimic, Candice; Globus, Ruth

    2017-01-01

    Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

  8. Antioxidant modulation in response to heavy metal induced oxidative stress in Cladophora glomerata.

    Science.gov (United States)

    Murugan, K; Harish, S R

    2007-11-01

    The present investigation was carried out to study the induction of oxidative stress subjected to heavy metal environment. Lipoperoxides showed positive correlation at heavy metal accumulation sites indicating the tissue damage resulting from the reactive oxygen species and resulted in unbalance to cellular redox status. The high activities of ascorbate peroxidase and superoxide dismutase probably counter balance this oxidative stress. Glutathione and soluble phenols decreased, whereas dehydroascorbate content increased in the algae from polluted sites. The results suggested that alga responded to heavy metals effectively by antioxidant compounds and scavenging enzymes.

  9. Oxidative Stress and DNA Methylation in Prostate Cancer

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    Krishna Vanaja Donkena

    2010-01-01

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

  10. Influence of extra-cellular and intra-cellular acting thiol oxidants on the 45calcium uptake by the islets of Langerhans of the rat

    International Nuclear Information System (INIS)

    Haegele, R.G.

    1981-01-01

    The glucose-stimulated calcium uptake by the islets of Langerhans is dependent on the intra-cellular GSH/GSSG ratios. The inhibition of calcium uptake is not the consequence of a direct oxidation of membrane-fixed thiol groups. In contrast, direct oxidation of extra cellular thiols leads to an increase in calcium uptake when intra-cellular oxidation is simultaneously prevented. Since this effect only occurs at high intra-cellular GSH/GSSG ratios it can be assumed that the redox state of extra-cellular thiols is dependent on the redox state of the intra-cellular GSH/GSSG ratios. These findings support the theory that the oxidation of extra-cellular thiols by thiol oxidants leads to an increase in calcium uptake and that the extent of uptake is higher, the more the redox state of the extra-cellular thiols tends towards the reduced state prior to oxidation. (orig./MG) [de

  11. Oxidative Stress in BPH

    Directory of Open Access Journals (Sweden)

    Murat Savas

    2009-01-01

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

  12. Infusion of Hibiscus sabdariffa L. Modulates Oxidative Stress in Patients with Marfan Syndrome

    Science.gov (United States)

    Soto, María Elena; Zuñiga-Muñoz, Alejandra; Guarner Lans, Verónica; Duran-Hernández, Erendira Janet; Pérez-Torres, Israel

    2016-01-01

    Marfan syndrome (MFS) is associated with progressive aortic dilatation, endothelial dysfunction, and oxidative stress that contribute to the early acute dissection of the vessel and can end up in rupture of the aorta and sudden death. Many studies have described that the organic acids from Hibiscus sabdariffa Linne (HSL) calyces increase cellular antioxidant capacity and decrease oxidative stress. Here we evaluate if the antioxidant properties of HSL infusion improve oxidative stress in MFS patients. Activities of extra cellular super oxide dismutase (ECSOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSSG-R), glutathione (GSH), lipid peroxidation (LPO) index, total antioxidant capacity (TAC), and ascorbic acid were determined in plasma from MFS patients. Values before and after 3 months of the treatment with 2% HSL infusion were compared in control and MFS subjects. After treatment, there was a significant decrease in ECSOD (p = 0.03), EGPx (p = 0.04), GST (p = 0.03), GSH (p = 0.01), and TAC and ascorbic acid (p = 0.02) but GSSG-R activity (p = 0.04) and LPO (p = 0.02) were increased in MFS patients in comparison to patients receiving the HSL treatment and C subjects. Therefore, the infusion of HSL calyces has antioxidant properties that allow an increase in antioxidant capacity of both the enzymatic and nonenzymatic systems, in the plasma of the MSF patients. PMID:27413258

  13. Infusion of Hibiscus sabdariffa L. Modulates Oxidative Stress in Patients with Marfan Syndrome.

    Science.gov (United States)

    Soto, María Elena; Zuñiga-Muñoz, Alejandra; Guarner Lans, Verónica; Duran-Hernández, Erendira Janet; Pérez-Torres, Israel

    2016-01-01

    Marfan syndrome (MFS) is associated with progressive aortic dilatation, endothelial dysfunction, and oxidative stress that contribute to the early acute dissection of the vessel and can end up in rupture of the aorta and sudden death. Many studies have described that the organic acids from Hibiscus sabdariffa Linne (HSL) calyces increase cellular antioxidant capacity and decrease oxidative stress. Here we evaluate if the antioxidant properties of HSL infusion improve oxidative stress in MFS patients. Activities of extra cellular super oxide dismutase (ECSOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSSG-R), glutathione (GSH), lipid peroxidation (LPO) index, total antioxidant capacity (TAC), and ascorbic acid were determined in plasma from MFS patients. Values before and after 3 months of the treatment with 2% HSL infusion were compared in control and MFS subjects. After treatment, there was a significant decrease in ECSOD (p = 0.03), EGPx (p = 0.04), GST (p = 0.03), GSH (p = 0.01), and TAC and ascorbic acid (p = 0.02) but GSSG-R activity (p = 0.04) and LPO (p = 0.02) were increased in MFS patients in comparison to patients receiving the HSL treatment and C subjects. Therefore, the infusion of HSL calyces has antioxidant properties that allow an increase in antioxidant capacity of both the enzymatic and nonenzymatic systems, in the plasma of the MSF patients.

  14. Glucose-6-phosphate dehydrogenase protects Escherichia coli from tellurite-mediated oxidative stress.

    Directory of Open Access Journals (Sweden)

    Juan M Sandoval

    Full Text Available The tellurium oxyanion tellurite induces oxidative stress in most microorganisms. In Escherichia coli, tellurite exposure results in high levels of oxidized proteins and membrane lipid peroxides, inactivation of oxidation-sensitive enzymes and reduced glutathione content. In this work, we show that tellurite-exposed E. coli exhibits transcriptional activation of the zwf gene, encoding glucose 6-phosphate dehydrogenase (G6PDH, which in turn results in augmented synthesis of reduced nicotinamide adenine dinucleotide phosphate (NADPH. Increased zwf transcription under tellurite stress results mainly from reactive oxygen species (ROS generation and not from a depletion of cellular glutathione. In addition, the observed increase of G6PDH activity was paralleled by accumulation of glucose-6-phosphate (G6P, suggesting a metabolic flux shift toward the pentose phosphate shunt. Upon zwf overexpression, bacterial cells also show increased levels of antioxidant molecules (NADPH, GSH, better-protected oxidation-sensitive enzymes and decreased amounts of oxidized proteins and membrane lipids. These results suggest that by increasing NADPH content, G6PDH plays an important role in E. coli survival under tellurite stress.

  15. Acute effects of nandrolone decanoate on oxidative stress in isolated rat heart

    Directory of Open Access Journals (Sweden)

    Jevđević Maja

    2015-01-01

    Full Text Available Abuse of anabolic-androgenic steroids (AAS produces side effects in different tissues, with oxidative stress linked to their pathophysiology, being involved in fibrosis, cellular proliferation, and tumorigenesis. The aim of this study was to examine the acute effects of nandrolone decanoate (ND on oxidative stress in isolated rat heart. The hearts of male Wistar albino were excised and perfused according to the Langendorff technique at gradually increasing coronary perfusion pressures (40-120 cmH2O. The hearts were perfused with ND at doses of 1, 10 and 100 μM. Oxidative stress markers, including the index of lipid peroxidation (thiobarbituric acid reactive substances (TBARS, nitric oxide (nitrites; NO2-, the superoxide anion radical (O2- and hydrogen peroxide (H2O2 were measured in the coronary venous effluent. Our results showed that acute effects of ND do not promote the production of reactive oxygen species (ROS. Our finding pointed out that the highest concentration of ND may even possess some anti-oxidative potential, which should be examined further.

  16. Bursopentin (BP5 protects dendritic cells from lipopolysaccharide-induced oxidative stress for immunosuppression.

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    Tao Qin

    Full Text Available Dendritic cells (DCs play a vital role in the regulation of immune-mediated inflammatory diseases. Thus, DCs have been regarded as a major target for the development of immunomodulators. However, oxidative stress could disturb inflammatory regulation in DCs. Here, we examined the effect of bursopentine (BP5, a novel pentapeptide isolated from chicken bursa of fabricius, on the protection of DCs against oxidative stress for immunosuppression. BP5 showed potent protective effects against the lipopolysaccharide (LPS-induced oxidative stress in DCs, including nitric oxide, reactive oxygen species and lipid peroxidation. Furthermore, BP5 elevated the level of cellular reductive status through increasing the reduced glutathione (GSH and the GSH/GSSG ratio. Concomitant with these, the activities of several antioxidative redox enzymes, including glutathione peroxidase (GPx, catalase (CAT and superoxide dismutase (SOD, were obviously enhanced. BP5 also suppressed submucosal DC maturation in the LPS-stimulated intestinal epithelial cells (ECs/DCs coculture system. Finally, we found that heme oxygenase 1 (HO-1 was remarkably upregulated by BP5 in the LPS-induced DCs, and played an important role in the suppression of oxidative stress and DC maturation. These results suggested that BP5 could protect the LPS-activated DCs against oxidative stress and have potential applications in DC-related inflammatory responses.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  18. Buffer modulation of menadione-induced oxidative stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Lushchak, Oleh V; Bayliak, Maria M; Korobova, Olha V; Levine, Rodney L; Lushchak, Volodymyr I

    2009-01-01

    The objective of this study was to compare, in vivo, the effects of bicarbonate and phosphate buffers on survival and menadione-induced oxidative stress in yeast cells. The latter were treated with different concentrations of menadione in the presence of these two buffers. At 25 mM concentration of buffers, menadione only slightly reduced yeast surviving; at 50 mM concentration, cell killing by menadione was much more pronounced in bicarbonate than in phosphate buffer. Although the content of protein carbonyl groups did not show development of oxidative stress under menadione-induced stress, inactivation of aconitase and decrease in glutathione level mirrored its induction. However, cellular glutathione and aconitase activity decrease did not correlate with yeast survival. In vitro, aconitase was more quickly inactivated in 50 mM carbonate, than in 50 mM phosphate buffer. The possible involvement of the carbonate radical in these processes is discussed.

  19. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    International Nuclear Information System (INIS)

    Shin, Jung Ar; Chung, Jin Sil; Cho, Sang-Ho; Kim, Hyung Jung; Yoo, Young Do

    2013-01-01

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H 2 O 2 ) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H 2 O 2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells

  20. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  1. Oxidative stress induced by zearalenone in porcine granulosa cells and its rescue by curcumin in vitro.

    Directory of Open Access Journals (Sweden)

    Xunsi Qin

    Full Text Available Oxidative stress (OS, as a signal of aberrant intracellular mechanisms, plays key roles in maintaining homeostasis for organisms. The occurrence of OS due to the disorder of normal cellular redox balance indicates the overproduction of reactive oxygen species (ROS and/or deficiency of antioxidants. Once the balance is broken down, repression of oxidative stress is one of the most effective ways to alleviate it. Ongoing studies provide remarkable evidence that oxidative stress is involved in reproductive toxicity induced by various stimuli, such as environmental toxicants and food toxicity. Zearalenone (ZEA, as a toxic compound existing in contaminated food products, is found to induce mycotoxicosis that has a significant impact on the reproduction of domestic animals, especially pigs. However, there is no information about how ROS and oxidative stress is involved in the influence of ZEA on porcine granulosa cells, or whether the stress can be rescued by curcumin. In this study, ZEA-induced effect on porcine granulosa cells was investigated at low concentrations (15 μM, 30 μM and 60 μM. In vitro ROS levels, the mRNA level and activity of superoxide dismutase, glutathione peroxidase and catalase were obtained. The results showed that in comparison with negative control, ZEA increased oxidative stress with higher ROS levels, reduced the expression and activity of antioxidative enzymes, increased the intensity of fluorogenic probes 2', 7'-Dichlorodihydrofluorescin diacetate and dihydroethidium in flow cytometry assay and fluorescence microscopy. Meanwhile, the activity of glutathione (GSH did not change obviously following 60 μM ZEA treatment. Furthermore, the underlying protective mechanisms of curcumin on the ZEA-treated porcine granulosa cells were investigated. The data revealed that curcumin pre-treatment significantly suppressed ZEA-induced oxidative stress. Collectively, porcine granulosa cells were sensitive to ZEA, which may induce

  2. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

    Science.gov (United States)

    Azzam, Edouard I.; Jay-Gerin, Jean-Paul; Pain, Debkumar

    2013-01-01

    Cellular exposure to ionizing radiation leads to oxidizing events that alter atomic structure through direct interactions of radiation with target macromolecules or via products of water radiolysis. Further, the oxidative damage may spread from the targeted to neighboring, non-targeted bystander cells through redox-modulated intercellular communication mechanisms. To cope with the induced stress and the changes in the redox environment, organisms elicit transient responses at the molecular, cellular and tissue levels to counteract toxic effects of radiation. Metabolic pathways are induced during and shortly after the exposure. Depending on radiation dose, dose-rate and quality, these protective mechanisms may or may not be sufficient to cope with the stress. When the harmful effects exceed those of homeostatic biochemical processes, induced biological changes persist and may be propagated to progeny cells. Physiological levels of reactive oxygen and nitrogen species play critical roles in many cellular functions. In irradiated cells, levels of these reactive species may be increased due to perturbations in oxidative metabolism and chronic inflammatory responses, thereby contributing to the long-term effects of exposure to ionizing radiation on genomic stability. Here, in addition to immediate biological effects of water radiolysis on DNA damage, we also discuss the role of mitochondria in the delayed outcomes of ionization radiation. Defects in mitochondrial functions lead to accelerated aging and numerous pathological conditions. Different types of radiation vary in their linear energy transfer (LET) properties, and we discuss their effects on various aspects of mitochondrial physiology. These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes. PMID:22182453

  3. Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

    Directory of Open Access Journals (Sweden)

    Daniëlle M. P. H. J. Boesten

    2013-01-01

    Full Text Available Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose polymerase-1 (PARP-1 and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline in human fibroblasts (HF cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP. Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

  4. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  6. Long-Term Exercise Protects against Cellular Stresses in Aged Mice

    Directory of Open Access Journals (Sweden)

    Irina Belaya

    2018-01-01

    Full Text Available The current study examined the effect of aging and long-term wheel-running on the expression of heat shock protein (HSP, redox regulation, and endoplasmic reticulum (ER stress markers in tibialis anterior (T.A. and soleus muscle of mice. Male mice were divided into young (Y, 3-month-old, old-sedentary (OS, 24-month-old, and old-exercise (OE, 24-month-old groups. The OE group started voluntary wheel-running at 3 months and continued until 24 months of age. Aging was associated with a higher thioredoxin-interacting protein (TxNiP level, lower thioredoxin-1 (TRX-1 to TxNiP ratio—a determinant of redox regulation and increased CHOP, an indicator of ER stress-related apoptosis signaling in both muscles. Notably, GRP78, a key indicator of ER stress, was selectively elevated in T.A. Long-term exercise decreased TxNiP in T.A. and soleus muscles and increased the TRX-1/TxNiP ratio in soleus muscle of aged mice. Inducible HSP70 and constituent HSC70 were upregulated, whereas CHOP was reduced after exercise in soleus muscle. Thus, our data demonstrated that aging induced oxidative stress and activated ER stress-related apoptosis signaling in skeletal muscle, whereas long-term wheel-running improved redox regulation, ER stress adaptation and attenuated ER stress-related apoptosis signaling. These findings suggest that life-long exercise can protect against age-related cellular stress.

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

    Science.gov (United States)

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

    2013-09-01

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

  8. Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants.

    Science.gov (United States)

    Rayner, Cassie L; Bottle, Steven E; Gole, Glen A; Ward, Micheal S; Barnett, Nigel L

    2016-01-01

    Nitroxides have been exploited as profluorescent probes for the detection of oxidative stress. In addition, they deliver potent antioxidant action and attenuate reactive oxygen species (ROS) in various models of oxidative stress, with these results ascribed to superoxide dismutase or redox and radical-scavenging actions. Our laboratory has developed a range of novel, biostable, isoindoline nitroxide-based antioxidants, DCTEIO and CTMIO. In this study we compared the efficiency of these novel compounds as antioxidant therapies in reducing ROS both in vivo (rat model) and in vitro (661W photoreceptor cells), with the established antioxidant resveratrol. By assessing changes in fluorescence intensity of a unique redox-responsive probe in the rat retina in vivo, we evaluated the ability of antioxidant therapy to (1) ameliorate ROS production and (2) reverse the accumulation of ROS after complete, acute ischemia followed by reperfusion (I/R). I/R injury induced a marked decrease in fluorescence intensity over 60 min of reperfusion, which was successfully ameliorated with each of the antioxidants. DCTEIO and CTMIO reversed the accumulation of ROS when administered intraocularly post ischemic insult, whereas, the effect of resveratrol was not significant. We also investigated our novel agents' capacity to prevent ROS-mediated metabolic dysfunction in the 661W photoreceptor cell line. Cellular stress induced by the oxidant, tert-butyl hydroperoxide, resulted in a loss of spare mitochondrial respiratory capacity (SMRC) and in the extracellular acidification rate in 661W cells. DCTEIO antioxidant administration successfully reduced the loss of SMRC. Together, these findings show we can quantify dynamic changes in cellular oxidative status in vivo and suggest that nitroxide-based antioxidants may provide greater protection against oxidative stress than the current state-of-the-art antioxidant treatments for ROS-mediated diseases. Copyright © 2015 Elsevier Ltd. All rights

  9. Beneficial Effect of Jojoba Seed Extracts on Hyperglycemia-Induced Oxidative Stress in RINm5f Beta Cells.

    Science.gov (United States)

    Belhadj, Sahla; Hentati, Olfa; Hamdaoui, Ghaith; Fakhreddine, Khaskhoussi; Maillard, Elisa; Dal, Stéphanie; Sigrist, Séverine

    2018-03-20

    Hyperglycemia occurs during diabetes and insulin resistance. It causes oxidative stress by increasing reactive oxygen species (ROS) levels, leading to cellular damage. Polyphenols play a central role in defense against oxidative stress. In our study, we investigated the antioxidant properties of simmondsin, a pure molecule present in jojoba seeds, and of the aqueous extract of jojoba seeds on fructose-induced oxidative stress in RINm5f beta cells. The exposure of RINm5f beta cells to fructose triggered the loss of cell viability (-48%, p jojoba seed extract makes jojoba a powerful agent to prevent the destruction of RINm5f beta cells induced by hyperglycemia.

  10. The iron-sulfur cluster assembly network component NARFL is a key element in the cellular defense against oxidative stress.

    Science.gov (United States)

    Corbin, Monique V; Rockx, Davy A P; Oostra, Anneke B; Joenje, Hans; Dorsman, Josephine C

    2015-12-01

    Aim of this study was to explore cellular changes associated with increased resistance to atmospheric oxygen using high-resolution DNA and RNA profiling combined with functional studies. Two independently selected oxygen-resistant substrains of HeLa cells (capable of proliferating at >80% O2, i.e. hyperoxia) were compared with their parental cells (adapted to growth at 20% O2, but unable to grow at >80% O2). A striking consistent alteration found to be associated with the oxygen-resistant state appeared to be an amplified and overexpressed region on chromosome 16p13.3 harboring 21 genes. The driver gene of this amplification was identified by functional studies as NARFL, which encodes a component of the cytosolic iron-sulfur cluster assembly system. In line with this result we found the cytosolic c-aconitase activity as well as the nuclear protein RTEL1, both Fe-S dependent proteins, to be protected by NARFL overexpression under hyperoxia. In addition, we observed a protective effect of NARFL against hyperoxia-induced loss of sister-chromatid cohesion. NARFL thus appeared to be a key factor in the cellular defense against hyperoxia-induced oxidative stress in human cells. Our findings suggest that new insight into age-related degenerative processes may come from studies that specifically address the involvement of iron-sulfur proteins. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes.

    Science.gov (United States)

    Dutta, Eryn H; Behnia, Faranak; Boldogh, Istvan; Saade, George R; Taylor, Brandie D; Kacerovský, Marian; Menon, Ramkumar

    2016-02-01

    In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation. Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM. Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups. Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence. Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM. Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome. This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of

  12. Sirtuins: Molecular Traffic Lights in the Crossroad of Oxidative Stress, Chromatin Remodeling, and Transcription

    Directory of Open Access Journals (Sweden)

    Ramkumar Rajendran

    2011-01-01

    Full Text Available Transcription is regulated by acetylation/deacetylation reactions of histone and nonhistone proteins mediated by enzymes called KATs and HDACs, respectively. As a major mechanism of transcriptional regulation, protein acetylation is a key controller of physiological processes such as cell cycle, DNA damage response, metabolism, apoptosis, and autophagy. The deacetylase activity of class III histone deacetylases or sirtuins depends on the presence of NAD+ (nicotinamide adenine dinucleotide, and therefore, their function is closely linked to cellular energy consumption. This activity of sirtuins connects the modulation of chromatin dynamics and transcriptional regulation under oxidative stress to cellular lifespan, glucose homeostasis, inflammation, and multiple aging-related diseases including cancer. Here we provide an overview of the recent developments in relation to the diverse biological activities associated with sirtuin enzymes and stress responsive transcription factors, DNA damage, and oxidative stress and relate the involvement of sirtuins in the regulation of these processes to oncogenesis. Since the majority of the molecular mechanisms implicated in these pathways have been described for Sirt1, this sirtuin family member is more extensively presented in this paper.

  13. Retinal Pigment Epithelial Cell Culture and Cooperation of L-carnitine in Reducing Stress Induced Cellular Damage

    International Nuclear Information System (INIS)

    Shamsi, Farrukh A.; Al-Rajhi, Ali A.; Athmanathan, S.; Boulton, M.; Chaudhry, Imtiaz A.

    2006-01-01

    Purpose was to show that L-carnitine (LC) is capable of reducing non-oxidative stress in the retinal pigment epithelial cells (RPE) of the human eye. The RPE cells were cultured from donor eyes, obtained immediately after post-mortem. The interaction between bovine serum albumin (BSA) and non-oxidative (sodium hydroxide and methyl methane sulphonate) stress-inducers was observed by recording the change in the absorption profiles of the interacting molecules after incubation in light for 5 hours and after treatment with LC. The isolated and cultured RPE cells from the human eyes were treated with sodium hydroxide or methyl methane sulphonate and/or LC for 5 hours under light, and the qualitative effect on cell morphology after treatment was analyzed by staining cells with Giemsa and visualization by light microscopy. The cell morphology was also qualitatively analyzed by scanning electron microscopy (SEM). L-carnitine and stress-inducers interact with BSA and bring about changes in the spectral profile of the interacted molecules. Light microscopy as well as SEM show that the changes in the cellular morphology, induced by 100 uM concentrations of non-oxidative stress-inducers, are considerably reduced in the presence of 100 uM LC. However, L-carnitine alone does not cause any qualitative damage to the cell morphology during incubation under similar conditions. The results give a preliminary indication that LC has ability to reduce the changes brought about by the non-oxidative stress-inducers in the RPF cells in culture. (author)

  14. Stress analysis of two-dimensional cellular materials with thick cell struts

    International Nuclear Information System (INIS)

    Lim, Do Hyung; Kim, Han Sung; Kim, Young Ho; Kim, Yoon Hyuk; Al-Hassani, S.T.S.

    2008-01-01

    Finite element analyses (FEA) were performed to thoroughly validate the collapse criteria of cellular materials presented in our previous companion paper. The maximum stress (von-Mises stress) on the cell strut surface and the plastic collapse stress were computed for two-dimensional (2D) cellular materials with thick cell struts. The results from the FEA were compared with those from theoretical criteria of authors. The FEA results were in good agreement with the theoretical results. The results indicate that when bending moment, axial and shear forces are considered, the maximum stress on the strut surface gives significantly different values in the tensile and compressive parts of the cell wall as well as in the two loading directions. Therefore, for the initial yielding of ductile cellular materials and the fracture of brittle cellular materials, in which the maximum stress on the strut surface is evaluated, it is necessary to consider not only the bending moment but also axial and shear forces. In addition, this study shows that for regular cellular materials with the identical strut geometry for all struts, the initial yielding and the plastic collapse under a biaxial state of stress occur not only in the inclined cell struts but also in the vertical struts. These FEA results support the theoretical conclusion of our previous companion paper that the anisotropic 2D cellular material has a truncated yield surface not only on the compressive quadrant but also on the tensile quadrant

  15. Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Quaroni, Andrea [Department of Biomedical Sciences, Cornell University, Veterinary Research Tower, Cornell University, Ithaca, NY 14853–6401 (United States); Autore, Giuseppina [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Severino, Lorella [Department of Pathology and Animal Health, Division of Toxicology, School of Veterinary Medicine, University of Naples “Federico II”, Via Delpino 1, 80137 Naples (Italy); Marzocco, Stefania, E-mail: smarzocco@unisa.it [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy)

    2015-06-01

    Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.

  16. Oxidative Stress Regulation on Endothelial Cells by Hydrophilic Astaxanthin Complex: Chemical, Biological, and Molecular Antioxidant Activity Evaluation

    Directory of Open Access Journals (Sweden)

    M. Zuluaga

    2017-01-01

    Full Text Available An imbalance in the reactive oxygen species (ROS homeostasis is involved in the pathogenesis of oxidative stress-related diseases. Astaxanthin, a xanthophyll carotenoid with high antioxidant capacities, has been shown to prevent the first stages of oxidative stress. Here, we evaluate the antioxidant capacities of astaxanthin included within hydroxypropyl-beta-cyclodextrin (CD-A to directly and indirectly reduce the induced ROS production. First, chemical methods were used to corroborate the preservation of astaxanthin antioxidant abilities after inclusion. Next, antioxidant scavenging properties of CD-A to inhibit the cellular and mitochondrial ROS by reducing the disturbance in the redox state of the cell and the infiltration of lipid peroxidation radicals were evaluated. Finally, the activation of endogenous antioxidant PTEN/AKT, Nrf2/HO-1, and NQOI gene and protein expression supported the protective effect of CD-A complex on human endothelial cells under stress conditions. Moreover, a nontoxic effect on HUVEC was registered after CD-A complex supplementation. The results reported here illustrate the need to continue exploring the interesting properties of this hydrophilic antioxidant complex to assist endogenous systems to counteract the ROS impact on the induction of cellular oxidative stress state.

  17. The influence of N-acetyl-L-cysteine on oxidative stress and nitric oxide synthesis in stimulated macrophages treated with a mustard gas analogue

    Directory of Open Access Journals (Sweden)

    Smith Milton

    2008-06-01

    Full Text Available Abstract Background Sulphur mustard gas, 2, 2'-dichlorodiethyl sulphide (HD, is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES, are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO production via suppression of inducible NO synthase (iNOS protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds. Results We found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels. NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages. Conclusion The present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and

  18. Cellular Stress Response to Engineered Nanoparticles: Effect of Size, Surface Coating, and Cellular Uptake

    Science.gov (United States)

    CELLULAR STRESS RESPONSE TO ENGINEERED NANOPARTICLES: EFFECT OF SIZE, SURFACE COATING, AND CELLULAR UPTAKE RY Prasad 1, JK McGee2, MG Killius1 D Ackerman2, CF Blackman2 DM DeMarini2 , SO Simmons2 1 Student Services Contractor, US EPA, RTP, NC 2 US EPA, RTP, NC The num...

  19. Selective neuronal vulnerability to oxidative stress in the brain

    Directory of Open Access Journals (Sweden)

    Xinkun Wang

    2010-03-01

    Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

  20. Differentiation-Associated Downregulation of Poly(ADP-Ribose Polymerase-1 Expression in Myoblasts Serves to Increase Their Resistance to Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Gábor Oláh

    Full Text Available Poly(ADP-ribose polymerase 1 (PARP-1, the major isoform of the poly (ADP-ribose polymerase family, is a constitutive nuclear and mitochondrial protein with well-recognized roles in various essential cellular functions such as DNA repair, signal transduction, apoptosis, as well as in a variety of pathophysiological conditions including sepsis, diabetes and cancer. Activation of PARP-1 in response to oxidative stress catalyzes the covalent attachment of the poly (ADP-ribose (PAR groups on itself and other acceptor proteins, utilizing NAD+ as a substrate. Overactivation of PARP-1 depletes intracellular NAD+ influencing mitochondrial electron transport, cellular ATP generation and, if persistent, can result in necrotic cell death. Due to their high metabolic activity, skeletal muscle cells are particularly exposed to constant oxidative stress insults. In this study, we investigated the role of PARP-1 in a well-defined model of murine skeletal muscle differentiation (C2C12 and compare the responses to oxidative stress of undifferentiated myoblasts and differentiated myotubes. We observed a marked reduction of PARP-1 expression as myoblasts differentiated into myotubes. This alteration correlated with an increased resistance to oxidative stress of the myotubes, as measured by MTT and LDH assays. Mitochondrial function, assessed by measuring mitochondrial membrane potential, was preserved under oxidative stress in myotubes compared to myoblasts. Moreover, basal respiration, ATP synthesis, and the maximal respiratory capacity of mitochondria were higher in myotubes than in myoblasts. Inhibition of the catalytic activity of PARP-1 by PJ34 (a phenanthridinone PARP inhibitor exerted greater protective effects in undifferentiated myoblasts than in differentiated myotubes. The above observations in C2C12 cells were also confirmed in a rat-derived skeletal muscle cell line (L6. Forced overexpression of PARP1 in C2C12 myotubes sensitized the cells to oxidant

  1. BRCA1 and Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-04-03

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

  2. Low-Dose Ionizing Radiation Exposure, Oxidative Stress and Epigenetic Programing of Health and Disease.

    Science.gov (United States)

    Tharmalingam, Sujeenthar; Sreetharan, Shayenthiran; Kulesza, Adomas V; Boreham, Douglas R; Tai, T C

    2017-10-01

    Ionizing radiation exposure from medical diagnostic imaging has greatly increased over the last few decades. Approximately 80% of patients who undergo medical imaging are exposed to low-dose ionizing radiation (LDIR). Although there is widespread consensus regarding the harmful effects of high doses of radiation, the biological effects of low-linear energy transfer (LET) LDIR is not well understood. LDIR is known to promote oxidative stress, however, these levels may not be large enough to result in genomic mutations. There is emerging evidence that oxidative stress causes heritable modifications via epigenetic mechanisms (DNA methylation, histone modification, noncoding RNA regulation). These epigenetic modifications result in permanent cellular transformations without altering the underlying DNA nucleotide sequence. This review summarizes the major concepts in the field of epigenetics with a focus on the effects of low-LET LDIR (stress on epigenetic gene modification. In this review, we show evidence that suggests that LDIR-induced oxidative stress provides a mechanistic link between LDIR and epigenetic gene regulation. We also discuss the potential implication of LDIR exposure during pregnancy where intrauterine fetal development is highly susceptible to oxidative stress-induced epigenetic programing.

  3. High hydrostatic pressure leads to free radicals accumulation in yeast cells triggering oxidative stress.

    Science.gov (United States)

    Bravim, Fernanda; Mota, Mainã M; Fernandes, A Alberto R; Fernandes, Patricia M B

    2016-08-01

    Saccharomyces cerevisiae is a unicellular organism that during the fermentative process is exposed to a variable environment; hence, resistance to multiple stress conditions is a desirable trait. The stress caused by high hydrostatic pressure (HHP) in S. cerevisiae resembles the injuries generated by other industrial stresses. In this study, it was confirmed that gene expression pattern in response to HHP displays an oxidative stress response profile which is expanded upon hydrostatic pressure release. Actually, reactive oxygen species (ROS) concentration level increased in yeast cells exposed to HHP treatment and an incubation period at room pressure led to a decrease in intracellular ROS concentration. On the other hand, ethylic, thermic and osmotic stresses did not result in any ROS accumulation in yeast cells. Microarray analysis revealed an upregulation of genes related to methionine metabolism, appearing to be a specific cellular response to HHP, and not related to other stresses, such as heat and osmotic stresses. Next, we investigated whether enhanced oxidative stress tolerance leads to enhanced tolerance to HHP stress. Overexpression of STF2 is known to enhance tolerance to oxidative stress and we show that it also leads to enhanced tolerance to HHP stress. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

    2013-01-15

    Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The

  5. MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women.

    Science.gov (United States)

    Diamanti-Kandarakis, Evanthia; Papalou, Olga; Kandaraki, Eleni A; Kassi, Georgia

    2017-02-01

    Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders. © 2017 European Society of Endocrinology.

  6. Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

    International Nuclear Information System (INIS)

    Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-Mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

    2011-01-01

    β-Naphthoflavone (BNF) is a strong inducer of cytochrome P450 1A enzymes, and exerts liver tumor-promoting activity through enhancement of oxidative stress responses in rats. This study investigated the role of the tissue environment surrounding hepatocellular preneoplastic lesions in the early tumor-promotion stage by BNF, using enzymatically modified isoquercitrin (EMIQ) as an anti-oxidative chemopreventive agent. Male F344 rats were fed a diet containing BNF (0.5%) for 6 weeks, with or without EMIQ (0.2%) in the drinking water, 2 weeks after initiation with N-diethylnitrosamine, and were subjected to two-thirds partial hepatectomy 1 week after starting BNF-promotion. BNF-treatment increased concentrations of liver thiobarbituric acid-reactive substances, single liver cells expressing glutathione S-transferase placental form or heme oxygenase (HO)-1, and concomitant apoptosis and proliferation of liver cells. Transcript upregulation of anti-oxidative enzymes (Aldh1a1 and Nqo1), cell cycle-related molecules (Cdc20 and Cdkn2b) and inflammation-related molecules including proinflammatory cytokines (Ccl2, Col1a1, Il6, Nos2 and Serpine1) was also evident. Furthermore, BNF increased HO-1-expressing Kupffer cells and liver cells expressing tumor necrosis factor receptor 1 (TNFR1) and the TNFR1-associated death domain. Most of these BNF-induced fluctuations disappeared or were suppressed by EMIQ in conjunction with suppression of tumor-promotion. Tnf transcript levels with BNF were also suppressed by EMIQ. These results suggest that BNF-induced oxidative stress causes single liver cell toxicity, allowing subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFα-signaling, contributing to tumor promotion. Kupffer cells may act to protect against inflammatory stimuli induced as a result of oxidative cellular stress by BNF, causing proinflammatory cytokine level fluctuations.

  7. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chuan-Ho, E-mail: chtang@nmmba.gov.tw [Institute of Marine Biodiversity and Evolutionary Biology, National Dong Hwa University, Pingtung, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Lin, Ching-Yu [Institute of Environmental Health, National Taiwan University, Taipei City, Taiwan, ROC (China); Lee, Shu-Hui [Center of General Education, National Kaohsiung Marine University, Kaohsiung, Taiwan, ROC (China); Wang, Wei-Hsien [National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Department of Marine Biotechnology and Resources and Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC (China)

    2014-03-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  8. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    International Nuclear Information System (INIS)

    Tang, Chuan-Ho; Lin, Ching-Yu; Lee, Shu-Hui; Wang, Wei-Hsien

    2014-01-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  9. Impact of Heat Stress on Cellular and Transcriptional Adaptation of Mammary Epithelial Cells in Riverine Buffalo (Bubalus Bubalis).

    Science.gov (United States)

    Kapila, Neha; Sharma, Ankita; Kishore, Amit; Sodhi, Monika; Tripathi, Pawan K; Mohanty, Ashok K; Mukesh, Manishi

    2016-01-01

    The present study aims to identify the heat responsive genes and biological pathways in heat stressed buffalo mammary epithelial cells (MECs). The primary mammary epithelial cells of riverine buffalo were exposed to thermal stress at 42°C for one hour. The cells were subsequently allowed to recover at 37°C and harvested at different time intervals (30 min to 48 h) along with control samples (un-stressed). In order to assess the impact of heat stress in buffalo MECs, several in-vitro cellular parameters (lactate dehydrogenase activity, cell proliferation assay, cellular viability, cell death and apoptosis) and transcriptional studies were conducted. The heat stress resulted in overall decrease in cell viability and cell proliferation of MECs while induction of cellular apoptosis and necrosis. The transcriptomic profile of heat stressed MECs was generated using Agilent 44 K bovine oligonucleotide array and at cutoff criteria of ≥3-or ≤3 fold change, a total of 153 genes were observed to be upregulated while 8 genes were down regulated across all time points post heat stress. The genes that were specifically up-regulated or down-regulated were identified as heat responsive genes. The upregulated genes in heat stressed MECs belonged to heat shock family viz., HSPA6, HSPB8, DNAJB2, HSPA1A. Along with HSPs, genes like BOLA, MRPL55, PFKFB3, PSMC2, ENDODD1, ARID5A, and SENP3 were also upregulated. Microarray data revealed that the heat responsive genes belonged to different functional classes viz., chaperons; immune responsive; cell proliferation and metabolism related. Gene ontology analysis revealed enrichment of several biological processes like; cellular process, metabolic process, response to stimulus, biological regulation, immune system processes and signaling. The transcriptome analysis data was further validated by RT-qPCR studies. Several HSP (HSP40, HSP60, HSP70, HSP90, and HSPB1), apoptotic (Bax and Bcl2), immune (IL6, TNFα and NF-kβ) and oxidative

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  11. Oxidative Stress in Fish induced by Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Anton Kováčik

    2017-05-01

    Full Text Available Environmental pollutants represent a risk factor for human and animals in all areas of occurrence. Environmental pollution caused by anthropogenic activities is a major problem in many countries. Numbers of studies deals with cumulation of xenobiotics in tissues but not all respond to the real impact on living organisms. Freshwater fishes are exposed to several anthropogenic contaminants. The most commonly studied are three metals: mercury (Hg, lead (Pb, cadmium (Cd. These contaminants could have several impacts to oxidative stress. In the normal healthy cell, ROS and pro-oxidant products are detoxified by antioxidant defences. Redox-active or Redox-inactive metals may cause an increase in production of reactive oxygen species (ROS. Mercury has a high affinity for thiol groups, and can non-specifically affect several enzymes, e. g. GSH (glutathione, which can induce GSH depletion and oxidative stress in tissue, also can induce lipid peroxidation, and mitochondrial dysfunction. The toxicity of Cd to aquatic species depends on speciation, with the free ion, Cd2+ concentration being proportional to bioavailability. Cadmium toxicity worsened of Ca, Na, and Mg ions homeostasis. Lead can be toxic to nervous and skeletal systems; at cellular level can cause apoptosis, also can affect mitochondria, neurotransmitters, and can substitute for Ca.

  12. [The evaluation of selected oxidative stress parameters in patients with hyperthyroidism].

    Science.gov (United States)

    Andryskowski, Grzegorz; Owczarek, Tomasz

    2007-07-01

    Hyperthyroidism induces the acceleration of the basic metabolism and increases cellular oxygen utilization, consequently intensifies reactive oxygen species production and disturbs the oxidant-antioxidant balance. The objective of this study was to evaluate the selected oxidative stress parameters in patients with hyperthyroidism by analysis of the reactive oxygen species neutralizing enzymes activity--superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT), the estimation of free radical processes intensity--concentration of malondialdehyde (MDA), sulfhydryl groups (SH) in proteins and by quantification of the serum total antioxidant status (TAS). . Twenty-seven patients treated for hyperthyroidism and 12 healthy individuals were enrolled in the study. Enzyme activity (SOD, GSHPx, CAT), MDA and concentration of SH groups were analysed in erythrocytes, while TAS was measured in serum. Patients with hyperthyroidism compared with healthy subjects were characterized by a higher GSHPx activity in erythrocytes, lower serum TAS, the lower content of SH groups in proteins and the lower MDA concentration in erythrocytes. Our results suggest that hyperthyroidism increases oxidative stress and disturbs oxidant-antioxidant balance in the body. Thyreostatic treatment, if not leads to whole metabolic compensation, may only reduce oxidant-antioxidant disorders, however is not able to eliminate them entirely.

  13. Oxidative stress: development and progression of breast cancer:review article

    Directory of Open Access Journals (Sweden)

    Arash Salmaninejad

    2017-04-01

    Full Text Available Breast cancer is the most commonly diagnosed cancer in women worldwide. Enormous advancement has been made over the last decades in understanding the biology of breast cancer. Nevertheless, the molecular mechanisms regulating progression, gaining of invasive and metastatic phenotypes, and therapeutic resistance are still not completely understood. Oxidative stress initiate by disbalance in redox status of body. In this case, increase of free radicals in body cause tissue damage. One of the significant species of free radicals is reactive oxygen species (ROS that produced by various metabolic pathways, comprising aerobic metabolism in the mitochondrial respiratory chain. They play a serious role in cellular physiology and pathophysiology likewise beginning and evolution of numerous types of cancers. ROS overproduction is deleterious to cells, and considered key-factors for the development of numerous diseases, such as cardiovascular disorders, neurodegenerative diseases, and cancer. Cancer cells are commonly submitted to upper ROS levels that further incite malignant phenotype through motivation to preserved proliferation, angiogenesis, death evasion, invasiveness, and metastasis. ROS impress various signaling pathways, comprising mitogenic pathways and growth factors, and also controls numerous cellular processes, containing cell proliferation, thus stimulates the undisciplined growth of cells which inspires the development of tumors and initiates the progression of carcinogenesis. The importance of ROS on breast cancer development and etiology is being increasingly clarified. Nevertheless, fewer consideration has been given to the progress of redox system-targeted strategies for breast cancer treatment. Augmented oxidative stress caused by reactive species can diminish the body’s antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are core factors in the development of cancer. Bimolecular reactions cause

  14. Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective

    DEFF Research Database (Denmark)

    Møller, Ian Max; Rogowska-Wrzesinska, Adelina; Rao, R S P

    2011-01-01

    Proteins can become oxidatively modified in many different ways, either by direct oxidation of amino acid side chains and protein backbone or indirectly by conjugation with oxidation products of polyunsaturated fatty acids and carbohydrates. While reversible oxidative modifications are thought...... to be relevant in physiological processes, irreversible oxidative modifications are known to contribute to cellular damage and disease. The most well-studied irreversible protein oxidation is carbonylation. In this work we first examine how protein carbonylation occurs via metal-catalyzed oxidation (MCO) in vivo...... and in vitro with an emphasis on cellular metal ion homeostasis and metal binding. We then review proteomic methods currently used for identifying carbonylated proteins and their sites of modification. Finally, we discuss the identified carbonylated proteins and the pattern of carbonylation sites in relation...

  15. Synergistic effect of aluminum and ionizing radiation upon ultrastructure, oxidative stress and apoptotic alterations in Paneth cells of rat intestine.

    Science.gov (United States)

    Eltahawy, N A; Elsonbaty, S M; Abunour, S; Zahran, W E

    2017-03-01

    Environmental and occupational exposure to aluminum along with ionizing radiation results in serious health problems. This study was planned to investigate the impact of oxidative stress provoked by exposure to ionizing radiation with aluminum administration upon cellular ultra structure and apoptotic changes in Paneth cells of rat small intestine . Animals received daily aluminum chloride by gastric gavage at a dose 0.5 mg/Kg BW for 4 weeks. Whole body gamma irradiation was applied at a dose 2 Gy/week up to 8 Gy. Ileum malondialdehyde, advanced oxidative protein products, protein carbonyl and tumor necrosis factor-alpha were assessed as biomarkers of lipid peroxidation, protein oxidation and inflammation respectively along with superoxide dismutase, catalase, and glutathione peroxidase activities as enzymatic antioxidants. Moreover, analyses of cell cycle division and apoptotic changes were evaluated by flow cytometry. Intestinal cellular ultra structure was investigated using transmission electron microscope.Oxidative and inflammatory stresses assessment in the ileum of rats revealed that aluminum and ionizing radiation exposures exhibited a significant effect upon the increase in oxidative stress biomarkers along with the inflammatory marker tumor necrosis factor-α accompanied by a significant decreases in the antioxidant enzyme activities. Flow cytometric analyses showed significant alterations in the percentage of cells during cell cycle division phases along with significant increase in apoptotic cells. Ultra structurally, intestinal cellular alterations with marked injury in Paneth cells at the sites of bacterial translocation in the crypt of lumens were recorded. The results of this study have clearly showed that aluminum and ionizing radiation exposures induced apoptosis with oxidative and inflammatory disturbance in the Paneth cells of rat intestine, which appeared to play a major role in the pathogenesis of cellular damage. Furthermore, the

  16. Effects of Graphene Oxide and Oxidized Carbon Nanotubes on the Cellular Division, Microstructure, Uptake, Oxidative Stress, and Metabolic Profiles.

    Science.gov (United States)

    Hu, Xiangang; Ouyang, Shaohu; Mu, Li; An, Jing; Zhou, Qixing

    2015-09-15

    Nanomaterial oxides are common formations of nanomaterials in the natural environment. Herein, the nanotoxicology of typical graphene oxide (GO) and carboxyl single-walled carbon nanotubes (C-SWCNT) was compared. The results showed that cell division of Chlorella vulgaris was promoted at 24 h and then inhibited at 96 h after nanomaterial exposure. At 96 h, GO and C-SWCNT inhibited the rates of cell division by 0.08-15% and 0.8-28.3%, respectively. Both GO and C-SWCNT covered the cell surface, but the uptake percentage of C-SWCNT was 2-fold higher than that of GO. C-SWCNT induced stronger plasmolysis and mitochondrial membrane potential loss and decreased the cell viability to a greater extent than GO. Moreover, C-SWCNT-exposed cells exhibited more starch grains and lysosome formation and higher reactive oxygen species (ROS) levels than GO-exposed cells. Metabolomics analysis revealed significant differences in the metabolic profiles among the control, C-SWCNT and GO groups. The metabolisms of alkanes, lysine, octadecadienoic acid and valine was associated with ROS and could be considered as new biomarkers of ROS. The nanotoxicological mechanisms involved the inhibition of fatty acid, amino acid and small molecule acid metabolisms. These findings provide new insights into the effects of GO and C-SWCNT on cellular responses.

  17. Oxidative stress mediated mitochondrial and vascular lesions as markers in the pathogenesis of Alzheimer disease.

    Science.gov (United States)

    Aliev, G; Priyadarshini, M; Reddy, V P; Grieg, N H; Kaminsky, Y; Cacabelos, R; Ashraf, G Md; Jabir, N R; Kamal, M A; Nikolenko, V N; Zamyatnin, A A; Benberin, V V; Bachurin, S O

    2014-01-01

    Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer's disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients.

  18. Acrolein toxicity involves oxidative stress caused by glutathione depletion in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Kwolek-Mirek, M; Bednarska, S; Bartosz, G; Biliński, T

    2009-08-01

    Exposure of yeast cells to allyl alcohol results in intracellular production of acrolein. The toxicity of so formed acrolein involves oxidative stress, as (1) strains deficient in antioxidant defense are hypersensitive to allyl alcohol, (2) exposure to allyl alcohol increases the level of thiobarbituric-acid-reactive substances and decreases glutathione level in the cells, (3) hypoxic and anoxic atmosphere and antioxidants protect against allyl alcohol toxicity, and (4) allyl alcohol causes activation of Yap1p. No increased formation of reactive oxygen species was detected in cells exposed to allyl alcohol, so oxidative stress is due to depletion of cellular thiols and thus alteration in the redox state of yeast cells.

  19. Stress Distribution in Graded Cellular Materials Under Dynamic Compression

    Directory of Open Access Journals (Sweden)

    Peng Wang

    Full Text Available Abstract Dynamic compression behaviors of density-homogeneous and density-graded irregular honeycombs are investigated using cell-based finite element models under a constant-velocity impact scenario. A method based on the cross-sectional engineering stress is developed to obtain the one-dimensional stress distribution along the loading direction in a cellular specimen. The cross-sectional engineering stress is contributed by two parts: the node-transitive stress and the contact-induced stress, which are caused by the nodal force and the contact of cell walls, respectively. It is found that the contact-induced stress is dominant for the significantly enhanced stress behind the shock front. The stress enhancement and the compaction wave propagation can be observed through the stress distributions in honeycombs under high-velocity compression. The single and double compaction wave modes are observed directly from the stress distributions. Theoretical analysis of the compaction wave propagation in the density-graded honeycombs based on the R-PH (rigid-plastic hardening idealization is carried out and verified by the numerical simulations. It is found that stress distribution in cellular materials and the compaction wave propagation characteristics under dynamic compression can be approximately predicted by the R-PH shock model.

  20. Oxidative stress homeostasis in grapevine (Vitis vinifera L.

    Directory of Open Access Journals (Sweden)

    Luisa C Carvalho

    2015-03-01

    Full Text Available Plants can maintain growth and reproductive success by sensing changes in the environment and reacting through mechanisms at molecular, cellular, physiological and developmental levels. Each stress condition prompts a unique response although some overlap between the reactions to abiotic stress (drought, heat, cold, salt or high light and to biotic stress (pathogens does occur. A common feature in the response to all stresses is the onset of oxidative stress, through the production of reactive oxygen species (ROS. As hydrogen peroxide and superoxide are involved in stress signaling, a tight control in ROS homeostasis requires a delicate balance of systems involved in their generation and degradation. If the plant lacks the capacity to generate scavenging potential, this can ultimately lead to death. In grapevine, antioxidant homeostasis can be considered at whole plant levels and during the development cycle. The most striking example lies in berries and their derivatives, such as wine, with nutraceutical properties associated with their antioxidant capacity. Antioxidant homeostasis is tightly regulated in leaves, assuring a positive balance between photosynthesis and respiration, explaining the tolerance of many grapevine varieties to extreme environments.In this review we will focus on antioxidant metabolites, antioxidant enzymes, transcriptional regulation and cross-talk with hormones prompted by abiotic stress conditions. We will also discuss three situations that require specific homeostasis balance: biotic stress, the oxidative burst in berries at veraison and in vitro systems. The genetic plasticity of the antioxidant homeostasis response put in evidence by the different levels of tolerance to stress presented by grapevine varieties will be addressed. The gathered information is relevant to foster varietal adaptation to impending climate changes, to assist breeders in choosing the more adapted varieties and to suitable viticulture

  1. Cellular stress induces a protective sleep-like state in C. elegans.

    Science.gov (United States)

    Hill, Andrew J; Mansfield, Richard; Lopez, Jessie M N G; Raizen, David M; Van Buskirk, Cheryl

    2014-10-20

    Sleep is recognized to be ancient in origin, with vertebrates and invertebrates experiencing behaviorally quiescent states that are regulated by conserved genetic mechanisms. Despite its conservation throughout phylogeny, the function of sleep remains debated. Hypotheses for the purpose of sleep include nervous-system-specific functions such as modulation of synaptic strength and clearance of metabolites from the brain, as well as more generalized cellular functions such as energy conservation and macromolecule biosynthesis. These models are supported by the identification of synaptic and metabolic processes that are perturbed during prolonged wakefulness. It remains to be seen whether perturbations of cellular homeostasis in turn drive sleep. Here we show that under conditions of cellular stress, including noxious heat, cold, hypertonicity, and tissue damage, the nematode Caenorhabditis elegans engages a behavioral quiescence program. The stress-induced quiescent state displays properties of sleep and is dependent on the ALA neuron, which mediates the conserved soporific effect of epidermal growth factor (EGF) ligand overexpression. We characterize heat-induced quiescence in detail and show that it is indeed dependent on components of EGF signaling, providing physiological relevance to the behavioral effects of EGF family ligands. We find that after noxious heat exposure, quiescence-defective animals show elevated expression of cellular stress reporter genes and are impaired for survival, demonstrating the benefit of stress-induced behavioral quiescence. These data provide evidence that cellular stress can induce a protective sleep-like state in C. elegans and suggest that a deeply conserved function of sleep is to mitigate disruptions of cellular homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

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    B. Relja

    2012-01-01

    Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

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

    Science.gov (United States)

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

    2013-02-01

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

  4. Association of Oxidative Stress with Psychiatric Disorders.

    Science.gov (United States)

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

    2016-01-01

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

  5. Role of glutathione metabolism status in the definition of some cellular parameters and oxidative stress tolerance of Saccharomyces cerevisiae cells growing as biofilms.

    Science.gov (United States)

    Gales, Grégoire; Penninckx, Michel; Block, Jean-Claude; Leroy, Pierre

    2008-08-01

    The resistance of Saccharomyces cerevisiae to oxidative stress (H(2)O(2) and Cd(2+)) was compared in biofilms and planktonic cells, with the help of yeast mutants deleted of genes related to glutathione metabolism and oxidative stress. Biofilm-forming cells were found predominantly in the G1 stage of the cell cycle. This might explain their higher tolerance to oxidative stress and the young replicative age of these cells in an old culture. The reduced glutathione status of S. cerevisiae was affected by the growth phase and apparently plays an important role in oxidative stress tolerance in cells growing as a biofilm.

  6. Oxidative Stress, Synaptic Dysfunction, and Alzheimer's Disease.

    Science.gov (United States)

    Tönnies, Eric; Trushina, Eugenia

    2017-01-01

    Alzheimer's disease (AD) is a devastating neurodegenerative disorder without a cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding of the disease mechanism hinders the development of efficacious therapeutic approaches. The loss of synapses in the affected brain regions correlates best with cognitive impairment in AD patients and has been considered as the early mechanism that precedes neuronal loss. Oxidative stress has been recognized as a contributing factor in aging and in the progression of multiple neurodegenerative diseases including AD. Increased production of reactive oxygen species (ROS) associated with age- and disease-dependent loss of mitochondrial function, altered metal homeostasis, and reduced antioxidant defense directly affect synaptic activity and neurotransmission in neurons leading to cognitive dysfunction. In addition, molecular targets affected by ROS include nuclear and mitochondrial DNA, lipids, proteins, calcium homeostasis, mitochondrial dynamics and function, cellular architecture, receptor trafficking and endocytosis, and energy homeostasis. Abnormal cellular metabolism in turn could affect the production and accumulation of amyloid-β (Aβ) and hyperphosphorylated Tau protein, which independently could exacerbate mitochondrial dysfunction and ROS production, thereby contributing to a vicious cycle. While mounting evidence implicates ROS in the AD etiology, clinical trials with antioxidant therapies have not produced consistent results. In this review, we will discuss the role of oxidative stress in synaptic dysfunction in AD, innovative therapeutic strategies evolved based on a better understanding of the complexity of molecular mechanisms of AD, and the dual role ROS play in health and disease.

  7. Two-Dimensional Algal Collection and Assembly by Combining AC-Dielectrophoresis with Fluorescence Detection for Contaminant-Induced Oxidative Stress Sensing

    Directory of Open Access Journals (Sweden)

    Coralie Siebman

    2015-06-01

    Full Text Available An alternative current (AC dielectrophoretic lab-on-chip setup was evaluated as a rapid tool of capture and assembly of microalga Chlamydomonas reinhardtii in two-dimensional (2D close-packed arrays. An electric field of 100 V·cm−1, 100 Hz applied for 30 min was found optimal to collect and assemble the algae into single-layer structures of closely packed cells without inducing cellular oxidative stress. Combined with oxidative stress specific staining and fluorescence microscopy detection, the capability of using the 2D whole-cell assembly on-chip to follow the reactive oxygen species (ROS production and oxidative stress during short-term exposure to several environmental contaminants, including mercury, methylmercury, copper, copper oxide nanoparticles (CuO-NPs, and diuron was explored. The results showed significant increase of the cellular ROS when C. reinhardtii was exposed to high concentrations of methylmercury, CuO-NPs, and 10−5 M Cu. Overall, this study demonstrates the potential of combining AC-dielectrophoretically assembled two-dimensional algal structures with cell metabolic analysis using fluorescence staining, as a rapid analytical tool for probing the effect of contaminants in highly impacted environment.

  8. Global transcriptome profile of Cryptococcus neoformans during exposure to hydrogen peroxide induced oxidative stress.

    Directory of Open Access Journals (Sweden)

    Rajendra Upadhya

    Full Text Available The ability of the opportunistic fungal pathogen Cryptococcus neoformans to resist oxidative stress is one of its most important virulence related traits. To cope with the deleterious effect of cellular damage caused by the oxidative burst inside the macrophages, C. neoformans has developed multilayered redundant molecular responses to neutralize the stress, to repair the damage and to eventually grow inside the hostile environment of the phagosome. We used microarray analysis of cells treated with hydrogen peroxide (H(2O(2 at multiple time points in a nutrient defined medium to identify a transcriptional signature associated with oxidative stress. We discovered that the composition of the medium in which fungal cells were grown and treated had a profound effect on their capacity to degrade exogenous H(2O(2. We determined the kinetics of H(2O(2 breakdown by growing yeast cells under different conditions and accordingly selected an appropriate media composition and range of time points for isolating RNA for hybridization. Microarray analysis revealed a robust transient transcriptional response and the intensity of the global response was consistent with the kinetics of H(2O(2 breakdown by treated cells. Gene ontology analysis of differentially expressed genes related to oxidation-reduction, metabolic process and protein catabolic processes identified potential roles of mitochondrial function and protein ubiquitination in oxidative stress resistance. Interestingly, the metabolic pathway adaptation of C. neoformans to H(2O(2 treatment was remarkably distinct from the response of other fungal organisms to oxidative stress. We also identified the induction of an antifungal drug resistance response upon the treatment of C. neoformans with H(2O(2. These results highlight the complexity of the oxidative stress response and offer possible new avenues for improving our understanding of mechanisms of oxidative stress resistance in C. neoformans.

  9. [Stress-induced cellular adaptive mutagenesis].

    Science.gov (United States)

    Zhu, Linjiang; Li, Qi

    2014-04-01

    The adaptive mutations exist widely in the evolution of cells, such as antibiotic resistance mutations of pathogenic bacteria, adaptive evolution of industrial strains, and cancerization of human somatic cells. However, how these adaptive mutations are generated is still controversial. Based on the mutational analysis models under the nonlethal selection conditions, stress-induced cellular adaptive mutagenesis is proposed as a new evolutionary viewpoint. The hypothetic pathway of stress-induced mutagenesis involves several intracellular physiological responses, including DNA damages caused by accumulation of intracellular toxic chemicals, limitation of DNA MMR (mismatch repair) activity, upregulation of general stress response and activation of SOS response. These responses directly affect the accuracy of DNA replication from a high-fidelity manner to an error-prone one. The state changes of cell physiology significantly increase intracellular mutation rate and recombination activity. In addition, gene transcription under stress condition increases the instability of genome in response to DNA damage, resulting in transcription-associated DNA mutagenesis. In this review, we summarize these two molecular mechanisms of stress-induced mutagenesis and transcription-associated DNA mutagenesis to help better understand the mechanisms of adaptive mutagenesis.

  10. Hydrogen-peroxide-induced oxidative stress responses in Desulfovibrio vulgaris Hildenborough

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, A.; He, Z.; Redding-Johanson, A.M.; Mukhopadhyay, A.; Hemme, C.L.; Joachimiak, M.P.; Bender, K.S.; Keasling, J.D.; Stahl, D.A.; Fields, M.W.; Hazen, T.C.; Arkin, A.P.; Wall, J.D.; Zhou, J.; Luo, F.; Deng, Y.; He, Q.

    2010-07-01

    To understand how sulphate-reducing bacteria respond to oxidative stresses, the responses of Desulfovibrio vulgaris Hildenborough to H{sub 2}O{sub 2}-induced stresses were investigated with transcriptomic, proteomic and genetic approaches. H{sub 2}O{sub 2} and induced chemical species (e.g. polysulfide, ROS) and redox potential shift increased the expressions of the genes involved in detoxification, thioredoxin-dependent reduction system, protein and DNA repair, and decreased those involved in sulfate reduction, lactate oxidation and protein synthesis. A gene coexpression network analysis revealed complicated network interactions among differentially expressed genes, and suggested possible importance of several hypothetical genes in H{sub 2}O{sub 2} stress. Also, most of the genes in PerR and Fur regulons were highly induced, and the abundance of a Fur regulon protein increased. Mutant analysis suggested that PerR and Fur are functionally overlapped in response to stresses induced by H{sub 2}O{sub 2} and reaction products, and the upregulation of thioredoxin-dependent reduction genes was independent of PerR or Fur. It appears that induction of those stress response genes could contribute to the increased resistance of deletion mutants to H{sub 2}O{sub 2}-induced stresses. In addition, a conceptual cellular model of D. vulgaris responses to H{sub 2}O{sub 2} stress was constructed to illustrate that this bacterium may employ a complicated molecular mechanism to defend against the H{sub 2}O{sub 2}-induced stresses.

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

    Science.gov (United States)

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

    2018-05-01

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

  12. Role of Inflammation and Oxidative Stress Mediators in Gliomas

    Directory of Open Access Journals (Sweden)

    Alfredo Conti

    2010-04-01

    Full Text Available Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

  13. Role of Inflammation and Oxidative Stress Mediators in Gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Conti, Alfredo, E-mail: alfredo.conti@unime.it; Gulì, Carlo; La Torre, Domenico; Tomasello, Chiara; Angileri, Filippo F.; Aguennouz, M’Hammed [Department of Neuroscience and Department of Oncology, University of Messina, Policlinico Universitario, Via Consolare Valeria 1, 98125, Messina (Italy)

    2010-04-26

    Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

  14. Role of Inflammation and Oxidative Stress Mediators in Gliomas

    International Nuclear Information System (INIS)

    Conti, Alfredo; Gulì, Carlo; La Torre, Domenico; Tomasello, Chiara; Angileri, Filippo F.; Aguennouz, M’Hammed

    2010-01-01

    Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment

  15. hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

    OpenAIRE

    Nicolas Paquet; Mark N. Adams; Nicholas W. Ashton; Christine Touma; Roland Gamsjaeger; Liza Cubeddu; Vincent Leong; Sam Beard; Emma Bolderson; Catherine H. Botting; Kenneth J. O’Byrne; Derek J. Richard

    2016-01-01

    The maintenance of genome stability is an essential cellular process to prevent the development of diseases including cancer. hSSB1 (NABP2/ OBFC2A) is a critical component of the DNA damage response where it participates in the repair of double-strand DNA breaks and in base excision repair of oxidized guanine residues (8-oxoguanine) by aiding the localization of the human 8-oxoguanine glycosylase (hOGG1) to damaged DNA. Here we demonstrate that following oxidative stress, hSSB1 is stabilized ...

  16. Radical Roles for RAGE in the Pathogenesis of Oxidative Stress in Cardiovascular Diseases and Beyond

    Directory of Open Access Journals (Sweden)

    Radha Ananthakrishnan

    2013-10-01

    Full Text Available Oxidative stress is a central mechanism by which the receptor for advanced glycation endproducts (RAGE mediates its pathological effects. Multiple experimental inquiries in RAGE-expressing cultured cells have demonstrated that ligand-RAGE interaction mediates generation of reactive oxygen species (ROS and consequent downstream signal transduction and regulation of gene expression. The primary mechanism by which RAGE generates oxidative stress is via activation of NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS production. Recent studies indicating that the cytoplasmic domain of RAGE binds to the formin mDia1 provide further support for the critical roles of this pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand S100B. In vivo, in multiple distinct disease models in animals, RAGE action generates oxidative stress and modulates cellular/tissue fate in range of disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm formation. Blockade or genetic deletion of RAGE was shown to be protective in these settings. Indeed, beyond cardiovascular disease, evidence is accruing in human subjects linking levels of RAGE ligands and soluble RAGE to oxidative stress in disorders such as doxorubicin toxicity, acetaminophen toxicity, neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key strategy for the prevention of the deleterious consequences of oxidative stress, particularly in chronic disease.

  17. Oxidative Stress Function in Women over 40 Years of Age, Considering Their Lifestyle.

    Science.gov (United States)

    Gonçalves Mota, Maria Paula; Santos, Zirlene; Soares, Jorge; Pereira, Ana; Fonseca, Sandra; Peixoto, Francisco; Gaivão, Isabel; Oliveira, Maria

    2017-01-01

    Aging is dependent on biological processes that determine the aging of the organism at the cellular level. The Oxidative Stress Theory of Aging might explain some of the age-related changes in cell macromolecules. Moreover, exposome and lifestyle may also induce changes in cell damage induced by oxidative stress. The aim of the present study was to analyze the related redox changes in lymphocyte function of healthy women over 40 years old. Three groups: younger (YG: 40-49 years), middle aged (MAG: 50-59 years), and older (OG: ≥60 years) were evaluated on anthropometric variables, blood pressure, cardiovascular fitness, lifestyle habits, perceived stress, DNA damage, malondialdehyde, catalase activity, and total antioxidant capacity. Physical activity and cardiovascular fitness were significantly higher in YG and MAG as compared to the OG. Systolic blood pressure increased significantly with group age. Frequency and total amount of alcohol intake were lower in the OG and higher in the MAG. No significant differences were observed between the three groups in oxidative stress parameters. Only alcohol consumption was associated with the higher DNA FPG-sensitive sites, and only in the YG ( p  stress parameters measured in the healthy women over the age of 40 who took part in the study. Conscious lifestyle behaviors (decrease in alcohol and smoking habits) could have impaired the expected age-related oxidative stress increase.

  18. Oxidative stress, cancer, and sleep deprivation: is there a logical link in this association?

    Science.gov (United States)

    Noguti, Juliana; Andersen, Monica Levy; Cirelli, Chiara; Ribeiro, Daniel Araki

    2013-09-01

    Sleep disorders are associated with various human pathologies and interfere with biological processes essential for health and quality of life. On the other hand, cancer is one of the most common diseases worldwide with an average of 1,500 deaths per day in the USA. Is there a factor common to both sleep disorders and cancer that serves to link these conditions? It is a normal process for cellular metabolism to produce reactive oxidant series (ROS). However, when the production of ROS overcomes the antioxidant capacity of the cell to eliminate these products, the resulting state is called oxidative stress. Oxidative DNA damage may participate in ROS-induced carcinogenesis. Moreover, ROS are also produced in the sleep deprivation process. The aim of this article is to review pathways and mechanisms that may point to oxidative stress as a link between sleep deprivation and cancer.

  19. Protective Effects of Black Rice Extracts on Oxidative Stress Induced by tert-Butyl Hydroperoxide in HepG2 Cells

    Science.gov (United States)

    Lee, Seon-Mi; Choi, Youngmin; Sung, Jeehye; Kim, Younghwa; Jeong, Heon-Sang; Lee, Junsoo

    2014-01-01

    Black rice contains many biologically active compounds. The aim of this study was to investigate the protective effects of black rice extracts (whole grain extract, WGE and rice bran extract, RBE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. Cellular reactive oxygen species (ROS), antioxidant enzyme activities, malondialdehyde (MDA) and glutathione (GSH) concentrations were evaluated as biomarkers of cellular oxidative status. Cells pretreated with 50 and 100 μg/mL of WGE or RBE were more resistant to oxidative stress in a dose-dependent manner. The highest WGE and BRE concentrations enhanced GSH concentrations and modulated antioxidant enzyme activities (glutathione reductase, glutathione-S-transferase, catalase, and superoxide dismutase) compared to TBHP-treated cells. Cells treated with RBE showed higher protective effect compared to cells treated with WGE against oxidative insult. Black rice extracts attenuated oxidative insult by inhibiting cellular ROS and MDA increase and by modulating antioxidant enzyme activities in HepG2 cells. PMID:25580401

  20. Pharmacological inhibition of arachidonate 15-lipoxygenase (ALOX15) protects human spermatozoa against oxidative stress.

    Science.gov (United States)

    Walters, Jessica L H; De Iuliis, Geoffry N; Dun, Matthew D; Aitken, Robert John; McLaughlin, Eileen A; Nixon, Brett; Bromfield, Elizabeth G

    2018-03-13

    One of the leading causes of male infertility is defective sperm function, a pathology that commonly arises from oxidative stress in the germline. Lipid peroxidation events in the sperm plasma membrane result in the generation of cytotoxic aldehydes such as 4-hydroxynonenal (4HNE), which accentuate the production of reactive oxygen species (ROS) and cause cellular damage. One of the key enzymes involved in the metabolism of polyunsaturated fatty acids to 4HNE in somatic cells is arachidonate 15-lipoxygenase (ALOX15). Although ALOX15 has yet to be characterized in human spermatozoa, our previous studies have revealed a strong link between ALOX15 activity and the levels of oxidative stress and 4HNE in mouse germ cell models. In view of these data, we sought to assess the function of ALOX15 in mature human spermatozoa and determine whether the pharmacological inhibition of this enzyme could influence the level of oxidative stress experienced by these cells. By driving oxidative stress in vitro with exogenous H2O2, our data reveal that 6,11-dihydro[1]benzothiopyrano[4,3-b]indole (PD146176; a selective ALOX15 inhibitor), was able to significantly reduce several deleterious, oxidative insults in spermatozoa. Indeed, PD146176 attenuated the production of ROS, as well as membrane lipid peroxidation and 4HNE production in human spermatozoa. Accordingly, ALOX15 inhibition also protected the functional competence of these cells to acrosome react and bind homologous human zonae pellucidae. Together, these results implicate ALOX15 in the propagation of an oxidative stress cascade within human spermatozoa and offer insight into potential therapeutic avenues to address male fertility that arises from oxidative stress.

  1. Using multiple biomarkers and determinants to obtain a better measurement of oxidative stress: a latent variable structural equation model approach.

    Science.gov (United States)

    Eldridge, Ronald C; Flanders, W Dana; Bostick, Roberd M; Fedirko, Veronika; Gross, Myron; Thyagarajan, Bharat; Goodman, Michael

    2017-09-01

    Since oxidative stress involves a variety of cellular changes, no single biomarker can serve as a complete measure of this complex biological process. The analytic technique of structural equation modeling (SEM) provides a possible solution to this problem by modelling a latent (unobserved) variable constructed from the covariance of multiple biomarkers. Using three pooled datasets, we modelled a latent oxidative stress variable from five biomarkers related to oxidative stress: F 2 -isoprostanes (FIP), fluorescent oxidation products, mitochondrial DNA copy number, γ-tocopherol (Gtoc) and C-reactive protein (CRP, an inflammation marker closely linked to oxidative stress). We validated the latent variable by assessing its relation to pro- and anti-oxidant exposures. FIP, Gtoc and CRP characterized the latent oxidative stress variable. Obesity, smoking, aspirin use and β-carotene were statistically significantly associated with oxidative stress in the theorized directions; the same exposures were weakly and inconsistently associated with the individual biomarkers. Our results suggest that using SEM with latent variables decreases the biomarker-specific variability, and may produce a better measure of oxidative stress than do single variables. This methodology can be applied to similar areas of research in which a single biomarker is not sufficient to fully describe a complex biological phenomenon.

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

    Directory of Open Access Journals (Sweden)

    Fereshteh Ahmadinejad

    2017-07-01

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

  3. Anthelminthic drug niclosamide sensitizes the responsiveness of cervical cancer cells to paclitaxel via oxidative stress-mediated mTOR inhibition

    International Nuclear Information System (INIS)

    Chen, Liping; Wang, Li; Shen, Haibin; Lin, Hui; Li, Dan

    2017-01-01

    Drug repurposing represents an alternative therapeutic strategy to cancer treatment. The potent anti-cancer activities of a FDA-approved anthelminthic drug niclosamide have been demonstrated in various cancers. However, whether niclosamide is active against cervical cancer is unknown. In this study, we investigated the effects of niclosamide alone and its combination with paclitaxel in cervical cancer in vitro and in vivo. We found that niclosamide significantly inhibited proliferation and induced apoptosis of a panel of cervical cancer cell lines, regardless of their cellular origin and genetic pattern. Niclosamide also inhibited tumor growth in cervical cancer xenograft mouse model. Importantly, niclosamide significantly enhanced the responsiveness of cervical cancer cell to paclitaxel. We further found that niclosamide induced mitochondrial dysfunctions via inhibiting mitochondrial respiration, complex I activity and ATP generation, which led to oxidative stress. ROS scavenge agent N-acetyl-L-cysteine (NAC) completely reversed the effects of niclosamide in increasing cellular ROS, inhibiting proliferation and inducing apoptosis, suggesting that oxidative stress induction is the mechanism of action of niclosamide in cervical cancer cells. In addition, niclosamide significantly inhibited mammalian target of rapamycin (mTOR) signaling pathway in cervical cancer cells and its inhibitory effect on mTOR is modulated by oxidative stress. Our work suggests that niclosamide is a useful addition to the treatment armamentarium for cervical cancer and induction of oxidative stress may be a potential therapeutic strategy in cervical cancer. - Highlights: • Niclosamide is active against cervical cancer cells in vitro and in vivo. • Niclosamide sensitizes cervical cancer cell response to paclitaxel. • Niclosamide induces mitochondrial dysfunction and oxidative damage. • Niclosamide inhibits mTOR signaling in an oxidative stress-dependent manner.

  4. Carica Papaya Seed Extract Enhances Cellular Response to Stress ...

    African Journals Online (AJOL)

    Therefore, the present study was carried out to investigate the role of Carica papaya seed (CPS) extract that contains, Benzyl Isothiocyanates, one of the inducers of phase II enzymes in the regulation of cellular stress. The cellular responses were observed in U937 cells (human monocyte/macrophage cell line) at the ...

  5. Non invasive Imaging based Detection and Mapping of Brain Oxidative Stress and its Correlation with Cognative Functions

    Science.gov (United States)

    2017-05-14

    relationship between the brain oxidative status and stress at a cellular, physiological as well as a psychological level. These stressors, in turn, have...neuropsychological tests: cognitive performance, perceptual reasoning , working memory, processing speed and perceived stress scale were performed. Brain...following tests for verbal compression, working memory, perceptual reasoning and processing speed paper pencil tests were conducted. Each subject took more

  6. Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

    Directory of Open Access Journals (Sweden)

    Elizabeth Moreno-Arriola

    2014-01-01

    Full Text Available Caenorhabditis elegans is a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic level in vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes. C. elegans displays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance of C. elegans as an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

  7. Glutaredoxin 1 (GRX1) inhibits oxidative stress and apoptosis of chondrocytes by regulating CREB/HO-1 in osteoarthritis.

    Science.gov (United States)

    Sun, Jie; Wei, Xuelei; Lu, Yandong; Cui, Meng; Li, Fangguo; Lu, Jie; Liu, Yunjiao; Zhang, Xi

    2017-10-01

    GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current study. Protein and mRNA expressions were measured by Western blot and RT-qPCR. Oxidative stress was detected by the measurement of MDA and SOD contents. Cells apoptosis were detected by Annexin V-FITC/PI and caspase-3 activity assays. We found that the mRNA and protein expressions of GRX1 were significantly down-regulated in osteoarthritis tissues and cells. GRX1 overexpression increased the mRNA and protein expression of CREB and HO-1. Meanwhile, GRX1 overexpression inhibited oxidative stress and apoptosis in osteoarthritis chondrocytes. Furthermore, we found that GRX1 overexpression regulated HO-1 by increasing CREB, and that HO-1 regulated oxidative stress and apoptosis in osteoarthritis chondrocytes. Thus, GRX1 overexpression constrains oxidative stress and apoptosis in osteoarthritis chondrocytes by regulating CREB/HO-1, providing a novel insight into the molecular mechanism and potential treatment of osteoarthritis. Copyright © 2017. Published by Elsevier Ltd.

  8. Effect of patchouli alcohol on the regulation of heat shock-induced oxidative stress in IEC-6 cells.

    Science.gov (United States)

    Liu, Xiaoxi; Jiang, Linshu; Liu, Fenghua; Chen, Yuping; Xu, Lei; Li, Deyin; Ma, Yunfei; Li, Huanrong; Xu, Jianqin

    2016-08-01

    Purpose Patchouli alcohol (PA) is used to treat gastrointestinal dysfunction. The purpose of this study was to ascertain the function of PA in the regulated process of oxidative stress in rat intestinal epithelial cells (IEC-6). Materials and methods Oxidative stress was stimulated by exposing IEC-6 cells to heat shock (42 °C for 3 h). IEC-6 cells in treatment groups were pretreated with various concentrations of PA (10, 40, and 80 ng/mL) for 3 h before heat shock. Results Heat shock caused damage to the morphology of IEC-6 cells, and increased reactive oxygen species (ROS) level and malondialdehyde (MDA) content. Moreover, mRNA and protein expression by target genes related to oxidative stress in heat shock were also altered. Specifically, the mRNA expression by HSP70, HSP90, GSH-px, NRF2 nd HO-1were all increased, and Nrf2 and Keap1 protein expression were increased after heat shock. However, pretreatment with PA weakened the level of damage to the cellular morphology, and decreased the MDA content caused by heat shock, indicating PA had cytoprotective activities. Pretreatment with PA at high dose significantly increased generation of intracellular ROS. Compared with the heat shock group alone, PA pretreatment significantly decreased the mRNA expression by HSP70, HSP90, SOD, CAT, GSH-px, KEAP1 and HO-1. Furthermore, the high dose of PA significantly increased Nrf2 protein expression, while both the intermediate and high dose of PA significantly increased HO-1 protein expression. Conclusion Heat-shock-induced oxidative stress in IEC-6 cells, and PA could alleviate the Nrf2-Keap1 cellular oxidative stress responses.

  9. Oxidative stress upregulates the NMDA receptor on cerebrovascular endothelium.

    Science.gov (United States)

    Betzen, Christian; White, Robin; Zehendner, Christoph M; Pietrowski, Eweline; Bender, Bianca; Luhmann, Heiko J; Kuhlmann, Christoph R W

    2009-10-15

    N-methyl-d-aspartate receptor (NMDA-R)-mediated oxidative stress has been implicated in blood-brain barrier (BBB) disruption in a variety of neuropathological diseases. Although some interactions between both phenomena have been elucidated, possible influences of reactive oxygen species (ROS) on the NMDA-R itself have so far been neglected. The objective of this study was to examine how the cerebroendothelial NMDA-R is affected by exposure to oxidative stress and to assess possible influences on BBB integrity. RT-PCR confirmed several NMDA-R subunits (NR1, NR2B-D) expressed in the bEnd3 cell line (murine cerebrovascular endothelial cells). NR1 protein expression after exposure to ROS was observed via in-cell Western. The functionality of the expressed NMDA-R was determined by measuring DiBAC fluorescence in ROS-preexposed cells upon stimulation with the specific agonist NMDA. Finally, the effects on barrier integrity were evaluated using the ECIS system to detect changes in monolayer impedance upon NMDA-R stimulation after exposure to ROS. The expression of NR1 significantly (p<0.001) increased 72 h after 30 min exposure to superoxide (+33.8+/-7.5%), peroxynitrite (+84.9+/-10.7%), or hydrogen peroxide (+92.8+/-7.6%), resulting in increased cellular response to NMDA-R stimulation and diminished monolayer impedance. We conclude that oxidative stress upregulates NMDA-R on cerebrovascular endothelium and thus heightens susceptibility to glutamate-induced BBB disruption.

  10. Catalase therapy corrects oxidative stress-induced pathophysiology in incipient diabetic retinopathy.

    Science.gov (United States)

    Giordano, Courtney R; Roberts, Robin; Krentz, Kendra A; Bissig, David; Talreja, Deepa; Kumar, Ashok; Terlecky, Stanley R; Berkowitz, Bruce A

    2015-05-01

    Preclinical studies have highlighted retinal oxidative stress in the pathogenesis of diabetic retinopathy. We evaluated whether a treatment designed to enhance cellular catalase reduces oxidative stress in retinal cells cultured in high glucose and in diabetic mice corrects an imaging biomarker responsive to antioxidant therapy (manganese-enhanced magnetic resonance imaging [MEMRI]). Human retinal Müller and pigment epithelial cells were chronically exposed to normal or high glucose levels and treated with a cell-penetrating derivative of the peroxisomal enzyme catalase (called CAT-SKL). Hydrogen peroxide (H2O2) levels were measured using a quantitative fluorescence-based assay. For in vivo studies, streptozotocin (STZ)-induced diabetic C57Bl/6 mice were treated subcutaneously once a week for 3 to 4 months with CAT-SKL; untreated age-matched nondiabetic controls and untreated diabetic mice also were studied. MEMRI was used to analytically assess the efficacy of CAT-SKL treatment on diabetes-evoked oxidative stress-related pathophysiology in vivo. Similar analyses were performed with difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. After catalase transduction, high glucose-induced peroxide production was significantly lowered in both human retinal cell lines. In diabetic mice in vivo, subnormal intraretinal uptake of manganese was significantly improved by catalase supplementation. In addition, in the peroxisome-rich liver of treated mice catalase enzyme activity increased and oxidative damage (as measured by lipid peroxidation) declined. On the other hand, DFMO was largely without effect in these in vitro or in vivo assays. This proof-of-concept study raises the possibility that augmentation of catalase is a therapy for treating the retinal oxidative stress associated with diabetic retinopathy.

  11. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  12. Ageing-Associated Oxidative Stress and Inflammation Are Alleviated by Products from Grapes

    Directory of Open Access Journals (Sweden)

    K. S. Petersen

    2016-01-01

    Full Text Available Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, as well as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the ever-increasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation.

  13. Role of enzymatic free radical scavengers in management of oxidative stress in autoimmune disorders.

    Science.gov (United States)

    Srivastava, Shikha; Singh, Deependra; Patel, Satish; Singh, Manju R

    2017-08-01

    Autoimmune disorders are distinct with over production and accumulation of free radicals due to its undisclosed genesis. The cause of numerous disorders as cancer, arthritis, psoriasis, diabetes, alzheimer's, cardiovascular disease, Parkinson's, respiratory distress syndrome, colitis, crohn's, pulmonary fibrosis, obesity and ageing have been associated with immune dysfunction and oxidative stress. In an oxidative stress, reactive oxygen species generally provoke the series of oxidation at cellular level. The buildup of free radicals in turn triggers various inflammatory cells causing release of various inflammatory interleukins, cytokines, chemokines, and tumor necrosis factors which mediate signal transduction and transcription pathways as nuclear factor- kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1 (HIF-1α) and nuclear factor-erythroid 2-related factor (Nrf2). The imbalance could only be combat by supplementing natural defensive antioxidant enzymes such as superoxide dismutase and catalase. The efficiency of these enzymes is enhanced by use of colloidal carriers which include cellular carriers, vesicular and particulate systems like erythrocytes, leukocytes, platelets, liposomes, transferosomes, solid lipid nanoparticles, microspheres, emulsions. Thus this review provides a platform for understanding importance of antioxidant enzymes and its therapeutic applications in treatment of various autoimmune disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Mitochondrial enzymes and endoplasmic reticulum calcium stores as targets of oxidative stress in neurodegenerative diseases.

    Science.gov (United States)

    Gibson, Gary E; Huang, Hsueh-Meei

    2004-08-01

    Considerable evidence indicates that oxidative stress accompanies age-related neurodegenerative diseases. Specific mechanisms by which oxidative stress leads to neurodegeneration are unknown. Two targets of oxidative stress that are known to change in neurodegenerative diseases are the mitochondrial enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC) and endoplasmic reticulum calcium stores. KGDHC activities are diminished in all common neurodegenerative diseases and the changes are particularly well documented in Alzheimer's disease (AD). A second change that occurs in cells from AD patients is an exaggerated endoplasmic reticulum calcium store [i.e., bombesin-releasable calcium stores (BRCS)]. H(2)O(2), a general oxidant, changes both variables in the same direction as occurs in disease. Other oxidants selectively alter these variables. Various antioxidants were used to help define the critical oxidant species that modifies these responses. All of the antioxidants diminish the oxidant-induced carboxy-dichlorofluorescein (cDCF) detectable reactive oxygen species (ROS), but have diverse actions on these cellular processes. For example, alpha-keto-beta-methyl-n-valeric acid (KMV) diminishes the H(2)O(2) effects on BRCS, while trolox and DMSO exaggerate the response. Acute trolox treatment does not alter H(2)O(2)-induced changes in KGDHC, whereas chronic treatment with trolox increases KGDHC almost threefold. The results suggest that KGDHC and BRCS provide targets by which oxidative stress may induce neurodegeneration and a useful tool for selecting antioxidants for reversing age-related neurodegeneration.

  15. Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Saquib, Quaiser [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Attia, Sabry M. [Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh (Saudi Arabia); Siddiqui, Maqsood A. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Aboul-Soud, Mourad A.M. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Biochemistry Department, Faculty of Agriculture, Cairo University, 12613 Giza (Egypt); Al-Khedhairy, Abdulaziz A. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Giesy, John P. [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Biomedical and Veterinary Biosciences and Toxicology Centre, University of Saskatchewan, Saskatoon, Canada S7N 5B3 (Canada); Zoology Department and Center for Integrative Toxicology, Michigan State University, East Lansing 48824 (United States); Musarrat, Javed, E-mail: musarratj1@yahoo.com [Department of Zoology, College of Science, King Saud University, Riyadh (Saudi Arabia); Department of Microbiology, Faculty of Agricultural Sciences, AMU, Aligarh (India)

    2012-02-15

    Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G{sub 2}/M arrest and appearance of a distinctive SubG{sub 1} peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced

  16. Phorate-induced oxidative stress, DNA damage and transcriptional activation of p53 and caspase genes in male Wistar rats

    International Nuclear Information System (INIS)

    Saquib, Quaiser; Attia, Sabry M.; Siddiqui, Maqsood A.; Aboul-Soud, Mourad A.M.; Al-Khedhairy, Abdulaziz A.; Giesy, John P.; Musarrat, Javed

    2012-01-01

    Male Wistar rats exposed to a systemic organophosphorus insecticide, phorate [O,O-diethyl S-[(ethylthio) methyl] phosphorothioate] at varying oral doses of 0.046, 0.092 or 0.184 mg phorate/kg bw for 14 days, exhibited substantial oxidative stress, cellular DNA damage and activation of apoptosis-related p53, caspase 3 and 9 genes. The histopathological changes including the pyknotic nuclei, inflammatory leukocyte infiltrations, renal necrosis, and cardiac myofiber degeneration were observed in the liver, kidney and heart tissues. Biochemical analysis of catalase and glutathione revealed significantly lesser activities of antioxidative enzymes and lipid peroxidation in tissues of phorate exposed rats. Furthermore, generation of intracellular reactive oxygen species and reduced mitochondrial membrane potential in bone marrow cells confirmed phorate-induced oxidative stress. Significant DNA damage was measured through comet assay in terms of the Olive tail moment in bone marrow cells of treated animals as compared to control. Cell cycle analysis also demonstrated the G 2 /M arrest and appearance of a distinctive SubG 1 peak, which signified induction of apoptosis. Up-regulation of tumor suppressor p53 and caspase 3 and 9 genes, determined by quantitative real-time PCR and enzyme-linked immunosorbent assay, elucidated the activation of intrinsic apoptotic pathways in response to cellular stress. Overall, the results suggest that phorate induces genetic alterations and cellular toxicity, which can adversely affect the normal cellular functioning in rats. -- Highlights: ► This is the first report on molecular toxicity of phorate in an in vivo test system. ► Phorate induces biochemical and histological changes in liver, kidney and heart. ► Rats treated with phorate exhibited DNA damage in bone marrow cells. ► Phorate induces apoptosis, oxidative stress and alters mitochondrial fluorescence. ► Phorate induces transcriptional changes and enhanced activities of

  17. Assessment of cellular responses to oxidative stress using MCF-7 breast cancer cells, black seed (N. Sativa L.) extracts and H2O2.

    Science.gov (United States)

    Farah, Ibrahim O

    2005-12-01

    Black seed (N. Sativa L) is an oriental spice of the family Ranunculaceae that has long been rationally used as a natural medicine for treatment of many acute as well as chronic conditions including cardiovascular disease and immunological disorders. It has been used in the treatment of diabetes, hypertension, and dermatological conditions. There have been very few studies on the effects of N. Sativa as a chemoprevention of chronic diseases as well as in cancer prevention and/or therapy. Oxidative stress is a condition that underlies many acute as well as chronic conditions. The combination and role of oxidative stress and antioxidants in vivo is still a matter of conjecture. Our objective for the present study was to expose MCF-7 breast cancer cells in vitro (as a chronic disease example) to aqueous and alcohol extracts and in combination with H[2]O[2] as an oxidative stressor. Measurement of cell survival under various concentrations and mixtures was conducted using standard cell culture techniques, exposure protocols in 96 well plates and Fluorospectrosphotometry. Following cellular growth to 90% confluencey, exposure to water (WE) and ethanol (AE) extracts of N. sativa and H[2]O[2] was performed. Cell survival indices were calculated from percent survival using regression analysis. Results showed that the alcohol extract and its mixtures were able to influence the survival of MCF-7 cells (indices ranged from 357.15- 809.50 mug/ml in descending potency for H[2]O[2]+AE to the mix of 3). In contrast, H[2]O[2] alone reduced effectively the survival of MCF-7 cells and the least effective combinations in descending potency were AE+H[2]O[2], WE+H[2]O[2], AE+WE, and WE+AE+H[2]O[2]. Mixtures other than AE+H[2]O[2] showed possible interactions and loss of potency. In conclusion, N. Sativa alone or in combination with oxidative stress was found to be effective (in vitro) in influencing the survival of MCF-7 breast cancer cells, unveiling promising opportunities in the

  18. Assessment of Cellular Responses to Oxidative Stress using MCF-7 Breast Cancer Cells, Black Seed (N. Sativa L. Extracts and H2O2

    Directory of Open Access Journals (Sweden)

    Ibrahim O. Farah

    2005-12-01

    Full Text Available Black seed (N. Sativa L is an oriental spice of the family Ranunculaceae that has long been rationally used as a natural medicine for treatment of many acute as well as chronic conditions including cardiovascular disease and immunological disorders. It has been used in the treatment of diabetes, hypertension, and dermatological conditions. There have been very few studies on the effects of N. Sativa as a chemoprevention of chronic diseases as well as in cancer prevention and/or therapy. Oxidative stress is a condition that underlies many acute as well as chronic conditions. The combination and role of oxidative stress and antioxidants in vivo is still a matter of conjecture. Our objective for the present study was to expose MCF-7 breast cancer cells in vitro (as a chronic disease example to aqueous and alcohol extracts and in combination with H2O2 as an oxidative stressor. Measurement of cell survival under various concentrations and mixtures was conducted using standard cell culture techniques, exposure protocols in 96 well plates and Fluorospectrosphotometry. Following cellular growth to 90% confluencey, exposure to water (WE and ethanol (AE extracts of N. sativa and H2O2 was performed. Cell survival indices were calculated from percent survival using regression analysis. Results showed that the alcohol extract and its mixtures were able to influence the survival of MCF-7 cells (indices ranged from 357.15- 809.50 Bg/ml in descending potency for H2O2+AE to the mix of 3. In contrast, H2O2 alone reduced effectively the survival of MCF-7 cells and the least effective combinations in descending potency were AE+H2O2, WE+H2O2, AE+WE, and WE+AE+H2O2. Mixtures other than AE+H2O2 showed possible interactions and loss of potency. In conclusion, N. Sativa alone or in combination with oxidative stress was found to be effective (in vitro in influencing the survival of MCF-7 breast cancer cells, unveiling promising opportunities in the field of cancer

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  20. Involvement of oxygen reactive species in the cellular response of carcinoma cells to irradiation

    International Nuclear Information System (INIS)

    Tulard, A.

    2004-06-01

    After a presentation of oxygen reactive species and their sources, the author describes the enzymatic and non-enzymatic anti-oxidative defenses, the physiological roles of oxygen reactive species, the oxidative stress, the water radiolysis, the anti-oxidative enzymes and the effects of ionizing radiations. The author then reports an investigation on the contribution of oxygen reactive species in the cellular response to irradiation, and an investigation on the influence of the breathing chain on the persistence of a radio-induced oxidative stress. He also reports a research on molecular mechanisms involved in the cellular radio-sensitivity

  1. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress

    Science.gov (United States)

    Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S.

    2016-01-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  2. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Therese Wilhelm

    2016-05-01

    Full Text Available Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es. Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3% rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing, and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and

  3. Slow Replication Fork Velocity of Homologous Recombination-Defective Cells Results from Endogenous Oxidative Stress.

    Science.gov (United States)

    Wilhelm, Therese; Ragu, Sandrine; Magdalou, Indiana; Machon, Christelle; Dardillac, Elodie; Técher, Hervé; Guitton, Jérôme; Debatisse, Michelle; Lopez, Bernard S

    2016-05-01

    Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects in homologous recombination reveal the initial endogenous stress(es). Homologous recombination-defective cells consistently exhibit a spontaneously reduced replication speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as a major endogenous source of replication speed deceleration in homologous recombination-defective cells. The treatment of homologous recombination-defective cells with the antioxidant N-acetyl-cysteine or the maintenance of the cells at low O2 levels (3%) rescues both the replication fork speed, as monitored by single-molecule analysis (molecular combing), and the associated mitotic extra centrosome frequency. Reciprocally, the exposure of wild-type cells to H2O2 reduces the replication fork speed and generates mitotic extra centrosomes. Supplying deoxynucleotide precursors to H2O2-exposed cells rescued the replication speed. Remarkably, treatment with N-acetyl-cysteine strongly expanded the nucleotide pool, accounting for the replication speed rescue. Remarkably, homologous recombination-defective cells exhibit a high level of endogenous reactive oxygen species. Consistently, homologous recombination-defective cells accumulate spontaneous γH2AX or XRCC1 foci that are abolished by treatment with N-acetyl-cysteine or maintenance at 3% O2. Finally, oxidative stress stimulated homologous recombination, which is suppressed by supplying deoxynucleotide precursors. Therefore, the cellular redox status strongly impacts genome duplication and transmission. Oxidative stress should generate replication stress through different mechanisms, including DNA damage and nucleotide pool imbalance. These data highlight the intricacy of endogenous replication and oxidative stresses, which are both evoked during tumorigenesis and senescence initiation

  4. Manganese scavenging and oxidative stress response mediated by type VI secretion system in Burkholderia thailandensis.

    Science.gov (United States)

    Si, Meiru; Zhao, Chao; Burkinshaw, Brianne; Zhang, Bing; Wei, Dawei; Wang, Yao; Dong, Tao G; Shen, Xihui

    2017-03-14

    Type VI secretion system (T6SS) is a versatile protein export machinery widely distributed in Gram-negative bacteria. Known to translocate protein substrates to eukaryotic and prokaryotic target cells to cause cellular damage, the T6SS has been primarily recognized as a contact-dependent bacterial weapon for microbe-host and microbial interspecies competition. Here we report contact-independent functions of the T6SS for metal acquisition, bacteria competition, and resistance to oxidative stress. We demonstrate that the T6SS-4 in Burkholderia thailandensis is critical for survival under oxidative stress and is regulated by OxyR, a conserved oxidative stress regulator. The T6SS-4 is important for intracellular accumulation of manganese (Mn 2+ ) under oxidative stress. Next, we identified a T6SS-4-dependent Mn 2+ -binding effector TseM, and its interacting partner MnoT, a Mn 2+ -specific TonB-dependent outer membrane transporter. Similar to the T6SS-4 genes, expression of mnoT is regulated by OxyR and is induced under oxidative stress and low Mn 2+ conditions. Both TseM and MnoT are required for efficient uptake of Mn 2+ across the outer membrane under Mn 2+ -limited and -oxidative stress conditions. The TseM-MnoT-mediated active Mn 2+ transport system is also involved in contact-independent bacteria-bacteria competition and bacterial virulence. This finding provides a perspective for understanding the mechanisms of metal ion uptake and the roles of T6SS in bacteria-bacteria competition.

  5. Biomarkers of oxidative stress and DNA damage in agricultural workers: A pilot study

    International Nuclear Information System (INIS)

    Muniz, Juan F.; McCauley, Linda; Scherer, J.; Lasarev, M.; Koshy, M.; Kow, Y.W.; Nazar-Stewart, Valle; Kisby, G.E.

    2008-01-01

    Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers and applicators (p < 0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects

  6. Nutrients and Oxidative Stress: Friend or Foe?

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    Bee Ling Tan

    2018-01-01

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

  7. Nutrients and Oxidative Stress: Friend or Foe?

    Science.gov (United States)

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

    2018-01-01

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

  8. Impact of oxidative stress on exercising skeletal muscle.

    Science.gov (United States)

    Steinbacher, Peter; Eckl, Peter

    2015-04-10

    It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

  9. Nutrigenetics and modulation of oxidative stress.

    Science.gov (United States)

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

    2012-01-01

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

  10. The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications.

    Science.gov (United States)

    Hu, Jianmin; Li, Hongde; Luo, Xiangjian; Li, Yueshuo; Bode, Ann; Cao, Ya

    2017-11-01

    Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a "double-edged sword" to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers. © 2017 UICC.

  11. Radiation oxidative stress in cancer induction and prevention

    International Nuclear Information System (INIS)

    Meher, Prabodha Kumar; Mishra, Kaushala Prasad

    2017-01-01

    Exposure of cells to ionizing radiation causes generation of intracellular reactive oxygen species (ROS) which are implicated in the mechanism of carcinogenesis. Molecular steps involved in the transformation of normal cells to cancer cells have been enigmatic but generally believed to arise from aberration in cellular redox homeostasis. In normal cell function, a delicate balance is maintained between ROS generated in the metabolic process and level of endogenous antioxidant defense. ROS are known to regulate various cellular functions, such as cell division, signal transduction, and apoptosis. Cells experience oxidative stress when excess production of ROS occurs inside a cell upon exposure to external stress or agents. This redox imbalance affects the cellular functions due to DNA strand breaks, chromosomal aberrations, gene mutations, alteration in signal transduction, and inhibition of apoptosis leading to induction of cancer and other diseases. Radiation-induced ROS are involved in initiation and promotion of carcinogenesis. Therefore, detoxification of ROS by exogenous antioxidants including dietary polyphenols offers an important strategy for cancer prevention. Recent research results have shown that resistance of cancer stem cells to therapies is linked to low level of ROS. Interestingly, in vitro and in vivo experiments have reported that radiotherapy- and chemotherapy-induced ROS in cytosol sensitize the tumor cells to death, resulting in tumor growth retardation. This review is an attempt to delineate mechanisms of ROS in carcinogenesis and prevention by dietary compounds. Natural polyphenols and dietary antioxidants hold potential to prevent cancer. Interventions in ROS-mediated signal alteration, apoptosis activation, and modulation of epigenetic processes may offer effective cancer prevention strategy. (author)

  12. The impact of peroxisomes on cellular aging and death

    NARCIS (Netherlands)

    Manivannan, Selvambigai; Scheckhuber, Christian Quintus; Veenhuis, Marten; Klei, Ida Johanna van der

    2012-01-01

    Peroxisomes are ubiquitous eukaryotic organelles, which perform a plethora of functions including hydrogen peroxide metabolism and β-oxidation of fatty acids. Reactive oxygen species produced by peroxisomes are a major contributing factor to cellular oxidative stress, which is supposed to

  13. Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death

    Directory of Open Access Journals (Sweden)

    Puja Khanna

    2015-06-01

    Full Text Available Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Both in vivo and in vitro studies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-α and IL (interleukins-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-κB signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticles in vivo. In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle- induced oxidative stress and propose possible strategies to circumvent nanotoxicity.

  14. Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death.

    Science.gov (United States)

    Khanna, Puja; Ong, Cynthia; Bay, Boon Huat; Baeg, Gyeong Hun

    2015-06-30

    Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Both in vivo and in vitro studies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS) levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-α and IL (interleukins)-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-κB) signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticles in vivo . In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle- induced oxidative stress and propose possible strategies to circumvent nanotoxicity.

  15. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Xiaochun Duan

    2016-01-01

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

  16. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Science.gov (United States)

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

    2016-01-01

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

  17. Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis.

    Directory of Open Access Journals (Sweden)

    Mahua G Choudhury

    in significant increase of NO efflux accompanied with decrease of hydration status/cell volume of hepatic cells. However, the reasons for these cell volume-sensitive changes of NO efflux from the liver of singhi catfish are not fully understood with the available data. Nonetheless, enhanced or decreased production of NO from the perfused liver under osmotic stress, in presence of stress hormones and oxidative stress reflected its potential role in cellular homeostasis and also for better adaptations under environmental challenges. This is the first report of osmosensitive and oxidative stress-induced changes of NO production and efflux from the liver of any teleosts. Further, the level of expression of iNOS in this singhi catfish could also serve as an important indicator to determine the pathological status of the external environment.

  18. A STUDY OF OXIDATIVE STRESS IN DIABETES

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    Babu Rao

    2015-06-01

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

  19. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro.

    Science.gov (United States)

    Wang, Xu; Wu, Qinghua; Liu, Aimei; Anadón, Arturo; Rodríguez, José-Luis; Martínez-Larrañaga, María-Rosa; Yuan, Zonghui; Martínez, María-Aránzazu

    2017-11-01

    Paracetamol (APAP) is one of the most widely used and popular over-the-counter analgesic and antipyretic drugs in the world when used at therapeutic doses. APAP overdose can cause severe liver injury, liver necrosis and kidney damage in human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with APAP, and various antioxidants were evaluated to investigate their protective roles against APAP-induced liver and kidney toxicities. To date, almost no review has addressed the APAP toxicity in relation to oxidative stress. This review updates the research conducted over the past decades into the production of reactive oxygen species (ROS), reactive nitrogen species (RNS), and oxidative stress as a result of APAP treatments, and ultimately their correlation with the toxicity and metabolism of APAP. The metabolism of APAP involves various CYP450 enzymes, through which oxidative stress might occur, and such metabolic factors are reviewed within. The therapeutics of a variety of compounds against APAP-induced organ damage based on their anti-oxidative effects is also discussed, in order to further understand the role of oxidative stress in APAP-induced toxicity. This review will throw new light on the critical roles of oxidative stress in APAP-induced toxicity, as well as on the contradictions and blind spots that still exist in the understanding of APAP toxicity, the cellular effects in terms of organ injury and cell signaling pathways, and finally strategies to help remedy such against oxidative damage.

  20. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    International Nuclear Information System (INIS)

    Mercado, Nicolas; Thimmulappa, Rajesh; Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E.; Biswal, Shyam; Ito, Kazuhiro; Barnes, Peter J.

    2011-01-01

    Research highlights: → Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. → HDAC inhibition decreases Nrf2 protein stability. → HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. → HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H 2 O 2 ) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H 2 O 2 -induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  1. Decreased histone deacetylase 2 impairs Nrf2 activation by oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mercado, Nicolas [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Thimmulappa, Rajesh [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Thomas, Catherine M.R.; Fenwick, Peter S.; Chana, Kirandeep K.; Donnelly, Louise E. [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Biswal, Shyam [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (United States); Ito, Kazuhiro [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom); Barnes, Peter J., E-mail: p.j.barnes@imperial.ac.uk [Airway Disease Section, National Heart and Lung Institute, Imperial College, London SW3 6LY (United Kingdom)

    2011-03-11

    Research highlights: {yields} Nrf2 anti-oxidant function is impaired when HDAC activity is inhibited. {yields} HDAC inhibition decreases Nrf2 protein stability. {yields} HDAC2 is involved in reduced Nrf2 stability and both correlate in COPD samples. {yields} HDAC inhibition increases Nrf2 acetylation. -- Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in cellular defence against oxidative stress by inducing the expression of multiple anti-oxidant genes. However, where high levels of oxidative stress are observed, such as chronic obstructive pulmonary disease (COPD), Nrf2 activity is reduced, although the molecular mechanism for this defect is uncertain. Here, we show that down-regulation of histone deacetylase (HDAC) 2 causes Nrf2 instability, resulting in reduced anti-oxidant gene expression and increase sensitivity to oxidative stress. Although Nrf2 protein was clearly stabilized after hydrogen peroxide (H{sub 2}O{sub 2}) stimulation in a bronchial epithelial cell line (BEAS2B), Nrf2 stability was decreased and Nrf2 acetylation increased in the presence of an HDAC inhibitor, trichostatin A (TSA). TSA also reduced Nrf2-regulated heme-oxygenase-1 (HO-1) expression in these cells, and this was confirmed in acute cigarette-smoke exposed mice in vivo. HDAC2 knock-down by RNA interference resulted in reduced H{sub 2}O{sub 2}-induced Nrf2 protein stability and activity in BEAS2B cells, whereas HDAC1 knockdown had no effect. Furthermore, monocyte-derived macrophages obtained from healthy volunteers (non-smokers and smokers) and COPD patients showed a significant correlation between HDAC2 expression and Nrf2 expression (r = 0.92, p < 0.0001). Thus, reduced HDAC2 activity in COPD may account for increased Nrf2 acetylation, reduced Nrf2 stability and impaired anti oxidant defences.

  2. Evasion of Apoptosis as a Cellular Stress Response in Cancer

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2010-01-01

    Full Text Available One of the hallmarks of human cancers is the intrinsic or acquired resistance to apoptosis. Evasion of apoptosis can be part of a cellular stress response to ensure the cell's survival upon exposure to stressful stimuli. Apoptosis resistance may contribute to carcinogenesis, tumor progression, and also treatment resistance, since most current anticancer therapies including chemotherapy as well as radio- and immunotherapies primarily act by activating cell death pathways including apoptosis in cancer cells. Hence, a better understanding of the molecular mechanisms regarding how cellular stress stimuli trigger antiapoptotic mechanisms and how this contributes to tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to overcome apoptosis resistance mechanisms in cancers.

  3. Toxicity and oxidative stress of canine mesenchymal stromal cells from adipose tissue in different culture passages

    Directory of Open Access Journals (Sweden)

    Arícia Gomes Sprada

    2015-12-01

    Full Text Available Abstract: Stem cells in regenerative therapy have received attention from researchers in recent decades. The culture of these cells allows studies about their behavior and metabolism. Thus, cell culture is the basis for cell therapy and tissue engineering researches. A major concern regarding the use of cultivated stem cell in human or veterinary clinical routine is the risk of carcinogenesis. Cellular activities require a balanced redox state. However, when there is an imbalance in this state, oxidative stress occurs. Oxidative stress contributes to cytotoxicity, which may result in cell death or genomic alterations, favoring the development of cancer cells. The aim of this study was to determine whether there are differences in the behavior of cultured mesenchymal stem cells from canine adipose tissue according to its site of collection (omentum and subcutaneous evaluating the rate of proliferation, viability, level of oxidative stress and cytotoxicity over six passages. For this experiment, two samples of adipose tissue from subcutaneous and omentum where taken from a female dog corpse, 13 years old, Pitbull. The results showed greater levels of oxidative stress in the first and last passages of both groups, favoring cytotoxicity and cell death.

  4. Is the Oxidative Stress Really a Disease?

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    Fogarasi Erzsébet

    2016-03-01

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

  5. Plumbagin, a vitamin K3 analogue, abrogates lipopolysaccharide-induced oxidative stress, inflammation and endotoxic shock via NF-κB suppression.

    Science.gov (United States)

    Checker, Rahul; Patwardhan, Raghavendra S; Sharma, Deepak; Menon, Jisha; Thoh, Maikho; Sandur, Santosh K; Sainis, Krishna B; Poduval, T B

    2014-04-01

    Plumbagin has been reported to modulate cellular redox status and suppress NF-κB. In the present study, we investigated the effect of plumbagin on lipopolysaccharide (LPS)-induced endotoxic shock, oxidative stress and inflammatory parameters in vitro and in vivo. Plumbagin inhibited LPS-induced nitric oxide, TNF-α, IL-6 and prostaglandin-E2 production in a concentration-dependent manner in RAW 264.7 cells without inducing any cell death. Plumbagin modulated cellular redox status in RAW cells. Plumbagin treatment significantly reduced MAPkinase and NF-κB activation in macrophages. Plumbagin prevented mice from endotoxic shock-associated mortality and decreased serum levels of pro-inflammatory markers. Plumbagin administration ameliorated LPS-induced oxidative stress in peritoneal macrophages and splenocytes. Plumbagin also attenuated endotoxic shock-associated changes in liver and lung histopathology and decreased the activation of ERK and NF-κB in liver. These findings demonstrate the efficacy of plumbagin in preventing LPS-induced endotoxemia and also provide mechanistic insights into the anti-inflammatory effects of plumbagin.

  6. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  7. Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Woo, Kyoungja; Moon, Jihyung; Choi, Kyu-Sil; Seong, Tae-Yeon; Yoon, Kwon-Ha

    2009-01-01

    We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F 5 -Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F 5 -LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.

  8. Growth Inhibition of Osteosarcoma Cell Lines in 3D Cultures: Role of Nitrosative and Oxidative Stress.

    Science.gov (United States)

    Gorska, Magdalena; Krzywiec, Pawel Bieniasz; Kuban-Jankowska, Alicja; Zmijewski, Michal; Wozniak, Michal; Wierzbicka, Justyna; Piotrowska, Anna; Siwicka, Karolina

    2016-01-01

    3D cell cultures have revolutionized the understanding of cell behavior, allowing culture of cells with the possibility of resembling in vivo intercellular signaling and cell-extracellular matrix interaction. The effect of limited oxygen penetration into 3D culture of highly metastatic osteosarcoma 143B cells in terms of expression of nitro-oxidative stress markers was investigated and compared to standard 2D cell culture. Human osteosarcoma (143B cell line) cells were cultured as monolayers, in collagen and Matrigel. Cell viability, gene expression of nitro-oxidative stress markers, and vascular endothelial growth factor were determined using Trypan blue assay, quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Three-dimensional environments modify nitro-oxidative stress and influence gene expression and cell proliferation of OS 143B cells. Commercial cell lines might not constitute a good model of 3D cultures for bone tissue engineering, as they are highly sensitive to hypoxia, and hypoxic conditions can induce oxidation of the cellular environment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  9. Hepatoprotective properties of kombucha tea against TBHP-induced oxidative stress via suppression of mitochondria dependent apoptosis.

    Science.gov (United States)

    Bhattacharya, Semantee; Gachhui, Ratan; Sil, Parames C

    2011-06-01

    Kombucha, a fermented tea (KT) is claimed to possess many beneficial properties. Recent studies have suggested that KT prevents paracetamol and carbon tetrachloride-induced hepatotoxicity. We investigated the beneficial role of KT was against tertiary butyl hydroperoxide (TBHP) induced cytotoxicity and cell death in murine hepatocytes. TBHP is a well known reactive oxygen species (ROS) inducer, and it induces oxidative stress in organ pathophysiology. In our experiments, TBHP caused a reduction in cell viability, enhanced the membrane leakage and disturbed the intra-cellular antioxidant machineries while simultaneous treatment of the cells with KT and this ROS inducer maintained membrane integrity and prevented the alterations in the cellular antioxidant status. These findings led us to explore the detailed molecular mechanisms involved in the protective effect of KT. TBHP introduced apoptosis as the primary phenomena of cell death as evidenced by flow cytometric analyses. In addition, ROS generation, changes in the mitochondrial membrane potential, cytochrome c release, activation of caspases (3 and 9) and Apaf-1 were detected confirming involvement of mitochondrial pathway in this pathophysiology. Simultaneous treatment of KT with TBHP, on the other hand, protected the cells against oxidative injury and maintained their normal physiology. In conclusion, KT was found to modulate the oxidative stress induced apoptosis in murine hepatocytes probably due to its antioxidant activity and functioning via mitochondria dependent pathways and could be beneficial against liver diseases, where oxidative stress is known to play a crucial role. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Antioxidant effect of melanoidins after induction of oxidative stress in isolated rat hepatocytes

    OpenAIRE

    Torres Rodríguez, Mª Carmen; Codoñer Franch, Pilar; Muñiz, Pilar; González, Maria Luisa; Boix, Laura; Valls Bellés, Victoria

    2002-01-01

    Se estudia el efecto de las melanoidinas en el estrés oxidativo inducido por adriamicina en hepatocitos aislados de rata. Las melanoidinas presentan un efecto protector, incrementando la viabilidad celular y protegiendo a los lípidos y a las proteínas del estrés oxidativo Melanoidins have a protective effect over macromolecules. They increase cellular viability and protect lipids and proteins from oxidative stress

  11. Oxidative Stress in Aging: Advances in Proteomic Approaches

    Directory of Open Access Journals (Sweden)

    Daniel Ortuño-Sahagún

    2014-01-01

    Full Text Available Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL. Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS], which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8, naked mole-rat (Heterocephalus glaber, and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS and oxidative stress in aging.

  12. The role of oxidative stress in the ochratoxin A-mediated toxicity in proximal tubular cells.

    Science.gov (United States)

    Schaaf, G J; Nijmeijer, S M; Maas, R F M; Roestenberg, P; de Groene, E M; Fink-Gremmels, J

    2002-11-20

    Balkan endemic nephropathy (BEN), a disease characterized by progressive renal fibrosis in human patients, has been associated with exposure to ochratoxin A (OTA). This mycotoxin is a frequent contaminant of human and animal food products, and is toxic to all animal species tested. OTA predominantly affects the kidney and is known to accumulate in the proximal tubule (PT). The induction of oxidative stress is implicated in the toxicity of this mycotoxin. In the present study, primary rat PT cells and LLC-PK(1) cells, which express characteristics of the PT, were used to investigate the OTA-mediated oxidative stress response. OTA exposure of these cells resulted in a concentration-dependent elevation of reactive oxygen species (ROS) levels, depletion of cellular glutathione (GSH) levels and an increase in the formation of 8-oxoguanine. The OTA-induced ROS response was significantly reduced following treatment with alpha-tocopherol (TOCO). However, this chain-braking anti-oxidant did not reduce the cytotoxicity of OTA and was unable to prevent the depletion of total GSH levels in OTA-exposed cells. In contrast, pre-incubation of the cell with N-acetyl-L-cysteine (NAC) completely prevented the OTA-induced increase in ROS levels as well as the formation of 8-oxoguanine and completely protected against the cytotoxicity of OTA. In addition, NAC treatment also limited the GSH depletion in OTA-exposed PT- and LLC-PK(1) cells. From these data, we conclude that oxidative stress contributes to the tubular toxicity of OTA. Subsequently, cellular GSH levels play a pivotal role in limiting the short-term toxicity of this mycotoxin in renal tubular cells.

  13. Chlorpyrifos induces oxidative stress in oligodendrocyte progenitor cells

    International Nuclear Information System (INIS)

    Saulsbury, Marilyn D.; Heyliger, Simone O.; Wang, Kaiyu; Johnson, Deadre J.

    2009-01-01

    There are increasing concerns regarding the relative safety of chlorpyrifos (CPF) to various facets of the environment. Although published works suggest that CPF is relatively safe in adult animals, recent evidence indicates that juveniles, both animals and humans, may be more sensitive to CPF toxicity than adults. In young animals, CPF is neurotoxic and mechanistically interferes with cellular replication and cellular differentiation, which culminates in the alteration of synaptic neurotransmission in neurons. However, the effects of CPF on glial cells are not fully elucidated. Here we report that chlorpyrifos is toxic to oligodendrocyte progenitors. In addition, CPF produced dose-dependent increases in 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCF-DA) and dihydroethidium (DHE) fluorescence intensities relative to the vehicle control. Moreover, CPF toxicity is associated with nuclear condensation and elevation of caspase 3/7 activity and Heme oxygenase-1 mRNA expression. Pan-caspase inhibitor QVDOPh and cholinergic receptor antagonists' atropine and mecamylamine failed to protect oligodendrocyte progenitors from CPF-induced injury. Finally, glutathione (GSH) depletion enhanced CPF-induced toxicity whereas nitric oxide synthetase inhibitor L-NAME partially protected progenitors and the non-specific antioxidant vitamin E (alpha-tocopherol) completely spared cells from injury. Collectively, this data suggests that CPF induced toxicity is independent of cholinergic stimulation and is most likely caused by the induction of oxidative stress.

  14. Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells*

    Science.gov (United States)

    Yogalingam, Gouri; Lee, Amanda R.; Mackenzie, Donald S.; Maures, Travis J.; Rafalko, Agnes; Prill, Heather; Berguig, Geoffrey Y.; Hague, Chuck; Christianson, Terri; Bell, Sean M.; LeBowitz, Jonathan H.

    2017-01-01

    Neutrophil myeloperoxidase (MPO) catalyzes the H2O2-dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N-retinylidene-N-retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N-retinylidene-N-retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death. PMID:28115520

  15. Cellular Uptake and Delivery of Myeloperoxidase to Lysosomes Promote Lipofuscin Degradation and Lysosomal Stress in Retinal Cells.

    Science.gov (United States)

    Yogalingam, Gouri; Lee, Amanda R; Mackenzie, Donald S; Maures, Travis J; Rafalko, Agnes; Prill, Heather; Berguig, Geoffrey Y; Hague, Chuck; Christianson, Terri; Bell, Sean M; LeBowitz, Jonathan H

    2017-03-10

    Neutrophil myeloperoxidase (MPO) catalyzes the H 2 O 2 -dependent oxidation of chloride anion to generate hypochlorous acid, a potent antimicrobial agent. Besides its well defined role in innate immunity, aberrant degranulation of neutrophils in several inflammatory diseases leads to redistribution of MPO to the extracellular space, where it can mediate tissue damage by promoting the oxidation of several additional substrates. Here, we demonstrate that mannose 6-phosphate receptor-mediated cellular uptake and delivery of MPO to lysosomes of retinal pigmented epithelial (RPE) cells acts to clear this harmful enzyme from the extracellular space, with lysosomal-delivered MPO exhibiting a half-life of 10 h. Lysosomal-targeted MPO exerts both cell-protective and cytotoxic functions. From a therapeutic standpoint, MPO catalyzes the in vitro degradation of N -retinylidene- N -retinylethanolamine, a toxic form of retinal lipofuscin that accumulates in RPE lysosomes and drives the pathogenesis of Stargardt macular degeneration. Furthermore, chronic cellular uptake and accumulation of MPO in lysosomes coincides with N -retinylidene- N -retinylethanolamine elimination in a cell-based model of macular degeneration. However, lysosomal-delivered MPO also disrupts lysosomal acidification in RPE cells, which coincides with nuclear translocation of the lysosomal stress-sensing transcription factor EB and, eventually, cell death. Based on these findings we predict that under periods of acute exposure, cellular uptake and lysosomal degradation of MPO mediates elimination of this harmful enzyme, whereas chronic exposure results in progressive accumulation of MPO in lysosomes. Lysosomal-accumulated MPO can be both cell-protective, by promoting the degradation of toxic retinal lipofuscin deposits, and cytotoxic, by triggering lysosomal stress and cell death. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Wnt1 Neuroprotection Translates into Improved Neurological Function during Oxidant Stress and Cerebral Ischemia Through AKT1 and Mitochondrial Apoptotic Pathways

    Directory of Open Access Journals (Sweden)

    Zhao Zhong Chong

    2010-01-01

    Full Text Available Although essential for the development of the nervous system, Wnt1 also has been associated with neurodegenerative disease and cognitive loss during periods of oxidative stress. Here we show that endogenous expression of Wnt1 is suppressed during oxidative stress in both in vitro and in vivo experimental models. Loss of endogenous Wnt1 signaling directly correlates with neuronal demise and increased functional deficit, illustrating that endogenous neuronal Wnt1 offers a vital level of intrinsic cellular protection against oxidative stress. Furthermore, transient overexpression of Wnt1 or application of exogenous Wnt1 recombinant protein is necessary to preserve neurological function and rescue neurons from apoptotic membrane phosphatidylserine externalization and genomic DNA degradation, since blockade of Wnt1 signaling with a Wnt1 antibody or dickkopf related protein 1 abrogates neuronal protection by Wnt1. Wnt1 ultimately relies upon the activation of Akt1, the modulation of mitochondrial membrane permeability, and the release of cytochrome c to control the apoptotic cascade, since inhibition of Wnt1 signaling, the phosphatidylinositol 3-kinase pathway, or Akt1 activity abrogates the ability of Wnt1 to block these apoptotic components. Our work identifies Wnt1 and its downstream signaling as cellular targets with high clinical potential for novel treatment strategies for multiple disorders precipitated by oxidative stress.

  17. Induction of stress responses by polluting agents which dis-regulate cellular homeostasis

    International Nuclear Information System (INIS)

    Mothersill, Carmel

    2001-01-01

    There is growing concern both in the scientific community and among the general public about the effects of exposure to low levels of radiation and environmental chemicals. The increased incidence of cancer, reproduction disorders and allergies have been associated with ambient environmental exposure to these pollutants. The pollution burden is generally made up of a mixture of agents, occurring at concentrations of the individual compounds which are not considered harmful and which are below the action level. Individual pollutants can act through a variety of primary toxicity mechanisms. However the resulting secondary and tertiary toxicity mechanisms which affect cellular homeostasis might be more common. These resulting stress responses, including oxidative stress, have been associated with effects that include increased level of death during cell division, increased levels of mutation and increased tolerance of mutations in cell populations, increased levels of cytogenetic abnormalities and many other symptoms. These effects are linked to a persistent increase in (oxidative) stress and are particularly evident in the haematopoietic system (possibly due to the high rate self of renewal in that system). Therefore prolonged exposure to mixtures of chemicals and radiation might result in additive and synergistic stress responses which can induce long-term delayed effects, often in progeny or in cells not directly exposed to the agent/s. The existence of a common (oxidative) stress mechanism means that the effects of individual pollutants may not be considered in isolation. Rather the total pollution burden may need to be measured using a response rather than a dose based scoring or ranking system. Improved understanding of toxicity mechanisms and effects underpins improved risk assessment and identification of biomarkers. The immune system plays a pivotal role in maintaining health status, and disruption of immune functions can lead to increased susceptibility to

  18. Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

    Directory of Open Access Journals (Sweden)

    Mohammad T. Elnakish

    2015-01-01

    Full Text Available Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models.

  19. Oxidative Stress and Antioxidant System in Periodontitis

    Science.gov (United States)

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

    2017-01-01

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

  20. Linking Alzheimer's disease to insulin resistance: the FoxO response to oxidative stress.

    Science.gov (United States)

    Manolopoulos, K N; Klotz, L-O; Korsten, P; Bornstein, S R; Barthel, A

    2010-11-01

    Oxidative stress is an important determinant not only in the pathogenesis of Alzheimer's disease (AD), but also in insulin resistance (InsRes) and diabetic complications. Forkhead box class O (FoxO) transcription factors are involved in both insulin action and the cellular response to oxidative stress, thereby providing a potential integrative link between AD and InsRes. For example, the expression of intra- and extracellular antioxidant enzymes, such as manganese-superoxide dismutase and selenoprotein P, is regulated by FoxO proteins, as is the expression of important hepatic enzymes of gluconeogenesis. Here, we review the molecular mechanisms involved in the pathogenesis of AD and InsRes and discuss the function of FoxO proteins in these processes. Both InsRes and oxidative stress may promote the transcriptional activity of FoxO proteins, resulting in hyperglycaemia and a further increased production of reactive oxygen species (ROS). The consecutive activation of c-Jun N-terminal kinases and inhibition of Wingless (Wnt) signalling may result in the formation of β-amyloid plaques and τ protein phosphorylation. Wnt inhibition may also result in a sustained activation of FoxO proteins with induction of apoptosis and neuronal loss, thereby completing a vicious circle from oxidative stress, InsRes and hyperglycaemia back to the formation of ROS and consecutive neurodegeneration. In view of their central function in this model, FoxO proteins may provide a potential molecular target for the treatment of both InsRes and AD.

  1. Enantioselective oxidative stress and oxidative damage caused by Rac- and S-metolachlor to Scenedesmus obliquus.

    Science.gov (United States)

    Liu, Huijun; Xia, YiLu; Cai, Weidan; Zhang, Yina; Zhang, Xiaoqiang; Du, Shaoting

    2017-04-01

    The rational use and environmental security of chiral pesticides has gained the interest of many researchers. The enantioselective effects of Rac- and S-metolachlor on oxidative stress in Scenedesmus obliquus were determined in this study. Stronger green fluorescence was observed in response to S-metolachlor treatment than to Rac-metolachlor treatment, suggesting that more reactive oxygen species (ROS) were stimulated by S-metolachlor. ROS levels following S-metolachlor treatment were 1.92-, 8.31-, and 1.08-times higher than those observed following Rac-metolachlor treatment at 0.1, 0.2, and 0.3 mg/L, respectively. Superoxide dismutase (SOD) and catalase (CAT) were stimulated with increasing herbicide concentrations, with S-metolachlor exhibiting a greater effect. Oxidative damage in terms of chlorophyll (Chl) content, cellular membrane permeability, and cellular ultrastructures of S. obliquus were investigated. Chla and Chlb contents in algae treated with Rac-metolachlor were 2-6-fold higher than those in algae treated with S-metolachlor at 0.1, 0.2, and 0.3 mg/L. The cellular membrane permeability of algae exposed to 0.3 mg/L Rac- and S-metolachlor was 6.19- and 42.5-times that of the control. Correlation analysis implied that ROS are the major factor responsible for the oxidative damage caused by Rac- and S-metolachlor. Damage to the chloroplasts and cell membrane of S. obliquus, low production of starch granules, and an increased number of vacuoles were observed upon ultrastructural morphology analysis by transmission electron microscope. These results indicate that S-metolachlor has a greater effect on S. obliquus than Rac-metolachlor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Cellular packing, mechanical stress and the evolution of multicellularity

    Science.gov (United States)

    Jacobeen, Shane; Pentz, Jennifer T.; Graba, Elyes C.; Brandys, Colin G.; Ratcliff, William C.; Yunker, Peter J.

    2018-03-01

    The evolution of multicellularity set the stage for sustained increases in organismal complexity1-5. However, a fundamental aspect of this transition remains largely unknown: how do simple clusters of cells evolve increased size when confronted by forces capable of breaking intracellular bonds? Here we show that multicellular snowflake yeast clusters6-8 fracture due to crowding-induced mechanical stress. Over seven weeks ( 291 generations) of daily selection for large size, snowflake clusters evolve to increase their radius 1.7-fold by reducing the accumulation of internal stress. During this period, cells within the clusters evolve to be more elongated, concomitant with a decrease in the cellular volume fraction of the clusters. The associated increase in free space reduces the internal stress caused by cellular growth, thus delaying fracture and increasing cluster size. This work demonstrates how readily natural selection finds simple, physical solutions to spatial constraints that limit the evolution of group size—a fundamental step in the evolution of multicellularity.

  3. Plant Abiotic Stress Proteomics: The Major Factors Determining Alterations in Cellular Proteome

    Science.gov (United States)

    Kosová, Klára; Vítámvás, Pavel; Urban, Milan O.; Prášil, Ilja T.; Renaut, Jenny

    2018-01-01

    HIGHLIGHTS: Major environmental and genetic factors determining stress-related protein abundance are discussed.Major aspects of protein biological function including protein isoforms and PTMs, cellular localization and protein interactions are discussed.Functional diversity of protein isoforms and PTMs is discussed. Abiotic stresses reveal profound impacts on plant proteomes including alterations in protein relative abundance, cellular localization, post-transcriptional and post-translational modifications (PTMs), protein interactions with other protein partners, and, finally, protein biological functions. The main aim of the present review is to discuss the major factors determining stress-related protein accumulation and their final biological functions. A dynamics of stress response including stress acclimation to altered ambient conditions and recovery after the stress treatment is discussed. The results of proteomic studies aimed at a comparison of stress response in plant genotypes differing in stress adaptability reveal constitutively enhanced levels of several stress-related proteins (protective proteins, chaperones, ROS scavenging- and detoxification-related enzymes) in the tolerant genotypes with respect to the susceptible ones. Tolerant genotypes can efficiently adjust energy metabolism to enhanced needs during stress acclimation. Stress tolerance vs. stress susceptibility are relative terms which can reflect different stress-coping strategies depending on the given stress treatment. The role of differential protein isoforms and PTMs with respect to their biological functions in different physiological constraints (cellular compartments and interacting partners) is discussed. The importance of protein functional studies following high-throughput proteome analyses is presented in a broader context of plant biology. In summary, the manuscript tries to provide an overview of the major factors which have to be considered when interpreting data from proteomic

  4. Oxidative Stress in BPH.

    Science.gov (United States)

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

    2009-01-01

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

  5. Cellular Stress, Excessive Apoptosis, and the Effect of Metformin in a Mouse Model of Type 2 Diabetic Embryopathy

    Science.gov (United States)

    Wu, Yanqing; Wang, Fang; Fu, Mao; Wang, Cheng; Quon, Michael J.

    2015-01-01

    Increasing prevalence of type 2 diabetes in women of childbearing age has led to a higher incidence of diabetes-associated birth defects. We established a model of type 2 diabetic embryopathy by feeding 4-week-old female mice a high-fat diet (HFD) (60% fat). After 15 weeks on HFD, the mice showed characteristics of type 2 diabetes mellitus (DM) and were mated with lean male mice. During pregnancy, control dams fed a normal diet (10% fat) were maintained on either normal diet or HFD, serving as a control group with elevated circulating free fatty acids. DM dams produced offspring at a rate of 11.3% for neural tube defect (NTD) formation, whereas no embryos in the control groups developed NTDs. Elevated markers of oxidative stress, endoplasmic reticulum stress, caspase activation, and neuroepithelial cell apoptosis (causal events in type 1 diabetic embryopathy) were observed in embryos of DM dams. DM dams treated with 200 mg/kg metformin in drinking water ameliorated fasting hyperglycemia, glucose intolerance, and insulin resistance with consequent reduction of cellular stress, apoptosis, and NTDs in their embryos. We conclude that cellular stress and apoptosis occur and that metformin effectively reduces type 2 diabetic embryopathy in a useful rodent model. PMID:25720389

  6. Mitochondrial Dysfunction and Oxidative Stress in Asthma: Implications for Mitochondria-Targeted Antioxidant Therapeutics

    Directory of Open Access Journals (Sweden)

    P. Hemachandra Reddy

    2011-02-01

    Full Text Available Asthma is a complex, inflammatory disorder characterized by airflow obstruction of variable degrees, bronchial hyper-responsiveness, and airway inflammation. Asthma is caused by environmental factors and a combination of genetic and environmental stimuli. Genetic studies have revealed that multiple loci are involved in the etiology of asthma. Recent cellular, molecular, and animal-model studies have revealed several cellular events that are involved in the progression of asthma, including: increased Th2 cytokines leading to the recruitment of inflammatory cells to the airway, and an increase in the production of reactive oxygen species and mitochondrial dysfunction in the activated inflammatory cells, leading to tissue injury in the bronchial epithelium. Further, aging and animal model studies have revealed that mitochondrial dysfunction and oxidative stress are involved and play a large role in asthma. Recent studies using experimental allergic asthmatic mouse models and peripheral cells and tissues from asthmatic humans have revealed antioxidants as promising treatments for people with asthma. This article summarizes the latest research findings on the involvement of inflammatory changes, and mitochondrial dysfunction/oxidative stress in the development and progression of asthma. This article also addresses the relationship between aging and age-related immunity in triggering asthma, the antioxidant therapeutic strategies in treating people with asthma.

  7. Coordination of frontline defense mechanisms under severe oxidative stress.

    Science.gov (United States)

    Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.

  8. Global Transcriptional Responses to Osmotic, Oxidative, and Imipenem Stress Conditions in Pseudomonas putida

    DEFF Research Database (Denmark)

    Bojanovic, Klara; D'Arrigo, Isotta; Long, Katherine

    2017-01-01

    functional roles in the cellular response to stress conditions. The data show a larger fraction of differentially expressed sRNAs than of mRNAs with >5-fold expression changes. The work provides detailed insights into the mechanisms through which P. putida responds to different stress conditions...... intergenic and antisense transcripts, were detected, increasing the number of identified sRNA transcripts in the strain by a factor of 10. Unique responses to each type of stress are documented, including both the extent and dynamics of the gene expression changes. The work adds rich detail to previous......Bacteria cope with and adapt to stress by modulating gene expression in response to specific environmental cues. In this study, the transcriptional response of Pseudomonas putida KT2440 to osmotic, oxidative, and imipenem stress conditions at two time points was investigated via identification...

  9. Species as Stressors: Heterospecific Interactions and the Cellular Stress Response under Global Change.

    Science.gov (United States)

    Gunderson, Alex R; King, Emily E; Boyer, Kirsten; Tsukimura, Brian; Stillman, Jonathon H

    2017-07-01

    Anthropogenic global change is predicted to increase the physiological stress of organisms through changes in abiotic conditions such as temperature, pH, and pollution. However, organisms can also experience physiological stress through interactions with other species, especially parasites, predators, and competitors. The stress of species interactions could be an important driver of species' responses to global change as the composition of biological communities change through factors such as distributional and phenological shifts. Interactions between biotic and abiotic stressors could also induce non-linear physiological stress responses under global change. One of the primary means by which organisms deal with physiological stress is through the cellular stress response (CSR), which is broadly the upregulation of a conserved set of genes that facilitate the removal and repair of damaged macromolecules. Here, we present data on behavioral interactions and CSR gene expression for two competing species of intertidal zone porcelain crab (Petrolisthes cinctipes and Petrolisthes manimaculis). We found that P. cinctipes and P. manimaculis engage in more agonistic behaviors when interacting with heterospecifics than conspecifics; however, we found no evidence that heterospecific interactions induced a CSR in these species. In addition to our new data, we review the literature with respect to CSR induction via species interactions, focusing on predator-prey systems and heterospecific competition. We find extensive evidence for predators to induce cellular stress and aspects of the CSR in prey, even in the absence of direct physical contact between species. Effects of heterospecific competition on the CSR have been studied far less, but we do find evidence that agonistic interactions with heterospecifics can induce components of the CSR. Across all published studies, there is clear evidence that species interactions can lead to cellular stress and induction of the CSR

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

    NARCIS (Netherlands)

    D. Rook (Denise)

    2013-01-01

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

  11. Cellular uptake of folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Kyoungja [Nano-Materials Research Center, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of)], E-mail: kjwoo@kist.re.kr; Moon, Jihyung [Nano-Materials Research Center, Korea Institute of Science and Technology, P. O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Department of Materials Science and Engineering, Korea University, 5-1, Anam-Dong, Sungbook-Ku, Seoul, 136-713 (Korea, Republic of); Choi, Kyu-Sil [Division of Molecular Imaging, Samsung Biomedical Research Institute, Samsung Medical Center, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Seong, Tae-Yeon [Department of Materials Science and Engineering, Korea University, 5-1, Anam-Dong, Sungbook-Ku, Seoul, 136-713 (Korea, Republic of); Yoon, Kwon-Ha [Institute for Radiological Imaging Science, Wonkwang University School of Medicine, 344-2, Shinyong, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2009-05-15

    We prepared five folate-conjugated lipophilic superparamagnetic iron oxide nanoparticles (F{sub 5}-Liposuperparamagnetic iron oxide nanoparticles(SPIONs), 5.5 and 11 nm) and investigated their cellular uptake with KB cells, which is one of the representative folate-receptor over-expressing human epidermoid carcinoma cells, using MRI. The cellular uptake tests with the respective 5.5 and 11 nm F{sub 5}-LipoSPIONs at a fixed particle concentration showed appreciable amount of receptor-mediated uptakes and the specificity was higher in 5.5 nm SPIONs, due to its higher folic acid (FA) density, without inhibition. However, the numbers of the particles taken up under FA inhibition were similar, irrespective of their sizes.

  12. Green tea polyphenol epigallocatechin-3-gallate differentially modulates oxidative stress in PC12 cell compartments

    International Nuclear Information System (INIS)

    Raza, Haider; John, Annie

    2005-01-01

    Tea polyphenols have been reported to be potent antioxidants and beneficial in oxidative stress related diseases. Prooxidant effects of tea polyphenols have also been reported in cell culture systems. In the present study, we have studied oxidative stress in the subcellular compartments of PC12 cells after treatment with different concentrations of the green tea polyphenol, epigallocatechin-3-gallate (EGCG). We have demonstrated that EGCG has differentially affected the production of reactive oxygen species (ROS), glutathione (GSH) metabolism and cytochrome P450 2E1 activity in the different subcellular compartments in PC12 cells. Our results have shown that although the cell survival was not inhibited by EGCG, there was, however, an increased DNA breakdown and activation of apoptotic markers, caspase 3 and poly- (ADP-ribose) polymerase (PARP) at higher concentrations of EGCG treatment. Our results suggest that the differential effects of EGCG might be related to the alterations in oxidative stress, GSH pools and CYP2E1 activity in different cellular compartments. These results may have implications in determining the chemopreventive therapeutic use of tea polyphenols in vivo

  13. Proteome Profiling of Heat, Oxidative, and Salt Stress Responses in Thermococcus kodakarensis KOD1

    Directory of Open Access Journals (Sweden)

    Baolei eJia

    2015-06-01

    Full Text Available The thermophilic species, Thermococcus kodakarensis KOD1, a model microorganism for studying hyperthermophiles, has adapted to optimal growth under conditions of high temperature and salinity. However, the environmental conditions for the strain are not always stable, and this strain might face different stresses. In the present study, we compared the proteome response of T. kodakarensis to heat, oxidative, and salt stresses using two-dimensional electrophoresis, and protein spots were identified through MALDI-TOF/MS. Fifty-nine, forty-two, and twenty-nine spots were induced under heat, oxidative, and salt stresses, respectively. Among the up-regulated proteins, four proteins (a hypothetical protein, pyridoxal biosynthesis lyase, peroxiredoxin, and protein disulphide oxidoreductase were associated with all three stresses. Gene ontology analysis showed that these proteins were primarily involved metabolic and cellular processes. The KEGG pathway analysis suggested that the main metabolic pathways involving these enzymes were related to carbohydrate metabolism, secondary metabolite synthesis, and amino acid biosynthesis. These data might enhance our understanding of the functions and molecular mechanisms of thermophilic Archaea for survival and adaptation in extreme environments.

  14. Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

    Science.gov (United States)

    Downs, C A; McDougall, Kathleen E; Woodley, Cheryl M; Fauth, John E; Richmond, Robert H; Kushmaro, Ariel; Gibb, Stuart W; Loya, Yossi; Ostrander, Gary K; Kramarsky-Winter, Esti

    2013-01-01

    Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

  15. Heat-stress and light-stress induce different cellular pathologies in the symbiotic dinoflagellate during coral bleaching.

    Directory of Open Access Journals (Sweden)

    C A Downs

    Full Text Available Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex, usually by expulsion or xenophagy (symbiophagy of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2 s(-1 PAR at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.

  16. Telomerase activity and cellular aging might be positively modified by a yoga-based lifestyle intervention.

    Science.gov (United States)

    Kumar, Shiv Basant; Yadav, Rashmi; Yadav, Raj Kumar; Tolahunase, Madhuri; Dada, Rima

    2015-06-01

    Recent studies showed that a brief yoga-based lifestyle intervention was efficacious in reducing levels of oxidative stress and cellular aging in obese men. The objective of this case report was to assess the efficacy of this intervention in reducing the levels of biochemical markers of cellular ageing, oxidative stress, and inflammation at baseline (day 0), at the end of active intervention (day 10), and follow-up at day 90. Single case report from a prospective ongoing study with pre-post design assessing the level of various markers of cellular aging. Integral Health Clinic, an outpatient facility conducting meditation and yoga-based lifestyle intervention programs for management of chronic diseases. A 31-year-old man with class I obesity (body-mass index, 29.5 kg/m(2)) who presented to the medicine outpatient department at All India Institute of Medical Sciences, New Delhi, India, with a history of fatigue, difficulty losing weight, and lack of motivation. He noted a marked decrease in his energy level, particularly in the afternoon. A pretested intervention program included asanas (postures), pranayama (breathing exercises), stress management, group discussions, lectures, and individualized advice. From baseline (day 0) to day 90, the activity of telomerase and levels of β-endorphins, plasma cortisol, and interleukin-6 increased, and a sustained reduction in oxidative stress markers, such as reactive oxygen species and 8-hydroxy-2-deoxy-guanosine levels. Adopting yoga/meditation-based lifestyle modification causes reversal of markers of aging, mainly oxidative stress, telomerase activity, and oxidative DNA damage. This may not only delay aging and prolong a youthful healthy life but also delay or prevent onset of several lifestyle-related diseases, of which oxidative stress and inflammation are the chief cause. This report suggests this simple lifestyle intervention may be therapeutic for oxidative DNA damage and oxidative stress.

  17. Oxidative stress increases internal calcium stores and reduces a key mitochondrial enzyme.

    Science.gov (United States)

    Gibson, Gary E; Zhang, Hui; Xu, Hui; Park, Larry C H; Jeitner, Thomas M

    2002-03-16

    Fibroblasts from patients with genetic and non-genetic forms of Alzheimer's disease (AD) show many abnormalities including increased bombesin-releasable calcium stores (BRCS), diminished activities of the mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC), and an altered ability to handle oxidative stress. The link between genetic mutations (and the unknown primary event in non-genetic forms) and these other cellular abnormalities is unknown. To determine whether oxidative stress could be a convergence point that produces the other AD-related changes, these experiments tested in fibroblasts the effects of H(2)O(2), in the presence or absence of select antioxidants, on BRCS and KGDHC. H(2)O(2) concentrations that elevated carboxy-dichlorofluorescein (c-H(2)DCF)-detectable ROS increased BRCS and decreased KGDHC activity. These changes are in the same direction as those in fibroblasts from AD patients. Acute treatments with the antioxidants Trolox, or DMSO decreased c-H(2)DCF-detectable ROS by about 90%, but exaggerated the H(2)O(2)-induced increases in BRCS by about 4-fold and did not alter the reduction in KGDHC. Chronic pretreatments with Trolox more than doubled the BRCS, tripled KGDHC activities, and reduced the effects of H(2)O(2). Pretreatment with DMSO or N-acetyl cysteine diminished the BRCS and either had no effect, or exaggerated the H(2)O(2)-induced changes in these variables. The results demonstrate that BRCS and KGDHC are more sensitive to H(2)O(2) derived species than c-H(2)DCF, and that oxidized derivatives of the antioxidants exaggerate the actions of H(2)O(2). The findings support the hypothesis that select abnormalities in oxidative processes are a critical part of a cascade that leads to the cellular abnormalities in cells from AD patients.

  18. Evaluation of cellular effects of fine particulate matter from combustion of solid fuels used for indoor heating on the Navajo Nation using a stratified oxidative stress response model

    Science.gov (United States)

    Li, Ning; Champion, Wyatt M.; Imam, Jemal; Sidhu, Damansher; Salazar, Joseph R.; Majestic, Brian J.; Montoya, Lupita D.

    2018-06-01

    Communities in the Navajo Nation face public health burdens caused in part by the combustion of wood and coal for indoor heating using stoves that are old or in disrepair. Wood and coal combustion emits particulate matter (PM) with aerodynamic diameter combustion-derived PM2.5 on Navajo Nation residents. This study tested the hypothesis that PM2.5 generated from solid fuel combustion in stoves commonly used by Navajo residents would induce stratified oxidative stress responses ranging from activation of antioxidant defense to inflammation and cell death in mouse macrophages (RAW 264.7). PM2.5 emitted from burning Ponderosa Pine (PP) and Utah Juniper (UJ) wood and Black Mesa (BM) and Fruitland (FR) coal in a stove representative of those widely used by Navajo residents were collected, and their aqueous suspensions used for cellular exposure. PM from combustion of wood had significantly more elemental carbon (EC) (15%) and soluble Ni (0.0029%) than the samples from coal combustion (EC: 3%; Ni: 0.0019%) and was also a stronger activator of antioxidant enzyme heme oxygenase-1 (11-fold increase vs. control) than that from coal (5-fold increase). Only PM from PP-wood (12-fold) and BM-coal (3-fold) increased the release of inflammatory cytokine tumor necrosis factor alpha. Among all samples, PP-wood consistently had the strongest oxidative stress and inflammatory effects. PM components, i.e. low-volatility organic carbon, EC, Cu, Ni and K were positively correlated with the cellular responses. Results showed that, at the concentrations tested, emissions from all fuels did not have significant cytotoxicity. These findings suggest that PM2.5 emitted from combustion of wood and coal commonly used by Navajo residents may negatively impact the health of this community.

  19. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    Science.gov (United States)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  20. Oxidative Stress in Cardiovascular Diseases: Involvement of Nrf2 Antioxidant Redox Signaling in Macrophage Foam Cells Formation

    Directory of Open Access Journals (Sweden)

    Bee Kee Ooi

    2017-11-01

    Full Text Available Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells. Nuclear factor erythroid 2-related factor 2 (Nrf2 is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes. Nrf2 has been demonstrated to be involved in the protection against foam cells formation by regulating the expression of antioxidant proteins (HO-1, Prxs, and GPx1, ATP-binding cassette (ABC efflux transporters (ABCA1 and ABCG1 and scavenger receptors (scavenger receptor class B (CD36, scavenger receptor class A (SR-A and lectin-type oxidized LDL receptor (LOX-1. However, Nrf2 has also been reported to exhibit pro-atherogenic effects. A better understanding on the mechanism of Nrf2 in oxidative stress-induced cardiac injury, as well as the regulation of cholesterol uptake and efflux, are required before it can serve as a novel therapeutic target for cardiovascular diseases prevention and treatment.

  1. Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise.

    Science.gov (United States)

    Funes, Lorena; Carrera-Quintanar, Lucrecia; Cerdán-Calero, Manuela; Ferrer, Miguel D; Drobnic, Franchek; Pons, Antoni; Roche, Enrique; Micol, Vicente

    2011-04-01

    Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.

  2. Small molecular antioxidants effectively protect from PUVA-induced oxidative stress responses underlying fibroblast senescence and photoaging.

    Science.gov (United States)

    Briganti, Stefania; Wlaschek, Meinhard; Hinrichs, Christina; Bellei, Barbara; Flori, Enrica; Treiber, Nicolai; Iben, Sebastian; Picardo, Mauro; Scharffetter-Kochanek, Karin

    2008-09-01

    Exposure of human fibroblasts to 8-methoxypsoralen plus ultraviolet-A irradiation (PUVA) results in stress-induced cellular senescence in fibroblasts. We here studied the role of the antioxidant defense system in the accumulation of reactive oxygen species (ROS) and the effect of the antioxidants alpha-tocopherol, N-acetylcysteine, and alpha-lipoic acid on PUVA-induced cellular senescence. PUVA treatment induced an immediate and increasing generation of intracellular ROS. Supplementation of PUVA-treated fibroblasts with alpha-tocopherol (alpha-Toc), N-acetylcysteine (NAC), or alpha-lipoic acid (alpha-LA) abrogated the increased ROS generation and rescued fibroblasts from the ROS-dependent changes into the cellular senescence phenotype, such as cytoplasmic enlargement, enhanced expression of senescence-associated-beta-galactosidase and matrix-metalloproteinase-1, hallmarks of photoaging and intrinsic aging. PUVA treatment disrupted the integrity of cellular membranes and impaired homeostasis and function of the cellular antioxidant system with a significant decrease in glutathione and hydrogen peroxide-detoxifying enzymes activities. Supplementation with NAC, alpha-LA, and alpha-Toc counteracted these changes. Our data provide causal evidence that (i) oxidative stress due to an imbalance in the overall cellular antioxidant capacity contributes to the induction and maintenance of the PUVA-induced fibroblast senescence and that (ii) low molecular antioxidants protect effectively against these deleterious alterations.

  3. Mechanisms involved in the development of diabetic retinopathy induced by oxidative stress.

    Science.gov (United States)

    Guzman, David Calderón; Olguín, Hugo Juárez; García, Ernestina Hernández; Peraza, Armando Valenzuela; de la Cruz, Diego Zamora; Soto, Monica Punzo

    2017-01-01

    Diabetic retinopathy (DR) is one of the main complications in patients with diabetes and has been the leading cause of visual loss since 1990. Oxidative stress is a biological process resulting from excessive production of reactive oxygen species (ROS). This process contributes to the development of many diseases and disease complications. ROS interact with various cellular components to induce cell injury. Fortunately, there is an antioxidan t system that protects organisms against ROS. Indeed, when ROS exceed antioxidant capacity, the resulting cell injury can cause diverse physiological and pathological changes that could lead to a disease like DR. This paper reviews the possible mechanisms of common and novel biomarkers involved in the development of DR and explores how these biomarkers could be used to monitor the damage induced by oxidative stress in DR, which is a significant complication in people with diabetes. The poor control of glucemy in pacients with DB has been shown contribute to the development of complications in eyes as DR.

  4. Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress

    Directory of Open Access Journals (Sweden)

    C. Castillo

    2018-04-01

    Full Text Available Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR, it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL was purified from skimmed goat milk. Recombinant human erythropoietin (Epo was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1 h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP; cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15 min of oxygen and glucose deprivation (OGD and the neuroprotective drugs EpoL or Epo were incubated for 2 h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases. Keywords: Erythropoietin, Erythropoietin receptor, Neuroprotection, Oxidative stress

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

    Science.gov (United States)

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

    2008-10-01

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

  6. Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

    Directory of Open Access Journals (Sweden)

    Jeffrey G. Pelton

    2011-09-01

    Full Text Available Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately

  7. Metabolomics of Oxidative Stress in Recent Studies of Endogenous and Exogenously Administered Intermediate Metabolites

    Science.gov (United States)

    Liu, Jia; Litt, Lawrence; Segal, Mark R.; Kelly, Mark J. S.; Pelton, Jeffrey G.; Kim, Myungwon

    2011-01-01

    Aerobic metabolism occurs in a background of oxygen radicals and reactive oxygen species (ROS) that originate from the incomplete reduction of molecular oxygen in electron transfer reactions. The essential role of aerobic metabolism, the generation and consumption of ATP and other high energy phosphates, sustains a balance of approximately 3000 essential human metabolites that serve not only as nutrients, but also as antioxidants, neurotransmitters, osmolytes, and participants in ligand-based and other cellular signaling. In hypoxia, ischemia, and oxidative stress, where pathological circumstances cause oxygen radicals to form at a rate greater than is possible for their consumption, changes in the composition of metabolite ensembles, or metabolomes, can be associated with physiological changes. Metabolomics and metabonomics are a scientific disciplines that focuse on quantifying dynamic metabolome responses, using multivariate analytical approaches derived from methods within genomics, a discipline that consolidated innovative analysis techniques for situations where the number of biomarkers (metabolites in our case) greatly exceeds the number of subjects. This review focuses on the behavior of cytosolic, mitochondrial, and redox metabolites in ameliorating or exacerbating oxidative stress. After reviewing work regarding a small number of metabolites—pyruvate, ethyl pyruvate, and fructose-1,6-bisphosphate—whose exogenous administration was found to ameliorate oxidative stress, a subsequent section reviews basic multivariate statistical methods common in metabolomics research, and their application in human and preclinical studies emphasizing oxidative stress. Particular attention is paid to new NMR spectroscopy methods in metabolomics and metabonomics. Because complex relationships connect oxidative stress to so many physiological processes, studies from different disciplines were reviewed. All, however, shared the common goal of ultimately developing

  8. Broad MICA/B Expression in the Small Bowel Mucosa: A Link between Cellular Stress and Celiac Disease

    Science.gov (United States)

    Allegretti, Yessica L.; Bondar, Constanza; Guzman, Luciana; Cueto Rua, Eduardo; Chopita, Nestor; Fuertes, Mercedes; Zwirner, Norberto W.; Chirdo, Fernando G.

    2013-01-01

    The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role. PMID:24058482

  9. Dichloroacetate Decreases Cell Health and Activates Oxidative Stress Defense Pathways in Rat Alveolar Type II Pneumocytes

    Directory of Open Access Journals (Sweden)

    Alexis Valauri-Orton

    2015-01-01

    Full Text Available Dichloroacetate (DCA is a water purification byproduct that is known to be hepatotoxic and hepatocarcinogenic and to induce peripheral neuropathy and damage macrophages. This study characterizes the effects of the haloacetate on lung cells by exposing rat alveolar type II (L2 cells to 0–24 mM DCA for 6–24 hours. Increasing DCA concentration and the combination of increasing DCA concentration plus longer exposures decrease measures of cellular health. Length of exposure has no effect on oxidative stress biomarkers, glutathione, SOD, or CAT. Increasing DCA concentration alone does not affect total glutathione or its redox ratio but does increase activity in the SOD/CAT oxidative stress defense pathway. These data suggest that alveolar type II cells rely on SOD and CAT more than glutathione to combat DCA-induced stress.

  10. C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.

    Science.gov (United States)

    Lee, Y H; Kim, H S; Kim, J S; Yu, M K; Cho, S D; Jeon, J G; Yi, H K

    2016-04-01

    Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases. © International & American Associations

  11. Effects of Marine Oils, Digested with Human Fluids, on Cellular Viability and Stress Protein Expression in Human Intestinal Caco-2 Cells

    Directory of Open Access Journals (Sweden)

    Cecilia Tullberg

    2017-11-01

    Full Text Available In vitro digestion of marine oils has been reported to promote lipid oxidation, including the formation of reactive aldehydes (e.g., malondialdehyde (MDA and 4-hydroxy-2-hexenal (HHE. We aimed to investigate if human in vitro digestion of supplemental levels of oils from algae, cod liver, and krill, in addition to pure MDA and HHE, affect intestinal Caco-2 cell survival and oxidative stress. Cell viability was not significantly affected by the digests of marine oils or by pure MDA and HHE (0–90 μM. Cellular levels of HSP-70, a chaperone involved in the prevention of stress-induced protein unfolding was significantly decreased (14%, 28%, and 14% of control for algae, cod and krill oil, respectively; p ≤ 0.05. The oxidoreductase thioredoxin-1 (Trx-1 involved in reducing oxidative stress was also lower after incubation with the digested oils (26%, 53%, and 22% of control for algae, cod, and krill oil, respectively; p ≤ 0.001. The aldehydes MDA and HHE did not affect HSP-70 or Trx-1 at low levels (8.3 and 1.4 μM, respectively, whilst a mixture of MDA and HHE lowered Trx-1 at high levels (45 μM, indicating less exposure to oxidative stress. We conclude that human digests of the investigated marine oils and their content of MDA and HHE did not cause a stress response in human intestinal Caco-2 cells.

  12. Mitochondrial oxidative stress and cardiac ageing.

    Science.gov (United States)

    Martín-Fernández, Beatriz; Gredilla, Ricardo

    According with different international organizations, cardiovascular diseases are becoming the first cause of death in western countries. Although exposure to different risk factors, particularly those related to lifestyle, contribute to the etiopathogenesis of cardiac disorders, the increase in average lifespan and aging are considered major determinants of cardiac diseases events. Mitochondria and oxidative stress have been pointed out as relevant factors both in heart aging and in the development of cardiac diseases such as heart failure, cardiac hypertrophy and diabetic cardiomyopathy. During aging, cellular processes related with mitochondrial function, such as bioenergetics, apoptosis and inflammation are altered leading to cardiac dysfunction. Increasing our knowledge about the mitochondrial mechanisms related with the aging process, will provide new strategies in order to improve this process, particularly the cardiovascular ones. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Chronic pain, perceived stress, and cellular aging: an exploratory study

    Directory of Open Access Journals (Sweden)

    Sibille Kimberly T

    2012-02-01

    Full Text Available Abstract Background Chronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL, a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of TL as a biological marker reflecting the burden of chronic pain and psychosocial stress has not yet been explored. Findings The relationship between chronic pain, stress, and TL was analyzed in 36 ethnically diverse, older adults, half of whom reported no chronic pain and the other half had chronic knee osteoarthritis (OA pain. Subjects completed a physical exam, radiographs, health history, and psychosocial questionnaires. Blood samples were collected and TL was measured by quantitative polymerase chain reaction (qPCR. Four groups were identified characterized by pain status and the Perceived Stress Scale scores: 1 no pain/low stress, 2 no pain/high stress, chronic pain/low stress, and 4 chronic pain/high stress. TL differed between the pain/stress groups (p = 0.01, controlling for relevant covariates. Specifically, the chronic pain/high stress group had significantly shorter TL compared to the no pain/low stress group. Age was negatively correlated with TL, particularly in the chronic pain/high stress group (p = 0.03. Conclusions Although preliminary in nature and based on a modest sample size, these findings indicate that cellular aging may be more pronounced in older adults experiencing high levels of perceived stress and chronic pain.

  14. A Nucleocytoplasmic Shuttling Protein in Oxidative Stress Tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Ow, David W.; Song, Wen

    2003-03-26

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

  15. High-Fat Diet Induces Oxidative Stress and MPK2 and HSP83 Gene Expression in Drosophila melanogaster

    OpenAIRE

    Trindade de Paula, Mariane; Poetini Silva, M?rcia R?sula; Machado Araujo, St?fani; Cardoso Bortolotto, Vandreza; Barreto Meichtry, Luana; Zemolin, Ana Paula Pegoraro; Wallau, Gabriel L.; Jesse, Cristiano Ricardo; Franco, Jeferson Lu?s; Posser, Tha?s; Prigol, Marina

    2016-01-01

    The consumption of a high-fat diet (HFD) causes alteration in normal metabolism affecting lifespan of flies; however molecular mechanism associated with this damage in flies is not well known. This study evaluates the effects of ingestion of a diet supplemented with 10% and 20% of coconut oil, which is rich in saturated fatty acids, on oxidative stress and cells stress signaling pathways. After exposure to the diet for seven days, cellular and mitochondrial viability, lipid peroxidation and a...

  16. Upregulation of cytosolic NADP+-dependent isocitrate dehydrogenase by hyperglycemia protects renal cells against oxidative stress.

    Science.gov (United States)

    Lee, Soh-Hyun; Ha, Sun-Ok; Koh, Ho-Jin; Kim, KilSoo; Jeon, Seon-Min; Choi, Myung-Sook; Kwon, Oh-Shin; Huh, Tae-Lin

    2010-02-28

    Hyperglycemia-induced oxidative stress is widely recognized as a key mediator in the pathogenesis of diabetic nephropathy, a complication of diabetes. We found that both expression and enzymatic activity of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) were upregulated in the renal cortexes of diabetic rats and mice. Similarly, IDPc was induced in murine renal proximal tubular OK cells by high hyperglycemia, while it was abrogated by co-treatment with the antioxidant N-Acetyl-Cysteine (NAC). In OK cells, increased expression of IDPc by stable transfection prevented hyperglycemia-mediated reactive oxygen species (ROS) production, subsequent cellular oxidative stress and extracellular matrix accumulation, whereas these processes were all stimulated by decreased IDPc expression. In addition, production of NADPH and GSH in the cytosol was positively correlated with the expression level of IDPc in OK cells. These results together indicate that upregulation of IDPc in response to hyperglycemia might play an essential role in preventing the progression of diabetic nephropathy, which is accompanied by ROS-induced cellular damage and fibrosis, by providing NADPH, the reducing equivalent needed for recycling reduced glutathione and low molecular weight antioxidant thiol proteins.

  17. Impact of Oxidative Stress in Fetal Programming

    OpenAIRE

    Thompson, Loren P.; Al-Hasan, Yazan

    2012-01-01

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

  18. Mulberry Fruit Extract Affords Protection against Ethyl Carbamate-Induced Cytotoxicity and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Wei Chen

    2017-01-01

    Full Text Available Ethyl carbamate (EC is a food and environmental toxicant and is a cause of concern for human exposure. Several studies indicated that EC-induced toxicity was associated with oxidative stress. Mulberry fruits are reported to have a wide range of bioactive compounds and pharmacological activities. The present study was therefore aimed to investigate the protective property of mulberry fruit extract (MFE on EC-induced cytotoxicity and oxidative stress. Chemical composition analysis showed that total phenolic content and total flavonoid content in MFE were 502.43 ± 5.10 and 219.12 ± 4.45 mg QE/100 g FW. Cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside were the major anthocyanins in MFE. In vitro antioxidant studies (DPPH, ABTS, and FRAP assays jointly exhibited the potent antioxidant capacity of MFE. Further study indicated that MFE protected human liver HepG2 cells from EC-induced cytotoxicity by scavenging overproduced cellular ROS. EC treatment promoted intracellular glutathione (GSH depletion and caused mitochondrial membrane potential (MMP collapse, as well as mitochondrial membrane lipid peroxidation, whereas MFE pretreatment significantly inhibited GSH depletion and restored the mitochondrial membrane function. Overall, our study suggested that polyphenolic-rich MFE could afford a potent protection against EC-induced cytotoxicity and oxidative stress.

  19. Oxidative stress in primary glomerular diseases

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity.

    Science.gov (United States)

    Zhou, Shutong; Yu, Dongni; Ning, Shangyong; Zhang, Heli; Jiang, Lei; He, Lei; Li, Miao; Sun, Mingxiao

    2015-01-01

    The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and β cell dysfunction in obesity. In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 β cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed. ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 β cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in β cells. Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with β cell dysfunction through ROS production. © 2015 S. Karger AG, Basel.

  1. Oxidative stress and psychological functioning among medical students

    Directory of Open Access Journals (Sweden)

    Rani Srivastava

    2014-01-01

    Full Text Available Background: Oxidative stress has gained attention recently in behavioral medicine and has been reported to be associated with various psychological disturbances and their prognoses. Objectives: Study aims to evaluate the oxidative stress (malonylaldehyde (MDA levels and its relation with psychological factors (dimensions of personality, levels of anxiety, stress, and depression among medical/paramedical students of 1 st and 3 rd year. Materials and Methods: A total of 150 students; 75 from 1 st year (2010-2011 and75 from 3 rd year (2009-2010; of medical and paramedical background were assessed on level of MDA (oxidative stress and personality variables, that is, level of anxiety, stress, and depression. These psychological variables were correlated with the level of their oxidative stress. Results: Findings revealed that both groups are influenced by oxidative stress and their psychological variables are also compatible in order to confirm their vulnerabilities to stress. Conclusions: Stress in 3 rd year students was significantly higher and it was noted that it adversely affects the psychological parameters. Hence, special attention on mental health aspect in these students may be given.

  2. Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

    International Nuclear Information System (INIS)

    Feltens, Ralph; Moegel, Iljana; Roeder-Stolinski, Carmen; Simon, Jan-Christoph; Herberth, Gunda; Lehmann, Irina

    2010-01-01

    Chlorobenzene is a volatile organic compound (VOC) that is widely used as a solvent, degreasing agent and chemical intermediate in many industrial settings. Occupational studies have shown that acute and chronic exposure to chlorobenzene can cause irritation of the mucosa of the upper respiratory tract and eyes. Using in vitro assays, we have shown in a previous study that human bronchial epithelial cells release inflammatory mediators such as the cytokine monocyte chemoattractant protein-1 (MCP-1) in response to chlorobenzene. This response is mediated through the NF-κB signaling pathway. Here, we investigated the effects of monochlorobenzene on human lung cells, with emphasis on potential alterations of the redox equilibrium to clarify whether the chlorobenzene-induced inflammatory response in lung epithelial cells is caused via an oxidative stress-dependent mechanism. We found that expression of cellular markers for oxidative stress, such as heme oxygenase 1 (HO-1), glutathione S-transferase π1 (GSTP1), superoxide dismutase 1 (SOD1), prostaglandin-endoperoxide synthase 2 (PTGS2) and dual specificity phosphatase 1 (DUSP1), were elevated in the presence of monochlorobenzene. Likewise, intracellular reactive oxygen species (ROS) were increased in response to exposure. However, in the presence of the antioxidants N-(2-mercaptopropionyl)-glycine (MPG) or bucillamine, chlorobenzene-induced upregulation of marker proteins and release of the inflammatory mediator MCP-1 are suppressed. These results complement our previous findings and point to an oxidative stress-mediated inflammatory response following chlorobenzene exposure.

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

    Science.gov (United States)

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

    2014-11-01

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

  4. Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

    Science.gov (United States)

    Kim, Sun Yee; Park, Jeen-Woo

    2003-03-01

    Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

  5. Oxidative Stress, Bone Marrow Failure, and Genome Instability in Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Christine Richardson

    2015-01-01

    Full Text Available Reactive oxygen species (ROS can be generated by defective endogenous reduction of oxygen by cellular enzymes or in the mitochondrial respiratory pathway, as well as by exogenous exposure to UV or environmental damaging agents. Regulation of intracellular ROS levels is critical since increases above normal concentrations lead to oxidative stress and DNA damage. A growing body of evidence indicates that the inability to regulate high levels of ROS leading to alteration of cellular homeostasis or defective repair of ROS-induced damage lies at the root of diseases characterized by both neurodegeneration and bone marrow failure as well as cancer. That these diseases may be reflective of the dynamic ability of cells to respond to ROS through developmental stages and aging lies in the similarities between phenotypes at the cellular level. This review summarizes work linking the ability to regulate intracellular ROS to the hematopoietic stem cell phenotype, aging, and disease.

  6. Effects of stress on the oxide layer thickness and post-oxidation creep strain of zircaloy-4

    International Nuclear Information System (INIS)

    Lim, Sang Ho; Yoon, Young Ku

    1986-01-01

    Effects of compressive stress generated in the oxide layer and its subsequent relief on oxidation rate and post-oxidation creep characteristics of zircaloy-4 were investigated by oxidation studies in steam with and without applied tensile stress and by creep testing at 700 deg C in high purity argon. The thickness of oxide layer increased with the magnitude of tensile stress applied during oxidation at 650 deg C in steam whereas similar phenomenon was not observed during oxidation at 800 deg C. Zircaloy-4 specimens oxidized at 600 deg C in steam without applied stress exhibited higher creep strain than that shown by unoxidized specimens when creep-tested in argon. Zircaloy-4 specimens oxidized at 600 deg C steam under the applied stress of 8.53MPa and oxidized at 800 deg C under the applied stress of 0 and 8.53MPa exhibited lower strain than that shown by unoxidized specimen. The above experimental results were accounted for on the basis of interactions among applied stress during oxidation, compressive stress generated in the oxide layer and elasticity of zircaloy-4 matrix. (Author)

  7. Alkylation of the tumor suppressor PTEN activates Akt and β-catenin signaling: a mechanism linking inflammation and oxidative stress with cancer.

    Directory of Open Access Journals (Sweden)

    Tracy M Covey

    2010-10-01

    Full Text Available PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal and α,β-enones (prostaglandin A(2, Δ12-prostaglandin J(2 and 15-deoxy-Δ-12,14-prostaglandin J(2 covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging.

  8. Comparison of Oxidative Stresses Mediated by Different Crystalline Forms and Surface Modification of Titanium Dioxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Karim Samy El-Said

    2015-01-01

    Full Text Available Titanium dioxide nanoparticles (TiO2 NPs are manufactured worldwide for use in a wide range of applications. There are two common crystalline forms of TiO2 anatase and rutile with different physical and chemical characteristics. We previously demonstrated that an increased DNA damage response is mediated by anatase crystalline form compared to rutile. In the present study, we conjugated TiO2 NPs with polyethylene glycol (PEG in order to reduce the genotoxicity and we evaluated some oxidative stress parameters to obtain information on the cellular mechanisms of DNA damage that operate in response to TiO2 NPs different crystalline forms exposure in hepatocarcinoma cell lines (HepG2. Our results indicated a significant increase in oxidative stress mediated by the anatase form of TiO2 NPs compared to rutile form. On the other hand, PEG modified TiO2 NPs showed a significant decrease in oxidative stress as compared to TiO2 NPs. These data suggested that the genotoxic potential of TiO2 NPs varies with crystalline form and surface modification.

  9. Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Zhanpeng Wang

    2016-01-01

    Full Text Available Accumulating evidence has indicated that oxidative stress (OS is associated with the development of hepatocellular carcinoma (HCC. However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV and hepatitis C virus (HCV infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD. The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.

  10. Impact of Oxidative Stress in Fetal Programming

    Directory of Open Access Journals (Sweden)

    Loren P. Thompson

    2012-01-01

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

  11. Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress Responses

    OpenAIRE

    Iwai Ohbayashi; Munetaka Sugiyama

    2018-01-01

    The nucleolus is the most prominent nuclear domain, where the core processes of ribosome biogenesis occur vigorously. All these processes are finely orchestrated by many nucleolar factors to build precisely ribosome particles. In animal cells, perturbations of ribosome biogenesis, mostly accompanied by structural disorders of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest, senescence, or apoptosis, which is called nucleolar stress response. The best-characterized p...

  12. Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Tiange Li

    2017-01-01

    Full Text Available Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP on hydrogen peroxide (H2O2-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H2O2-induced intracellular reactive oxygen species (ROS generation and cell viability reduction in a dose-dependent manner. Further, GHP concentration-dependently induced heme oxygenase-1 (HO-1 expression and increased nuclear factor-erythroid 2-related factor 2 (Nrf2 nuclear translocation. Moreover, pretreatment of GHP increased the activation of p38 mitogen-activated protein kinase (p38 MAPK and extracellular signal-regulated protein kinase 1/2 (ERK1/2, which were shown to contribute to Nrf2-mediated HO-1 expression. Taken together, GHP protected HepG2 cells from oxidative stress by activation of Nrf2 and HO-1 via p38 MAPK and ERK1/2 signaling pathways. Our findings indicate that bovine casein glycomacropeptide hydrolysates might be a potential ingredient in the treatment of oxidative stress-related disorders and further studies are needed to investigate the protective effects in vivo.

  13. Free radicals, oxidative stress and importance of antioxidants in human health

    Directory of Open Access Journals (Sweden)

    K.I. Priyadarsini

    2011-07-01

    Full Text Available Reactive oxygen species (ROS is a collective term used for oxygen containing free radicals, depending on their reactivity and oxidizing ability. ROS participate in a variety of chemical reactions with biomolecules leading to a pathological condition known as oxidative stress. Antioxidants are employed to protect biomolecules from the damaging effects of such ROS. In the beginning, antioxidant research was mainly aimed at understanding free radical reactions of ROS with antioxidants employing biochemical assays and kinetic methods. Later on, studies began to be directed to monitor the ability of anti-oxidants to modulate cellular signaling proteins like receptors, secondary messengers, transcription factors, etc. Of late several studies have indicated that antioxidants can also have deleterious effects on human health depending on dosage and bio-availability. It is therefore, necessary to validate the utility of antioxidants in improvement of human health in order to take full advantage of their therapeutic potential.

  14. Cellular inactivation of nitric oxide induces p53-dependent ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research August 2016; 15 (8): 1595-1603 ... Cellular inactivation of nitric oxide induces p53-dependent apoptosis in ... apoptosis induced by a selective iNOS inhibitor, N-[(3-aminomethyl) benzyl] acetamidine (1400W), .... and nitrate. ... Nitrite production was measured in culture media.

  15. A comparative study of the effect of oxidative stress on the cytoskeleton in human cortical neurons

    International Nuclear Information System (INIS)

    Allani, Pramod K.; Sum, Tak; Bhansali, Suraj G.; Mukherjee, Suman K.; Sonee, Manisha

    2004-01-01

    Cytoskeleton disruption is a process by which oxidative stress disrupts cellular function. This study compares and contrasts the effect of oxidative stress on the three major cytoskeleton filaments, microfilaments (MFs), microtubule (MT), and vimentin in human cortical neuronal cell line (HCN2). HCN2 cells were treated with 100 μM tertiary butylhydroperoxide (t-BuOOH), a free radical generating neurotoxin for 1, 3, or 6 h. Cell viability studies demonstrated significant cell death although the morphology studies showed that there was a substantial loss in neurites of neurons treated with t-BuOOH for 6 h. Because the cytoskeleton plays a role in neurite outgrowth, the effect of oxidative stress on the cytoskeletal was studied. In neurons subjected to oxidative stress for 30 min or 1 h, there were no major changes in microfilament distribution though there was altered distribution of microtubule and vimentin filaments as compared to controls. However, loss and disruption of all the three cytoskeletal filaments was observed at later times (3 and 6 h), which was confirmed by Western Blot analysis. Further studies were done to measure the gene expression levels of actin, tubulin, and vimentin. Results indicated that the overall loss of the cytoskeletal proteins in neurons treated with free radical generating toxin might not be a direct result of the downregulation of the cytoskeletal genes. This study shows that free radical generation in human neurons leads to the disruption of the cytoskeleton, though there may be a difference in the susceptibility to oxidative stress among the individual components of the cytoskeletal filaments

  16. Hypoxia, Oxidative Stress and Fat

    Directory of Open Access Journals (Sweden)

    Nikolaus Netzer

    2015-06-01

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

  17. Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10

    International Nuclear Information System (INIS)

    McCarthy, S.; Somayajulu, M.; Sikorska, M.; Borowy-Borowski, H.; Pandey, S.

    2004-01-01

    Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q 10 (CoQ 10 ) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ 10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ 10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ 10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ 10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins

  18. Oxidative stress inactivates cobalamin-independent methionine synthase (MetE in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Elise R Hondorp

    2004-11-01

    Full Text Available In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes the final step of methionine biosynthesis, cobalamin-independent methionine synthase (MetE. We found that E. coli cells subjected to transient oxidative stress during growth in minimal medium develop a methionine auxotrophy, which can be traced to an effect on MetE. Further experiments demonstrated that the purified enzyme is inactivated by oxidized glutathione (GSSG at a rate that correlates with protein oxidation. The unique site of oxidation was identified by selectively cleaving N-terminally to each reduced cysteine and analyzing the results by liquid chromatography mass spectrometry. Stoichiometric glutathionylation of MetE by GSSG occurs at cysteine 645, which is strategically located at the entrance to the active site. Direct evidence of MetE oxidation in vivo was obtained from thiol-trapping experiments in two different E. coli strains that contain highly oxidizing cytoplasmic environments. Moreover, MetE is completely oxidized in wild-type E. coli treated with the thiol-oxidizing agent diamide; reduced enzyme reappears just prior to the cells resuming normal growth. We argue that for E. coli experiencing oxidizing conditions in minimal medium, MetE is readily inactivated, resulting in cellular methionine limitation. Glutathionylation of the protein provides a strategy to modulate in vivo activity of the enzyme while protecting the active site from further damage, in an easily reversible manner. While glutathionylation of proteins is a fairly common mode of redox regulation in eukaryotes, very few proteins in E. coli are known to be modified in this manner. Our results are complementary to the independent findings of Leichert

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

    International Nuclear Information System (INIS)

    Jomova, Klaudia; Valko, Marian

    2011-01-01

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

  20. Edaravone leads to proteome changes indicative of neuronal cell protection in response to oxidative stress.

    Science.gov (United States)

    Jami, Mohammad-Saeid; Salehi-Najafabadi, Zahra; Ahmadinejad, Fereshteh; Hoedt, Esthelle; Chaleshtori, Morteza Hashemzadeh; Ghatrehsamani, Mahdi; Neubert, Thomas A; Larsen, Jan Petter; Møller, Simon Geir

    2015-11-01

    Neuronal cell death, in neurodegenerative disorders, is mediated through a spectrum of biological processes. Excessive amounts of free radicals, such as reactive oxygen species (ROS), has detrimental effects on neurons leading to cell damage via peroxidation of unsaturated fatty acids in the cell membrane. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been used for neurological recovery in several countries, including Japan and China, and it has been suggested that Edaravone may have cytoprotective effects in neurodegeneration. Edaravone protects nerve cells in the brain by reducing ROS and inhibiting apoptosis. To gain further insight into the cytoprotective effects of Edaravone against oxidative stress condition we have performed comparative two-dimensional gel electrophoresis (2DE)-based proteomic analyses on SH-SY5Y neuroblastoma cells exposed to oxidative stress and in combination with Edaravone. We showed that Edaravone can reverse the cytotoxic effects of H2O2 through its specific mechanism. We observed that oxidative stress changes metabolic pathways and cytoskeletal integrity. Edaravone seems to reverse the H2O2-mediated effects at both the cellular and protein level via induction of Peroxiredoxin-2. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Measurement of exercise-induced oxidative stress in lymphocytes.

    Science.gov (United States)

    Turner, James E; Bosch, Jos A; Aldred, Sarah

    2011-10-01

    Vigorous exercise is associated with oxidative stress, a state that involves modifications to bodily molecules due to release of pro-oxidant species. Assessment of such modifications provides non-specific measures of oxidative stress in human tissues and blood, including circulating lymphocytes. Lymphocytes are a very heterogeneous group of white blood cells, consisting of subtypes that have different functions in immunity. Importantly, exercise drastically changes the lymphocyte composition in blood by increasing the numbers of some subsets, while leaving other cells unaffected. This fact may imply that observed changes in oxidative stress markers are confounded by changes in lymphocyte composition. For example, lymphocyte subsets may differ in exposure to oxidative stress because of subset differences in cell division and the acquisition of cytotoxic effector functions. The aim of the present review is to raise awareness of interpretational issues related to the assessment of oxidative stress in lymphocytes with exercise and to address the relevance of lymphocyte subset phenotyping in these contexts.

  2. Protecting cells by protecting their vulnerable lysosomes: Identification of a new mechanism for preserving lysosomal functional integrity upon oxidative stress.

    Science.gov (United States)

    Pascua-Maestro, Raquel; Diez-Hermano, Sergio; Lillo, Concepción; Ganfornina, Maria D; Sanchez, Diego

    2017-02-01

    Environmental insults such as oxidative stress can damage cell membranes. Lysosomes are particularly sensitive to membrane permeabilization since their function depends on intraluminal acidic pH and requires stable membrane-dependent proton gradients. Among the catalog of oxidative stress-responsive genes is the Lipocalin Apolipoprotein D (ApoD), an extracellular lipid binding protein endowed with antioxidant capacity. Within the nervous system, cell types in the defense frontline, such as astrocytes, secrete ApoD to help neurons cope with the challenge. The protecting role of ApoD is known from cellular to organism level, and many of its downstream effects, including optimization of autophagy upon neurodegeneration, have been described. However, we still cannot assign a cellular mechanism to ApoD gene that explains how this protection is accomplished. Here we perform a comprehensive analysis of ApoD intracellular traffic and demonstrate its role in lysosomal pH homeostasis upon paraquat-induced oxidative stress. By combining single-lysosome in vivo pH measurements with immunodetection, we demonstrate that ApoD is endocytosed and targeted to a subset of vulnerable lysosomes in a stress-dependent manner. ApoD is functionally stable in this acidic environment, and its presence is sufficient and necessary for lysosomes to recover from oxidation-induced alkalinization, both in astrocytes and neurons. This function is accomplished by preventing lysosomal membrane permeabilization. Two lysosomal-dependent biological processes, myelin phagocytosis by astrocytes and optimization of neurodegeneration-triggered autophagy in a Drosophila in vivo model, require ApoD-related Lipocalins. Our results uncover a previously unknown biological function of ApoD, member of the finely regulated and evolutionary conserved gene family of extracellular Lipocalins. They set a lipoprotein-mediated regulation of lysosomal membrane integrity as a new mechanism at the hub of many cellular

  3. Obesity, reproduction and oxidative stress

    Directory of Open Access Journals (Sweden)

    Tamara V. Zhuk

    2017-12-01

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

  4. The imperative for controlled mechanical stresses in unraveling cellular mechanisms of mechanotransduction

    Directory of Open Access Journals (Sweden)

    Sorkin Adam M

    2006-05-01

    Full Text Available Abstract Background In vitro mechanotransduction studies are designed to elucidate cell behavior in response to a well-defined mechanical signal that is imparted to cultured cells, e.g. through fluid flow. Typically, flow rates are calculated based on a parallel plate flow assumption, to achieve a targeted cellular shear stress. This study evaluates the performance of specific flow/perfusion chambers in imparting the targeted stress at the cellular level. Methods To evaluate how well actual flow chambers meet their target stresses (set for 1 and 10 dyn/cm2 for this study at a cellular level, computational models were developed to calculate flow velocity components and imparted shear stresses for a given pressure gradient. Computational predictions were validated with micro-particle image velocimetry (μPIV experiments. Results Based on these computational and experimental studies, as few as 66% of cells seeded along the midplane of commonly implemented flow/perfusion chambers are subjected to stresses within ±10% of the target stress. In addition, flow velocities and shear stresses imparted through fluid drag vary as a function of location within each chamber. Hence, not only a limited number of cells are exposed to target stress levels within each chamber, but also neighboring cells may experience different flow regimes. Finally, flow regimes are highly dependent on flow chamber geometry, resulting in significant variation in magnitudes and spatial distributions of stress between chambers. Conclusion The results of this study challenge the basic premise of in vitro mechanotransduction studies, i.e. that a controlled flow regime is applied to impart a defined mechanical stimulus to cells. These results also underscore the fact that data from studies in which different chambers are utilized can not be compared, even if the target stress regimes are comparable.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-01

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

  7. Simvastatin and oxidative stress in humans

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anu Rahal

    2014-01-01

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

  9. Genetics of Oxidative Stress in Obesity

    Directory of Open Access Journals (Sweden)

    Azahara I. Rupérez

    2014-02-01

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

  10. Genetics of oxidative stress in obesity.

    Science.gov (United States)

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

    2014-02-20

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

  11. Oxidative stress resistance in Porphyromonas gingivalis

    Science.gov (United States)

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

    2012-01-01

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

  12. High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

    Science.gov (United States)

    Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

    2011-01-01

    Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

  13. Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind

    Directory of Open Access Journals (Sweden)

    Maria Pantelidou

    2017-02-01

    Full Text Available Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism.

  14. Oxidative Stress and Antioxidant Therapy in Critically Ill Polytrauma Patients with Severe Head Injury

    Directory of Open Access Journals (Sweden)

    Luca Loredana

    2015-05-01

    Full Text Available Traumatic Brain Injury (TBI is one of the leading causes of death among critically ill patients from the Intensive Care Units (ICU. After primary traumatic injuries, secondary complications occur, which are responsible for the progressive degradation of the clinical status in this type of patients. These include severe inflammation, biochemical and physiological imbalances and disruption of the cellular functionality. The redox cellular potential is determined by the oxidant/antioxidant ratio. Redox potential is disturbed in case of TBI leading to oxidative stress (OS. A series of agression factors that accumulate after primary traumatic injuries lead to secondary lesions represented by brain ischemia and hypoxia, inflammatory and metabolic factors, coagulopathy, microvascular damage, neurotransmitter accumulation, blood-brain barrier disruption, excitotoxic damage, blood-spinal cord barrier damage, and mitochondrial dysfunctions. A cascade of pathophysiological events lead to accelerated production of free radicals (FR that further sustain the OS. To minimize the OS and restore normal oxidant/antioxidant ratio, a series of antioxidant substances is recommended to be administrated (vitamin C, vitamin E, resveratrol, N-acetylcysteine. In this paper we present the biochemical and pathophysiological mechanism of action of FR in patients with TBI and the antioxidant therapy available.

  15. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    Science.gov (United States)

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention.

  16. The glutathione mimic ebselen inhibits oxidative stress but not endoplasmic reticulum stress in endothelial cells.

    Science.gov (United States)

    Ahwach, Salma Makhoul; Thomas, Melanie; Onstead-Haas, Luisa; Mooradian, Arshag D; Haas, Michael J

    2015-08-01

    Reactive oxygen species are associated with cardiovascular disease, diabetes, and atherosclerosis, yet the use of antioxidants in clinical trials has been ineffective at improving outcomes. In endothelial cells, high-dextrose-induced oxidative stress and endoplasmic reticulum stress promote endothelial dysfunction leading to the recruitment and activation of peripheral blood lymphocytes and the breakdown of barrier function. Ebselen, a glutathione peroxidase 1 (GPX1) mimic, has been shown to improve β-cell function in diabetes and prevent atherosclerosis. To determine if ebselen inhibits both oxidative stress and endoplasmic reticulum (ER) stress in endothelial cells, we examined its effects in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) with and without high-dextrose. Oxidative stress and ER stress were measured by 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence and ER stress alkaline phosphatase assays, respectively. GPX1 over-expression and knockdown were performed by transfecting cells with a GPX1 expression construct or a GPX1-specific siRNA, respectively. Ebselen inhibited dextrose-induced oxidative stress but not ER stress in both HUVEC and HCAEC. Ebselen also had no effect on tunicamycin-induced ER stress in HCAEC. Furthermore, augmentation of GPX1 activity directly by sodium selenite supplementation or transfection of a GPX1 expression plasmid decreased dextrose-induced oxidative stress but not ER stress, while GPX1 knockout enhanced oxidative stress but had no effect on ER stress. These results suggest that ebselen targets only oxidative stress but not ER stress. Copyright © 2015. Published by Elsevier Inc.

  17. Protective effects of hesperidin against oxidative stress of tert-butyl hydroperoxide in human hepatocytes.

    Science.gov (United States)

    Chen, Mingcang; Gu, Honggang; Ye, Yiyi; Lin, Bing; Sun, Lijuan; Deng, Weiping; Zhang, Jingzhe; Liu, Jianwen

    2010-10-01

    Increasing evidence regarding free radical generating agents and the inflammatory process suggest that accumulation of reactive oxygen species (ROS) could involve hepatotoxicity. Hesperidin, a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects that include antioxidant, anti-inflammatory, antihypercholesterolemic, and anticarcinogenic actions. However, the cytoprotection and mechanism of hesperidin to neutralize oxidative stress in human hepatic L02 cells remain unclear. In this work, we assessed the capability of hesperidin to prevent tert-butyl hydroperoxide (t-BuOOH)-induced cell damage by augmenting cellular antioxidant defense. Hesperidin significantly protected hepatocytes against t-BuOOH-induced cell cytotoxicity, such as mitochondrial membrane potential (MMP) deplete and lactate dehydrogenase (LDH) release. Hesperidin also remarkably prevented indicators of oxidative stress, such as the ROS and lipid peroxidation level in a dose-dependent manner. Western blot showed that hesperidin facilitated ERK/MAPK phosphorylation which appeared to be responsible for nuclear translocation of Nrf2, thereby inducing cytoprotective heme oxygenase-1 (HO-1) expression. Based on the results described above, it suggested that hesperidin has potential as a therapeutic agent in the treatment of oxidative stress-related hepatocytes injury and liver dysfunctions. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2018-03-30

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

  19. Bacterial Nitric Oxide Synthase Is Required for the Staphylococcus aureus Response to Heme Stress.

    Science.gov (United States)

    Surdel, Matthew C; Dutter, Brendan F; Sulikowski, Gary A; Skaar, Eric P

    2016-08-12

    Staphylococcus aureus is a pathogen that causes significant morbidity and mortality worldwide. Within the vertebrate host, S. aureus requires heme as a nutrient iron source and as a cofactor for multiple cellular processes. Although required for pathogenesis, excess heme is toxic. S. aureus employs a two-component system, the heme sensor system (HssRS), to sense and protect against heme toxicity. Upon activation, HssRS induces the expression of the heme-regulated transporter (HrtAB), an efflux pump that alleviates heme toxicity. The ability to sense and respond to heme is critical for the pathogenesis of numerous Gram-positive organisms, yet the mechanism of heme sensing remains unknown. Compound '3981 was identified in a high-throughput screen as an activator of staphylococcal HssRS that triggers HssRS independently of heme accumulation. '3981 is toxic to S. aureus; however, derivatives of '3981 were synthesized that lack toxicity while retaining HssRS activation, enabling the interrogation of the heme stress response without confounding toxic effects of the parent molecule. Using '3981 derivatives as probes of the heme stress response, numerous genes required for '3981-induced activation of HssRS were uncovered. Specifically, multiple genes involved in the production of nitric oxide were identified, including the gene encoding bacterial nitric oxide synthase (bNOS). bNOS protects S. aureus from oxidative stress imposed by heme. Taken together, this work identifies bNOS as crucial for the S. aureus heme stress response, providing evidence that nitric oxide synthesis and heme sensing are intertwined.

  20. Glutathionylation of the Bacterial Hsp70 Chaperone DnaK Provides a Link between Oxidative Stress and the Heat Shock Response.

    Science.gov (United States)

    Zhang, Hong; Yang, Jie; Wu, Si; Gong, Weibin; Chen, Chang; Perrett, Sarah

    2016-03-25

    DnaK is the major bacterial Hsp70, participating in DNA replication, protein folding, and the stress response. DnaK cooperates with the Hsp40 co-chaperone DnaJ and the nucleotide exchange factor GrpE. Under non-stress conditions, DnaK binds to the heat shock transcription factor σ(32)and facilitates its degradation. Oxidative stress results in temporary inactivation of DnaK due to depletion of cellular ATP and thiol modifications such as glutathionylation until normal cellular ATP levels and a reducing environment are restored. However, the biological significance of DnaK glutathionylation remains unknown, and the mechanisms by which glutathionylation may regulate the activity of DnaK are also unclear. We investigated the conditions under which Escherichia coli DnaK undergoesS-glutathionylation. We observed glutathionylation of DnaK in lysates of E. coli cells that had been subjected to oxidative stress. We also obtained homogeneously glutathionylated DnaK using purified DnaK in the apo state. We found that glutathionylation of DnaK reversibly changes the secondary structure and tertiary conformation, leading to reduced nucleotide and peptide binding ability. The chaperone activity of DnaK was reversibly down-regulated by glutathionylation, accompanying the structural changes. We found that interaction of DnaK with DnaJ, GrpE, or σ(32)becomes weaker when DnaK is glutathionylated, and the interaction is restored upon deglutathionylation. This study confirms that glutathionylation down-regulates the functions of DnaK under oxidizing conditions, and this down-regulation may facilitate release of σ(32)from its interaction with DnaK, thus triggering the heat shock response. Such a mechanism provides a link between oxidative stress and the heat shock response in bacteria. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    Directory of Open Access Journals (Sweden)

    Khadija Rebbani

    2016-01-01

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

  2. Mini-review: Biofilm responses to oxidative stress.

    Science.gov (United States)

    Gambino, Michela; Cappitelli, Francesca

    2016-01-01

    Biofilms constitute the predominant microbial style of life in natural and engineered ecosystems. Facing harsh environmental conditions, microorganisms accumulate reactive oxygen species (ROS), potentially encountering a dangerous condition called oxidative stress. While high levels of oxidative stress are toxic, low levels act as a cue, triggering bacteria to activate effective scavenging mechanisms or to shift metabolic pathways. Although a complex and fragmentary picture results from current knowledge of the pathways activated in response to oxidative stress, three main responses are shown to be central: the existence of common regulators, the production of extracellular polymeric substances, and biofilm heterogeneity. An investigation into the mechanisms activated by biofilms in response to different oxidative stress levels could have important consequences from ecological and economic points of view, and could be exploited to propose alternative strategies to control microbial virulence and deterioration.

  3. Chronic pain, perceived stress, and cellular aging: an exploratory study

    OpenAIRE

    Sibille, Kimberly T; Langaee, Taimour; Burkley, Ben; Gong, Yan; Glover, Toni L; King, Chris; Riley, Joseph L; Leeuwenburgh, Christiaan; Staud, Roland; Bradley, Laurence A; Fillingim, Roger B

    2012-01-01

    Abstract Background Chronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL), a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of...

  4. Biochemical basis of the high resistance to oxidative stress

    Indian Academy of Sciences (India)

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

  5. Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

    Science.gov (United States)

    Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

    2016-10-01

    Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H 2 O 2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H 2 O 2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Carlos R. Arias-Barreiro

    2010-06-01

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

  7. Redox signaling via the molecular chaperone BiP protects cells against endoplasmic reticulum-derived oxidative stress

    Science.gov (United States)

    Wang, Jie; Pareja, Kristeen A; Kaiser, Chris A; Sevier, Carolyn S

    2014-01-01

    Oxidative protein folding in the endoplasmic reticulum (ER) has emerged as a potentially significant source of cellular reactive oxygen species (ROS). Recent studies suggest that levels of ROS generated as a byproduct of oxidative folding rival those produced by mitochondrial respiration. Mechanisms that protect cells against oxidant accumulation within the ER have begun to be elucidated yet many questions still remain regarding how cells prevent oxidant-induced damage from ER folding events. Here we report a new role for a central well-characterized player in ER homeostasis as a direct sensor of ER redox imbalance. Specifically we show that a conserved cysteine in the lumenal chaperone BiP is susceptible to oxidation by peroxide, and we demonstrate that oxidation of this conserved cysteine disrupts BiP's ATPase cycle. We propose that alteration of BiP activity upon oxidation helps cells cope with disruption to oxidative folding within the ER during oxidative stress. DOI: http://dx.doi.org/10.7554/eLife.03496.001 PMID:25053742

  8. Relationship between hyposalivation and oxidative stress in aging mice.

    Science.gov (United States)

    Yamauchi, Yoshitaka; Matsuno, Tomonori; Omata, Kazuhiko; Satoh, Tazuko

    2017-07-01

    The increase in oxidative stress that accompanies aging has been implicated in the abnormal advance of aging and in the onset of various systemic diseases. However, the details of what effects the increase in oxidative stress that accompanies aging has on saliva secretion are not known. In this study, naturally aging mice were used to examine the stimulated whole saliva flow rate, saliva and serum oxidative stress, antioxidant level, submandibular gland H-E staining, and immunofluorescence staining to investigate the effect of aging on the volume of saliva secretion and the relationship with oxidative stress, as well as the effect of aging on the structure of salivary gland tissue. The stimulated whole saliva flow rate decreased significantly with age. Also, oxidative stress increased significantly with age. Antioxidant levels, however, decreased significantly with age. Structural changes of the submandibular gland accompanying aging included atrophy of parenchyma cells and fatty degeneration and fibrosis of stroma, and the submandibular gland weight ratio decreased. These results suggest that oxidative stress increases with age, not just systemically but also locally in the submandibular gland, and that oxidative stress causes changes in the structure of the salivary gland and is involved in hyposalivation.

  9. Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

    Science.gov (United States)

    Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

    2018-01-01

    Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Ripk3 regulates cardiac microvascular reperfusion injury: The role of IP3R-dependent calcium overload, XO-mediated oxidative stress and F-action/filopodia-based cellular migration.

    Science.gov (United States)

    Zhou, Hao; Wang, Jin; Zhu, Pingjun; Hu, Shunying; Ren, Jun

    2018-05-01

    Ripk3-mediated cellular apoptosis is a major contributor to the pathogenesis of myocardial ischemia reperfusion (IR) injury. However, the mechanisms by which Ripk3 influences microvascular homeostasis and endothelial apoptosis are not completely understood. In this study, loss of Ripk3 inhibited endothelial apoptosis, alleviated luminal swelling, maintained microvasculature patency, reduced the expression of adhesion molecules and limited the myocardial inflammatory response. In vitro, Ripk3 deficiency protected endothelial cells from apoptosis and migratory arrest induced by HR injury. Mechanistically, Ripk3 had the ability to migrate onto the endoplasmic reticulum (ER), leading to ER damage, as evidenced by increased IP3R and XO expression. The higher IP3R content was associated with cellular calcium overload, and increased XO expression was involved in cellular oxidative injury. Furthermore, IP3R-mediated calcium overload and XO-dependent oxidative damage were able to initiate cellular apoptosis. More importantly, IP3R and XO also caused F-actin degradation into G-actin via post-transcriptional modification of cofilin, impairing the formation of the filopodia and limiting the migratory response of endothelial cells. Altogether, our data confirmed that Ripk3 was involved in microvascular IR injury via regulation of IP3R-mediated calcium overload, XO-dependent oxidative damage and filopodia-related cellular migration, ultimately leading to endothelial apoptosis and migratory inhibition. These findings provide a potential target for treating cardiac microcirculatory IR injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Induction of oxidative stress related responses in Arabidopsis thaliana after uranium exposure

    International Nuclear Information System (INIS)

    Vanhoudt, N.

    2009-01-01

    Uranium contamination in the environment has resulted from releases linked with nuclear fuel cycle activities and from industries extracting and processing materials containing naturally occurring radionuclides (for example phosphate industry). Uranium toxicity effects are predominantly studied on man and animal species, but little information is available for plants. If phytomanagement of uranium contaminated soils is considered, biological effects on the vegetation have to be investigated. Information on the contamination impact can also be used for risk assessment and derivation of clean-up standards. Plants can experience oxidative stress when they are exposed to environmental stress situations (for example exposure to heavy metals). Reactive oxygen species (ROS) are produced in both stressed and unstressed cells potentially leading to cellular damage. Consequently, plants have developed an antioxidative defence system comprising ROS-scavenging enzymes (e.g. SOD (superoxide dismutase), CAT (catalase) and metabolites (e.g. ascorbate, glutathione). Previous results showed that uranium exposure can cause an imbalance between the oxidative and antioxidative capacities of the plant cells. The present study aimed to analyse biological effects induced in Arabidopsis thaliana after bioaccumulation of uranium and to define possible dose-effect relationships. Subtle effects on the antioxidative defence system (enzymes, metabolites viewed as early responses for individual disturbances (growth, nutrient profile) were analysed

  12. Oxidative stress response after laparoscopic versus conventional sigmoid resection

    DEFF Research Database (Denmark)

    Madsen, Michael Tvilling; Kücükakin, Bülent; Lykkesfeldt, Jens

    2012-01-01

    Surgery is accompanied by a surgical stress response, which results in increased morbidity and mortality. Oxidative stress is a part of the surgical stress response. Minimally invasive laparoscopic surgery may result in reduced oxidative stress compared with open surgery. Nineteen patients...... scheduled for sigmoid resection were randomly allocated to open or laparoscopic sigmoid resection in a double-blind, prospective clinical trial. Three biochemical markers of oxidative stress (malondialdehyde, ascorbic acid, and dehydroascorbic acid) were measured at 6 different time points (preoperatively......, 1 h, 6 h, 24 h, 48 h, and 72 h postoperatively). There were no statistical significant differences between laparoscopic and open surgery for any of the 3 oxidative stress parameters. Malondialdehyde was reduced 1 hour postoperatively (P...

  13. Primary and secondary oxidative stress in Bacillus

    NARCIS (Netherlands)

    Mols, Maarten; Abee, Tjakko

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

  14. Primary and secondary oxidative stress in Bacillus

    NARCIS (Netherlands)

    Mols, J.M.; Abee, T.

    2011-01-01

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

  15. Xanthine Oxidase Inhibitor, Allopurinol, Prevented Oxidative Stress, Fibrosis, and Myocardial Damage in Isoproterenol Induced Aged Rats.

    Science.gov (United States)

    Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Alam, Md Ashraful

    2015-01-01

    We evaluated the preventive effect of allopurinol on isoproterenol (ISO) induced myocardial infarction in aged rats. Twelve- to fourteen-month-old male Long Evans rats were divided into three groups: control, ISO, and ISO + allopurinol. At the end of the study, all rats were sacrificed for blood and organ sample collection to evaluate biochemical parameters and oxidative stress markers analyses. Histopathological examinations were also conducted to assess inflammatory cell infiltration and fibrosis in heart and kidneys. Our investigation revealed that the levels of oxidative stress markers were significantly increased while the level of cellular antioxidants, catalase activity, and glutathione concentration in ISO induced rats decreased. Treatment with allopurinol to ISO induced rats prevented the elevated activities of AST, ALT, and ALP enzymes, and the levels of lipid peroxidation products and increased reduced glutathione concentration. ISO induced rats also showed massive inflammatory cells infiltration and fibrosis in heart and kidneys. Furthermore, allopurinol treatment prevented the inflammatory cells infiltration and fibrosis in ISO induced rats. In conclusion, the results of our study suggest that allopurinol treatment is capable of protecting heart of ISO induced myocardial infarction in rats probably by preventing oxidative stress, inflammation, and fibrosis.

  16. Chironomus riparius exposure to fullerene-contaminated sediment results in oxidative stress and may impact life cycle parameters

    International Nuclear Information System (INIS)

    Waissi, G.C.; Bold, S.; Pakarinen, K.; Akkanen, J.; Leppänen, M.T.; Petersen, E.J.; Kukkonen, J.V.K.

    2017-01-01

    Highlights: • FullerenesC_6_0 were tested to C. riparius with acute and chronic exposures. • The rapid uptake of fullerenes by C. riparius observed after an acute experiment. • Oxidative stress was localized in tissues under microvilli layer. - Abstract: A key component of understanding the potential environmental risks of fullerenes (C_6_0) is their potential effects on benthic invertebrates. Using the sediment dwelling invertebrate Chironomus riparius we explored the effects of acute (12 h and 24 h) and chronic (10 d, 15 d, and 28 d) exposures of sediment associated fullerenes. The aims of this study were to assess the impact of exposure to C_6_0 in the sediment top layer ((0.025, 0.18 and 0.48) C_6_0 mg/cm"2) on larval growth, oxidative stress and emergence rates and to quantify larval body burdens in similarly exposed organisms. Oxidative stress localization was observed in the tissues next to the microvilli and exoskeleton through a method for identifying oxidative stress reactions generated by reactive oxygen species. Rapid intake of fullerenes was shown in acute experiments, whereas body residues decreased after chronic exposure. Transmission electron microscopy analysis revealed oxidative damage and structural changes in cells located between the lipid droplets and next to the microvilli layer in fullerene exposed samples. Fullerene associated sediments also caused changes in the emergence rate of males and females, suggesting that the cellular interactions described above or other effects from the fullerenes may influence reproduction rates.

  17. Role of Zn doping in oxidative stress mediated cytotoxicity of TiO2 nanoparticles in human breast cancer MCF-7 cells

    Science.gov (United States)

    Ahamed, Maqusood; Khan, M. A. Majeed; Akhtar, Mohd Javed; Alhadlaq, Hisham A.; Alshamsan, Aws

    2016-07-01

    We investigated the effect of Zn-doping on structural and optical properties as well as cellular response of TiO2 nanoparticles (NPs) in human breast cancer MCF-7 cells. A library of Zn-doped (1-10 at wt%) TiO2 NPs was prepared. Characterization data indicated that dopant Zn was incorporated into the lattice of host TiO2. The average particle size of TiO2 NPs was decreases (38 to 28 nm) while the band gap energy was increases (3.35 eV-3.85 eV) with increasing the amount of Zn-doping. Cellular data demonstrated that Zn-doped TiO2 NPs induced cytotoxicity (cell viability reduction, membrane damage and cell cycle arrest) and oxidative stress (reactive oxygen species generation & glutathione depletion) in MCF-7 cells and toxic intensity was increases with increasing the concentration of Zn-doping. Molecular data revealed that Zn-doped TiO2 NPs induced the down-regulation of super oxide dismutase gene while the up-regulation of heme oxygenase-1 gene in MCF-7 cells. Cytotoxicity induced by Zn-doped TiO2 NPs was efficiently prevented by N-acetyl-cysteine suggesting that oxidative stress might be the primarily cause of toxicity. In conclusion, our data indicated that Zn-doping decreases the particle size and increases the band gap energy as well the oxidative stress-mediated toxicity of TiO2 NPs in MCF-7 cells.

  18. Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells.

    Science.gov (United States)

    Poletto, Mattia; Yang, Di; Fletcher, Sally C; Vendrell, Iolanda; Fischer, Roman; Legrand, Arnaud J; Dianov, Grigory L

    2017-09-29

    Ataxia telangiectasia (A-T) is a syndrome associated with loss of ATM protein function. Neurodegeneration and cancer predisposition, both hallmarks of A-T, are likely to emerge as a consequence of the persistent oxidative stress and DNA damage observed in this disease. Surprisingly however, despite these severe features, a lack of functional ATM is still compatible with early life, suggesting that adaptation mechanisms contributing to cell survival must be in place. Here we address this gap in our knowledge by analysing the process of human fibroblast adaptation to the lack of ATM. We identify profound rearrangement in cellular proteostasis occurring very early on after loss of ATM in order to counter protein damage originating from oxidative stress. Change in proteostasis, however, is not without repercussions. Modulating protein turnover in ATM-depleted cells also has an adverse effect on the DNA base excision repair pathway, the major DNA repair system that deals with oxidative DNA damage. As a consequence, the burden of unrepaired endogenous DNA lesions intensifies, progressively leading to genomic instability. Our study provides a glimpse at the cellular consequences of loss of ATM and highlights a previously overlooked role for proteostasis in maintaining cell survival in the absence of ATM function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Diabetic Cardiovascular Disease Induced by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Yosuke Kayama

    2015-10-01

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

  20. Oxidative Stress in Patients With Nongenital Warts

    Directory of Open Access Journals (Sweden)

    Sezai Sasmaz

    2005-01-01

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

  1. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Asieh Hosseini

    2013-01-01

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

  2. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Science.gov (United States)

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

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

  3. A systematic review of p53 regulation of oxidative stress in skeletal muscle.

    Science.gov (United States)

    Beyfuss, Kaitlyn; Hood, David A

    2018-12-01

    p53 is a tumor suppressor protein involved in regulating a wide array of signaling pathways. The role of p53 in the cell is determined by the type of imposed oxidative stress, its intensity and duration. The last decade of research has unravelled a dual nature in the function of p53 in mediating the oxidative stress burden. However, this is dependent on the specific properties of the applied stress and thus requires further analysis. A systematic review was performed following an electronic search of Pubmed, Google Scholar, and ScienceDirect databases. Articles published in the English language between January 1, 1990 and March 1, 2017 were identified and isolated based on the analysis of p53 in skeletal muscle in both animal and cell culture models. Literature was categorized according to the modality of imposed oxidative stress including exercise, diet modification, exogenous oxidizing agents, tissue manipulation, irradiation, and hypoxia. With low to moderate levels of oxidative stress, p53 is involved in activating pathways that increase time for cell repair, such as cell cycle arrest and autophagy, to enhance cell survival. However, with greater levels of stress intensity and duration, such as with irradiation, hypoxia, and oxidizing agents, the role of p53 switches to facilitate increased cellular stress levels by initiating DNA fragmentation to induce apoptosis, thereby preventing aberrant cell proliferation. Current evidence confirms that p53 acts as a threshold regulator of cellular homeostasis. Therefore, within each modality, the intensity and duration are parameters of the oxidative stressor that must be analyzed to determine the role p53 plays in regulating signaling pathways to maintain cellular health and function in skeletal muscle. Acadl: acyl-CoA dehydrogenase, long chain; Acadm: acyl-CoA dehydrogenase, C-4 to C-12 straight chain; AIF: apoptosis-inducing factor; Akt: protein kinase B (PKB); AMPK: AMP-activated protein kinase; ATF-4: activating

  4. The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice.

    Science.gov (United States)

    Kirkpatrick, Meg; Benoit, Janina; Everett, Wyll; Gibson, Jennifer; Rist, Michael; Fredette, Nicholas

    2015-09-01

    Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Hypertension and physical exercise: The role of oxidative stress.

    Science.gov (United States)

    Korsager Larsen, Monica; Matchkov, Vladimir V

    2016-01-01

    Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress and endothelial function. The aim of this review is to investigate the effect of oxidative stress in relation to hypertension and physical exercise, including the role of NO in the pathogenesis of hypertension. Endothelial dysfunction and decreased NO levels have been found to have the adverse effects in the correlation between oxidative stress and hypertension. Most of the previous studies found that aerobic exercise significantly decreased blood pressure and oxidative stress in hypertensive subjects, but the intense aerobic exercise can also injure endothelial cells. Isometric exercise decreases normally only systolic blood pressure. An alternative exercise, Tai chi significantly decreases blood pressure and oxidative stress in normotensive elderly, but the effect in hypertensive subjects has not yet been studied. Physical exercise and especially aerobic training can be suggested as an effective intervention in the prevention and treatment of hypertension and cardiovascular disease via reduction in oxidative stress. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  6. Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Lovelace, Erica S.; Wagoner, Jessica; MacDonald, James; Bammler, Theo; Bruckner, Jacob; Brownell, Jessica; Beyer, Richard; Zink, Erika M.; Kim, Young-Mo; Kyle, Jennifer E.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Metz, Thomas O.; Farin, Federico; Oberlies, Nicholas H.; Polyak, Steve

    2015-08-28

    Silymarin (SM), a natural product, is touted as a liver protectant and preventer of both chronic inflammation and diseases. To define how SM elicits these effects at a systems level, we performed transcriptional profiling, metabolomics, and signaling studies in human liver and T cell lines. Multiple pathways associated with cellular stress and metabolism were modulated by SM treatment within 0.5 to four hours: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4). Metabolomics analyses revealed suppression of glycolytic, TCA cycle, and amino acid metabolism by SM treatment. Antiinflammatory effects arose with prolonged (i.e. 24 hours) SM exposure, with suppression of multiple proinflammatory mRNAs and nuclear factor kappa B (NF-κB) and forkhead box O (FOXO) signaling. Studies with murine knock out cells revealed that SM inhibition of both mTOR and NF-κB was partially AMPK dependent, while SM inhibition of the mTOR pathway in part required DDIT4. Thus, SM activates stress and repair responses that culminate in an anti-inflammatory phenotype. Other natural products induced similar stress responses, which correlated with their ability to suppress inflammation. Therefore, natural products like SM may be useful as tools to define how metabolic, stress, and repair pathways regulate cellular inflammation.

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

    African Journals Online (AJOL)

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

  8. Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

    Science.gov (United States)

    Mohammad, Mohammad K; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

    2012-01-01

    Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. PMID:23026831

  9. Oxidative stress, aging, and diseases

    Directory of Open Access Journals (Sweden)

    Liguori I

    2018-04-01

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

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

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    Evon S. Ereifej

    2018-02-01

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

  11. 51Cr release and oxidative stress in the lens

    International Nuclear Information System (INIS)

    Stewart-DeHaan, P.J.; Sanwal, M.; Creighton, M.O.; Inch, W.R.; Trevithick, J.R.

    1989-01-01

    Examination of the opaque areas of human cortical cataracts has shown that a large portion of the opacity could be attributed to the globules found there. We tested models involving globule formation as a result of oxidative damage to rat lens cells in culture and whole chick embryo lenses. When cell monolayers from a lens cell line were exposed to oxidizing conditions they developed globules on the cell surface. The cells were protected from damage by the addition of glutathione and vitamin C. Thirteen-day chick embryo lenses were also incubated in oxidizing conditions and the amount of cellular damage was assessed using a chromium-51 release assay we have developed. After 24 hr the percent 51Cr in the medium increased by an average of 20% as a result of 10 mM hydrogen peroxide treatment. The addition of the 10 mM vitamin C to the hydrogen peroxide significantly reduced the 51Cr leakage to the control level. Light microscopy of sections of the lens showed a breakdown of the equatorial fibre arrangement in the presence of H2O2, while addition of vitamin C restored the fibre organization to almost normal. The findings suggest that oxidative stress is an important step in cataractogenesis and point towards the use of water soluble antioxidants as protective agents

  12. Exploring the Role of Genetic Variability and Lifestyle in Oxidative Stress Response for Healthy Aging and Longevity

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    Giuseppe Passarino

    2013-08-01

    Full Text Available Oxidative stress is both the cause and consequence of impaired functional homeostasis characterizing human aging. The worsening efficiency of stress response with age represents a health risk and leads to the onset and accrual of major age-related diseases. In contrast, centenarians seem to have evolved conservative stress response mechanisms, probably derived from a combination of a diet rich in natural antioxidants, an active lifestyle and a favorable genetic background, particularly rich in genetic variants able to counteract the stress overload at the level of both nuclear and mitochondrial DNA. The integration of these factors could allow centenarians to maintain moderate levels of free radicals that exert beneficial signaling and modulator effects on cellular metabolism. Considering the hot debate on the efficacy of antioxidant supplementation in promoting healthy aging, in this review we gathered the existing information regarding genetic variability and lifestyle factors which potentially modulate the stress response at old age. Evidence reported here suggests that the integration of lifestyle factors (moderate physical activity and healthy nutrition and genetic background could shift the balance in favor of the antioxidant cellular machinery by activating appropriate defense mechanisms in response to exceeding external and internal stress levels, and thus possibly achieving the prospect of living a longer life.

  13. Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress

    Science.gov (United States)

    McAllister, Kimberly; Worth, Leroy; Haugen, Astrid C.; Meyer, Joel N.; Domann, Frederick E.; Van Houten, Bennett; Mostoslavsky, Raul; Bultman, Scott J.; Baccarelli, Andrea A.; Begley, Thomas J.; Sobol, Robert W.; Hirschey, Matthew D.; Ideker, Trey; Santos, Janine H.; Copeland, William C.; Tice, Raymond R.; Balshaw, David M.; Tyson, Frederick L.

    2014-01-01

    Background: Cells respond to environmental stressors through several key pathways, including response to reactive oxygen species (ROS), nutrient and ATP sensing, DNA damage response (DDR), and epigenetic alterations. Mitochondria play a central role in these pathways not only through energetics and ATP production but also through metabolites generated in the tricarboxylic acid cycle, as well as mitochondria–nuclear signaling related to mitochondria morphology, biogenesis, fission/fusion, mitophagy, apoptosis, and epigenetic regulation. Objectives: We investigated the concept of bidirectional interactions between mitochondria and cellular pathways in response to environmental stress with a focus on epigenetic regulation, and we examined DNA repair and DDR pathways as examples of biological processes that respond to exogenous insults through changes in homeostasis and altered mitochondrial function. Methods: The National Institute of Environmental Health Sciences sponsored the Workshop on Mitochondria, Energetics, Epigenetics, Environment, and DNA Damage Response on 25–26 March 2013. Here, we summarize key points and ideas emerging from this meeting. Discussion: A more comprehensive understanding of signaling mechanisms (cross-talk) between the mitochondria and nucleus is central to elucidating the integration of mitochondrial functions with other cellular response pathways in modulating the effects of environmental agents. Recent studies have highlighted the importance of mitochondrial functions in epigenetic regulation and DDR with environmental stress. Development and application of novel technologies, enhanced experimental models, and a systems-type research approach will help to discern how environmentally induced mitochondrial dysfunction affects key mechanistic pathways. Conclusions: Understanding mitochondria–cell signaling will provide insight into individual responses to environmental hazards, improving prediction of hazard and susceptibility to

  14. Fatty acids and oxidative stress in psychiatric disorders

    OpenAIRE

    Tonello Lucio; Cocchi Massimo; Tsaluchidu Sofia; Puri Basant K

    2008-01-01

    Abstract Background The aim of this study was to determine whether there is published evidence for increased oxidative stress in neuropsychiatric disorders. Methods A PubMed search was carried out using the MeSH search term 'oxidative stress' in conjunction with each of the DSM-IV-TR diagnostic categories of the American Psychiatric Association in order to identify potential studies. Results There was published evidence of increased oxidative stress in the following DSM-IV-TR diagnostic categ...

  15. Agent-Based Modeling of Mitochondria Links Sub-Cellular Dynamics to Cellular Homeostasis and Heterogeneity.

    Directory of Open Access Journals (Sweden)

    Giovanni Dalmasso

    Full Text Available Mitochondria are semi-autonomous organelles that supply energy for cellular biochemistry through oxidative phosphorylation. Within a cell, hundreds of mobile mitochondria undergo fusion and fission events to form a dynamic network. These morphological and mobility dynamics are essential for maintaining mitochondrial functional homeostasis, and alterations both impact and reflect cellular stress states. Mitochondrial homeostasis is further dependent on production (biogenesis and the removal of damaged mitochondria by selective autophagy (mitophagy. While mitochondrial function, dynamics, biogenesis and mitophagy are highly-integrated processes, it is not fully understood how systemic control in the cell is established to maintain homeostasis, or respond to bioenergetic demands. Here we used agent-based modeling (ABM to integrate molecular and imaging knowledge sets, and simulate population dynamics of mitochondria and their response to environmental energy demand. Using high-dimensional parameter searches we integrated experimentally-measured rates of mitochondrial biogenesis and mitophagy, and using sensitivity analysis we identified parameter influences on population homeostasis. By studying the dynamics of cellular subpopulations with distinct mitochondrial masses, our approach uncovered system properties of mitochondrial populations: (1 mitochondrial fusion and fission activities rapidly establish mitochondrial sub-population homeostasis, and total cellular levels of mitochondria alter fusion and fission activities and subpopulation distributions; (2 restricting the directionality of mitochondrial mobility does not alter morphology subpopulation distributions, but increases network transmission dynamics; and (3 maintaining mitochondrial mass homeostasis and responding to bioenergetic stress requires the integration of mitochondrial dynamics with the cellular bioenergetic state. Finally, (4 our model suggests sources of, and stress conditions

  16. Yeast signaling pathways in the oxidative stress response

    Energy Technology Data Exchange (ETDEWEB)

    Ikner, Aminah [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States); Shiozaki, Kazuhiro [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States)]. E-mail: kshiozaki@ucdavis.edu

    2005-01-06

    Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed.

  17. Yeast signaling pathways in the oxidative stress response

    International Nuclear Information System (INIS)

    Ikner, Aminah; Shiozaki, Kazuhiro

    2005-01-01

    Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed

  18. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Jacob Barbara A

    2009-02-01

    Full Text Available Abstract Background HIV-infected individuals are at increased risk for acute and chronic airway disease even though there is no evidence that the virus can infect the lung epithelium. Although HIV-related proteins including gp120 and Tat can directly cause oxidant stress and cellular dysfunction, their effects in the lung are unknown. The goal of this study was to determine the effects of HIV-1 transgene expression in rats on alveolar epithelial barrier function. Alveolar epithelial barrier function was assessed by determining lung liquid clearance in vivo and alveolar epithelial monolayer permeability in vitro. Oxidant stress in the alveolar space was determined by measuring the glutathione redox couple by high performance liquid chromatography, and the expression and membrane localization of key tight junction proteins were assessed. Finally, the direct effects of the HIV-related proteins gp120 and Tat on alveolar epithelial barrier formation and tight junction protein expression were determined. Results HIV-1 transgene expression caused oxidant stress within the alveolar space and impaired epithelial barrier function even though there was no evidence of overt inflammation within the airways. The expression and membrane localization of the tight junction proteins zonula occludens-1 and occludin were decreased in alveolar epithelial cells from HIV-1 transgenic rats. Further, treating alveolar epithelial monolayers from wild type rats in vitro with recombinant gp120 or Tat for 24 hours reproduced many of the effects on zonula occludens-1 and occludin expression and membrane localization. Conclusion Taken together, these data indicate that HIV-related proteins cause oxidant stress and alter the expression of critical tight junction proteins in the alveolar epithelium, resulting in barrier dysfunction.

  19. Oxidative Stress and Antioxidant Potential of One Hundred Medicinal Plants.

    Science.gov (United States)

    Hassan, Waseem; Noreen, Hamsa; Rehman, Shakila; Gul, Shehnaz; Kamal, Mohammad Amjad; Kamdem, Jean Paul; Zaman, Bakht; da Rocha, Joao B T

    2017-01-01

    Reactive species are produced in biological system because of redox reactions. The imbalance in pro-oxidant and antioxidant homeostasis leads to the production of toxic reactive oxygen and nitrogen species like hydrogen peroxide, organic peroxides, hydroxyl radicals, superoxide anion and nitric oxide. Inactivation of metabolic enzymes, oxidation of biomolecules and cellular damage are some of the prominent characteristics of reactive species. Similarly, oxidative stress has been associated with more than one hundred (100) pathologies such as atherosclerosis, diabetes, cardiovascular diseases, pancreatic and liver diseases, joint disorders, cardiac fibrosis, acute respiratory distress syndrome, neurological diseases (amyotrophic lateral sclerosis, Huntington's disorder, Parkinson's disease and Alzheimer's disease), ageing and cancer etc. The toxicity of reactive species is balanced by the integrated antioxidant systems, which include enzymatic and non-enzymatic antioxidants. Antioxidant therapies or defenses protect the biological sites by removing or quenching the free radicals (prooxidants). Medicinal plants can not only protect the oxidative damage, but also play a vital role in health maintenance and prevention of chronic degenerative diseases. This review will provide a valuable discussion of one hundred (100) well known medicinal plants, which may add to the optimization of antioxidants rank. Besides, some of the antioxidant evaluation techniques or mechanisms via which medicinal plants act as antioxidants are also described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Benoist d’Azy, Cédric; Pereira, Bruno; Chiambaretta, Frédéric

    2016-01-01

    Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: “oxidative stress” or “oxidant stress” or “nitrative stress” or “oxidative damage” or “nitrative damage” or “antioxidative stress” or “antioxidant stress” or “antinitrative stress” and “glaucoma”. We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20–2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84–1.74) to 2.62 in aqueous humor (95%CI 1.60–3.65). Despite a decrease in antioxidative stress marker in serum (effect size = –0.41; 95%CI –0.72 to –0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20–5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88–9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78–16.6, P stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some

  1. Oxidative stress parameters in localized scleroderma patients.

    Science.gov (United States)

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

    2016-11-01

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

  2. H2O2 mediates ALA-induced glutathione and ascorbate accumulation in the perception and resistance to oxidative stress in Solanum lycopersicum at low temperatures.

    Science.gov (United States)

    Liu, Tao; Hu, Xiaohui; Zhang, Jiao; Zhang, Junheng; Du, Qingjie; Li, Jianming

    2018-02-15

    Low temperature is a crucial factor influencing plant growth and development. The chlorophyll precursor, 5-aminolevulinic acid (ALA) is widely used to improve plant cold tolerance. However, the interaction between H 2 O 2 and cellular redox signaling involved in ALA-induced resistance to low temperature stress in plants remains largely unknown. Here, the roles of ALA in perceiving and regulating low temperature-induced oxidative stress in tomato plants, together with the roles of H 2 O 2 and cellular redox states, were characterized. Low concentrations (10-25 mg·L - 1 ) of ALA enhanced low temperature-induced oxidative stress tolerance of tomato seedlings. The most effective concentration was 25 mg·L - 1 , which markedly increased the ratio of reduced glutathione and ascorbate (GSH and AsA), and enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Furthermore, gene expression of respiratory burst oxidase homolog1 and H 2 O 2 content were upregulated with ALA treatment under normal conditions. Treatment with exogenous H 2 O 2 , GSH, and AsA also induced plant tolerance to oxidative stress at low temperatures, while inhibition of GSH and AsA syntheses significantly decreased H 2 O 2 -induced oxidative stress tolerance. Meanwhile, scavenging or inhibition of H 2 O 2 production weakened, but did not eliminate, GSH- or AsA- induced tomato plant tolerance to oxidative stress at low temperatures. Appropriate concentrations of ALA alleviated the low temperature-induced oxidative stress in tomato plants via an antioxidant system. The most effective concentration was 25 mg·L - 1 . The results showed that H 2 O 2 induced by exogenous ALA under normal conditions is crucial and may be the initial step for perception and signaling transmission, which then improves the ratio of GSH and AsA. GSH and AsA may then interact with H 2 O 2 signaling, resulting in enhanced antioxidant capacity

  3. Effect of antibiotics on cellular stress generated in Shiga toxin-producing Escherichia coli O157:H7 and non-O157 biofilms.

    Science.gov (United States)

    Angel Villegas, Natalia; Baronetti, José; Albesa, Inés; Etcheverría, Analía; Becerra, M Cecilia; Padola, Nora L; Paraje, M Gabriela

    2015-10-01

    Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, with the main virulence factor of this bacterium being its capacity to secrete Shiga toxins (Stxs). Therefore, the use of certain antibiotics for the treatment of this infection, which induces the liberation of Stxs, is controversial. Reactive oxygen and nitrogen species are also involved in the pathogenesis of different diseases. The purpose of this study was to analyze the effects of antibiotics on biofilms of STEC and the relationships between cellular stress and the release of Stx. To this end, biofilms of reference and clinical strains were treated with antibiotics (ciprofloxacin, fosfomycin and rifaximin) and the production of oxidants, the antioxidant defense system and toxin release were evaluated. Ciprofloxacin altered the prooxidant-antioxidant balance, with a decrease of oxidant metabolites and an increase of superoxide dismutase and catalase activity, being associated with high-levels of Stx production. Furthermore, inhibition of oxidative stress by exogenous antioxidants was correlated with a reduction in the liberation of Stx, indicating the participation of this phenomenon in the release of this toxin. In contrast, fosfomycin and rifaximin produced less alteration with a minimal production of Stx. Our data show that treatment of biofilm-STEC with these antibiotics induces oxidative stress-mediated release of Stx. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells.

    Science.gov (United States)

    Zhang, Xing-Wei; Li, Wei-Fen; Li, Wei-Wei; Ren, Kan-Han; Fan, Chao-Ming; Chen, Ying-Ying; Shen, Yue-Liang

    2011-03-01

     Scutellaria baicalensis Georgi (Labiatae) (SbG), one of the fifty fundamental herbs of Chinese herbology, has been reported to have anti-asthmatic, antifungal, antioxidative, and anti-inflammatory activities.  This study was designed to determine the protective effects of the extract of SbG against the acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells (HUVEC).  The MTT reduction assay was employed to determine cell viability. The total cellular glutathione (GSH) level was detected using a colorimetric GSH assay kit. Cellular GSH production was conducted by detecting the mRNA expression levels of γ-glutamylcysteine ligase catalytic subunit and modifier subunit.  Concentration-dependent cytotoxic effects of acrolein were observed while SbG could effectively protect the acrolein-induced oxidative damage. The protective mechanism was investigated, showing that the increased GSH content in the SbG-incubated HUVE cells was associated with the protective effects of SbG-treated cells. Further RT-PCR data confirmed the elevated mRNA expressions of GSH synthesis enzymes.  The current study strongly indicated that SbG could be a potential antioxidant against oxidative stress in treating cardiovascular diseases.

  5. Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

    Science.gov (United States)

    Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

    2018-08-01

    Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

  6. Oxidative Stress, Apoptosis, and Mitochondrial Function in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Sonia Sifuentes-Franco

    2018-01-01

    Full Text Available Diabetic nephropathy (DN is the second most frequent and prevalent complication of diabetes mellitus (DM. The increase in the production of oxidative stress (OS is induced by the persistent hyperglycemic state capable of producing oxidative damage to the macromolecules (lipids, carbohydrates, proteins, and nucleic acids. OS favors the production of oxidative damage to the histones of the double-chain DNA and affects expression of the DNA repairer enzyme which leads to cell death from apoptosis. The chronic hyperglycemic state unchains an increase in advanced glycation end-products (AGE that interact through the cellular receptors to favor activation of the transcription factor NF-κB and the protein kinase C (PKC system, leading to the appearance of inflammation, growth, and augmentation of synthesis of the extracellular matrix (ECM in DN. The reactive oxygen species (ROS play an important role in the pathogenesis of diabetic complications because the production of ROS increases during the persistent hyperglycemia. The primary source of the excessive production of ROS is the mitochondria with the capacity to exceed production of endogenous antioxidants. Due to the fact that the mechanisms involved in the development of DN have not been fully clarified, there are different approaches to specific therapeutic targets or adjuvant management alternatives in the control of glycemia in DN.

  7. Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase

    OpenAIRE

    Brown, Charles O.; Salem, Kelley; Wagner, Brett A.; Bera, Soumen; Singh, Neeraj; Tiwari, Ajit; Choudhury, Amit; Buettner, Garry R.; Goel, Apollina

    2012-01-01

    IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plu...

  8. Chatty Mitochondria: Keeping Balance in Cellular Protein Homeostasis.

    Science.gov (United States)

    Topf, Ulrike; Wrobel, Lidia; Chacinska, Agnieszka

    2016-08-01

    Mitochondria are multifunctional cellular organelles that host many biochemical pathways including oxidative phosphorylation (OXPHOS). Defective mitochondria pose a threat to cellular homeostasis and compensatory responses exist to curtail the source of stress and/or its consequences. The mitochondrial proteome comprises proteins encoded by the nuclear and mitochondrial genomes. Disturbances in protein homeostasis may originate from mistargeting of nuclear encoded mitochondrial proteins. Defective protein import and accumulation of mistargeted proteins leads to stress that triggers translation alterations and proteasomal activation. These cytosolic pathways are complementary to the mitochondrial unfolded protein response (UPRmt) that aims to increase the capacity of protein quality control mechanisms inside mitochondria. They constitute putative targets for interventions aimed at increasing the fitness, stress resistance, and longevity of cells and organisms. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Diet-induced obesity associated with steatosis, oxidative stress, and inflammation in liver.

    Science.gov (United States)

    Peng, Yanhua; Rideout, Drew; Rakita, Steven; Lee, James; Murr, Michel

    2012-01-01

    Obesity induces steatosis and increases oxidative stress, as well as chronic inflammation in the liver. The balance between lipogenesis and lipolysis is disrupted in obese animals. At a cellular level, the changes in metabolic sensors and energy regulators are poorly understood. We hypothesized that diet-induced steatosis increases oxidative stress, inflammation, and changes the metabolic regulators to promote energy storage in mice. The setting was a university-affiliated basic science research laboratory. Four-week-old C57BL mice were fed a high-fat diet (n = 8) or regular chow (n = 8) for 7 weeks. The liver sections were stained for fat content and immunofluorescence. Liver homogenates were used for protein analysis by immunoblotting and mRNA analysis by reverse transcriptase-polymerase chain reaction. The gels were quantified using densitometry P ≤ .05 was considered significant. The high-fat diet upregulated protein kinase-C atypical isoforms ζ and λ and decreased glucose tolerance and the interaction of insulin receptor substrate 2 with phosphoinositide kinase-3. The high-fat diet increased the transcriptional factors liver X receptor (4321 ± 98 versus 2981 ± 80) and carbohydrate response element-binding protein (5132 ± 135 versus 3076 ± 91), the lipogenesis genes fatty acid binding protein 5, stearoyl-co-enzyme A desaturase-1, and acetyl-co-enzyme A carboxylase protein, and fatty acid synthesis. The high-fat diet decreased 5'-adenosine monophosphate-activated protein kinase (2561 ± 78 versus 1765 ± 65), glucokinase-3β (2.214 ± 34 versus 3356 ± 86), and SIRT1 (2015 ± 76 versus 3567 ± 104) and increased tumor necrosis factor-α (3415 ± 112 versus 2042 ± 65), nuclear factor kappa B (5123 ± 201 versus 2562 ± 103), cyclooxygenase-2 (4230 ± 113 versus 2473 ± 98), nicotinamide-adenine dinucleotide phosphate oxidase (3501 ± 106 versus 1600 ± 69) and reactive oxygen species production (all P high-fat diet impairs glucose tolerance and hepatic

  10. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kume, Toshiaki; Izumi, Yasuhiko [Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29, Simoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan); Park, Si-Bum [Laboratory of Industrial Microbiology, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun [Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Hirata, Takashi [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan); Faculty of Rehabilitation, Shijonawategakuen University, 5-11-10, Hojo, Daitou-shi, Osaka 574-0011 (Japan); Sugawara, Tatsuya, E-mail: sugawara@kais.kyoto-u.ac.jp [Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502 (Japan)

    2016-04-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

  11. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress

    International Nuclear Information System (INIS)

    Furumoto, Hidehiro; Nanthirudjanar, Tharnath; Kume, Toshiaki; Izumi, Yasuhiko; Park, Si-Bum; Kitamura, Nahoko; Kishino, Shigenobu; Ogawa, Jun; Hirata, Takashi; Sugawara, Tatsuya

    2016-01-01

    Oxidative stress is a well-known cause of multiple diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a central role in cellular antioxidative responses. In this study, we investigated the effects of novel fatty acid metabolite derivatives of linoleic acid generated by the gut lactic acid bacteria Lactobacillus plantarum on the Nrf2-ARE pathway. 10-Oxo-trans-11-octadecenoic acid (KetoC) protected HepG2 cells from cytotoxicity induced by hydrogen peroxide. KetoC also significantly increased cellular Nrf2 protein levels, ARE-dependent transcription, and the gene expression of antioxidative enzymes such as heme oxygenase-1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H:quinone oxidoreductase 1 (NQO1) in HepG2 cells. Additionally, a single oral dose administration of KetoC also increased antioxidative gene expression and protein levels of Nrf2 and HO-1 in mouse organs. Since other fatty acid metabolites and linoleic acid did not affect cellular antioxidative responses, the cytoprotective effect of KetoC may be because of its α,β-unsaturated carbonyl moiety. Collectively, our data suggested that KetoC activated the Nrf2-ARE pathway to enhance cellular antioxidative responses in vitro and in vivo, which further suggests that KetoC may prevent multiple diseases induced by oxidative stress. - Highlights: • We evaluated the effect of modified fatty acids generated by Lactobacillus plantarum. • 10-Oxo-trans-11-ocatadecenoic acid (KetoC) protected cells from oxidative stress. • KetoC activated the Nrf2-ARE pathway to promote antioxidative gene expression. • KetoC promoted the expression of antioxidative enzymes in mice organs. • The cytoprotective effect of KetoC was because of α,β-unsaturated carbonyl moiety.

  12. Ceruloplasmin Oxidation, a Feature of Parkinson's Disease CSF, Inhibits Ferroxidase Activity and Promotes Cellular Iron Retention

    KAUST Repository

    Olivieri, S.

    2011-12-14

    Parkinson\\'s disease is a neurodegenerative disorder characterized by oxidative stress and CNS iron deposition. Ceruloplasmin is an extracellular ferroxidase that regulates cellular iron loading and export, and hence protects tissues from oxidative damage. Using two-dimensional electrophoresis, we investigated ceruloplasmin patterns in the CSF of human Parkinson\\'s disease patients. Parkinson\\'s disease ceruloplasmin profiles proved more acidic than those found in healthy controls and in other human neurological diseases (peripheral neuropathies, amyotrophic lateral sclerosis, and Alzheimer\\'s disease); degrees of acidity correlated with patients\\' pathological grading. Applying an unsupervised pattern recognition procedure to the two-dimensional electrophoresis images, we identified representative pathological clusters. In vitro oxidation of CSF in two-dimensional electrophoresis generated a ceruloplasmin shift resembling that observed in Parkinson\\'s disease and co-occurred with an increase in protein carbonylation. Likewise, increased protein carbonylation was observed in Parkinson\\'s disease CSF, and the same modification was directly identified in these samples on ceruloplasmin. These results indicate that ceruloplasmin oxidation contributes to pattern modification in Parkinson\\'s disease. From the functional point of view, ceruloplasmin oxidation caused a decrease in ferroxidase activity, which in turn promotes intracellular iron retention in neuronal cell lines as well as in primary neurons, which are more sensitive to iron accumulation. Accordingly, the presence of oxidized ceruloplasmin in Parkinson\\'s disease CSF might be used as a marker for oxidative damage and might provide new insights into the underlying pathological mechanisms.

  13. Cellular Stress to Low Gamma-ray Dose

    International Nuclear Information System (INIS)

    Manzanares-Acuna, E.; Vega-Carrillo, H. R.; Letechipia de Leon, C.; Guzman Enriquez, L. J.; Garcia-Talavera, M.

    2004-01-01

    The purpose of this study was to evaluate the effect of low gamma ray intensity upon Hsp 70 expression in human lymphocytes. the heat shock proteins (Hsp) family, are a group of proteins present in all living organism, therefore there are highly conserved and are related to adaptation and evolution. At cellular level these proteins acts as chaperones correcting denatured proteins. when a stress agent, such heavy metals, UV, heat, etc. is affecting a cell a response to this aggression is triggered through overexpression of Hsp. Several studies has been carried out in which the cellular effect are observed, mostly of these studies uses large doses, but very few studies are related with low doses. Blood of healthy volunteers was obtained and the lymphocytes were isolated by ficoll-histopaque gradient. Experimental lots were irradiated in a ''137Cs gamma-ray. Hsp70 expression was found since 0.5 cGy, indicating a threshold to very low doses of gamma rays. (Author) 27 refs

  14. Reticular dysgenesis–associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress

    Science.gov (United States)

    Rissone, Alberto; Weinacht, Katja Gabriele; la Marca, Giancarlo; Bishop, Kevin; Giocaliere, Elisa; Jagadeesh, Jayashree; Felgentreff, Kerstin; Dobbs, Kerry; Al-Herz, Waleed; Jones, Marypat; Chandrasekharappa, Settara; Kirby, Martha; Wincovitch, Stephen; Simon, Karen Lyn; Itan, Yuval; DeVine, Alex; Schlaeger, Thorsten; Schambach, Axel; Sood, Raman

    2015-01-01

    Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy-depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD. PMID:26150473

  15. Coal and tire burning mixtures containing ultrafine and nanoparticulate materials induce oxidative stress and inflammatory activation in macrophages.

    Science.gov (United States)

    Gasparotto, Juciano; Somensi, Nauana; Caregnato, Fernanda F; Rabelo, Thallita K; DaBoit, Kátia; Oliveira, Marcos L S; Moreira, José C F; Gelain, Daniel P

    2013-10-01

    Ultra-fine and nano-particulate materials resulting from mixtures of coal and non-coal fuels combustion for power generation release to the air components with toxic potential. We evaluated toxicological and inflammatory effects at cellular level that could be induced by ultrafine/nanoparticles-containing ashes from burning mixtures of coal and tires from an American power plant. Coal fly ashes (CFA) samples from the combustion of high-S coal and tire-derived fuel, the latter about 2-3% of the total fuel feed, in a 100-MW cyclone utility boiler, were suspended in the cell culture medium of RAW 264.7 macrophages. Cell viability, assessed by MTT reduction, SRB incorporation and contrast-phase microscopy analysis demonstrated that CFA did not induce acute toxicity. However, CFA at 1mg/mL induced an increase of approximately 338% in intracellular TNF-α, while release of this proinflammatory cytokine was increased by 1.6-fold. The expression of the inflammatory mediator CD40 receptor was enhanced by 2-fold, the receptor for advanced glycation endproducts (RAGE) had a 5.7-fold increase and the stress response protein HSP70 was increased nearly 12-fold by CFA at 1mg/mL. Although CFA did not induce cell death, parameters of oxidative stress and reactive species production were found to be altered at several degrees, such as nitrite accumulation (22% increase), DCFH oxidation (3.5-fold increase), catalase (5-fold increase) and superoxide dismutase (35% inhibition) activities, lipoperoxidation (4.2 fold-increase) and sulfhydryl oxidation (40% decrease in free SH groups). The present results suggest that CFA containing ultra-fine and nano-particulate materials from coal and tire combustion may induce sub-chronic cell damage, as they alter inflammatory and oxidative stress parameters at the molecular and cellular levels, but do not induce acute cell death. © 2013.

  16. Regulation of taurine transport at the blood-placental barrier by calcium ion, PKC activator and oxidative stress conditions

    Directory of Open Access Journals (Sweden)

    Lee Na-Young

    2010-08-01

    Full Text Available Abstract Background In the present study, we investigated the changes of uptake and efflux transport of taurine under various stress conditions using rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT cells, as in vitro blood-placental barrier (BPB model. Methods The transport of taurine in TR-TBT cells were characterized by cellular uptake study using radiolabeled taurine. The efflux of taurine was measured from the amount of radiolabeled taurine remaining in the cells after the uptake of radiolabeled taurine for 60 min. Results Taurine uptake was significantly decreased by phosphorylation of protein kinase C (PKC activator in TR-TBT cells. Also, calcium ion (Ca2+ was involved in taurine transport in TR-TBT cells. Taurine uptake was inhibited and efflux was enhanced under calcium free conditions in the cells. In addition, oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of oxidative stress inducing agents. Tumor necrosis factor-α (TNF-α, lipopolysaccharide (LPS and diethyl maleate (DEM significantly increased taurine uptake, but H2O2 and nitric oxide (NO donor decreased taurine uptake in the cells. Taurine efflux was down-regulated by TNF-α in TR-TBT cells. Conclusion Taurine transport in TR-TBT cells were regulated diversely at extracellular Ca2+ level, PKC activator and oxidative stress conditions. It suggested that variable stresses affected the taurine supplies from maternal blood to fetus and taurine level of fetus.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  18. Oxidative Stress in Myopia

    Directory of Open Access Journals (Sweden)

    Bosch-Morell Francisco

    2015-01-01

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

  19. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

    Science.gov (United States)

    Nitta, Masayuki; Kozono, David; Kennedy, Richard; Stommel, Jayne; Ng, Kimberly; Zinn, Pascal O; Kushwaha, Deepa; Kesari, Santosh; Inda, Maria-del-Mar; Wykosky, Jill; Furnari, Frank; Hoadley, Katherine A; Chin, Lynda; DePinho, Ronald A; Cavenee, Webster K; D'Andrea, Alan; Chen, Clark C

    2010-05-24

    Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

  20. Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy.

    Directory of Open Access Journals (Sweden)

    Masayuki Nitta

    Full Text Available Despite the critical role of Epidermal Growth Factor Receptor (EGFR in glioblastoma pathogenesis, EGFR targeted therapies have achieved limited clinical efficacy. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction. A directed RNAi screen revealed that glioblastoma cells over-expressing EGFRvIII, an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER genes required for the repair of Reactive Oxygen Species (ROS-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1. Subsequent studies revealed that EGFRvIII over-expression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

  1. The impact of match-play tennis in a hot environment on indirect markers of oxidative stress and antioxidant status

    Science.gov (United States)

    Knez, Wade L; Périard, JP

    2014-01-01

    Objectives The purpose of this study was to determine the impact of changes in oxidative stress and antioxidant status in response to playing tennis in HOT (∼36°C and 35% relative humidity (RH)) and COOL (∼22°C and 70% RH) conditions. Methods 10 male tennis players undertook two matches for an effective playing time (ie, ball in play) of 20 min, corresponding to ∼122 and ∼107 min of total play in HOT and COOL conditions, respectively. Core body temperature, body mass and indirect markers of oxidative stress (diacrons reactive oxygen metabolic test) and antioxidant status (biological antioxidant potential test) were assessed immediately prematch, midmatch and postmatch, and 24 and 48 h into recovery. Results Regardless of the condition, oxidative stress remained similar throughout play and into recovery. Likewise, match-play tennis in the COOL had no impact on antioxidant status. However, antioxidants status increased significantly in the HOT compared with COOL environment (pantioxidant status. These data suggest that the heat stress observed in the HOT environment may provide a necessary signal for the upregulation of antioxidant defence, dampening cellular damage. PMID:24668382

  2. Chironomus riparius exposure to fullerene-contaminated sediment results in oxidative stress and may impact life cycle parameters

    Energy Technology Data Exchange (ETDEWEB)

    Waissi, G.C., E-mail: greta.waissi@uef.fi [Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu (Finland); Bold, S. [GEOMAR Helmholtz Centre of Ocean for Research Kiel (Germany); Pakarinen, K.; Akkanen, J. [Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu (Finland); Leppänen, M.T. [Finnish Environment Institute, Jyväskylä (Finland); Petersen, E.J. [Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD (United States); Kukkonen, J.V.K. [University of Jyväskylä, Department of Biological and Environmental Science, Jyväskylä (Finland)

    2017-01-15

    Highlights: • FullerenesC{sub 60} were tested to C. riparius with acute and chronic exposures. • The rapid uptake of fullerenes by C. riparius observed after an acute experiment. • Oxidative stress was localized in tissues under microvilli layer. - Abstract: A key component of understanding the potential environmental risks of fullerenes (C{sub 60}) is their potential effects on benthic invertebrates. Using the sediment dwelling invertebrate Chironomus riparius we explored the effects of acute (12 h and 24 h) and chronic (10 d, 15 d, and 28 d) exposures of sediment associated fullerenes. The aims of this study were to assess the impact of exposure to C{sub 60} in the sediment top layer ((0.025, 0.18 and 0.48) C{sub 60} mg/cm{sup 2}) on larval growth, oxidative stress and emergence rates and to quantify larval body burdens in similarly exposed organisms. Oxidative stress localization was observed in the tissues next to the microvilli and exoskeleton through a method for identifying oxidative stress reactions generated by reactive oxygen species. Rapid intake of fullerenes was shown in acute experiments, whereas body residues decreased after chronic exposure. Transmission electron microscopy analysis revealed oxidative damage and structural changes in cells located between the lipid droplets and next to the microvilli layer in fullerene exposed samples. Fullerene associated sediments also caused changes in the emergence rate of males and females, suggesting that the cellular interactions described above or other effects from the fullerenes may influence reproduction rates.

  3. 13 reasons why the brain is susceptible to oxidative stress

    Directory of Open Access Journals (Sweden)

    James Nathan Cobley

    2018-05-01

    Full Text Available The human brain consumes 20% of the total basal oxygen (O2 budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity through redox signalling (i.e. positive functionality. Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e. negative functionality. To advance mechanistic understanding, we rationalise 13 reasons why the brain is susceptible to oxidative stress. Key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation. We review RNA oxidation as an underappreciated cause of oxidative stress. The complex interplay between each reason dictates neuronal susceptibility to oxidative stress in a dynamic context and neural identity dependent manner. Our discourse sets the stage for investigators to interrogate the biochemical basis of oxidative stress in the brain in health and disease.

  4. Formation of cellular films consisting of wurtzite-type zinc oxide nanosheets by mediation of phosphate anions

    International Nuclear Information System (INIS)

    Yamabi, Satoshi; Yahiro, Junko; Iwai, Satoko; Imai, Hiroaki

    2005-01-01

    We successfully prepared a wide variety of wurtzite-type zinc oxide films exhibiting columnar, cellular and densely packed morphologies in a simple aqueous solution system containing phosphate anions. As the phosphate concentration increased, the shape of crystalline units composing the films varied from hexagonal needles into seaweed-like sheets. A novel type of open cellular structures was obtained by assembly of nanoscale zinc oxide sheets covered with phosphate. Specific adsorption of phosphate anions on (001) of the wurtzite-type crystal flattened the crystal grains, and then induced the structural evolution into a cellular form. A blue shift of the absorption edge suggested that the quantum size effect occurred in the nanoscale platy crystals composing the cellular films

  5. Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

    Directory of Open Access Journals (Sweden)

    Ken Shinmura

    2013-01-01

    Full Text Available The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

  6. Lutein as protective agent against neonatal oxidative stress

    Directory of Open Access Journals (Sweden)

    Giuseppe Buonocore

    2014-06-01

    Full Text Available Free radicals (FR are important for a correct development of neonatal organs and tissues. However, newborn and fetus have profoundly impaired antioxidant system. In these subjects, oxidative stress (OS may be detrimental by activating deleterious cellular processes. Decreasing FR and restoring oxidative imbalance certainly appear to be beneficial in perinatal period. Among the therapeutic antioxidant approaches in newborns, lutein, a compound belonging to the xanthophyll family of carotenoids, is one of the emerging strategies. Humans cannot synthesize lutein, hence the intake primarily depends on diet. In the neonatal period, fresh, non-processed human milk is the main dietary source of lutein, while infant formula is lacking it. Lutein has antioxidant and anti-inflammatory properties. Lutein supplementation in human newborns during the first days of life has been demonstrated to decrease plasma biomarkers of OS and increase antioxidant capacities. Numerous experimental study have demonstrated that lutein effectively neutralizes oxidants and modulates inflammatory processes, showing particular protective effects on macula and photoreceptors against phototoxicity and oxidative injury. Only few clinical studies evaluated the effectiveness of lutein in reducing preterm and term infant morbidity, reporting no definitive results. The challenge for the future is to better clarify the timing, the optimal dose and the duration of lutein intervention in perinatal period and to verify its impact on infants’ health. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  7. Cognitive impairment and Alzheimer’s disease: Links with oxidative stress and cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Alejandra Sekler

    2008-08-01

    Full Text Available Alejandra Sekler1,2, José M Jiménez2, Leonel Rojo2, Edgard Pastene3, Patricio Fuentes4, Andrea Slachevsky4, Ricardo B Maccioni1,21Center of Cognitive Neurosciences, International Center for Biomedicine (ICC, Santiago, Chile; 2Laboratory of Cellular, Molecular Biology and Neurosciences, Faculty of Sciences, Universidad de Chile, Santiago, Chile; 3Department of Pharmacy, Faculty of Pharmacy, University of Concepcion, Concepción, Chile; 4Unidad de Neurología Cognitiva y Demencias, Servicio de Neurología, Hospital del Salvador, Santiago, ChileAbstract: Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD, Parkinson’s disease and amyotrophic lateral sclerosis. We carried out an in-depth study of cognitive impairment and its relationships with oxidative stress markers such as ferric-reducing ability of plasma (FRAP, plasma malondialdehyde and total antioxidative capacity (TAC, as well as cholesterol parameters, in two subsets of subjects, AD patients (n = 59 and a control group of neurologically normal subjects (n = 29, attending the University Hospital Salvador in Santiago, Chile. Cognitive impairment was assessed by a set of neuropsychological tests (Mini-Mental State Examination, Boston Naming Test, Ideomotor Praxia by imitation, Semantic Verbal Fluency of animals or words with initial A, Test of Memory Alteration, Frontal Assessment Battery, while the levels of those oxidative stress markers and cholesterol metabolism parameters were determined according with standard bioassays in fresh plasma samples of the two subgroups of patients. No significant differences were observed when the cholesterol parameters (low-, high-density lipoprotein, total cholesterol of the AD group were compared with normal controls. Interestingly, a correlation was evidenced when the levels of cognitive impairment were analyzed with respect to the plasma antioxidant capacity (AOC of

  8. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Sha Li

    2015-11-01

    Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  9. [Effect of occupational stress on oxidation/antioxidant capacity in nurses].

    Science.gov (United States)

    Cao, Lili; Tian, Honger; Zhang, Qingdong; Zhu, Xinyun; Zhan, Yongguo; Su, Jingguo; Xu, Tian; Zhu, Huabin; Liu, Ling

    2014-02-01

    To investigate the effect of occupational stress on the oxidation/antioxidant capacity in nurses. A total of 131 nurses were included as study subjects. The occupational health information collection system (based on the Internet of things) was used for measurement of occupational stress. Levels of hydroxyl free radicals and antioxidant enzymes were determined. The serum level of superoxide dismutase (SOD) was the highest in nurses under the age of 30 and the lowest in those over 45 (P occupational stress factors for SOD. Job hazards were negative occupational stress factors for POD. Psychological satisfaction was negative occupational stress reaction for hydroxyl free radicals. Calmness was positive occupational stress reaction for SOD, and daily stress was a negative one. The positive occupational stress reactions for GSH-Px were psychological satisfaction and job satisfaction, and daily stress was negative reaction. Nurses with higher occupational stress have stronger oxidation and weaker antioxidant capacity, which intensifies oxidant-antioxidant imbalance and leads to oxidative stress damage.

  10. Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism.

    Science.gov (United States)

    He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Junna; Xie, Yanzhao; Chen, Yanxia

    2017-01-01

    Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H 2 O 2 ). Shh alleviated the apoptosis rate of H 2 O 2 -induced neurons. Shh also increased neuritogenesis injuried by H 2 O 2 in primary cortical neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS), increased the activities of SOD and and decreased the productions of MDA. In addition, Shh protected mitochondrial functions, elevated the cellular ATP levels and amelioratesd the impairment of mitochondrial complex II activities of cortical neurons induced by H 2 O 2 . In conclusion, all these results suggest that Shh acts as a prosurvival factor playing an essential role to neurite outgrowth of cortical neuron under H 2 O 2 -induced oxidative stress, possibly through counteracting ROS release and preventing mitochondrial dysfunction and ATP as well as mitochondrial complex II activities against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Harmonising measurements of 8-oxo-7,8-dihydro-2'-deoxyguanosine in cellular DNA and urine

    DEFF Research Database (Denmark)

    Møller, Peter; Cooke, Marcus S; Collins, Andrew

    2012-01-01

    Levels of oxidatively damaged cellular DNA and urinary excretion of damaged 2'-deoxyribonuclosides are widely measured in biomonitoring studies examining the role of oxidative stress induced by environmental exposures, lifestyle factors and development of disease. This has promoted efforts to har...

  12. Black rice extract protected HepG2 cells from oxidative stress-induced cell death via ERK1/2 and Akt activation

    Science.gov (United States)

    Yoon, Jaemin; Ham, Hyeonmi; Sung, Jeehye; Kim, Younghwa; Choi, Youngmin; Lee, Jeom-Sig; Jeong, Heon-Sang; Lee, Junsoo

    2014-01-01

    BACKGROUND/OBJECTIVES The objective of this study was to evaluate the protective effect of black rice extract (BRE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. MATERIALS/METHODS Methanolic extract from black rice was evaluated for the protective effect on TBHP-induced oxidative injury in HepG2 cells. Several biomarkers that modulate cell survival and death including reactive oxygen species (ROS), caspase-3 activity, and related cellular kinases were determined. RESULTS TBHP induced cell death and apoptosis by a rapid increase in ROS generation and caspase-3 activity. Moreover, TBHP-induced oxidative stress resulted in a transient ERK1/2 activation and a sustained increase of JNK1/2 activation. While, BRE pretreatment protects the cells against oxidative stress by reducing cell death, caspase-3 activity, and ROS generation and also by preventing ERKs deactivation and the prolonged JNKs activation. Moreover, pretreatment of BRE increased the activation of ERKs and Akt which are pro-survival signal proteins. However, this effect was blunted in the presence of ERKs and Akt inhibitors. CONCLUSIONS These results suggest that activation of ERKs and Akt pathway might be involved in the cytoprotective effect of BRE against oxidative stress. Our