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Sample records for cellular oxidative stress

  1. Oxidative stress action in cellular aging

    OpenAIRE

    Monique Cristine de Oliveira; João Paulo Ferreira Schoffen

    2010-01-01

    Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the fac...

  2. Oxidative stress action in cellular aging

    Directory of Open Access Journals (Sweden)

    Monique Cristine de Oliveira

    2010-12-01

    Full Text Available Various theories try to explain the biological aging by changing the functions and structure of organic systems and cells. During lifetime, free radicals in the oxidative stress lead to lipid peroxidation of cellular membranes, homeostasis imbalance, chemical residues formation, gene mutations in DNA, dysfunction of certain organelles, and the arise of diseases due to cell death and/or injury. This review describes the action of oxidative stress in the cells aging process, emphasizing the factors such as cellular oxidative damage, its consequences and the main protective measures taken to prevent or delay this process. Tests with antioxidants: vitamins A, E and C, flavonoids, carotenoids and minerals, the practice of caloric restriction and physical exercise, seeking the beneficial effects on human health, increasing longevity, reducing the level of oxidative stress, slowing the cellular senescence and origin of certain diseases, are discussed.Diferentes teorias tentam explicar o envelhecimento biológico através da alteração das funções e estrutura dos sistemas orgânicos e células. Ao longo da vida, os radicais livres presentes no estresse oxidativo conduzem à peroxidação dos lipídios das membranas celulares, desequilíbrio da homeostase, formação de resíduos químicos, mutações gênicas no DNA, disfunção de certas organelas, bem como ao surgimento de doenças devido à lesão e/ou morte celular. Nesta revisão descreve-se a ação do estresse oxidativo no processo de envelhecimento das células, enfatizando fatores como os danos oxidativos celulares, suas conseqüências e as principais medidas protetoras adotadas para se prevenir ou retardar este processo. Testes com antioxidantes: vitaminas A, E e C, flavonóides, carotenóides e minerais; a prática de restrição calórica e exercícios físicos, que buscam efeitos benéficos sobre a saúde humana, aumentando a longevidade, reduzindo o nível de estresse oxidativo

  3. Fluorosis Caused Cellular Apoptosis and Oxidative Stress of Rat Kidneys

    Institute of Scientific and Technical Information of China (English)

    SONG Yang; WANG Jin-cheng; XU Hui; DU Zhen-wu; ZHANG Gui-zhen; SELIM Hamid Abdu; LI Guang-sheng

    2013-01-01

    As the strongest electronegative element,fluorine can stimulate the production of superoxide radicals in cells.In view of the important roles of kidneys in bone metabolism,the authors analyzed the quantitative pathomorphological characteristics of renal damage and the potential cellular apoptosis and oxidative stress mechanisms in rats treated with excessive fluoride.Wistar rats were exposed to 50 mg F-(110.5 mg NaF)/L,100 mg F-(221.0 mg NaF)/Land 150 mg F (331.5 mg NaF)/L in drinking water for 70 and 140 d,respectively.Microscope with image analysis was used to quantitate pathomorphological changes in renal tissues of the rats.Reactive oxygen species(ROS),the cell cycle and apoptosis of renal cells were measured by flow cytometry and TUNEL technique(terminal deoxynucleotidyl transferase dUTP nick end labeling),respectively.The ion concentrations in serum and renal functional parameters were detected by automatic biochemical analyzer.Quantitative analysis results demonstrate the expanded Bowman's space of glomerulus and obvious dilatation of renal tubule.TUNEL technique revealed that NBT/BCIP (nitro blue tetrazoliurn/5-bromo-4-chloro-3′-indolylphosphate,p-toluidine salt)-staining positive apoptotic cells selectively located in medullocortical junction areas.The data suggest that renal damage in chronic fluorostic rats is associated with the cellular apoptosis and oxidative stress.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Oxidative Stress and Anxiety: Relationship and Cellular Pathways

    OpenAIRE

    Jaouad Bouayed; Hassan Rammal; Rachid Soulimani

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  6. Oxidative stress-induced proteome alterations target different cellular pathways in human myoblasts

    DEFF Research Database (Denmark)

    Baraibar, Martin A; Hyzewicz, Janek; Rogowska-Wrzesinska, Adelina;

    2011-01-01

    Although increased oxidative stress has been associated with the impairment of proliferation and function of adult human muscle stem cells, proteins either involved in the stress response or damaged by oxidation have not been identified. A parallel proteomics approach was performed for analyzing...... are mainly cytosolic and involved in carbohydrate metabolism, cellular assembly, cellular homeostasis, and protein synthesis and degradation. Pathway analysis revealed skeletal and muscular disorders, cell death, and cancer-related as the main molecular networks altered. Interestingly, these pathways...

  7. Redox Sensitivities of Global Cellular Cysteine Residues under Reductive and Oxidative Stress.

    Science.gov (United States)

    Araki, Kazutaka; Kusano, Hidewo; Sasaki, Naoyuki; Tanaka, Riko; Hatta, Tomohisa; Fukui, Kazuhiko; Natsume, Tohru

    2016-08-01

    The protein cysteine residue is one of the amino acids most susceptible to oxidative modifications, frequently caused by oxidative stress. Several applications have enabled cysteine-targeted proteomics analysis with simultaneous detection and quantitation. In this study, we employed a quantitative approach using a set of iodoacetyl-based cysteine reactive isobaric tags (iodoTMT) and evaluated the transient cellular oxidation ratio of free and reversibly modified cysteine thiols under DTT and hydrogen peroxide (H2O2) treatments. DTT treatment (1 mM for 5 min) reduced most cysteine thiols, irrespective of their cellular localizations. It also caused some unique oxidative shifts, including for peroxiredoxin 2 (PRDX2), uroporphyrinogen decarboxylase (UROD), and thioredoxin (TXN), proteins reportedly affected by cellular reactive oxygen species production. Modest H2O2 treatment (50 μM for 5 min) did not cause global oxidations but instead had apparently reductive effects. Moreover, with H2O2, significant oxidative shifts were observed only in redox active proteins, like PRDX2, peroxiredoxin 1 (PRDX1), TXN, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Overall, our quantitative data illustrated both H2O2- and reduction-mediated cellular responses, whereby while redox homeostasis is maintained, highly reactive thiols can potentiate the specific, rapid cellular signaling to counteract acute redox stress.

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

    DEFF Research Database (Denmark)

    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...

  9. Cellular and subcellular oxidative stress parameters following severe spinal cord injury.

    Science.gov (United States)

    Visavadiya, Nishant P; Patel, Samir P; VanRooyen, Jenna L; Sullivan, Patrick G; Rabchevsky, Alexander G

    2016-08-01

    The present study undertook a comprehensive assessment of the acute biochemical oxidative stress parameters in both cellular and, notably, mitochondrial isolates following severe upper lumbar contusion spinal cord injury (SCI) in adult female Sprague Dawley rats. At 24h post-injury, spinal cord tissue homogenate and mitochondrial fractions were isolated concurrently and assessed for glutathione (GSH) content and production of nitric oxide (NO(•)), in addition to the presence of oxidative stress markers 3-nitrotyrosine (3-NT), protein carbonyl (PC), 4-hydroxynonenal (4-HNE) and lipid peroxidation (LPO). Moreover, we assessed production of superoxide (O2(•-)) and hydrogen peroxide (H2O2) in mitochondrial fractions. Quantitative biochemical analyses showed that compared to sham, SCI significantly lowered GSH content accompanied by increased NO(•) production in both cellular and mitochondrial fractions. SCI also resulted in increased O2(•-) and H2O2 levels in mitochondrial fractions. Western blot analysis further showed that reactive oxygen/nitrogen species (ROS/RNS) mediated PC and 3-NT production were significantly higher in both fractions after SCI. Conversely, neither 4-HNE levels nor LPO formation were increased at 24h after injury in either tissue homogenate or mitochondrial fractions. These results indicate that by 24h post-injury ROS-induced protein oxidation is more prominent compared to lipid oxidation, indicating a critical temporal distinction in secondary pathophysiology that is critical in designing therapeutic approaches to mitigate consequences of oxidative stress. PMID:26760911

  10. Electrochemical Potential Gradient as a Quantitative in Vitro Test Platform for Cellular Oxidative Stress.

    Science.gov (United States)

    Bryant, Carson; Atha, Donald; Reipa, Vytas

    2016-01-01

    Oxidative stress in a biological system is often defined as a redox imbalance within cells or groups of cells within an organism. Reductive-oxidative (redox) imbalances in cellular systems have been implicated in several diseases, such as cancer. To better understand the redox environment within cellular systems, it is important to be able to characterize the relationship between the intensity of the oxidative environment, characterized by redox potential, and the biomolecular consequences of oxidative damage. In this study, we show that an in situ electrochemical potential gradient can serve as a tool to simulate exogenous oxidative stress in surface-attached mammalian cells. A culture plate design, which permits direct imaging and analysis of the cell viability, following exposure to a range of solution redox potentials, was developed. The in vitro oxidative stress test vessel consists of a cell growth flask fitted with two platinum electrodes that support a direct current along the flask bottom. The applied potential span and gradient slope can be controlled by adjusting the constant current magnitude across the vessel with spatially localized media potentials measured with a sliding reference electrode. For example, the viability of Chinese Hamster Ovary cells under a gradient of redox potentials indicated that cell death was initiated at approximately 0.4 V vs. standard hydrogen electrode (SHE) media potential and this potential could be modified with antioxidants. This experimental platform may facilitate studies of oxidative stress characteristics on different types of cells by enabling imaging live cell cultures that have been exposed to a gradient of exogenous redox potentials. PMID:27409641

  11. Thioredoxin-dependent Redox Regulation of Cellular Signaling and Stress Response through Reversible Oxidation of Methionines

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2011-06-01

    Generation of reactive oxygen species (ROS) is a common feature of many forms of stress to which plants are exposed. Successful adaptation to changing environmental conditions requires sensitive sensors of ROS such as protein-bound methionines that are converted to their corresponding methionine sulfoxides, which in turn can influence cellular signaling pathways. Such a signaling protein is calmodulin, which represents an early and central point in calcium signaling pathways important to stress response in plants. We describe recent work elucidating fundamental mechanisms of reversible methionine oxidation within calmodulin, including the sensitivity of individual methionines within plant and animal calmodulin to ROS, the structural and functional consequences of their oxidation, and the interactions of oxidized calmodulin with methionine sulfoxide reductase enzymes.

  12. Enhanced susceptibility of T lymphocytes to oxidative stress in the absence of the cellular prion protein.

    Science.gov (United States)

    Aude-Garcia, Catherine; Villiers, Christian; Candéias, Serge M; Garrel, Catherine; Bertrand, Caroline; Collin, Véronique; Marche, Patrice N; Jouvin-Marche, Evelyne

    2011-02-01

    The cellular prion glycoprotein (PrP(C)) is ubiquitously expressed but its physiologic functions remain enigmatic, particularly in the immune system. Here, we demonstrate in vitro and in vivo that PrP(C) is involved in T lymphocytes response to oxidative stress. By monitoring the intracellular level of reduced glutathione, we show that PrP(-/-) thymocytes display a higher susceptibility to H(2)O(2) exposure than PrP(+/+) cells. Furthermore, we find that in mice fed with a restricted diet, a regimen known to increase the intracellular level of ROS, PrP(-/-) thymocytes are more sensitive to oxidative stress. PrP(C) function appears to be specific for oxidative stress, since no significant differences are observed between PrP(-/-) and PrP(+/+) mice exposed to other kinds of stress. We also show a marked evolution of the redox status of T cells throughout differentiation in the thymus. Taken together, our results clearly ascribe to PrP(C) a protective function in thymocytes against oxidative stress.

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

    Science.gov (United States)

    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

  14. Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells.

    Science.gov (United States)

    Kobashigawa, Shinko; Kashino, Genro; Mori, Hiromu; Watanabe, Masami

    2015-03-01

    Ionizing radiation-induced cellular senescence is thought to be caused by nuclear DNA damage that cannot be repaired. However, here we found that radiation induces delayed increase of intracellular oxidative stress after irradiation. We investigated whether the relief of delayed oxidative stress by ascorbic acid would suppress the radiation-induced cellular senescence in Syrian golden hamster embryo (SHE) cells. We observed that the level of oxidative stress was drastically increased soon after irradiation, then declined to the level in non-irradiated cells, and increased again with a peak on day 3 after irradiation. We found that the inductions of cellular senescence after X-irradiation were reduced along with suppression of the delayed induction of oxidative stress by treatment with ascorbic acid, but not when oxidative stress occurred immediately after irradiation. Moreover, treatment of ascorbic acid inhibited p53 accumulation at 3 days after irradiation. Our data suggested a delayed increase of intracellular oxidative stress levels plays an important role in the process of radiation-induced cellular senescence by p53 accumulation.

  15. Naringin abrogated radiation induced oxidative stress through modulation of redox regulated cellular signaling system

    International Nuclear Information System (INIS)

    Ionizing radiation is widely used as major diagnostic and therapeutic applications. However, the deleterious effects of ionizing radiation are due to generation of reactive oxygen species. The amounts of ionizing radiation that can be given to treat malignant tumours are often limited by toxicity in the surrounding normal tissues and organs. The aim of this study was to investigate the role of Naringin (NG), a natural flavonoid, present in many plant parts against radiation induced oxidative stress with an evidence based exploration of the mechanism involved. Isolated murine splenocyte were irradiated with γ radiation (6 Gy) along with/without different concentrations of NG (50 and 100 μM). Biochemical, immunoblot, flow cytometry and immunofluorescence study was subject to be performed to observe its molecular mechanisms of action. Pretreatment with NG significantly prevented the radiation induced intracellular ROS generation, therefore prevented cellular TBARS formation and development of cellular nitrite. NG showed the significant reduction in nuclear DNA damage with respect to irradiated splenocyte through inhibition of DNA-PKcs and p-γH2AX. It recovered radiation induced reduced cell viability through modulation of redox regulated cell signaling system. It resulted in significant inhibition of radiation induced G1/S phase cell cycle arrest mediated by modulation of p53 dependent p21/WAF1 expression followed by Cyclin E and CDK2 expression. NG was involved in blocking radiation induced p38 function; reversed radiation mediated differential stress response through inhibition of NF-κB pathway. It prevented p-IKKα/β, p-IκBα, p-p65, COX2 expression. It also reversed the radiation induced p38/NF-κB guided inflammatory development. Thus it down regulated radiation induced CRP, MCP-1, and iNOS2 gene expression. This novel role of naringin provides a basis for therapeutic applications in future against radiation induced molecular and cellular functional

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  17. 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

  18. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state.

    Science.gov (United States)

    Kurutas, Ergul Belge

    2016-01-01

    Remarkable interest has risen in the idea that oxidative/nitrosative stress is mediated in the etiology of numerous human diseases. Oxidative/Nitrosative stress is the result of an disequilibrium in oxidant/antioxidant which reveals from continuous increase of Reactive Oxygen and Reactive Nitrogen Species production. The aim of this review is to emphasize with current information the importance of antioxidants which play the role in cellular responce against oxidative/nitrosative stress, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue. Products of lipid peroxidation have commonly been used as biomarkers of oxidative/nitrosative stress damage. Lipid peroxidation generates a variety of relatively stable decomposition end products, mainly α, β-unsaturated reactive aldehydes, such as malondialdehyde, 4-hydroxy-2-nonenal, 2-propenal (acrolein) and isoprostanes, which can be measured in plasma and urine as an indirect index of oxidative/nitrosative stress. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative/nitrosative stress or its consequences. They may act from directly scavenging free radicals to increasing antioxidative defences. Antioxidant deficiencies can develop as a result of decreased antioxidant intake, synthesis of endogenous enzymes or increased antioxidant utilization. Antioxidant supplementation has become an increasingly popular practice to maintain optimal body function. However, antoxidants exhibit pro-oxidant activity depending on the specific set of conditions. Of particular importance are their dosage and redox conditions in the cell. PMID:27456681

  19. Oxidative stress

    Directory of Open Access Journals (Sweden)

    Stevanović Jelka

    2012-01-01

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

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

    International Nuclear Information System (INIS)

    Highlights: •Oxidative stress impairs 3-MST-derived H2S production in isolated enzyme and in isolated mitochondria. •This impairs the stimulatory bioenergetic effects of H2S in hepatocytes. •This has implications for the pathophysiology of diseases with oxidative stress. -- Abstract: Recent data show that lower concentrations of hydrogen sulfide (H2S), as well as endogenous, intramitochondrial production of H2S 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/H2S pathway in vitro. Hydrogen peroxide (H2O2, 100–500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H2O2 (50–500 μM) caused a concentration-dependent decrease in production of H2S from 3-MP. In cultured murine hepatoma cells H2O2, (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 H2O2 (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/H2S 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

  1. 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.

  2. TGF-β/NF1/Smad4-mediated suppression of ANT2 contributes to oxidative stress in cellular senescence.

    Science.gov (United States)

    Kretova, Miroslava; Sabova, Ludmila; Hodny, Zdenek; Bartek, Jiri; Kollarovic, Gabriel; Nelson, Buck D; Hubackova, Sona; Luciakova, Katarina

    2014-12-01

    Oxidative stress and persistent activation of DNA damage response (DDR) are causally involved in the development of cellular senescence, a phenomenon implicated in fundamental (patho)physiological processes such as aging, fetal development and tumorigenesis. Here, we report that adenine nucleotide translocase-2 (ANT2) is consistently down-regulated in all three major forms of cellular senescence: replicative, oncogene-induced and drug-induced, in both normal and cancerous human cells. We previously reported formation of novel NF1/Smad transcription repressor complexes in growth-arrested fibroblasts. Here we show that such complexes form in senescent cells. Mechanistically, binding of the NF1/Smad complexes to the NF1-dependent repressor elements in the ANT2 gene promoter repressed ANT2 expression. Etoposide-induced formation of these complexes and repression of ANT2 were relatively late events co-incident with production and secretion of, and dependent on, TGF-β. siRNA-mediated knock-down of ANT2 in proliferating cells resulted in increased levels of reactive oxygen species (ROS) and activation of the DDR. Knock-down of ANT2, together with etoposide treatment, further intensified ROS production and DNA damage signaling, leading to enhanced apoptosis. Together, our data show that TGF-β-mediated suppression of ANT2 through NF1/Smad4 complexes contributes to oxidative stress and DNA damage during induction of cellular senescence. PMID:25220407

  3. Pummelo Protects Doxorubicin-Induced Cardiac Cell Death by Reducing Oxidative Stress, Modifying Glutathione Transferase Expression, and Preventing Cellular Senescence

    Directory of Open Access Journals (Sweden)

    L. Chularojmontri

    2013-01-01

    Full Text Available Citrus flavonoids have been shown to reduce cardiovascular disease (CVD risks prominently due to their antioxidant effects. Here we investigated the protective effect of pummelo (Citrus maxima, CM fruit juice in rat cardiac H9c2 cells against doxorubicin (DOX- induced cytotoxicity. Four antioxidant compositions (ascorbic acid, hesperidin, naringin, and gallic acid were determined by HPLC. CM significantly increased cardiac cell survival from DOX toxicity as evaluated by MTT assay. Reduction of cellular oxidative stress was monitored by the formation of DCF fluorescent product and total glutathione (GSH levels. The changes in glutathione-S-transferase (GST activity and expression were determined by enzyme activity assay and Western blot analysis, respectively. Influence of CM on senescence-associated β-galactosidase activity (SA-β-gal was also determined. The mechanisms of cytoprotection involved reduction of intracellular oxidative stress, maintaining GSH availability, and enhanced GST enzyme activity and expression. DOX-induced cellular senescence was also attenuated by long-term CM treatment. Thus, CM fruit juice can be promoted as functional fruit to protect cells from oxidative cell death, enhance the phase II GSTP enzyme activity, and decrease senescence phenotype population induced by cardiotoxic agent such as DOX.

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

    Science.gov (United States)

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

    2013-04-19

    Recent data show that lower concentrations of hydrogen sulfide (H2S), as well as endogenous, intramitochondrial production of H2S 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/H2S pathway in vitro. Hydrogen peroxide (H2O2, 100-500 μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H2O2 (50-500 μM) caused a concentration-dependent decrease in production of H2S from 3-MP. In cultured murine hepatoma cells H2O2, (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 H2O2 (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/H2S 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. PMID:23537657

  5. Nuclear Factor-κB Modulates Cellular Glutathione and Prevents Oxidative Stress in Cancer Cells

    OpenAIRE

    Meng, Qinghang; Peng, Zhimin; CHEN Liang; Si, Jutong; Dong, Zhongyun; Xia, Ying

    2010-01-01

    The NF-κB is best known for its role in inflammation. Here we show that constitutive NF-κB activity in cancer cells promotes the biosynthesis of redox scavenger glutathione (GSH), which in turn confers resistance to oxidative stress. Inhibition of NF-κB significantly decreases GSH in several lines of human leukemia and prostate cancer cells possessing high or moderate NF-κB activities. Concomitantly, NF-κB inhibition by pharmacological and molecular means sensitizes “NF-κB positive” cancer ce...

  6. Mst1-FoxO signaling protects Naive T lymphocytes from cellular oxidative stress in mice.

    Directory of Open Access Journals (Sweden)

    Juhyun Choi

    Full Text Available BACKGROUND: The Ste-20 family kinase Hippo restricts cell proliferation and promotes apoptosis for proper organ development in Drosophila. In C. elegans, Hippo homolog also regulates longevity. The mammalian Ste20-like protein kinase, Mst1, plays a role in apoptosis induced by various types of apoptotic stress. Mst1 also regulates peripheral naïve T cell trafficking and proliferation in mice. However, its functions in mammals are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the Mst1-FoxO signaling pathway plays a crucial role in survival, but not apoptosis, of naïve T cells. In Mst1(-/- mice, peripheral T cells showed impaired FoxO1/3 activation and decreased FoxO protein levels. Consistently, the FoxO targets, Sod2 and catalase, were significantly down-regulated in Mst1(-/- T cells, thereby resulting in elevated levels of intracellular reactive oxygen species (ROS and induction of apoptosis. Expression of constitutively active FoxO3a restored Mst1(-/- T cell survival. Crossing Mst1 transgenic mice (Mst1 Tg with Mst1(-/- mice reduced ROS levels and restored normal numbers of peripheral naïve T cells in Mst1 Tg;Mst1(-/- progeny. Interestingly, peripheral T cells from Mst1(-/- mice were hypersensitive to gamma-irradiation and paraquat-induced oxidative stresses, whereas those from Mst1 Tg mice were resistant. CONCLUSIONS/SIGNIFICANCE: These data support the hypothesis that tolerance to increased levels of intracellular ROS provided by the Mst1-FoxOs signaling pathway is crucial for the maintenance of naïve T cell homeostasis in the periphery.

  7. Nano-jewels in biology. Gold and platinum on diamond nanoparticles as antioxidant systems against cellular oxidative stress.

    Science.gov (United States)

    Martín, Roberto; Menchón, Cristina; Apostolova, Nadezda; Victor, Victor M; Alvaro, Mercedes; Herance, José Raúl; García, Hermenegildo

    2010-11-23

    Diamond nanoparticles (DNPs) obtained by explosive detonation have become commercially available. These commercial DNPs can be treated under Fenton conditions (FeSO(4) and H(2)O(2) at acidic pH) to obtain purer DNP samples with a small average particle size (4 nm) and a large population of surface OH groups (HO-DNPs). These Fenton-treated HO-DNPs have been used as a support of gold and platinum nanoparticles (≤2 nm average size). The resulting materials (Au/HO-DNP and Pt/HO-DNP) exhibit a high antioxidant activity against reactive oxygen species induced in a hepatoma cell line. In addition to presenting good biocompatibility, Au/HO- and Pt/HO-DNP exhibit about a two-fold higher antioxidant activity than glutathione, one of the reference antioxidant systems. The most active material against cellular oxidative stress was Au/HO-DNP. PMID:20939514

  8. 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)

    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)

  9. Epigallocatechin-3-gallate prevents oxidative stress-induced cellular senescence in human mesenchymal stem cells via Nrf2

    Science.gov (United States)

    Shin, Joo-Hyun; Jeon, Hyo-Jin; Park, Jihye; Chang, Mi-Sook

    2016-01-01

    Human mesenchymal stem cells (hMSCs) have great therapeutic potential due to their high plasticity, immune privileged status and ease of preparation, as well as a lack of ethical barriers to their use. However, their ultimate usefulness is limited by cellular senescence occurring secondary to increased cellular levels of reactive oxygen species (ROS) during their propagation in culture. The underlying molecular mechanisms responsible for this process in hMSCs remain unclear. An antioxidant polyphenol epigallocatechin-3-gallate (EGCG) found in green tea, is known to activate nuclear factor-erythroid 2-related factor 2 (Nrf2), a master transcriptional regulator of antioxidant genes. Herein, we examined the EGCG-mediated antioxidant mechanism in hMSCs exposed to ROS which involves Nrf2 activation. The H2O2-exposed hMSCs showed cellular senescence with significantly increased protein levels of acetyl-p53 and p21 in comparison with the untreated hMSCs, and these effects were prevented by pre-treatment with EGCG. By contrast, in Nrf2-knockdown hMSCs, EGCG lost its antioxidant effect, exhibiting high levels of acetyl-p53 and p21 following EGCG pre-treatment and H2O2 exposure. This indicates that Nrf2 and p53/p21 may be involved in the anti-senescent effect of EGCG in hMSCs. Taken together, these findings indicate the important role of EGCG in preventing oxidative stress-induced cellular senescence in hMSCs through Nrf2 activation, which has applications for the massive production of more suitable hMSCs for cell-based therapy. PMID:27498709

  10. The influence of sedimentation on metal accumulation and cellular oxidative stress markers in the Antarctic bivalve Laternula elliptica

    Science.gov (United States)

    Husmann, G.; Abele, D.; Monien, D.; Monien, P.; Kriews, M.; Philipp, E. E. R.

    2012-10-01

    Recent rapid climate warming at the western Antarctic Peninsula (WAP) results in elevated glacial melting, enhanced sedimentary run-off, increased turbidity and impact of ice-scouring in shallow coastal areas. Discharge of mineral suspension from volcanic bedrock ablation and chronic physical disturbance is expected to influence sessile filter feeders such as the Antarctic soft shell clam Laternula elliptica (King and Broderip, 1832). We investigated effects of sedimentary run-off on the accumulation of trace metals, and together with physical disturbance, the cumulative effect on oxidative stress parameters in younger and older L. elliptica from two stations in Potter Cove (King George Island, Antarctica) which are distinctly impacted by turbidity and ice-scouring. Fe, Mn, Sr, V and Zn concentrations were slightly higher in sediments of the station receiving more sediment run-off, but not enriched in bivalves of this station. The only element that increased in bivalves experimentally exposed to sediment suspension for 28 days was Mn. Concentration of the waste accumulation biomarker lipofuscin in nervous tissue was higher in L. elliptica from the “exposed” compared to the “less exposed” site, whereas protein carbonyl levels in bivalve mantle tissue were higher at the less sediment impacted site. Tissue metal content and lipofuscin in nervous tissue were generally higher in older compared to younger individuals from both field stations. We conclude that elevated sediment ablation does not per se result in higher metal accumulation in L. elliptica. Instead of direct absorbance from sediment particles, metal accumulation in gills seems to indicate uptake of compounds dissolved in the water column, whereas metals in digestive gland appear to originate from enriched planktonic or detritic food. Accumulation of cellular waste products and potentially reactive metals over lifetime presumably alters L. elliptica physiological performance with age and may

  11. Decreased SIRT3 in aged human mesenchymal stromal/stem cells increases cellular susceptibility to oxidative stress.

    Science.gov (United States)

    Wang, Xue-Qing; Shao, Yong; Ma, Chong-Yi; Chen, Wei; Sun, Lu; Liu, Wei; Zhang, Dong-Yang; Fu, Bi-Cheng; Liu, Kai-Yu; Jia, Zhi-Bo; Xie, Bao-Dong; Jiang, Shu-Lin; Li, Ren-Ke; Tian, Hai

    2014-11-01

    Sirtuin3 (SIRT3) is an important member of the sirtuin family of protein deacetylases that is localized to mitochondria and linked to lifespan extension in organisms ranging from yeast to humans. As aged cells have less regenerative capacity and are more susceptible to oxidative stress, we investigated the effect of ageing on SIRT3 levels and its correlation with antioxidant enzyme activities. Here, we show that severe oxidative stress reduces SIRT3 levels in young human mesenchymal stromal/stem cells (hMSCs). Overexpression of SIRT3 improved hMSCs resistance to the detrimental effects of oxidative stress. By activating manganese superoxide dismutase (MnSOD) and catalase (CAT), SIRT3 protects hMSCs from apoptosis under stress. SIRT3 expression, levels of MnSOD and CAT, as well as cell survival showed little difference in old versus young hMSCs under normal growth conditions, whereas older cells had a significantly reduced capacity to withstand oxidative stress compared to their younger counterparts. Expression of the short 28 kD SIRT3 isoform was higher, while the long 44 kD isoform expression was lower in young myocardial tissues compared with older ones. These results suggest that the active short isoform of SIRT3 protects hMSCs from oxidative injury by increasing the expression and activity of antioxidant enzymes. The expression of this short isoform decreases in cardiac tissue during ageing, leading to a reduced capacity for the heart to withstand oxidative stress. PMID:25210848

  12. Oxidative Stress and Psychological Disorders

    OpenAIRE

    Salim, Samina

    2014-01-01

    Oxidative stress is an imbalance between cellular production of reactive oxygen species and the counteracting antioxidant mechanisms. The brain with its high oxygen consumption and a lipid-rich environment is considered highly susceptible to oxidative stress or redox imbalances. Therefore, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have...

  13. Deranged Bioenergetics and Defective Redox Capacity in T Lymphocytes and Neutrophils Are Related to Cellular Dysfunction and Increased Oxidative Stress in Patients with Active Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Ko-Jen Li

    2012-01-01

    Full Text Available Urinary excretion of N-benzoyl-glycyl-Nε-(hexanonyllysine, a biomarker of oxidative stress, was higher in 26 patients with active systemic lupus erythematosus (SLE than in 11 non-SLE patients with connective tissue diseases and in 14 healthy volunteers. We hypothesized that increased oxidative stress in active SLE might be attributable to deranged bioenergetics, defective reduction-oxidation (redox capacity, or other factors. We demonstrated that, compared to normal cells, T lymphocytes (T and polymorphonuclear neutrophils (PMN of active SLE showed defective expression of facilitative glucose transporters GLUT-3 and GLUT-6, which led to increased intracellular basal lactate and decreased ATP production. In addition, the redox capacity, including intracellular GSH levels and the enzyme activity of glutathione peroxidase (GSH-Px and γ-glutamyl-transpeptidase (GGT, was decreased in SLE-T. Compared to normal cells, SLE-PMN showed decreased intracellular GSH levels, and GGT enzyme activity was found in SLE-PMN and enhanced expression of CD53, a coprecipitating molecule for GGT. We conclude that deranged cellular bioenergetics and defective redox capacity in T and PMN are responsible for cellular immune dysfunction and are related to increased oxidative stress in active SLE patients.

  14. A genome-wide screen in yeast identifies specific oxidative stress genes required for the maintenance of sub-cellular redox homeostasis.

    Directory of Open Access Journals (Sweden)

    Anita Ayer

    Full Text Available Maintenance of an optimal redox environment is critical for appropriate functioning of cellular processes and cell survival. Despite the importance of maintaining redox homeostasis, it is not clear how the optimal redox potential is sensed and set, and the processes that impact redox on a cellular/organellar level are poorly understood. The genetic bases of cellular redox homeostasis were investigated using a green fluorescent protein (GFP based redox probe, roGFP2 and a pH sensitive GFP-based probe, pHluorin. The use of roGFP2, in conjunction with pHluorin, enabled determination of pH-adjusted sub-cellular redox potential in a non-invasive and real-time manner. A genome-wide screen using both the non-essential and essential gene collections was carried out in Saccharomyces cerevisiae using cytosolic-roGFP2 to identify factors essential for maintenance of cytosolic redox state under steady-state conditions. 102 genes of diverse function were identified that are required for maintenance of cytosolic redox state. Mutations in these genes led to shifts in the half-cell glutathione redox potential by 75-10 mV. Interestingly, some specific oxidative stress-response processes were identified as over-represented in the data set. Further investigation of the role of oxidative stress-responsive systems in sub-cellular redox homeostasis was conducted using roGFP2 constructs targeted to the mitochondrial matrix and peroxisome and E(GSH was measured in cells in exponential and stationary phase. Analyses allowed for the identification of key redox systems on a sub-cellular level and the identification of novel genes involved in the regulation of cellular redox homeostasis.

  15. Oxidative stress by inorganic nanoparticles.

    Science.gov (United States)

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

    2016-05-01

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

  16. Regulation of autophagy in oxygen-dependent cellular stress.

    Science.gov (United States)

    Ryter, Stefan W; Choi, Augustine M K

    2013-01-01

    Oxidative stress caused by supraphysiological production of reactive oxygen species (ROS), can cause cellular injury associated with protein and lipid oxidation, DNA damage, and mitochondrial dysfunction. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of cell survival or cell death pathways. Recent studies suggest that autophagy, a cellular homeostatic process that governs the turnover of damaged organelles and proteins, may represent a general cellular and tissue response to oxidative stress. The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy may play multifunctional roles in cellular adaptation to stress, by maintaining mitochondrial integrity, and removing damaged proteins. Additionally, autophagy may play important roles in the regulation of inflammation and immune function. Modulation of the autophagic pathway has been reported in cell culture models of oxidative stress, including altered states of oxygen tension (i.e., hypoxia, hyperoxia), and exposure to oxidants. Furthermore, proteins that regulate autophagy may be subject to redox regulation. The heme oxygenase- 1 (HO)-1 enzyme system may have a role in the regulation of autophagy. Recent studies suggest that carbon monoxide (CO), a reaction product of HO activity which can alter mitochondrial function, may induce autophagy in cultured epithelial cells. In conclusion, current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems. PMID:23092322

  17. 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.

  18. Crystal structure of a murine α-class glutathione S-transferase involved in cellular defense against oxidative stress

    NARCIS (Netherlands)

    Krengel, Ute; Schröter, Klaus-Hasso; Hoier, Helga; Arkema, Anita; Kalk, Kor H.; Zimniak, Piotr; Dijkstra, Bauke W.

    1998-01-01

    Glutathione S-transferases (GSTs) are ubiquitous multifunctional enzymes which play a key role in cellular detoxification. The enzymes protect the cells against toxicants by conjugating them to glutathione. Recently, a novel subgroup of α-class GSTs has been identified with altered substrate specifi

  19. Sumo and the cellular stress response

    OpenAIRE

    Enserink, Jorrit M.

    2015-01-01

    The ubiquitin family member Sumo has important functions in many cellular processes including DNA repair, transcription and cell division. Numerous studies have shown that Sumo is essential for maintaining cell homeostasis when the cell encounters endogenous or environmental stress, such as osmotic stress, hypoxia, heat shock, genotoxic stress, and nutrient stress. Regulation of transcription is a key component of the Sumo stress response, and multiple mechanisms have been described by which ...

  20. Elucidation of lead-induced oxidative stress in Talinum triangulare roots by analysis of antioxidant responses and DNA damage at cellular level.

    Science.gov (United States)

    Kumar, Abhay; Prasad, M N V; Mohan Murali Achary, V; Panda, Brahma B

    2013-07-01

    Hydroponic experiments were performed with Talinum triangulare (Jacq.) Willd. focusing the root cellular biochemistry with special emphasis on DNA damage, structural, and elemental analyses in Pb(NO3)2 exposed with 0, 0.25, 0.5, 0.75, 1.0, and 1.25 mM for 7 days. Lead (Pb) increased reactive oxygen species production, lipid peroxidation, protein oxidation, cell death, and DNA damage and decreased the protein content in a dose-dependent manner. Likewise, a dose-dependent induction of antioxidative enzymes superoxide dismutase and catalase by Pb was evident. Ascorbate peroxidase on the other hand responded biphasically to Pb treatments by showing induction at low (0.25 and 0.50) and repression at high (0.75-1.25 mM) concentrations. The estimation of proline content also indicated a similar biphasic trend. Scanning electron microscope and energy-dispersive X-ray spectroscopy analysis showed that 1.25 mM Pb treatment resulted in ultrastructural modifications in roots and stem tissue that was marked by the change in the elemental profile. The findings pointed to the role of oxidative stress in the underlying Pb phytotoxicity and genotoxicity in T. triangulare. PMID:23263755

  1. Oxidative stress and anxiety

    OpenAIRE

    Bouayed, Jaouad; Rammal, Hassan; Soulimani, Rachid

    2009-01-01

    High O2 consumption, modest antioxidant defenses and a lipid-rich constitution make the brain highly vulnerable to redox imbalances. Oxidative damage in the brain causes nervous system impairment. Recently, oxidative stress has also been implicated in depression, anxiety disorders and high anxiety levels. The findings which establish a link between oxidative stress and pathological anxiety have inspired a number of other recent studies focusing on the link between oxidative status and normal ...

  2. The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.

    Science.gov (United States)

    Morris, Gerwyn; Walder, Ken; Puri, Basant K; Berk, Michael; Maes, Michael

    2016-09-01

    Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer's and Parkinson's disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

  3. The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.

    Science.gov (United States)

    Morris, Gerwyn; Walder, Ken; Puri, Basant K; Berk, Michael; Maes, Michael

    2016-09-01

    Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer's and Parkinson's disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling. PMID:26310971

  4. Radiation, nitric oxide and cellular death

    International Nuclear Information System (INIS)

    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

  5. Dynamics of active cellular response under stress

    Science.gov (United States)

    de, Rumi; Zemel, Assaf; Safran, Samuel

    2008-03-01

    Forces exerted by and on adherent cells are important for many physiological processes such as wound healing and tissue formation. In addition, recent experiments have shown that stem cell differentiation is controlled, at least in part, by the elasticity of the surrounding matrix. Using a simple theoretical model that includes the forces due to both the mechanosensitive nature of cells and the elastic response of the matrix, we predict the dynamics of orientation of cells. The model predicts many features observed in measurements of cellular forces and orientation including the increase with time of the forces generated by cells in the absence of applied stress and the consequent decrease of the force in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static stresses and of nearly perpendicular alignment for dynamically varying stresses. In addition, we predict the response of the cellular orientation to a sinusoidally varying applied stress as a function of frequency. The dependence of the cell orientation angle on the Poisson ratio of the surrounding material can be used to distinguish systems in which cell activity is controlled by stress from those where cell activity is controlled by strain. Reference: Nature Physics, vol. 3, pp 655 (2007).

  6. Oxidative stress in pregnancy and reproduction.

    Science.gov (United States)

    Duhig, Kate; Chappell, Lucy C; Shennan, Andrew H

    2016-09-01

    Oxidative stress is implicated in the pathophysiology of many reproductive complications including infertility, miscarriage, pre-eclampsia, fetal growth restriction and preterm labour. The presence of excess reactive oxygen species can lead to cellular damage of deoxyribonucleic acids, lipids and proteins. Antioxidants protect cells from peroxidation reactions, limiting cellular damage and helping to maintain cellular membrane integrity. There is overwhelming evidence for oxidative stress causing harm in reproduction. However, there is sparse evidence that supplementation with commonly used antioxidants (mostly vitamins C and E) makes any difference in overcoming oxidative stress or reversing disease processes. There may be potential for antioxidant therapy to ameliorate or prevent disease, but this requires a thorough understanding of the mechanism of action and specificity of currently used antioxidants. PMID:27630746

  7. Oxidative stress in neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    Xueping Chen; Chunyan Guo; Jiming Kong

    2012-01-01

    Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion (O2-) and hydroxyl radical (OH-), and non-radical hydrogen peroxide (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases, especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.

  8. Oxidative stress in neurodegenerative diseases.

    Science.gov (United States)

    Chen, Xueping; Guo, Chunyan; Kong, Jiming

    2012-02-15

    Reactive oxygen species are constantly produced in aerobic organisms as by-products of normal oxygen metabolism and include free radicals such as superoxide anion (O2 (-)) and hydroxyl radical (OH(-)), and non-radical hydrogen peroxide (H2O2). The mitochondrial respiratory chain and enzymatic reactions by various enzymes are endogenous sources of reactive oxygen species. Exogenous reactive oxygen species -inducing stressors include ionizing radiation, ultraviolet light, and divergent oxidizing chemicals. At low concentrations, reactive oxygen species serve as an important second messenger in cell signaling; however, at higher concentrations and long-term exposure, reactive oxygen species can damage cellular macromolecules such as DNA, proteins, and lipids, which leads to necrotic and apoptotic cell death. Oxidative stress is a condition of imbalance between reactive oxygen species formation and cellular antioxidant capacity due to enhanced ROS generation and/or dysfunction of the antioxidant system. Biochemical alterations in these macromolecular components can lead to various pathological conditions and human diseases, especially neurodegenerative diseases. Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal cells, often associated with cytoskeletal protein aggregates forming inclusions in neurons and/or glial cells. Deposition of abnormal aggregated proteins and disruption of metal ions homeostasis are highly associated with oxidative stress. The main aim of this review is to present as much detailed information as possible that is available on various neurodegenerative disorders and their connection with oxidative stress. A variety of therapeutic strategies designed to address these pathological processes are also described. For the future therapeutic direction, one specific pathway that involves the transcription factor nuclear factor erythroid 2-related factor 2 is receiving considerable attention.

  9. Interplay between Inflammation and Cellular Stress Triggered by Flaviviridae Viruses

    Science.gov (United States)

    Valadão, Ana L. C.; Aguiar, Renato S.; de Arruda, Luciana B.

    2016-01-01

    The Flaviviridae family comprises several human pathogens, including Dengue, Zika, Yellow Fever, West Nile, Japanese Encephalitis viruses, and Hepatitis C Virus. Those are enveloped, single-stranded positive sense RNA viruses, which replicate mostly in intracellular compartments associated to endoplasmic reticulum (ER) and Golgi complex. Virus replication results in abundant viral RNAs and proteins, which are recognized by cellular mechanisms evolved to prevent virus infection, resulting in inflammation and stress responses. Virus RNA molecules are sensed by Toll-like receptors (TLRs), RIG-I-like receptors (RIG-I and MDA5) and RNA-dependent protein kinases (PKR), inducing the production of inflammatory mediators and interferons. Simultaneously, the synthesis of virus RNA and proteins are distinguished in different compartments such as mitochondria, ER and cytoplasmic granules, triggering intracellular stress pathways, including oxidative stress, unfolded protein response pathway, and stress granules assembly. Here, we review the new findings that connect the inflammatory pathways to cellular stress sensors and the strategies of Flaviviridae members to counteract these cellular mechanisms and escape immune response. PMID:27610098

  10. Interplay between Inflammation and Cellular Stress Triggered by Flaviviridae Viruses.

    Science.gov (United States)

    Valadão, Ana L C; Aguiar, Renato S; de Arruda, Luciana B

    2016-01-01

    The Flaviviridae family comprises several human pathogens, including Dengue, Zika, Yellow Fever, West Nile, Japanese Encephalitis viruses, and Hepatitis C Virus. Those are enveloped, single-stranded positive sense RNA viruses, which replicate mostly in intracellular compartments associated to endoplasmic reticulum (ER) and Golgi complex. Virus replication results in abundant viral RNAs and proteins, which are recognized by cellular mechanisms evolved to prevent virus infection, resulting in inflammation and stress responses. Virus RNA molecules are sensed by Toll-like receptors (TLRs), RIG-I-like receptors (RIG-I and MDA5) and RNA-dependent protein kinases (PKR), inducing the production of inflammatory mediators and interferons. Simultaneously, the synthesis of virus RNA and proteins are distinguished in different compartments such as mitochondria, ER and cytoplasmic granules, triggering intracellular stress pathways, including oxidative stress, unfolded protein response pathway, and stress granules assembly. Here, we review the new findings that connect the inflammatory pathways to cellular stress sensors and the strategies of Flaviviridae members to counteract these cellular mechanisms and escape immune response. PMID:27610098

  11. Interplay between inflammation and cellular stress triggered by Flaviviridae viruses

    Directory of Open Access Journals (Sweden)

    Ana Luiza Chaves Valadão

    2016-08-01

    Full Text Available Flaviviruses, from Flaviviridae virus family, comprises several human pathogens, including Dengue, Zika, Yellow Fever, West Nile and Japanese Encephalitis viruses. Those are enveloped, single-stranded positive sense RNA viruses, and replicate mostly in intracellular compartments associated to endoplasmic reticulum (ER and Golgi complex. Virus replication results in abundant viral RNAs and proteins, which are recognized by cellular mechanisms evolved to prevent virus infection, resulting in inflammation and stress responses. Virus RNA molecules are sensed by Toll-like receptors (TLRs, RIG-I-like receptors (RIG-I and MDA5 and RNA-dependent protein kinases (PKR, inducing the production of inflammatory mediators and interferons. Simultaneously, the synthesis of virus RNA and proteins are distinguished in different compartments such as mitochondria, ER and cytoplasmic granules, triggering intracellular stress pathways, including oxidative stress, UPR pathway, and stress granules assembly. Here, we review the new findings that connect the inflammatory pathways to cellular stress sensors and the strategies of Flaviviridae members to counteract these cellular mechanisms and escape immune response.

  12. Managing the pools of cellular redox buffers and the control of oxidative stress during the ontogeny of drought-exposed mungbean (Vigna radiata L. – role of sulfur nutrition

    Directory of Open Access Journals (Sweden)

    Naser A. Anjum

    2015-01-01

    Full Text Available Impacts of increasing environmental stresses (such as drought on crop productivity can be sustainably minimized by optimizing mineral nutrients (such as sulfur, S. This study, based on a pot-culture experiment conducted in greenhouse condition, investigates S-mediated influence of drought stress (imposed at pre-flowering, flowering and pod-filling stages on growth, photosynthesis and tolerance of mungbean (Vigna radiata L. plants. Drought stress alone hampered photosynthesis functions, enhanced oxidative stress [measured in terms of H2O2; lipid peroxidation (LPO; electrolyte leakage (EL] and decreased the pools of cellular redox buffers (namely ascorbate (AsA; glutathione (GSH], and the overall plant growth (measured as leaf area and plant dry mass, maximally at flowering stage, followed by pre-flowering and pod-filling stages. Contrarily, S-supplementation to drought-affected plants (particularly at flowering stage improved the growth- and photosynthesis-related parameters considerably. This may be ascribed to S-induced enhancements in the pools of reduced AsA and GSH, which jointly manage the balance between the production and scavenging of H2O2 and stabilize cell membrane by decreasing LPO and EL. It is inferred that alleviation of drought-caused oxidative stress depends largely on the status of AsA and GSH via S-application to drought-stressed V. radiata at an appropriate stage of plant growth, when this nutrient is maximally or efficiently utilized.

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

    OpenAIRE

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

    Posttraumatic stress disorder (PTSD) is associated with elevated risk for a variety of age-related diseases and neurodegeneration. In this paper, we review evidence relevant to the hypothesis that chronic PTSD constitutes a form of persistent life stress that potentiates oxidative stress (OXS) and accelerates cellular aging. We provide an overview of empirical studies that have examined the effects of psychological stress on OXS, discuss the stress-perpetuating characteristics of PTSD, and th...

  14. Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways1

    Science.gov (United States)

    Solazzo, Stephanie A.; Ahmed, Muneeb; Schor-Bardach, Rachel; Yang, Wei; Girnun, Geoffrey D.; Rahmanuddin, Syed; Levchenko, Tatyana; Signoretti, Sabina; Spitz, Douglas R.; Torchilin, Vladimir

    2010-01-01

    Purpose: To determine if oxidative and nitrative stress and/or apoptosis contribute to increased coagulation when combining radiofrequency (RF) ablation with liposomal doxorubicin. Materials and Methods: Animal care committee approval was obtained. R3230 mammary adenocarcinomas in Fischer rats were treated with either RF ablation (n = 43), 1 mg of intravenously injected liposomal doxorubicin (n = 26), or combined therapy (n = 30) and were compared with control subjects (n = 11). A subset of animals receiving combination therapy (n = 24) were treated in the presence or absence of N-acetylcysteine (NAC) administered 24 hours and 1 hour before RF ablation. Tumors were analyzed 2 minutes to 72 hours after treatment to determine the temporal range of response by using immunohistochemical staining of the apoptosis marker cleaved caspase-3, phosphorylated γH2AX, and HSP70 and of markers of oxidative and nitrative stress (8-hydroxydeoxyguanosine [8-OHdG], 4-hydroxynonenal [4-HNE]–modified proteins, and nitrotyrosine [NT]). Statistical analyses, including t tests and analysis of variance for comparisons where appropriate, were performed. Results: By 4 hours after RF ablation alone, a 0.48-mm ± 0.13 (standard deviation) peripheral band with 57.0% ± 7.3 cleaved caspase-3 positive cells was noted at the ablation margin, whereas a 0.73-mm ± 0.18 band with 77.7% ± 6.3 positivity was seen for combination therapy (P < .03 for both comparisons). Combination therapy caused increased and earlier staining for 4-HNE–modified proteins, 8-OHdG, NT, and γH2AX with colocalization to cleaved caspase-3 staining. A rim of increased HSP70 was identified peripheral to the area of cleaved caspase-3. Parameters of oxidative and nitrative stress were significantly inhibited by NAC 1 hour following RF ablation, resulting in decreased cleaved caspase-3 positivity (0.28-mm ± 0.09 band of 25.9% ± 7.4 positivity vs 0.59-mm ± 0.11 band of 62.9% ± 6.0 positivity, P < .001 for both

  15. Oxidative Stress in Malaria

    OpenAIRE

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

    2012-01-01

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

  16. 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.

  17. Oxidative stress and the ageing endocrine system.

    Science.gov (United States)

    Vitale, Giovanni; Salvioli, Stefano; Franceschi, Claudio

    2013-04-01

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

  18. P53 family and cellular stress responses in cancer

    Directory of Open Access Journals (Sweden)

    Johanna ePflaum

    2014-10-01

    Full Text Available p53 is an important tumor suppressor gene, which is stimulated by cellular stress like ionizing radiation, hypoxia, carcinogens and oxidative stress. Upon activation p53 leads to cell cycle arrest and promotes DNA repair or induces apoptosis via several pathways. p63 and p73 are structural homologs of p53 that can act similarly to the protein but also hold functions distinct from p53. Today more than forty different isoforms of the p53 family members are known. They result from transcription via different promoters and alternative splicing. Some isoforms have carcinogenic properties and mediate resistance to chemotherapy. Therefore, expression patterns of the p53 family genes can offer prognostic information in several malignant tumors. Furthermore, the p53 family constitutes a potential target for cancer therapy. Small molecules (e.g. Nutlins, RITA, PRIMA-1, and MIRA-1 among others have been objects of intense research interest in recent years. They restore pro-apoptotic wild-type p53 function and were shown to break chemotherapeutic resistance. Due to p53 family interactions small molecules also influence p63 and p73 activity. Thus, the members of the p53 family are key players in the cellular stress response in cancer and are expected to grow in importance as therapeutic targets.

  19. 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.

  20. A genome-wide screen in yeast identifies specific oxidative stress genes required for the maintenance of sub-cellular redox homeostasis

    NARCIS (Netherlands)

    A. Ayer; S. Fellermeier; C. Fife; S.S. Li; G. Smits; A.J. Meyer; I.W. Dawes; G.G. Perrone

    2012-01-01

    Maintenance of an optimal redox environment is critical for appropriate functioning of cellular processes and cell survival. Despite the importance of maintaining redox homeostasis, it is not clear how the optimal redox potential is sensed and set, and the processes that impact redox on a cellular/o

  1. Potential Modulation of Sirtuins by Oxidative Stress

    Science.gov (United States)

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

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

  2. Potential Modulation of Sirtuins by Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Leonardo Santos

    2016-01-01

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

  3. OXIDATIVE STRESS AND PHYSICAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Dragan Radovanović

    2012-06-01

    Full Text Available The cells continuously produce free radicals and reactive oxygen species as a part of metabolic processes. Increased aerobic metabolism during exercise is a potential source of oxidative stress. Also, anaerobic physical activity and oxidative stress are interrelated because the intense anaerobic activity leads to damage proteins, lipids and nucleic acids in muscle cells and blood. Complex system of antioxidant defense, which has the enzymatic and non-enzymatic part, has a role in protecting tissues from excessive oxidative damage. Most of the research conducted so far about the impact of various forms of physical activity on levels of oxidative stress is confirmed by changes in biomarkers that indicate lipid peroxidation and proteins modification. Untrained persons, as opposed to trained, are more susceptible to major changes in the body caused by oxidative stress during physical activity. The results of researches have shown that there are no significant differences between the genders in the level of oxidative stress during physical activity and response to antioxidant supplementation possibly applied. It is interesting that, despite of numerous studies, the exact location of oxidative stress origin during physical activity has not been reliably established. In addition, research results provide insufficient evidence on the effectiveness of using antioxidant supplementation to increase the defense against oxidative stress. It is necessary further investigation about the redox status and oxidative stress during physical activity in adolescent athletes.

  4. Roles of TRPM2 in oxidative stress.

    Science.gov (United States)

    Takahashi, Nobuaki; Kozai, Daisuke; Kobayashi, Ryohei; Ebert, Maximilian; Mori, Yasuo

    2011-09-01

    Reactive oxygen species (ROS) play critical roles in cell death, diseases, and normal cellular processes. TRPM2 is a member of transient receptor potential (TRP) protein superfamily and forms a Ca(2+)-permeable nonselective cation channel activated by ROS, specifically by hydrogen peroxide (H(2)O(2)), and at least in part via second-messenger mechanisms. Accumulating evidence has indicated that TRPM2 mediates multiple cellular responses, after our finding that Ca(2+) influx via TRPM2 regulates H(2)O(2)-induced cell death. Recently, we have demonstrated that Ca(2+) influx through TRPM2 induces chemokine production in monocytes and macrophages, which aggravates inflammatory neutrophil infiltration in mice. However, understanding is still limited for in vivo physiological or pathophysiological significance of ROS-induced TRPM2 activation. In this review, we summarize mechanisms underlying activation of TRPM2 channels by oxidative stress and downstream biological responses, and discuss the biological importance of oxidative stress-activated TRP channels.

  5. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    OpenAIRE

    Morales, Cyndi R.; Pedrozo, Zully; Lavandero, Sergio; Hill, Joseph A.

    2014-01-01

    Significance: Autophagy is an evolutionarily ancient process of intracellular protein and organelle recycling required to maintain cellular homeostasis in the face of a wide variety of stresses. Dysregulation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) leads to oxidative damage. Both autophagy and ROS/RNS serve pathological or adaptive roles within cardiomyocytes, depending on the context. Recent Advances: ROS/RNS and autophagy communicate with each other via both tra...

  6. The impact of oxidative stress on hair.

    Science.gov (United States)

    Trüeb, R M

    2015-12-01

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

  7. The impact of oxidative stress on hair.

    Science.gov (United States)

    Trüeb, R M

    2015-12-01

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

  8. FREE RADICALS, REACTIVE OXYGEN SPECIES, OXIDATIVE STRESSES AND THEIR CLASSIFICATIONS.

    Science.gov (United States)

    Lushchak, V I

    2015-01-01

    The phrases "free radicals" and "reactive oxygen species" (ROS) are frequently used interchangeably although this is not always correct. This article gives a brief description of two mentioned oxygen forms. During the first two-three decades after ROS discovery in biological systems (1950-1970 years) they were considered only as damaging agents, but later their involvement in organism protection and regulation of the expression of certain genes was found. The physiological state of increased steady-state ROS level along with certain physiological effects has been called oxidative stress. This paper describes ROS homeostasis and provides several classifications of oxidative stresses. The latter are based on time-course and intensity principles. Therefore distinguishing between acute and chronic stresses on the basis of the dynamics, and the basal oxidative stress, low intensity oxidative stress, strong oxidative stress, and finally a very strong oxidative stress based on the intensity of the action of the inductor of the stress are described. Potential areas of research include the development of this field with complex classification of oxidative stresses, an accurate identification of cellular targets of ROS action, determination of intracellular spatial and temporal distribution of ROS and their effects, deciphering the molecular mechanisms responsible for cell response to ROS attacks, and their participation in the normal cellular functions, i.e. cellular homeostasis and its regulation.

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

    DEFF Research Database (Denmark)

    Jørgensen, Anders

    2013-01-01

    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...... 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......-oxodG and 8-oxoGuo, respectively). The main hypothesis was that psychological stress states are associated with increased DNA/RNA damage from oxidation. In a study of 40 schizophrenia patients and 40 healthy controls matched for age and gender, we found that 8-oxodG/8-oxoGuo excretion was increased...

  10. Measurement of oxidatively generated base damage in cellular DNA

    Energy Technology Data Exchange (ETDEWEB)

    Cadet, Jean, E-mail: jean.cadet@cea.fr [Laboratoire ' Lesions des Acides Nucleiques' , SCIB-UMR-E no3 (CEA/UJF), FRE CNRS 3200, Departement de Recherche Fondamentale sur la Matiere Condensee, CEA/Grenoble, F-38054 Grenoble Cedex 9 (France); Douki, Thierry; Ravanat, Jean-Luc [Laboratoire ' Lesions des Acides Nucleiques' , SCIB-UMR-E no3 (CEA/UJF), FRE CNRS 3200, Departement de Recherche Fondamentale sur la Matiere Condensee, CEA/Grenoble, F-38054 Grenoble Cedex 9 (France)

    2011-06-03

    This survey focuses on the critical evaluation of the main methods that are currently available for monitoring single and complex oxidatively generated damage to cellular DNA. Among chromatographic methods, HPLC-ESI-MS/MS and to a lesser extent HPLC-ECD which is restricted to a few electroactive nucleobases and nucleosides are appropriate for measuring the formation of single and clustered DNA lesions. Such methods that require optimized protocols for DNA extraction and digestion are sensitive enough for measuring base lesions formed under conditions of severe oxidative stress including exposure to ionizing radiation, UVA light and high intensity UVC laser pulses. In contrast application of GC-MS and HPLC-MS methods that are subject to major drawbacks have been shown to lead to overestimated values of DNA damage. Enzymatic methods that are based on the use of DNA repair glycosylases in order to convert oxidized bases into strand breaks are suitable, even if they are far less specific than HPLC methods, to deal with low levels of single modifications. Several other methods including immunoassays and {sup 32}P-postlabeling methods that are still used suffer from drawbacks and therefore are not recommended. Another difficult topic is the measurement of oxidatively generated clustered DNA lesions that is currently achieved using enzymatic approaches and that would necessitate further investigations.

  11. tRNA modifications regulate translation during cellular stress

    OpenAIRE

    Gu, Chen; Thomas J Begley; Peter C. Dedon

    2014-01-01

    The regulation of gene expression in response to stress is an essential cellular protection mechanism. Recent advances in tRNA modification analysis and genome-based codon bias analytics have facilitated studies that lead to a novel model for translational control, with translation elongation dynamically regulated during stress responses. Stress-induced increases in specific anticodon wobble bases are required for the optimal translation of stress response transcripts that are significantly b...

  12. Oxidative Stress and Major Depression

    OpenAIRE

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

    2014-01-01

    Background: Major causative factor for major depression is inflammation, autoimmune tissue damage and prolonged psychological stress, which leads to oxidative stress. The aim of this study was to know the association of free radicals and antioxidant status in subjects suffering from major depression.

  13. [Heme metabolism and oxidative stress].

    Science.gov (United States)

    Kaliman, P A; Barannik, T B

    2001-01-01

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

  14. Oxidative stress and Parkinson’s disease

    Science.gov (United States)

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

    2015-01-01

    Parkinson disease (PD) is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra pars compacta of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in PD. Environmental factors, such as neurotoxins, pesticides, insecticides, dopamine (DA) itself, and genetic mutations in PD-associated proteins contribute to mitochondrial dysfunction which precedes reactive oxygen species formation. In this mini review, we give an update of the classical pathways involving these mechanisms of neurodegeneration, the biochemical and molecular events that mediate or regulate DA neuronal vulnerability, and the role of PD-related gene products in modulating cellular responses to oxidative stress in the course of the neurodegenerative process. PMID:26217195

  15. Inflammatory and oxidative stress in rotavirus infection

    Science.gov (United States)

    Guerrero, Carlos A; Acosta, Orlando

    2016-01-01

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

  16. Cardiopulmonary Bypass and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Mustafa Zakkar

    2015-01-01

    Full Text Available The development of the cardiopulmonary bypass (CPB revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress.

  17. Dynamical theory of active cellular response to external stress.

    Science.gov (United States)

    De, Rumi; Safran, Samuel A

    2008-09-01

    We present a comprehensive, theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes both the forces that arise from the deformation of the matrix as well as forces due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate the time-dependent response of both the magnitude and the direction of the elastic dipole that characterizes the active forces exerted by the cell, for various situations. For static or quasistatic external stress, cells orient parallel to the stress while for high frequency dynamic external stress, cells orient nearly perpendicular. Both numerical and analytical calculations of these effects are presented. In addition we predict the relaxation time for the cellular response for both slowly and rapidly varying external stresses; several characteristic scaling regimes for the relaxation time as a function of applied frequency are predicted. We also treat the case of cells for which the regulation of the stress fibers and focal adhesions is controlled by strain (instead of stress) and show that the predicted dependence of the cellular orientation on the Poisson ratio of the matrix can differentiate strain vs stress regulation of cellular response.

  18. Dynamical theory of active cellular response to external stress

    Science.gov (United States)

    de, Rumi; Safran, Samuel A.

    2008-09-01

    We present a comprehensive, theoretical treatment of the orientational response to external stress of active, contractile cells embedded in a gel-like elastic medium. The theory includes both the forces that arise from the deformation of the matrix as well as forces due to the internal regulation of the stress fibers and focal adhesions of the cell. We calculate the time-dependent response of both the magnitude and the direction of the elastic dipole that characterizes the active forces exerted by the cell, for various situations. For static or quasistatic external stress, cells orient parallel to the stress while for high frequency dynamic external stress, cells orient nearly perpendicular. Both numerical and analytical calculations of these effects are presented. In addition we predict the relaxation time for the cellular response for both slowly and rapidly varying external stresses; several characteristic scaling regimes for the relaxation time as a function of applied frequency are predicted. We also treat the case of cells for which the regulation of the stress fibers and focal adhesions is controlled by strain (instead of stress) and show that the predicted dependence of the cellular orientation on the Poisson ratio of the matrix can differentiate strain vs stress regulation of cellular response.

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

    Science.gov (United States)

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

    2016-05-01

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

  20. 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.

  1. Oxidative stress in prostate hyperplasia and carcinogenesis.

    Science.gov (United States)

    Udensi, Udensi K; Tchounwou, Paul B

    2016-01-01

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

  2. Ethanol and oxidative stress.

    Science.gov (United States)

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

    2001-05-01

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

  3. Hemoglobin oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Croci, S.; Ortalli, I.; Pedrazzi, G. [University of Parma, Istituto di Scienze Fisiche, INFM-Udr Parma (Italy); Passeri, G. [University of Parma, Dipartimento di Medicina Interna e Scienze Biomediche (Italy); Piccolo, P. [University of Parma, Istituto di Clinica chirurgica Generale, Toracica e Vascolare (Italy)

    2000-07-15

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

  4. Cellular stress responses for monitoring and modulating ageing

    DEFF Research Database (Denmark)

    Demirovic, Dino; Schnebert, Sylvianne; Nizard, Carine;

    2013-01-01

    protectors and stimulators of homeodynamics, and create a kind of “gold-standard” for monitoring the efficacy of other potential antiageing and pro-survival natural and synthetic compounds. We have so far standardised an effective method for detecting all seven stress response pathways, by several......Cellular stress response is a crucial factor in maintaining efficient homeodynamics for survival, health and longevity. Both the immediate and delayed responses to external and internal stressors effectively determine the molecular biochemical and physiological stability in a dynamic...... and interactive manner. There are three main aspects of stress responses: (i) immediate stress response involving extra- and intra-cellular signaling during the period of disturbance and exposure to the stressors; (ii) delayed stress response involving sensors and modulators in the presence of stressors or after...

  5. ATM Couples Replication Stress and Metabolic Reprogramming during Cellular Senescence

    Directory of Open Access Journals (Sweden)

    Katherine M. Aird

    2015-05-01

    Full Text Available Replication stress induced by nucleotide deficiency plays an important role in cancer initiation. Replication stress in primary cells typically activates the cellular senescence tumor-suppression mechanism. Senescence bypass correlates with development of cancer, a disease characterized by metabolic reprogramming. However, the role of metabolic reprogramming in the cellular response to replication stress has been little explored. Here, we report that ataxia telangiectasia mutated (ATM plays a central role in regulating the cellular response to replication stress by shifting cellular metabolism. ATM inactivation bypasses senescence induced by replication stress triggered by nucleotide deficiency. This was due to restoration of deoxyribonucleotide triphosphate (dNTP levels through both upregulation of the pentose phosphate pathway via increased glucose-6-phosphate dehydrogenase (G6PD activity and enhanced glucose and glutamine consumption. These phenotypes were mediated by a coordinated suppression of p53 and upregulation of c-MYC downstream of ATM inactivation. Our data indicate that ATM status couples replication stress and metabolic reprogramming during senescence.

  6. Oxidative Stress in Aging-Matters of the Heart and Mind

    OpenAIRE

    Tai, T. C.; Krishnan Venkataraman; Sandhya Khurana

    2013-01-01

    Oxidative damage is considered to be the primary cause of several aging associated disease pathologies. Cumulative oxidative damage tends to be pervasive among cellular macromolecules, impacting proteins, lipids, RNA and DNA of cells. At a systemic level, events subsequent to oxidative damage induce an inflammatory response to sites of oxidative damage, often contributing to additional oxidative stress. At a cellular level, oxidative damage to mitochondria results in acidification of the cyto...

  7. Oxidative Stress and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Jie Li

    2013-12-01

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

  8. 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.

  9. Oxidative Stress Adaptation with Acute, Chronic and Repeated Stress

    OpenAIRE

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

    2012-01-01

    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,...

  10. The point about oxidative stress in molluscs

    Directory of Open Access Journals (Sweden)

    H Manduzio

    2005-07-01

    Full Text Available In the normal metabolism of the aerobic cell, oxygen is used for various biochemical reactions.Because of its two lone electrons of parallel spins, the molecular oxygen is stable. However, oxygengenerates Reactive Oxygenated Species or ROS by successive transfer of electrons. The ROS have astrong reactivity and can potentially interact with all other cellular components (lipids, proteins, DNA.They are at the origin of oxidations in chain by creating radicals. The cell has antioxidant systemswhich limit the effects of the ROS. These systems are composed of enzymes such as glutathionereductase, glutathione peroxidase, etc., and molecules of nonenzymatic nature like the reducedglutathione or vitamins. The production and the destruction of the radicals of oxygen coexist in a weakbalance. If this balance is broken in favour of the ROS, an oxidative stress is generated. Xenobioticscould influence this balance by catalysing production of ROS.

  11. 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.

  12. Skin aging and oxidative stress

    OpenAIRE

    Sayeeda Ahsanuddin; Minh Lam; Baron, Elma D.

    2016-01-01

    Skin aging occurs through two main pathways, intrinsic and extrinsic. These pathways have significant interaction in contributing to the aging phenotype, which includes skin laxity, wrinkling, pigmentation irregularities, and the appearance of neoplastic skin lesions. Here, we review the critical role that oxidative stress plays in skin aging, including its effects on signaling pathways involved in skin matrix formation and degradation, proteasome activity, as well as DNA structure. Furthermo...

  13. Oxidative stress, mitochondrial dysfunction and the mitochondria theory of aging.

    Science.gov (United States)

    Kong, Yahui; Trabucco, Sally E; Zhang, Hong

    2014-01-01

    Aging is characterized by a progressive decline in cellular function, organismal fitness and increased risk of age-associated diseases and death. One potential cause of aging is the progressive accumulation of dysfunctional mitochondria and oxidative damage with age. Considerable efforts have been made in our understanding of the role of mitochondrial dysfunction and oxidative stress in aging and age-associated diseases. This chapter outlines the interplay between oxidative stress and mitochondrial dysfunction, and discusses their impact on senescence, cell death, stem cell function, age-associated diseases and longevity.

  14. Oxidative stress in industrial fungi.

    Science.gov (United States)

    Li, Qiang; Harvey, Linda M; McNeil, Brian

    2009-01-01

    Fungi are amongst the most industrially important microorganisms in current use within the biotechnology industry. Most such fungal cultures are highly aerobic in nature, a character that has been frequently referred to in both reactor design and fungal physiology. The most fundamentally significant outcome of the highly aerobic growth environment in fermenter vessels is the need for the fungal culture to effectively combat in the intracellular environment the negative consequences of high oxygen transfer rates. The use of oxygen as the respiratory substrate is frequently reported to lead to the development of oxidative stress, mainly due to oxygen-derived free radicals, which are collectively termed as reactive oxygen species (ROS). Recently, there has been extensive research on the occurrence, extent, and consequences of oxidative stress in microorganisms, and the underlying mechanisms through which cells prevent and repair the damage caused by ROS. In the present study, we critically review the current understanding of oxidative stress events in industrially relevant fungi. The review first describes the current state of knowledge of ROS concisely, and then the various antioxidant strategies employed by fungal cells to counteract the deleterious effects, together with their implications in fungal bioprocessing are also discussed. Finally, some recommendations for further research are made. PMID:19514862

  15. 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

  16. Oxidative stress--a key emerging impact factor in health, ageing, lifestyle and aesthetics.

    Science.gov (United States)

    Kandola, K; Bowman, A; Birch-Machin, M A

    2015-12-01

    Oxidative stress is the resultant damage that arises due to redox imbalances, more specifically an increase in destructive free radicals and reduction in protection from antioxidants and the antioxidant defence pathways. Oxidation of lipids by reactive oxygen species (ROS) can damage cellular structures and result in premature cell death. At low levels, ROS-induced oxidative stress can be prevented through the action of antioxidants, however, when ROS are present in excess, inflammation and cytotoxicity eventually results leading to cellular oxidative stress damage. Increasing evidence for the role of oxidative stress in various diseases including neurological, dermatological, and cardiovascular diseases is now emerging. Mitochondria are the principal source (90%) of ROS in the cell, with superoxide radicals being generated when molecular oxygen is combined with free electrons. Given the key role of mitochondria in the generation of cellular oxidative stress it is worth considering this organelle and the process in more detail and to provide methods of intervention.

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

    Science.gov (United States)

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

    2008-01-01

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

  18. Management of oxidative stress by microalgae.

    Science.gov (United States)

    Cirulis, Judith T; Scott, J Ashley; Ross, Gregory M

    2013-01-01

    The aim of this review is to provide an overview of the current research on oxidative stress in eukaryotic microalgae and the antioxidant compounds microalgae utilize to control oxidative stress. With the potential to exploit microalgae for the large-scale production of antioxidants, interest in how microalgae manage oxidative stress is growing. Microalgae can experience increased levels of oxidative stress and toxicity as a result of environmental conditions, metals, and chemicals. The defence mechanisms for microalgae include antioxidant enzymes such as superoxide dismutase, catalase, peroxidases, and glutathione reductase, as well as non-enzymatic antioxidant molecules such as phytochelatins, pigments, polysaccharides, and polyphenols. Discussed herein are the 3 areas the literature has focused on, including how conditions stress microalgae and how microalgae respond to oxidative stress by managing reactive oxygen species. The third area is how beneficial microalgae antioxidants are when administered to cancerous mammalian cells or to rodents experiencing oxidative stress.

  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. Oxidative Stress in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Gábor Csányi

    2014-04-01

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

  1. Oxidative Stress and HPV Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Federico De Marco

    2013-02-01

    Full Text Available Extensive experimental work has conclusively demonstrated that infection with certain types of human papillomaviruses, the so-called high-risk human papillomavirus (HR-HPV, represent a most powerful human carcinogen. However, neoplastic growth is a rare and inappropriate outcome in the natural history of HPV, and a number of other events have to concur in order to induce the viral infection into the (very rare neoplastic transformation. From this perspective, a number of putative viral, host, and environmental co-factors have been proposed as potential candidates. Among them oxidative stress (OS is an interesting candidate, yet comparatively underexplored. OS is a constant threat to aerobic organisms being generated during mitochondrial oxidative phosphorylation, as well as during inflammation, infections, ionizing irradiation, UV exposure, mechanical and chemical stresses. Epithelial tissues, the elective target for HPV infection, are heavily exposed to all named sources of OS. Two different types of cooperative mechanisms are presumed to occur between OS and HPV: I The OS genotoxic activity and the HPV-induced genomic instability concur independently to the generation of the molecular damage necessary for the emergence of neoplastic clones. This first mode is merely a particular form of co-carcinogenesis; and II OS specifically interacts with one or more molecular stages of neoplastic initiation and/or progression induced by the HPV infection. This manuscript was designed to summarize available data on this latter hypothesis. Experimental data and indirect evidences on promoting the activity of OS in viral infection and viral integration will be reviewed. The anti-apoptotic and pro-angiogenetic role of NO (nitric oxide and iNOS (inducible nitric oxide synthase will be discussed together with the OS/HPV cooperation in inducing cancer metabolism adaptation. Unexplored/underexplored aspects of the OS interplay with the HPV-driven carcinogenesis

  2. Neuroendocrine system response modulates oxidative cellular damage in burn patients.

    Science.gov (United States)

    Xie, Xiao-Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko

    2007-02-01

    Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

  3. INVOLVEMENT OF OXIDATIVE STRESS IN THE PATHOGENESIS OF SCHIZOPHRENIA:FOCUS ON NOX ENZYMES

    OpenAIRE

    Schiavone, Stefania

    2011-01-01

    The imbalance between the production of reactive oxygen species (ROS) and the cellular antioxidant defence, determines a situation called “oxidative stress”. ROS react and oxidize cellular components, such as proteins or DNA, leading to cell death and severe tissue damage. The central nervous system (CNS) is particularly sensitive to oxidative stress because of high oxygen consumption, low antioxidant defense and abundance of lipids, which are prone to oxidation. For this reaso...

  4. 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.

  5. Etiologies of sperm oxidative stress.

    Science.gov (United States)

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

    2016-04-01

    Sperm is particularly susceptible to reactive oxygen species (ROS) during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN) leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions. PMID:27351024

  6. Inflammation, Oxidative Stress, and Obesity

    Directory of Open Access Journals (Sweden)

    José A. Morales-González

    2011-05-01

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

  7. Redox Modulation of Cellular Signaling and Metabolism Through Reversible Oxidation of Methionine Sensors in Calcium Regulatory Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bigelow, Diana J.; Squier, Thomas C.

    2005-01-17

    Adaptive responses associated with environmental stressors are critical to cell survival. These involve the modulation of central signaling protein functions through site-specific and enzymatically reversible oxidative modifications of methionines to coordinate cellular metabolism, energy utilization, and calcium signaling. Under conditions when cellular redox and antioxidant defenses are overwhelmed, the selective oxidation of critical methionines within selected protein sensors functions to down-regulate energy metabolism and the further generation of reactive oxygen species (ROS). Mechanistically, these functional changes within protein sensors take advantage of the helix-breaking character of methionine sulfoxide. Thus, depending on either the ecological niche of the organism or the cellular milieu of different organ systems, cellular metabolism can be fine-tuned to maintain optimal function in the face of variable amounts of collateral oxidative damage. The sensitivity of several calcium regulatory proteins to oxidative modification provides cellular sensors that link oxidative stress to cellular response and recovery. Calmodulin (CaM) is one such critical calcium regulatory protein, which is functionally sensitive to methionine oxidation. Helix destabilization resulting from the oxidation of either Met{sup 144} or Met{sup 145} results in the nonproductive association between CaM and target proteins. The ability of oxidized CaM to stabilize its target proteins in an inhibited state with an affinity similar to that of native (unoxidized) CaM permits this central regulatory protein to function as a cellular rheostat that down-regulates energy metabolism in response to oxidative stress. Likewise, oxidation of a methionine within a critical switch region of the regulatory protein phospholamban is expected to destabilize the phosphorylationdependent helix formation necessary for the release of enzyme inhibition, resulting in a down-regulation of the Ca-ATPase in

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

    OpenAIRE

    Namrata eChaudhari; Priti eTalwar; Avinash eParimisetty; Christian eLefebvre d'Hellencourt; Palaniyandi eRavanan

    2014-01-01

    Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse b...

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

    OpenAIRE

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

    2014-01-01

    Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse b...

  10. Oxidative Stress in Cystinosis Patients

    Directory of Open Access Journals (Sweden)

    Maria Helena Vaisbich

    2011-09-01

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

  11. A computable cellular stress network model for non-diseased pulmonary and cardiovascular tissue

    Directory of Open Access Journals (Sweden)

    Drubin David

    2011-10-01

    Full Text Available Abstract Background Humans and other organisms are equipped with a set of responses that can prevent damage from exposure to a multitude of endogenous and environmental stressors. If these stress responses are overwhelmed, this can result in pathogenesis of diseases, which is reflected by an increased development of, e.g., pulmonary and cardiac diseases in humans exposed to chronic levels of environmental stress, including inhaled cigarette smoke (CS. Systems biology data sets (e.g., transcriptomics, phosphoproteomics, metabolomics could enable comprehensive investigation of the biological impact of these stressors. However, detailed mechanistic networks are needed to determine which specific pathways are activated in response to different stressors and to drive the qualitative and eventually quantitative assessment of these data. A current limiting step in this process is the availability of detailed mechanistic networks that can be used as an analytical substrate. Results We have built a detailed network model that captures the biology underlying the physiological cellular response to endogenous and exogenous stressors in non-diseased mammalian pulmonary and cardiovascular cells. The contents of the network model reflect several diverse areas of signaling, including oxidative stress, hypoxia, shear stress, endoplasmic reticulum stress, and xenobiotic stress, that are elicited in response to common pulmonary and cardiovascular stressors. We then tested the ability of the network model to identify the mechanisms that are activated in response to CS, a broad inducer of cellular stress. Using transcriptomic data from the lungs of mice exposed to CS, the network model identified a robust increase in the oxidative stress response, largely mediated by the anti-oxidant NRF2 pathways, consistent with previous reports on the impact of CS exposure in the mammalian lung. Conclusions The results presented here describe the construction of a cellular stress

  12. 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

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

    International Nuclear Information System (INIS)

    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

  14. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

    Directory of Open Access Journals (Sweden)

    Wajdy Al-Awaida

    2014-10-01

    Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT.

  15. Two Lactococcus lactis thioredoxin paralogues play different roles in responses to arsenate and oxidative stress

    DEFF Research Database (Denmark)

    Efler, Petr; Kilstrup, Mogens; Johnsen, Stig;

    2015-01-01

    Thioredoxin (Trx) maintains intracellular thiol groups in a reduced state and is involved in a wide range of cellular processes, including ribonucleotide reduction, sulphur assimilation, oxidative stress responses and arsenate detoxification. The industrially important lactic acid bacterium Lacto...

  16. Role of oxidative stress in carbon nanotube-generated health effects

    DEFF Research Database (Denmark)

    Møller, Peter; Christophersen, Daniel Vest; Jensen, Ditte Marie;

    2014-01-01

    changes in the lungs, and cardiovascular disease. As oxidative stress and inflammation responses are implicated in the development of these diseases, converging lines of evidence indicate that exposure to CNTs is associated with increased risk of cardiopulmonary diseases through generation of a pro...... a dependency of oxidative stress on cellular responses to CNT exposure. CNT-mediated oxidative stress in cell cultures has been associated with elevated levels of lipid peroxidation products and oxidatively damaged DNA. Investigations of oxidative stress endpoints in animal studies have utilized pulmonary...

  17. Effect of omega-3 fatty acid oxidation products on the cellular and mitochondrial toxicity of BDE 47

    OpenAIRE

    Yeh, Andrew; Kruse, Shane E.; Marcinek, David J.; Gallagher, Evan P.

    2015-01-01

    High levels of the flame retardant 2,2′,4,4′-tetrabromodiphenyl ether (BDE 47) have been detected in Pacific salmon sampled near urban areas, raising concern over the safety of salmon consumption. However, salmon fillets also contain the antioxidants eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), whose oxidation products induce cellular antioxidant responses. Because oxidative stress is a mechanism of BDE 47 toxicity, we hypothesized that oxidized EPA and DHA can ameliorate the c...

  18. Obesity-Related Oxidative Stress: the Impact of Physical Activity and Diet Manipulation

    OpenAIRE

    Huang, Chun-Jung; McAllister, Matthew J.; Slusher, Aaron L.; Webb, Heather E.; Mock, J. Thomas; Acevedo, Edmund O.

    2015-01-01

    Obesity-related oxidative stress, the imbalance between pro-oxidants and antioxidants (e.g., nitric oxide), has been linked to metabolic and cardiovascular disease, including endothelial dysfunction and atherosclerosis. Reactive oxygen species (ROS) are essential for physiological functions including gene expression, cellular growth, infection defense, and modulating endothelial function. However, elevated ROS and/or diminished antioxidant capacity leading to oxidative stress can lead to dysf...

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    Xiaochun Duan

    2016-01-01

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

  1. 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.

  2. A Cellular Model for Screening Neuronal Nitric Oxide Synthase Inhibitors

    OpenAIRE

    Fang, Jianguo; Silverman, Richard B.

    2009-01-01

    Nitric oxide synthase (NOS) inhibitors are potential drug candidates because it has been well demonstrated that excessive production of NO critically contributes to a range of diseases. Most inhibitors have been screened in vitro using recombinant enzymes, leading to the discovery of a variety of potent compounds. To make inhibition studies more physiologically relevant and bridge the gap between the in vitro assay and in vivo studies, we report here a cellular model for screening NOS inhibit...

  3. Oxidative and nitrative stress in neurodegeneration.

    Science.gov (United States)

    Cobb, Catherine A; Cole, Marsha P

    2015-12-01

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

  4. 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....

  5. Gpx3-dependent responses against oxidative stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kho, Chang Won; Lee, Phil Young; Bae, Kwang-Hee; Kang, Sunghyun; Cho, Sayeon; Lee, Do Hee; Sun, Choong-Hyun; Yi, Gwan-Su; Park, Byoung Chul; Park, Sung Goo

    2008-02-01

    The yeast Saccharomyces cerevisiae has defense mechanisms identical to higher eukaryotes. It offers the potential for genome-wide experimental approaches owing to its smaller genome size and the availability of the complete sequence. It therefore represents an ideal eukaryotic model for studying cellular redox control and oxidative stress responses. S. cerevisiae Yap1 is a well-known transcription factor that is required for H2O2-dependent stress responses. Yap1 is involved in various signaling pathways in an oxidative stress response. The Gpx3 (Orp1/PHGpx3) protein is one of the factors related to these signaling pathways. It plays the role of a transducer that transfers the hydroperoxide signal to Yap1. In this study, using extensive proteomic and bioinformatics analyses, the function of the Gpx3 protein in an adaptive response against oxidative stress was investigated in wild-type, gpx3-deletion mutant, and gpx3-deletion mutant overexpressing Gpx3 protein strains. We identified 30 proteins that are related to the Gpx3- dependent oxidative stress responses and 17 proteins that are changed in a Gpx3-dependent manner regardless of oxidative stress. As expected, H2O2-responsive Gpx3-dependent proteins include a number of antioxidants related with cell rescue and defense. In addition, they contain a variety of proteins related to energy and carbohydrate metabolism, transcription, and protein fate. Based upon the experimental results, it is suggested that Gpx3-dependent stress adaptive response includes the regulation of genes related to the capacity to detoxify oxidants and repair oxidative stress-induced damages affected by Yap1 as well as metabolism and protein fate independent from Yap1. PMID:18309271

  6. Impact of Air Pollutants on Oxidative Stress in Common Autophagy-Mediated Aging Diseases

    Directory of Open Access Journals (Sweden)

    Mohamed Saber Numan

    2015-02-01

    Full Text Available Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS, Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur.

  7. Oxidative Stress and Transcriptional Regulation in Alzheimer’s Disease

    OpenAIRE

    Shi, Q; Gibson, G. E

    2007-01-01

    Alzheimer’s disease (AD) is defined by progressive impairments in memory and cognition and by the presence of extra-cellular neuritic plaques and intracellular neurofibrillary tangles. However, oxidative stress and impaired mitochondrial function always accompany AD. Mitochondria are a major site of production of free radicals [i.e., reactive oxygen species (ROS)] and primary targets of ROS. ROS are cytotoxic, and evidence of ROS-induced damage to cell membranes, proteins and DNA in AD is ove...

  8. Oxidative stress and cell adhesion in skin cancer

    OpenAIRE

    Hintsala, H.-R. (Hanna-Riikka)

    2016-01-01

    Abstract Skin is the largest organ in our body protecting us from ultraviolet radiation and xenobiotics. UV-radiation is a common cause of squamocellular carcinoma and melanoma of the skin that cause morbidity and mortality world wide. Reactive oxygen species are constantly formed by, for example, cellular respiration and UV-radiation, and they can readily react with virtually any macromolecule within cell structures causing damage to DNA, proteins and lipids. Oxidative stress (OS) is a h...

  9. Impact of Oxidative Stress on Exercising Skeletal Muscle

    OpenAIRE

    Peter Steinbacher; Peter Eckl

    2015-01-01

    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 ex...

  10. A STUDY OF OXIDATIVE STRESS IN DIABETES

    Directory of Open Access Journals (Sweden)

    Babu Rao

    2015-06-01

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

  11. Cellular memory of acquired stress resistance in Saccharomyces cerevisiae.

    Science.gov (United States)

    Guan, Qiaoning; Haroon, Suraiya; Bravo, Diego González; Will, Jessica L; Gasch, Audrey P

    2012-10-01

    Cellular memory of past experiences has been observed in several organisms and across a variety of experiences, including bacteria "remembering" prior nutritional status and amoeba "learning" to anticipate future environmental conditions. Here, we show that Saccharomyces cerevisiae maintains a multifaceted memory of prior stress exposure. We previously demonstrated that yeast cells exposed to a mild dose of salt acquire subsequent tolerance to severe doses of H(2)O(2). We set out to characterize the retention of acquired tolerance and in the process uncovered two distinct aspects of cellular memory. First, we found that H(2)O(2) resistance persisted for four to five generations after cells were removed from the prior salt treatment and was transmitted to daughter cells that never directly experienced the pretreatment. Maintenance of this memory did not require nascent protein synthesis after the initial salt pretreatment, but rather required long-lived cytosolic catalase Ctt1p that was synthesized during salt exposure and then distributed to daughter cells during subsequent cell divisions. In addition to and separable from the memory of H(2)O(2) resistance, these cells also displayed a faster gene-expression response to subsequent stress at >1000 genes, representing transcriptional memory. The faster gene-expression response requires the nuclear pore component Nup42p and serves an important function by facilitating faster reacquisition of H(2)O(2) tolerance after a second cycle of salt exposure. Memory of prior stress exposure likely provides a significant advantage to microbial populations living in ever-changing environments. PMID:22851651

  12. Exercise-induced dehydration with and without environmental heat stress results in increased oxidative stress.

    Science.gov (United States)

    Hillman, Angela R; Vince, Rebecca V; Taylor, Lee; McNaughton, Lars; Mitchell, Nigel; Siegler, Jason

    2011-10-01

    While in vitro work has revealed that dehydration and hyperthermia can elicit increased cellular and oxidative stress, in vivo research linking dehydration, hyperthermia, and oxidative stress is limited. The purpose of this study was to investigate the effects of exercise-induced dehydration with and without hyperthermia on oxidative stress. Seven healthy male, trained cyclists (power output (W) at lactate threshold (LT): 199 ± 19 W) completed 90 min of cycling exercise at 95% LT followed by a 5-km time trial (TT) in 4 trials: (i) euhydration in a warm environment (EU-W, control), (ii) dehydration in a warm environment (DE-W), (iii) euhydration in a thermoneutral environment (EU-T), and (iv) dehydration in a thermoneutral environment (DE-T) (W: 33.9 ± 0.9 °C; T: 23.0 ± 1.0 °C). Oxidized glutathione (GSSG) increased significantly postexercise in dehydration trials only (DE-W: p dehydration trials (p = 0.08 for both). Monocyte heat shock protein 72 (HSP72) concentration was increased (p = 0.01) while lymphocyte HSP32 concentration was decreased for all trials (p = 0.02). Exercise-induced dehydration led to an increase in GSSG concentration while maintenance of euhydration attenuated these increases regardless of environmental condition. Additionally, we found evidence of increased cellular stress (measured via HSP) during all trials independent of hydration status and environment. Finally, both 90-min and 5-km TT performances were reduced during only the DE-W trial, likely a result of combined cellular stress, hyperthermia, and dehydration. These findings highlight the importance of fluid consumption during exercise to attenuate thermal and oxidative stress during prolonged exercise in the heat.

  13. Is the Oxidative Stress Really a Disease?

    Directory of Open Access Journals (Sweden)

    Fogarasi Erzsébet

    2016-03-01

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

  14. OGG1 is essential in oxidative stress induced DNA demethylation.

    Science.gov (United States)

    Zhou, Xiaolong; Zhuang, Ziheng; Wang, Wentao; He, Lingfeng; Wu, Huan; Cao, Yan; Pan, Feiyan; Zhao, Jing; Hu, Zhigang; Sekhar, Chandra; Guo, Zhigang

    2016-09-01

    DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8-oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress-induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes. PMID:27251462

  15. Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation.

    Science.gov (United States)

    Mossakowski, Agata A; Pohlan, Julian; Bremer, Daniel; Lindquist, Randall; Millward, Jason M; Bock, Markus; Pollok, Karolin; Mothes, Ronja; Viohl, Leonard; Radbruch, Moritz; Gerhard, Jenny; Bellmann-Strobl, Judith; Behrens, Janina; Infante-Duarte, Carmen; Mähler, Anja; Boschmann, Michael; Rinnenthal, Jan Leo; Füchtemeier, Martina; Herz, Josephine; Pache, Florence C; Bardua, Markus; Priller, Josef; Hauser, Anja E; Paul, Friedemann; Niesner, Raluca; Radbruch, Helena

    2015-12-01

    The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation. PMID:26521072

  16. Oxidative Stress Related Diseases in Newborns

    Directory of Open Access Journals (Sweden)

    Yasemin Ozsurekci

    2016-01-01

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

  17. Oxidative Stress Related Diseases in Newborns.

    Science.gov (United States)

    Ozsurekci, Yasemin; Aykac, Kubra

    2016-01-01

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

  18. Role of Forkhead Transcription Factors in Diabetes-Induced Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Bhaskar Ponugoti

    2012-01-01

    Full Text Available Diabetes is a chronic metabolic disorder, characterized by hyperglycemia resulting from insulin deficiency and/or insulin resistance. Recent evidence suggests that high levels of reactive oxygen species (ROS and subsequent oxidative stress are key contributors in the development of diabetic complications. The FOXO family of forkhead transcription factors including FOXO1, FOXO3, FOXO4, and FOXO6 play important roles in the regulation of many cellular and biological processes and are critical regulators of cellular oxidative stress response pathways. FOXO1 transcription factors can affect a number of different tissues including liver, retina, bone, and cell types ranging from hepatocytes to microvascular endothelial cells and pericytes to osteoblasts. They are induced by oxidative stress and contribute to ROS-induced cell damage and apoptosis. In this paper, we discuss the role of FOXO transcription factors in mediating oxidative stress-induced cellular response.

  19. 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

  20. 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.

  1. [Oxidative stress in bipolar affective disorder].

    Science.gov (United States)

    Reininghaus, E Z; Zelzer, S; Reininghaus, B; Lackner, N; Birner, A; Bengesser, S A; Fellendorf, F T; Kapfhammer, H-P; Mangge, H

    2014-09-01

    The results of mortality studies have indicated that medical conditions, such as cardiovascular disease, obesity and diabetes are the most important causes of mortality among patients with bipolar disorder. The reasons for the increased incidence and mortality are not fully understood. Oxidative stress and an inadequate antioxidative system might be one missing link and could also help to further elucidate the pathophysiological basis of bipolar disorder. This article provides a comprehensive review of oxidative stress in general and about the existing data for bipolar disorder. In addition information is given about possible therapeutic strategies to reduce oxidative stress and the use in bipolar disorder. PMID:24441847

  2. Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions

    OpenAIRE

    Hassan, Waseem; Silva, Carlos Eduardo Barroso; Mohammadzai, Imdad Ullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J.

    2014-01-01

    Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related di...

  3. 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...

  4. Gene expression dynamics in the oxidative stress response of fission yeast

    DEFF Research Database (Denmark)

    Papadakis, Emmanouil

    , is known to damage cellular components. In humans, redox imbalance is associated withaging, cancer, atherosclerosis, Alzheimer’s and Parkinson’s disease among others. Therefore, studies investigating the cellular mechanisms employed in response to oxidative stress have markedly increased in recent years...

  5. Diabetes and Kidney Disease: Role of Oxidative Stress

    Science.gov (United States)

    Jha, Jay C.; Banal, Claudine; Chow, Bryna S.M.; Cooper, Mark E.

    2016-01-01

    Abstract Significance: Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657–684. PMID:26906673

  6. Peroxiredoxins, oxidative stress, and cell proliferation.

    Science.gov (United States)

    Immenschuh, Stephan; Baumgart-Vogt, Eveline

    2005-01-01

    Peroxiredoxins (Prxs) are a family of multifunctional antioxidant thioredoxin-dependent peroxidases that have been identified in a large variety of organisms. The major functions of Prxs comprise cellular protection against oxidative stress, modulation of intracellular signaling cascades that apply hydrogen peroxide as a second messenger molecule, and regulation of cell proliferation. In the present review, we discuss pertinent findings on the protein structure, the cell- and tissue-specific distribution, as well as the subcellular localization of Prxs. A particular emphasis is put on Prx I, which is the most abundant and ubiquitously distributed member of the mammalian Prxs. Major transcriptional and posttranslational regulatory mechanisms and signaling pathways that control Prx gene expression and activity are summarized. The interaction of Prx I with the oncogene products c-Abl and c-Myc and the regulatory role of Prx I for cell proliferation and apoptosis are highlighted. Recent findings on phenotypical alterations of mouse models with targeted disruptions of Prx genes are discussed, confirming the physiological functions of Prxs for antioxidant cell and tissue protection along with an important role as tumor suppressors.

  7. Patterns of biological effects of electromagnetic terahertz waves at frequencies of active cellular metabolites of post stressed changes in hemostasis

    Directory of Open Access Journals (Sweden)

    Vyacheslav F. Kirichuk

    2013-11-01

    Full Text Available There had been studied the influence of electromagnetic waves at terahertz frequencies of active cellular metabolites (nitric oxide 150.176-150.664 GHz and 129.0 GHz atmospheric oxygen on the changed parameters of homeostasis in experimental animals. It is shown that in the 15 minute exposure mode terahertz waves at frequencies of nitric oxide 150.176-150.664 GHz observed partial recovery of the changed parameters of homeostasis in stressed animals, and at 30 minute mode, the impact of these waves there is complete recovery of homeostatic parameters of male rats in a state of acute and prolonged immobilization stress.

  8. Oxidative stress and bivalves: a proteomic approach

    Directory of Open Access Journals (Sweden)

    B McDonagh

    2008-09-01

    Full Text Available Bivalves are of major importance in aquatic ecology, aquaculture, are widely used as sentinel species in environmental toxicology and show remarkable plasticity to molecular oxygen. Excess reactive oxygen species (ROS arising from molecular oxygen can cause oxidative stress and this is also a consequence of exposure to many common environmental pollutants. Indices of oxidative stress have therefore found favor as biomarkers of exposure and effect in environmental toxicology. However, there is a growing body of literature on the use of discovery-led proteomics methods to detect oxidative stress in bivalves. This is because proteins absorb up to 70 % of ROS leading to complication of the proteome. This article explores the background to these developments and assesses the practice and future potential of proteomics in the study of oxidative stress in bivalves.

  9. LINK BETWEEN OXIDATIVE STRESS AND INSULIN RESISTANCE

    Institute of Scientific and Technical Information of China (English)

    Lan-fang Li; Jian Li

    2007-01-01

    Many studies on oxidative stress, insulin resistance, and antioxidant treatment have shown that increased oxidative stress may accelerate the development of diabetic complications through the excessive glucose and free fatty acids metabolism in diabetic and insulin-resistant states. Many pathogenic mechanisms such as insulin receptor substrate phosphorylation are involved in insulin resistance induced by oxidative stress. And antioxidant treatments can show benefits in animal models of diabetes mellitus and insulin resistance. However, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating diabetic complications. Furthermore, it appears that oxidative stress is only one of the factors contributing to diabetic complications. Thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications.

  10. Oxidative Stress, Molecular Inflammation and Sarcopenia

    OpenAIRE

    Si-Jin Meng; Long-Jiang Yu

    2010-01-01

    Sarcopenia is the decline of muscle mass and strength with age. Evidence suggests that oxidative stress and molecular inflammation play important roles in age-related muscle atrophy. The two factors may interfere with the balance between protein synthesis and breakdown, cause mitochondrial dysfunction, and induce apoptosis. The purpose of this review is to discuss some of the major signaling pathways that are activated or inactivated during the oxidative stress and molecular inflammation seen...

  11. Oxidative Stress in Patients With Acne Vulgaris

    OpenAIRE

    2005-01-01

    Acne vulgaris is one of the common dermatological diseases and its pathogenesis is multifactorial. In this study, we aim to determine the effects of oxidative stress in acne vulgaris. Forty-three consecutive acne patients and 46 controls were enrolled. The parameters of oxidative stress such as catalase (CAT), glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), and malondialdehyde (MDA) in the venous blood of cases were measured spectrophotometrically. The values compared wi...

  12. Chrononutrition against Oxidative Stress in Aging

    OpenAIRE

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

    2013-01-01

    Free radicals and oxidative stress have been recognized as important factors in the biology of aging and in many age-associated degenerative diseases. Antioxidant systems deteriorate during aging. It is, thus, considered that one way to reduce the rate of aging and the risk of chronic disease is to avoid the formation of free radicals and reduce oxidative stress by strengthening antioxidant defences. Phytochemicals present in fruits, vegetables, grains, and other foodstuffs have been linked t...

  13. 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.

  14. Molecular and biochemical responses of Volvox carteri to oxidative stress

    Science.gov (United States)

    Lingappa, U.; Rankin-Gee, E. K.; Lera, M.; Bebour, B.; Marcu, O.

    2014-03-01

    Understanding the intracellular response to environmental stresses is a key aspect to understanding the limits of habitability for life as we know it. A wide range of relevant stressors, from heat shock to radiation, result in the intracellular production of reactive oxygen species (ROS). ROS are used physiologically as signaling molecules to cause changes in gene expression and metabolism. However, ROS, including superoxide (O2-) and peroxides, are also highly reactive molecules that cause oxidative damage to proteins, lipids and DNA. Here we studied stress response in the multicellular, eukaryotic green alga Volvox carteri, after exposure to heat shock conditions. We show that the ROS response to heat stress is paralleled by changes in photosynthetic metabolism, antioxidant enzyme activity and gene expression, and fluctuations in the elemental composition of cells. Metabolism, as measured by pulse amplitude modulated (PAM) fluorometry over two hours of heat stress, showed a linear decrease in the photosynthetic efficiency of Volvox. ROS quantification uncovered an increase in ROS in the culture medium, paralleled by a decrease in ROS within the Volvox colonies, suggesting an export mechanism is utilized to mitigate stress. Enzyme kinetics indicated an increase in superoxide dismutase (SOD) activity over the heat stress timecourse. Using X-ray fluorescence (XRF) at the Stanford Synchrotron Radiation Lightsource, we show that these changes coincide with cell-specific import/export and intracellular redistribution of transition elements and halides, suggesting that the cellular metallome is also engaged in mediating oxidative stress in Volvox.

  15. 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. PMID:27651846

  16. Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease.

    Science.gov (United States)

    Calabrese, Vittorio; Sultana, Rukhsana; Scapagnini, Giovanni; Guagliano, Eleonora; Sapienza, Maria; Bella, Rita; Kanski, Jaroslaw; Pennisi, Giovanni; Mancuso, Cesare; Stella, Anna Maria Giuffrida; Butterfield, D A

    2006-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive and memory decline, personality changes, and synapse loss. Increasing evidence indicates that factors such as oxidative and nitrosative stress, glutathione depletion, and impaired protein metabolism can interact in a vicious cycle, which is central to AD pathogenesis. In the present study, we demonstrate that brains of AD patients undergo oxidative changes classically associated with a strong induction of the so-called vitagenes, including the heat shock proteins (HSPs) heme oxygenase-1 (HO-1), HSP60, and HSP72, as well as thioredoxin reductase (TRXr). In inferior parietal brain of AD patients, a significant increase in the expression of HO-1 and TRXr was observed, whereas HO-2 expression was decreased, compared with controls. TRHr was not increased in AD cerebellum. Plasma GSH was decreased in AD patients, compared with the control group, and was associated with a significant increase in oxidative stress markers (i.e., GSSG, hydroxynonenal, protein carbonyl content, and nitrotyrosine). In AD lymphocytes, we observed an increased expression of inducible nitric oxide synthase, HO-1, Hsp72, HSP60, and TRXr. Our data support a role for nitrative stress in the pathogenesis of AD and indicate that the stress-responsive genes, such as HO-1 and TRXr, may represent important targets for novel cytoprotective strategies.

  17. MECANISMOS CELULARES EN RESPUESTA AL ESTRÉS:: SIRTUINAS Cellular mechanisms in response to stress: sirtuin

    Directory of Open Access Journals (Sweden)

    Nancy Paola Echeverri-Ruíz

    2010-07-01

    Full Text Available Desde hace algún tiempo se conoce el papel de la restricción calórica sobre la longevidad y la prevención de enfermedades crónicas, pero hasta hace poco los mecanismos celulares involucrados comienzan a ser elucidados. El estrés celular se podría definir como el estado en el que la célula no presenta las condiciones óptimas de supervivencia, siendo el oxidativo un tipo de estrés en el que se generan radicales libres nocivos para las estructuras celulares. La restricción calórica podría incrementar la resistencia celular a diferentes formas de estrés. Las sirtuinas, proteínas deacetilasas de histonas tipo III, están involucradas en la relación entre balance energético y transcripción génica, permitiendo que la célula responda a la restricción calórica y sobreviva a situaciones de estrés oxidativo. En esta relación las sirtuinas regulan genes de la familia FOXO, cMYC, hTERT, p53, entre otros. La activación o silenciamiento de estos genes es importante en los procesos de apoptosis, reparación y muerte celular.The role of caloric restriction on longevity and prevention of chronic diseases has been known for some time; recently, cellular mechanisms involved are beginning to be elucidated. Cellular stress could be defined as the state in which the cell does not present optimal survival conditions; oxidative stress is a type of stress in which free radicals harmful cell structures. Caloric restriction might increase cellular resistance to various forms of stress. Sirtuins, histone deacetylases type III proteins are involved in the relationship between energy balance and gene transcription, allowing cell to respond to caloric restriction and to survive to oxidative stress. In this relationship, sirtuins regulate FOXO family genes, cMYC, hTERT, p53, among others. Activation or silencing of those genes is important in the process of apoptosis, repair and cell death

  18. Estrogen and estrogen receptors in cardiovascular oxidative stress.

    Science.gov (United States)

    Arias-Loza, Paula-Anahi; Muehlfelder, Melanie; Pelzer, Theo

    2013-05-01

    The cardiovascular system of a premenopausal woman is prepared to adapt to the challenges of increased cardiac output and work load that accompany pregnancy. Thus, it is tempting to speculate whether enhanced adaptability of the female cardiovascular system might be advantageous under conditions that promote cardiovascular disease. In support of this concept, 17β-estradiol as the major female sex hormone has been shown to confer protective cardiovascular effects in experimental studies. Mechanistically, these have been partially linked to the prevention and protection against oxidative stress. Current evidence indicates that estrogens attenuate oxidative stress at two levels: first, by preventing generation of reactive oxygen species (ROS) and, second, by scavenging ROS in the myocardium and in the vasculature. The purpose of this review is to give an overview on current concepts on conditions and mechanisms by which estrogens protect the cardiovascular system against ROS-mediated cellular injury.

  19. Diabetic Cardiovascular Disease Induced by Oxidative Stress.

    Science.gov (United States)

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

    2015-10-23

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

    OpenAIRE

    Lačković Maja; Rovčanin B.; Pantović Maja; Ivković Maja; Petronijević Nataša; Damjanović A.

    2013-01-01

    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 p...

  1. Clinical Relevance of Biomarkers of Oxidative Stress

    DEFF Research Database (Denmark)

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

    2015-01-01

    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...... using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers...... still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others...

  2. Oxidative stress, mitochondrial damage and neurodegenerative diseases****

    Institute of Scientific and Technical Information of China (English)

    Chunyan Guo; Li Sun; Xueping Chen; Danshen Zhang

    2013-01-01

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

  3. Oxidative stress responses to a graded maximal exercise test in older adults following explosive-type resistance training

    Directory of Open Access Journals (Sweden)

    Roberta Ceci

    2014-01-01

    In conclusion, the adherence to an EMRT protocol is able to induce a cellular adaptation allowing healthy elderly trained subjects to cope with the oxidative stress induced by an acute exercise more effectively than the aged-matched sedentary subjects.

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

    Directory of Open Access Journals (Sweden)

    Graziamaria eCorbi

    2013-11-01

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

  5. 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)

    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)

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

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    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

  7. Therapeutic Approach of Nanotechnology for Oxidative Stress Induced Ocular Neurodegenerative Diseases.

    Science.gov (United States)

    Mitra, Rajendra N; Conley, Shannon M; Naash, Muna I

    2016-01-01

    Oxidative stress plays a role in many different forms of neurodegenerative ocular disease. The imbalance between the generation of endogenous reactive oxygen species (ROS) and their corresponding neutralization by endogenous antioxidant defense systems leads to cellular oxidative stress, oxidation of different bio-macromolecules, and eventually retinal disease. As a result, the administration of supplemental endogenous antioxidant materials or exogenous ROS scavengers is an interesting therapeutic approach for the treatment of forms of ocular disease associated with oxidative stress. Thus far, different dietary antioxidant supplements have been proven to be clinically reliable and effective, and different antioxidant gene therapy approaches are under investigation. In addition, various metal oxide nanoparticles were shown to be effective in defending against oxidative stress-associated injury. These benefits are due to free radical scavenging properties of the materials arising from non-stoichiometric crystal defects and oxygen deficiencies. Here we discuss the application of this approach to the protection of the retina. PMID:26427447

  8. Oxidative Stress, Molecular Inflammation and Sarcopenia

    Directory of Open Access Journals (Sweden)

    Si-Jin Meng

    2010-04-01

    Full Text Available Sarcopenia is the decline of muscle mass and strength with age. Evidence suggests that oxidative stress and molecular inflammation play important roles in age-related muscle atrophy. The two factors may interfere with the balance between protein synthesis and breakdown, cause mitochondrial dysfunction, and induce apoptosis. The purpose of this review is to discuss some of the major signaling pathways that are activated or inactivated during the oxidative stress and molecular inflammation seen in aged skeletal muscle. Combined interventions that may be required to reverse sarcopenia, such as exercise, caloric restriction, and nutrition, will also be discussed.

  9. Biomarkers of oxidative stress in antioxidant therapy

    Directory of Open Access Journals (Sweden)

    Wilfredo Mañon Rossi

    2016-04-01

    Full Text Available Biomarkers are used regularly in medical practice to provide objective markers of health status of a person, as well as the physiological response of the body to a pharmacological therapeutic intervention. In the specific case of the use of antioxidant products (antioxidant therapy, it is necessary to measure both biomarkers of oxidative stress level of the person as those that are specific to a physiological or pathological progression of a disease disorder. This paper describes the main biomarkers of oxidative general and specific stress as well as laboratory techniques, which should be taken into account when measuring the effectiveness of antioxidant therapies.

  10. Sex differences in molecular and cellular substrates of stress

    OpenAIRE

    Bangasser, Debra A.; Valentino, Rita J.

    2012-01-01

    Women are twice as likely as men to suffer from stress-related psychiatric disorders, like unipolar depression and post-traumatic stress disorder. Although the underlying neural mechanisms are not well characterized, the pivotal role of stress in the onset and severity of these diseases has led to the idea that sex differences in stress responses account for this sex bias. Corticotropin-releasing factor (CRF) orchestrates stress responses by acting both as a neurohormone to initiate the hypot...

  11. Cellular level loading and heating of superparamagnetic iron oxide nanoparticles.

    Science.gov (United States)

    Kalambur, Venkat S; Longmire, Ellen K; Bischof, John C

    2007-11-20

    Superparamagnetic iron oxide nanoparticles (NPs) hold promise for a variety of biomedical applications due to their properties of visualization using magnetic resonance imaging (MRI), heating with radio frequency (rf), and movement in an external magnetic field. In this study, the cellular loading (uptake) mechanism of dextran- and surfactant-coated iron oxide NPs by malignant prostate tumor cells (LNCaP-Pro5) has been studied, and the feasibility of traditional rf treatment and a new laser heating method was evaluated. The kinetics of cell loading was quantified using magnetophoresis and a colorimetric assay. The results showed that loading of surfactant-coated iron oxide NPs with LNCaP-Pro5 was saturable with time (at 24 h) and extracellular concentration (11 pg Fe/cell at 0.5 mg Fe/mL), indicating that the particles are taken up by an "adsorptive endocytosis" pathway. Dextran-coated NPs, however, were taken up less efficiently (1 pg Fe/cell at 0.5 mg Fe/mL). Loading did not saturate with concentration suggesting uptake by fluid-phase endocytosis. Magnetophoresis suggests that NP-loaded cells can be held using external magnetic fields in microcirculatory flow velocities in vivo or in an appropriately designed extracorporeal circuit. Loaded cells were heated using traditional rf (260A, 357 kHz) and a new laser method (532 nm, 7 ns pulse duration, 0.03 J/pulse, 20 pulse/s). Iron oxide in water was found to absorb sufficiently strongly at 532 nm such that heating of individual NPs and thus loaded cells (1 pg Fe/cell) was effective (10 pg Fe/cell) and longer duration (30 min) when compared to laser to accomplish cell destruction (50% viability at 10 pg Fe/cell). Scaling calculations show that the pulsed laser method can lead to single-cell (loaded with NPs) treatments (200 degrees C temperature change at the surface of an individual NP) unlike traditional rf heating methods which can be used only for bulk tissue level treatments. In a mixture of normal and NP

  12. The Nrf2 Activator Vinylsulfone Reduces High Glucose-Induced Neural Tube Defects by Suppressing Cellular Stress and Apoptosis.

    Science.gov (United States)

    Dong, Daoyin; Reece, E Albert; Yang, Peixin

    2016-08-01

    The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is one of the primary pathways responsible for the cellular defense system against oxidative stress. Oxidative stress-induced apoptosis is a causal event in diabetic embryopathy. Thus, the Nrf2 pathway may play an important role in the induction of diabetic embryopathy. In the present study, we investigated the potentially protective effect of the Nrf2 activator, vinylsulfone, on high glucose-induced cellular stress, apoptosis, and neural tube defects (NTDs). Embryonic day 8.5 (E8.5) whole mouse embryos were cultured in normal (5 mmol/L) or high (16.7 mmol/L) glucose conditions, with or without vinylsulfone. At a concentration of 10 μmol/L, vinylsulfone had an inhibitory effect on high glucose-induced NTD formation, but it was not significant. At a concentration of 20 μmol/L, vinylsulfone significantly reduced high glucose-induced NTDs. In addition, 20 μmol/L vinylsulfone abrogated the high glucose-induced oxidative stress markers lipid hydroperoxide (LPO), 4-hydroxynonenal (4-HNE), and nitrotyrosine-modified proteins. The high glucose-induced endoplasmic reticulum (ER) stress biomarkers were also suppressed by 20 μmol/L vinylsulfone through the inhibition of phosphorylated protein kinase RNA-like ER kinase (PERK), inositol requiring protein 1α (IRE1a), eukaryotic initiation factor 2α (eIF2a), upregulated C/EBP-homologous protein (CHOP), binding immunoglobulin protein (BiP), and x-box binding protein 1 (XBP1) messenger RNA splicing. Furthermore, 20 μmol/L vinylsulfone abolished caspase 3 and caspase 8 cleavage, markers of apoptosis, in embryos cultured under high glucose conditions. The Nrf2 activator, vinylsulfone, is protective against high glucose-induced cellular stress, caspase activation, and subsequent NTD formation. Our data suggest that vinylsulfone supplementation is a potential therapy for diabetes-associated neurodevelopmental defects. PMID:26802109

  13. Attenuation of Oxidative Stress of Erythrocytes by Plant-Derived Flavonoids, Orientin and Luteolin

    Directory of Open Access Journals (Sweden)

    Fang An

    2016-01-01

    Full Text Available Erythrocytes are easy to be injured by oxidative stress in their lifespan. Although there are several chemicals such as vitamin C (VC that would be able to reduce oxidative stress, natural herbal products still remain an interesting research area. The current study investigated the effects of two plant-derived flavonoids, orientin and luteolin, on erythrocytes and their possible mechanisms. This experiment was divided into nine groups, which were normal group, model group, VC control group, and treated groups with different doses of orientin and luteolin (10, 20, and 40 μg/mL, respectively. Hemolysis rate was determined by spectrophotometry. Antioxidative enzyme and products were evaluated by different methods. Erythrocyte cell surface and cellular structure were observed with scanning or transmission electron microscope, respectively. Oxidative stress induced significant increase in hemolysis rate of erythrocytes. Orientin or luteolin ameliorated hemolysis of erythrocytes in oxidative stress in a dose-dependent manner. Both orientin and luteolin reduced oxidative products and increased antioxidative enzyme activities. Moreover, orientin and luteolin attenuated oxidative stress induced damage of erythrocyte cell surface morphology and cellular structure. In conclusion, orientin and luteolin could protect human erythrocytes from oxidative damage by attenuating oxidative stress, protecting antioxidative enzyme activities, and preserving integrity of erythrocyte structure.

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

    International Nuclear Information System (INIS)

    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

  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. Caspase-2 protects against oxidative stress in vivo.

    Science.gov (United States)

    Shalini, S; Puccini, J; Wilson, C H; Finnie, J; Dorstyn, L; Kumar, S

    2015-09-17

    Caspase-2 belongs to the caspase family of cysteine proteases with established roles in apoptosis. Recently, caspase-2 has been implicated in nonapoptotic functions including maintenance of genomic stability and tumor suppression. Our previous studies demonstrated that caspase-2 also regulates cellular redox status and delays the onset of several ageing-related traits. In the current study, we tested stress tolerance ability in caspase-2-deficient (Casp2(-/-)) mice by challenging both young and old mice with a low dose of the potent reactive oxygen species (ROS) generator, PQ that primarily affects lungs. In both groups of mice, PQ induced pulmonary damage. However, the lesions in caspase-2 knockout mice were consistently and reproducibly more severe than those in wild-type (WT) mice. Furthermore, serum interleukin (IL)-1β and IL-6 levels were higher in PQ-exposed aged Casp2(-/-) mice indicating increased inflammation. Interestingly, livers from Casp2(-/-) mice displayed karyomegaly, a feature commonly associated with ageing and aneuploidy. Given that Casp2(-/-) mice show impaired antioxidant defense, we tested oxidative damage in these mice. Protein oxidation significantly increased in PQ-injected old Casp2(-/-) mice. Moreover, FoxO1, SOD2 and Nrf2 expression levels were reduced and induction of superoxide dismutase (SOD) and glutathione peroxidase activity was not observed in PQ-treated Casp2(-/-) mice. Strong c-Jun amino-terminal kinase (JNK) activation was observed in Casp2(-/-) mice, indicative of increased stress. Together, our data strongly suggest that caspase-2 deficiency leads to increased cellular stress largely because these mice fail to respond to oxidative stress by upregulating their antioxidant defense mechanism. This makes the mice more vulnerable to exogenous challenges and may partly explain the shorter lifespan of Casp2(-/-) mice.

  17. Caspase-2 protects against oxidative stress in vivo.

    Science.gov (United States)

    Shalini, S; Puccini, J; Wilson, C H; Finnie, J; Dorstyn, L; Kumar, S

    2015-09-17

    Caspase-2 belongs to the caspase family of cysteine proteases with established roles in apoptosis. Recently, caspase-2 has been implicated in nonapoptotic functions including maintenance of genomic stability and tumor suppression. Our previous studies demonstrated that caspase-2 also regulates cellular redox status and delays the onset of several ageing-related traits. In the current study, we tested stress tolerance ability in caspase-2-deficient (Casp2(-/-)) mice by challenging both young and old mice with a low dose of the potent reactive oxygen species (ROS) generator, PQ that primarily affects lungs. In both groups of mice, PQ induced pulmonary damage. However, the lesions in caspase-2 knockout mice were consistently and reproducibly more severe than those in wild-type (WT) mice. Furthermore, serum interleukin (IL)-1β and IL-6 levels were higher in PQ-exposed aged Casp2(-/-) mice indicating increased inflammation. Interestingly, livers from Casp2(-/-) mice displayed karyomegaly, a feature commonly associated with ageing and aneuploidy. Given that Casp2(-/-) mice show impaired antioxidant defense, we tested oxidative damage in these mice. Protein oxidation significantly increased in PQ-injected old Casp2(-/-) mice. Moreover, FoxO1, SOD2 and Nrf2 expression levels were reduced and induction of superoxide dismutase (SOD) and glutathione peroxidase activity was not observed in PQ-treated Casp2(-/-) mice. Strong c-Jun amino-terminal kinase (JNK) activation was observed in Casp2(-/-) mice, indicative of increased stress. Together, our data strongly suggest that caspase-2 deficiency leads to increased cellular stress largely because these mice fail to respond to oxidative stress by upregulating their antioxidant defense mechanism. This makes the mice more vulnerable to exogenous challenges and may partly explain the shorter lifespan of Casp2(-/-) mice. PMID:25531319

  18. Peroxisomes,oxidative stress,and inflammation

    Institute of Scientific and Technical Information of China (English)

    Stanley; R; Terlecky; Laura; J; Terlecky; Courtney; R; Giordano

    2012-01-01

    Peroxisomes are intracellular organelles mediating a wide variety of biosynthetic and biodegradative reactions.Included among these are the metabolism of hydrogen peroxide and other reactive species,molecules whose levels help define the oxidative state of cells.Loss of oxidative equilibrium in cells of tissues and organs potentiates inflammatory responses which can ultimately trigger human disease.The goal of this article is to review evidence for connections between peroxisome function,oxidative stress,and inflammation in the context of human health and degenerative disease.Dysregulated points in this nexus are identified and potential remedial approaches are presented.

  19. 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.

  20. Oxidative Stress in Aging-Matters of the Heart and Mind

    Directory of Open Access Journals (Sweden)

    T. C. Tai

    2013-09-01

    Full Text Available Oxidative damage is considered to be the primary cause of several aging associated disease pathologies. Cumulative oxidative damage tends to be pervasive among cellular macromolecules, impacting proteins, lipids, RNA and DNA of cells. At a systemic level, events subsequent to oxidative damage induce an inflammatory response to sites of oxidative damage, often contributing to additional oxidative stress. At a cellular level, oxidative damage to mitochondria results in acidification of the cytoplasm and release of cytochrome c, causing apoptosis. This review summarizes findings in the literature on oxidative stress and consequent damage on cells and tissues of the cardiovascular system and the central nervous system, with a focus on aging-related diseases that have well-documented evidence of oxidative damage in initiation and/or progression of the disease. The current understanding of the cellular mechanisms with a focus on macromolecular damage, impacted cellular pathways and gross morphological changes associated with oxidative damage is also reviewed. Additionally, the impact of calorific restriction with its profound impact on cardiovascular and neuronal aging is addressed.

  1. 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.

  2. Mitochondrial oxidative stress causes hyperphosphorylation of tau.

    Directory of Open Access Journals (Sweden)

    Simon Melov

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

  3. Clinical Perspective of Oxidative Stress in Sporadic ALS

    OpenAIRE

    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 elevate...

  4. 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.

  5. Dynamic modeling of cellular response to DNA damage based on p53 stress response networks

    Institute of Scientific and Technical Information of China (English)

    Jinpeng Qi; Yongsheng Ding; Shihuang Shao

    2009-01-01

    Under acute perturbations from the outside, cells can trigger self-defensive mechanisms to fight against genome stress. To investigate the cellular response to continuous ion radiation (IR), a dynamic model for p53 stress response networks at the cellular level is proposed. The model can successfully be used to simulate the dynamic processes of double-strand breaks (DSBs) generation and their repair, switch-like ataxia telangiectasia mutated (ATM) activation, oscillations occurring in the p53-MDM2 feedback loop, as well as toxins elimination triggered by p53 stress response networks. Especially, the model can predict the plausible outcomes of cellular response under different IR dose regimes.

  6. 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.

  7. 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)

    Highlights: • Uptake of TiO2 solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO2 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 TiO2 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 TiO2 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 TiO2 stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO2 exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO2/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

  8. Mitochondrial proteomics on human fibroblasts for identification of metabolic imbalance and cellular stress

    Directory of Open Access Journals (Sweden)

    Bross Peter

    2009-05-01

    Full Text Available Abstract Background Mitochondrial proteins are central to various metabolic activities and are key regulators of apoptosis. Disturbance of mitochondrial proteins is therefore often associated with disease. Large scale protein data are required to capture the mitochondrial protein levels and mass spectrometry based proteomics is suitable for generating such data. To study the relative quantities of mitochondrial proteins in cells from cultivated human skin fibroblasts we applied a proteomic method based on nanoLC-MS/MS analysis of iTRAQ-labeled peptides. Results When fibroblast cultures were exposed to mild metabolic stress – by cultivation in galactose medium- the amount of mitochondria appeared to be maintained whereas the levels of individual proteins were altered. Proteins of respiratory chain complex I and IV were increased together with NAD+-dependent isocitrate dehydrogenase of the citric acid cycle illustrating cellular strategies to cope with altered energy metabolism. Furthermore, quantitative protein data, with a median standard error below 6%, were obtained for the following mitochondrial pathways: fatty acid oxidation, citric acid cycle, respiratory chain, antioxidant systems, amino acid metabolism, mitochondrial translation, protein quality control, mitochondrial morphology and apoptosis. Conclusion The robust analytical platform in combination with a well-defined compendium of mitochondrial proteins allowed quantification of single proteins as well as mapping of entire pathways. This enabled characterization of the interplay between metabolism and stress response in human cells exposed to mild stress.

  9. Anticholinesterase Toxicity and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Dejan Milatovic

    2006-01-01

    Full Text Available Anticholinesterase compounds, organophosphates (OPs and carbamates (CMs are commonly used for a variety of purposes in agriculture and in human and veterinary medicine. They exert their toxicity in mammalian system primarily by virtue of acetylcholinesterase (AChE inhibition at the synapses and neuromuscular junctions, leading into the signs of hypercholinergic preponderance. However, the mechanism(s involved in brain/muscle damage appear to be linked with alteration in antioxidant and the scavenging system leading to free radical-mediated injury. OPs and CMs cause excessive formation of F2-isoprostanes and F4-neuroprostanes, in vivo biomarkers of lipid peroxidation and generation of reactive oxygen species (ROS, and of citrulline, a marker of NO/NOS and reactive nitrogen species (RNS generation. In addition, during the course of these excitatory processes and inhibition of AChE, a high rate of ATP consumption, coupled with the inhibition of oxidative phosphorylation, compromise the cell's ability to maintain its energy levels and excessive amounts of ROS and RNS may be generated. Pretreatment with N-methyl D-aspartate (NMDA receptor antagonist memantine, in combination with atropine sulfate, provides significant protection against inhibition of AChE, increases of ROS/RNS, and depletion of high-energy phosphates induced by DFP/carbofuran. Similar antioxidative effects are observed with a spin trapping agent, phenyl-N-tert-butylnitrone (PBN or chain breaking antioxidant vitamin E. This review describes the mechanisms involved in anticholinesterase-induced oxidative/nitrosative injury in target organs of OPs/CMs, and protection by various agents.

  10. Pseudorabies Virus Induces Viability Changes and Oxidative Stress in Swine Testis Cell-Line

    Directory of Open Access Journals (Sweden)

    Xiao-Zhan Zhang§1, Ye Chen§1, Hong-Liang Huang§2, Dong-Lei Xu1, Chang-Bao Ren2, Bi-Tao Liu1, Shuo Su1 and Zhao-Xin Tang1, 2*

    2013-11-01

    Full Text Available In this study, we evaluated the association between pseudorabies (PRV virus-induced viability changes and oxidative stress in vitro cultivated swine testis (ST cells. The kinetic of 2, 12, 24, 36 and 48 h during the cell culture with PRV by using a multiplicity of infection (MOI of 1 TCID50 per cell were adopted. The results suggested a complex relation between cell viability and oxidative stress during PRV infection. In the early stages of PRV infection, the cell viability was higher than the control group, and the state of cellular oxidative stress remained relatively stable. After 24 h, the cell viability began to decrease, and the amount of the cellular malondialdehyde in ST cells increased significantly, and the activities of superoxide dismutase and catalase decreased significantly (P<0.05. Meanwhile, the rising concentrations of cellular hydrogen peroxide were detected prior to the changes in cell viability and oxidative stress. In conclusion, the PRV infection of ST cells leads to oxidative stress, and this stress could play a crucial role on the cell viability as the PRV infection time progresses.

  11. Oxidative Stress in Cardiovascular Diseases and Obesity: Role of p66Shc and Protein Kinase C

    Directory of Open Access Journals (Sweden)

    Elena De Marchi

    2013-01-01

    Full Text Available Reactive oxygen species (ROS are a byproduct of the normal metabolism of oxygen and have important roles in cell signalling and homeostasis. An imbalance between ROS production and the cellular antioxidant defence system leads to oxidative stress. Environmental factors and genetic interactions play key roles in oxidative stress mediated pathologies. In this paper, we focus on cardiovascular diseases and obesity, disorders strongly related to each other; in which oxidative stress plays a fundamental role. We provide evidence of the key role played by p66Shc protein and protein kinase C (PKC in these pathologies by their intracellular regulation of redox balance and oxidative stress levels. Additionally, we discuss possible therapeutic strategies aimed at attenuating the oxidative damage in these diseases.

  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. 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. 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.

  15. A new cellular stress response that triggers centriolar satellite reorganization and ciliogenesis

    DEFF Research Database (Denmark)

    Villumsen, Bine H; Danielsen, Jannie R; Povlsen, Lou;

    2013-01-01

    Centriolar satellites are small, granular structures that cluster around centrosomes, but whose biological function and regulation are poorly understood. We show that centriolar satellites undergo striking reorganization in response to cellular stresses such as UV radiation, heat shock...

  16. Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development.

    Science.gov (United States)

    Aviram, Michael; Rosenblat, Mira

    2004-11-01

    Paraoxonases PON1 and PON3, which are both associated in serum with HDL, protect the serum lipids from oxidation, probably as a result of their ability to hydrolyze specific oxidized lipids. The activity of HDL-associated PON1 seems to involve an activity (phospholipase A2-like activity, peroxidase-like activity, lactonase activity) which produces LPC. To study the possible role of PON1 in macrophage foam cell formation and atherogenesis we used macrophages from control mice, from PON1 knockout mice, and from PON1 transgenic mice. Furthermore, we analyzed PON1-treated macrophages and PON1-transfected cells to demonstrate the contribution of PON1 to the attenuation of macrophage cholesterol and oxidized lipid accumulation and foam cell formation. PON1 was shown to inhibit cholesterol influx [by reducing the formation of oxidized LDL (Ox-LDL), increasing the breakdown of specific oxidized lipids in Ox-LDL, and decreasing macrophage uptake of Ox-LDL]. PON1 also inhibits cholesterol biosynthesis and stimulates HDL-mediated cholesterol efflux from macrophages. PON2 and PON3 protect against oxidative stress, with PON2 acting mainly at the cellular level. Whereas serum PON1 and PON3 were inactivated under oxidative stress, macrophage PON2 expression and activity were increased under oxidative stress, probably as a compensatory mechanism against oxidative stress. Intervention to increase the paraoxonases (cellular and humoral) by dietary or pharmacological means can reduce macrophage foam cell formation and attenuate atherosclerosis development. PMID:15454271

  17. APOPTOSIS, OXIDATIVE STRESS AND NEUROLOGICAL DISEASE

    Directory of Open Access Journals (Sweden)

    P. Formichi

    2012-01-01

    Full Text Available Apoptosis is a selective cell deletion process which requires the triggering of a specific cell death programme. Two main pathways determining cell death have been identified: the extrinsic or receptor-mediated pathway, activated in response to extracellular pro-apoptotic signals, and the intrinsic pathway, activated by extracellular receptor-independent stimuli or by intracellular insults, such as DNA damage and oxidative stress. All these stress signals are integrated by mitochondria which participate by releasing the main effectors of this process: a family of aspartic-specific proteases known as caspase. Today there is much evidence to suggest that deregulation of apoptosis is a key feature of many neurodegenerative disease. Our group sought cell models for the study of apoptotic pathways and for the evaluation of the role of apoptosis in specific neurodegenerative diseases. We focused on oxidative stress-induced apoptosis and activation of the intrinsic mitochondrial pathway. In our in-vitro model, lymphocytes from patients and control subjects were cultured both in basal conditions and with 2-deoxy-D-ribose (dRib, a reducing sugar which induces apoptosis through oxidative stress. In the last ten years, we evaluated the role of apoptosis in the pathogenesis of several neurodegenerative diseases: Ataxiatelangiectasia,Rett syndrome, Mitochondrial disease, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL. Here we report some of our ongoing and recently published articles.

  18. Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Claudia Consales

    2012-01-01

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

  19. Oxidative stress and the high altitude environment

    Directory of Open Access Journals (Sweden)

    Jakub Krzeszowiak

    2013-03-01

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

  20. 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...... able to identify surprisingly diverse sensitivity and resistance patterns as a function of gene knockout.......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...

  1. 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

  2. Oxidative stress and stress signaling: menace of diabetic cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    Loren E WOLD; Asli F CEYLAN-ISIK; Jun REN

    2005-01-01

    Cardiovascular disease is the most common cause of death in the diabetic population and is currently one of the leading causes of death in the United States and other industrialized countries. The health care expenses associated with cardiovascular disease are staggering, reaching more than US$350 billion in 2003. The risk factors for cardiovascular disease include high fat/cholesterol levels,alcoholism, smoking, genetics, environmental factors and hypertension, which are commonly used to gauge an individual's risk of cardiovascular disease and to track their progress during therapy. Most recently, these factors have become important in the early prevention of cardiovascular diseases. Oxidative stress, the imbalance between reactive oxygen species production and breakdown by endogenous antioxidants, has been implicated in the onset and progression of cardiovascular diseases such as congestive heart failure and diabetes-associated heart dysfunction (diabetic cardiomyopathy). Antioxidant therapy has shown promise in preventing the development of diabetic heart complications. This review focuses on recent advances in oxidative stress theory and antioxidant therapy in diabetic cardiomyopathy, with an emphasis on the stress signaling pathways hypothesized to be involved. Many of these stress signaling pathways lead to activation of reactive oxygen species, major players in the development and progression of diabetic cardiomyopathy.

  3. Oxidative stress and anti-oxidative mobilization in burn injury.

    Science.gov (United States)

    Parihar, Arti; Parihar, Mordhwaj S; Milner, Stephen; Bhat, Satyanarayan

    2008-02-01

    A severe burn is associated with release of inflammatory mediators which ultimately cause local and distant pathophysiological effects. Mediators including Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) are increased in affected tissue, which are implicated in pathophysiological events observed in burn patients. The purpose of this article is to understand the role of oxidative stress in burns, in order to develop therapeutic strategies. All peer-reviewed, original and review articles published in the English language literature relevant to the topic of oxidative stress in burns in animals and human subjects were selected for this review and the possible roles of ROS and RNS in the pathophysiology of burns are discussed. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources in burns. Free radicals have been found to have beneficial effects on antimicrobial action and wound healing. However following a burn, there is an enormous production of ROS which is harmful and implicated in inflammation, systemic inflammatory response syndrome, immunosuppression, infection and sepsis, tissue damage and multiple organ failure. Thus clinical response to burn is dependent on the balance between production of free radicals and its detoxification. Supplementation of antioxidants in human and animal models has proven benefit in decreasing distant organ failure suggesting a cause and effect relationship. We conclude that oxidative damage is one of the mechanisms responsible for the local and distant pathophysiological events observed after burn, and therefore anti-oxidant therapy might be beneficial in minimizing injury in burned patients.

  4. Oxidative stress in prostate hypertrophy and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Waldemar M. Przybyszewski

    2009-07-01

    Full Text Available Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90�0of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis.

  5. Role of oxidant stress in rheumatoid arthritis

    OpenAIRE

    GS, Lekshmi; BR, Suchit Roy; K., Parvathy; K., Geetha Damodaran

    2015-01-01

    Oxygen derived free radicals have been implicated in the causation of Rheumatoid arthritis (RA) [1].In this study, evidence of free radical injury and oxidative stress in patients with RA is compared with healthy subjects by estimating superoxide dismutase (SOD) and catalase, which are anti-oxidant enzymes in RBCs, Glucose 6 Phosphate Dehydrogenase (G6PD) in RBCs and serum Malon-di-aldehyde (MDA) levels. Serum MDA levels in RA could be used as a biochemical marker of disease activity and for ...

  6. 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 (peustress' - that manageable levels of life stress may enhance psychobiological resilience to oxidative damage.

  7. Mechanisms of oxidative stress in brain ischemia injury%氧化应激在脑缺血损伤中的作用机制

    Institute of Scientific and Technical Information of China (English)

    赵丹洋; 吴伟康

    2004-01-01

    Oxidative stress has been implicated in brain injury after ischemia, which is a complex cascade. These oxidants produced by oxidative stress are directly involved in oxidative damage with cellular macromolecules such as lipids, proteins and nucleic acids, which lead to cell death. Oxidants are also mediators in signaling involving mitochondria pathway, DNA repair enzymes, and transcription factor that may lead to apoptosis after cerebral ischemia. Antioxidangt enzymes (such as superoxide dismutase,etc) provide useful tools in dissecting the events involving oxidative stress in signaling and damage in ischemic brain injury. This review focuses on the mechanisms of oxidative stress during brain ischemia.

  8. Cellular effects of swim stress in the dorsal raphe nucleus

    OpenAIRE

    Kirby, Lynn G.; Pan, Yu-Zhen; Freeman-Daniels, Emily; Rani, Shobha; Nunan, John D.; Akanwa, Adaure; Beck, Sheryl G

    2007-01-01

    Swim stress regulates forebrain 5-hydroxytryptamine (5-HT) release in a complex manner and its effects are initiated in the serotonergic dorsal raphe nucleus (DRN). The purpose of this study was to examine the effects of swim stress on the physiology of DRN neurons in conjunction with 5-HT immunohistochemistry. Basic membrane properties, 5-HT1A and 5-HT1B receptor-mediated responses and glutamatergic excitatory postsynaptic currents (EPSCs) were measured using whole-cell patch clamp technique...

  9. Time dynamics of the Bacillus cereus exoproteome are shaped by cellular oxidation.

    Science.gov (United States)

    Madeira, Jean-Paul; Alpha-Bazin, Béatrice; Armengaud, Jean; Duport, Catherine

    2015-01-01

    At low density, Bacillus cereus cells release a large variety of proteins into the extracellular medium when cultivated in pH-regulated, glucose-containing minimal medium, either in the presence or absence of oxygen. The majority of these exoproteins are putative virulence factors, including toxin-related proteins. Here, B. cereus exoproteome time courses were monitored by nanoLC-MS/MS under low-oxidoreduction potential (ORP) anaerobiosis, high-ORP anaerobiosis, and aerobiosis, with a specific focus on oxidative-induced post-translational modifications of methionine residues. Principal component analysis (PCA) of the exoproteome dynamics indicated that toxin-related proteins were the most representative of the exoproteome changes, both in terms of protein abundance and their methionine sulfoxide (Met(O)) content. PCA also revealed an interesting interconnection between toxin-, metabolism-, and oxidative stress-related proteins, suggesting that the abundance level of toxin-related proteins, and their Met(O) content in the B. cereus exoproteome, reflected the cellular oxidation under both aerobiosis and anaerobiosis.

  10. Computer diagnosis in cardiology: Oxidative stress hypothesis

    OpenAIRE

    Ezekiel Uba Nwose; Graham Wilfred Ewing

    2009-01-01

    Background : Virtual scanning is one of the emerging technologies in complementary medicine practice. The diagnostic principle is hinged on perception and ultra weak light emission, while the treatment options associated with it includes diet, flash light, exercise and relaxation. However, a mechanism that links the diagnostic and treatment principles has yet to be elucidated. Aims: The objective here is to further explanation of oxidative stress concept as the biochemical basis of the techno...

  11. Oxidative stress in normal and diabetic rats.

    Science.gov (United States)

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (pvitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected. PMID:10523056

  12. Oxidant Stress in Renal Inflammation: Mechanisms and Remedies

    NARCIS (Netherlands)

    Ishola, D.A.

    2006-01-01

    Our overall hypothesis was that oxidant stress is a central player in renal inflammation; pharmacological reduction of oxidant stress should therefore relieve renal inflammation. We explored pro- and anti-oxidant mechanisms in three experimental renal injury models. OXIDANT-DEPENDENT RENAL INFLAMMAT

  13. Oxidative stress and male reproductive health

    Directory of Open Access Journals (Sweden)

    Robert J Aitken

    2014-02-01

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

  14. Glutamate receptors may not protect against oxidative stress in C. elegans

    Directory of Open Access Journals (Sweden)

    Alicia N. Minniti

    2012-01-01

    Full Text Available Oxidative stress is considered a significant contributor to cellular damage, which may accumulate and result in cellular and organism senescence and death. Oxidative stress and damage have been correlated with a number of central nervous system (CNS disorders in mammals, like Alzheimer’s and Parkinson’s diseases. Using the model organism Caenorhabditis elegans, the current study investigates the survival of mutant C. elegans strains under oxidative stress. Using strains containing mutations in the glr-1 and nmr-1 genes encoding subunits of ionotropic glutamate receptors, we found no significant differences of survival among wild type (WT and glutamate receptor mutants, though prior research has suggested the involvement of glutamatergic neurons in antioxidant defenses.

  15. 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

  16. The Nucleolus Takes Control of Protein Trafficking Under Cellular Stress

    OpenAIRE

    Nalabothula, Narasimharao; Indig, Fred E.; Carrier, France

    2010-01-01

    The nucleolus is a highly dynamic nuclear substructure that was originally described as the site of ribosome biogenesis. The advent of proteomic analysis has now allowed the identification of over 4500 nucleolus associated proteins with only about 30% of them associated with ribogenesis (1). The great number of nucleolar proteins not associated with traditionally accepted nucleolar functions indicates a role for the nucleolus in other cellular functions such as mitosis, cell-cycle progression...

  17. The mechanisms of up-regulation of dendritic cell activity by oxidative stress.

    Science.gov (United States)

    Batal, Ibrahim; Azzi, Jamil; Mounayar, Marwan; Abdoli, Rozita; Moore, Robert; Lee, Jack Y; Rosetti, Florencia; Wang, Chang; Fiorina, Paolo; Sackstein, Robert; Ichimura, Takaharu; Abdi, Reza

    2014-08-01

    Whereas DC have increasingly been recognized for their role in activating the inflammatory cascades during IRIs, the mechanisms by which oxidative stress enhances DC activation remain to be explored. We examined the role of oxidative stress on two important features of DC: T cell activation and trafficking. Bone marrow-derived OS-DC were compared with untreated DC. DC exposed to oxidative stress augmented allogeneic T cell proliferation and showed increased migration in a chemotaxis chamber. These results were confirmed by using hypoxanthine and xanthine oxidase as another inducer of oxidative stress. We used OT-II and OT-I mice to assess the effect of oxidative stress on DC activation of OVA-specific CD4(+) and CD8(+) T cells, respectively. Oxidative stress increased DC capacity to promote OVA-specific CD4(+) T cell activity, demonstrated by an increase in their proliferation and production of IFN-γ, IL-6, and IL-2 proinflammatory cytokines. Whereas oxidative stress increased the DC ability to stimulate IFN-γ production by OVA-specific CD8(+) T cells, cellular proliferation and cytotoxicity were not affected. Compared with untreated DC, oxidative stress significantly reduced the capacity of DC to generate T(regs), which were restored by using anti-IL-6. With regard to DC trafficking, whereas oxidative stress increased DC expression of p-Akt and p-NF-κB, targeting PI3Kγ and NF-κB pathways abrogated the observed increase in DC migration. Our data propose novel insights on the activation of DC by oxidative stress and provide rationales for targeted therapies, which can potentially attenuate IRI.

  18. Oxidative Stress in Obesity: A Critical Component in Human Diseases

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    Lucia Marseglia

    2014-12-01

    Full Text Available Obesity, a social problem worldwide, is characterized by an increase in body weight that results in excessive fat accumulation. Obesity is a major cause of morbidity and mortality and leads to several diseases, including metabolic syndrome, diabetes mellitus, cardiovascular, fatty liver diseases, and cancer. Growing evidence allows us to understand the critical role of adipose tissue in controlling the physic-pathological mechanisms of obesity and related comorbidities. Recently, adipose tissue, especially in the visceral compartment, has been considered not only as a simple energy depository tissue, but also as an active endocrine organ releasing a variety of biologically active molecules known as adipocytokines or adipokines. Based on the complex interplay between adipokines, obesity is also characterized by chronic low grade inflammation with permanently increased oxidative stress (OS. Over-expression of oxidative stress damages cellular structures together with under-production of anti-oxidant mechanisms, leading to the development of obesity-related complications. The aim of this review is to summarize what is known in the relationship between OS in obesity and obesity-related diseases.

  19. Roles of meditation on alleviation of oxidative stress and improvement of antioxidant system.

    Science.gov (United States)

    Mahagita, Chitrawina

    2010-11-01

    According to MEDLINE/Pubmed search to December 2009, the modulation effects of meditation on oxidative stress have been increasingly investigated for acute, short and long-term effects. Both invasive and noninvasive measurements have been utilized. Long-term transcendental and Zen meditators have been showed to diminish oxidative stress seen by a reduction of lipid peroxidation and biophoton emission. Glutathione level and activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase) have been facilitated in Yoga and Sudarshan Kriya practitioners. One year of Tai Chi training has been reported to promote superoxide dismutase activity and lessen lipid peroxidation. Performing diaphragmatic breathing after exhaustive exercise has attenuated oxidative stress faster than control. These data suggest possible roles of meditation and meditation-based techniques on the decrease of oxidative stress which may assist to prevent and/or alleviate deterioration of related diseases. However, further research needs to elucidate the cellular and molecular mechanisms which remain challenge to accomplish.

  20. Iron, Oxidative Stress and Gestational Diabetes

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    Taifeng Zhuang

    2014-09-01

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

  1. Neuro-oxidative-nitrosative stress in sepsis

    DEFF Research Database (Denmark)

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

    2011-01-01

    mitochondrial dysfunction by inhibiting the mitochondrial electron transport chain and uncoupling oxidative phosphorylation, which ultimately leads to neuronal bioenergetic failure. Furthermore, in certain 'at risk' areas of the brain, free radicals may induce neuronal apoptosis. In the present review, we......Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsis-induced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding...... brain parenchyma, due to failure of the local antioxidant systems. ROS/RNS cause structural membrane damage, induce inflammation, and scavenge nitric oxide (NO) to yield peroxynitrite (ONOO(-)). This activates the inducible NO synthase, which further compounds ONOO(-) formation. ROS/RNS cause...

  2. Procyanidins from grape seeds protect against phorbol ester-induced oxidative cellular and genotoxic damage

    Institute of Scientific and Technical Information of China (English)

    Yin LU; Wan-zhou ZHAO; Zai CHANG; Wen-xing CHEN; Lin LI

    2004-01-01

    AIM: To evaluate the inhibitory effects of Vitis vinifera procyanidins (PAs) on carcinogen-induced oxidative stress.METHODS: The single cell gel electrophoresis technique (comet assay) was employed to detect DNA damage induced by the carcinogen phorbol-12-myristate-13-acetate (PMA). The release of hydrogen peroxidase from polymorphonuclear leukocytes (PMNs) was assayed by the horseradish peroxidase-mediated oxidation of phenol red. The microplate assay was used to detect the presence of oxidative products by means of 2',7'-dichlorofiuorescindiacetate (DCFH-DA). The superoxide dismutase (SOD) activity of liver mitochondria was assayed, based on the ability of SOD to inhibit the generation of superoxidate anions by the xanthine-xanthine oxidase system. The malondialdehyde (MDA) level was determined by the thiobarbimric acid (TBA) assay. RESULTS: DNA of NIH3T3 cells was significantly damaged after addition of PMA. The length of the comet tail was observed ,while in normal cells the comet tail could not be observed. PAs showed significant protective effects on carcinogen PMA-induced DNA damage. Through assessment of DCFH-DA oxidation, PAs were shown to inhibit the PMA-induced release of hydrogen peroxide by PMNs, and to inhibit respiratory burst activity in NIH3T3 mouse fibroblasts. Ex vivo study showed that serum from rats administered with PAs displayed similar effects in a dose-dependent manner. In addition, PAs suppressed liver mitochondrial lipid peroxidation induced by PMA. PAs protected the activity of SOD and decreased the level of MDA in liver mitochondria damaged by PMA. CONCLUSION: Dietary PAs from grape seeds protect against carcinogen-induced oxidative cellular and genotoxic damage.

  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. The cellular response to curvature-induced stress

    Science.gov (United States)

    Biton, Y. Y.; Safran, S. A.

    2009-12-01

    We present a theoretical model to explain recent observations of the orientational response of cells to unidirectional curvature. Experiments show that some cell types when plated on a rigid cylindrical surface tend to reorient their shape and stress fibers along the axis of the cylinder, while others align their stress fibers perpendicular to that axis. Our model focuses on the competition of the shear stress—that results from cell adhesion and active contractility—and the anisotropic bending stiffness of the stress fibers. We predict the cell orientation angle that results from the balance of these two forces in a mechanical equilibrium. The conditions under which the different experimental observations can be obtained are discussed in terms of the theory.

  5. 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.

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

    Science.gov (United States)

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

    2010-03-01

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

  7. Contribution of Chinese prescription Kangen-karyu in the oxidative stress-related aging process

    OpenAIRE

    Yokozawa, Takako; Cho, Eun Ju

    2006-01-01

    Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study reports the anti-aging potential of Kangen-karyu and its related mechanisms under in vivo conditions with senescence-accelerated mice (SAM) and aging rats, and in a cellular system with stress-induced premature senescence (SIPS). Kangen-karyu attenuated oxidative stress by the inhibition of free radical generation and lipid peroxidation unde...

  8. Role of oxidative stress in female reproduction

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    Sharma Rakesh K

    2005-07-01

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

  9. Pathway and mechanism of oxidative stress in Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Current hypotheses of pathogenesis of neuronal degeneration in Alzheimer's disease (AD) have been proposed, including formation of free radicals, oxidative stress, mitochondrial dysfunction, inflammatory processes, genetic factors, environmental impact factors, apoptosis, and so on. Especially, oxidative stress plays an essential role in AD pathogenesis by the function of linking agent. Oxidative stress in AD mainly includes lipid peroxidation, protein oxidation and DNA oxidation. Lipid peroxidation plays a key role in the development and progression of AD. Protein oxidation is an important mechanism in AD. Oxidative damage to DNA may plays an important role in aging and AD.

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

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    Allison L Weber

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  11. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    OpenAIRE

    Sha Li; Hor-Yue Tan; Ning Wang; Zhang-Jin Zhang; Lixing Lao; Chi-Woon Wong; Yibin Feng

    2015-01-01

    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...

  12. 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....

  13. The effect of strength training on muscle cellular stress in prostate cancer patients on ADT

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    T S Nilsen

    2016-05-01

    Full Text Available Background Androgen deprivation therapy (ADT for prostate cancer (PCa is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT. Methods Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG (n=16 or a control group (CG (n=15 for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV, HSP60 and indicators of muscle cellular stress (heat shock protein (HSP 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins using Western blot and ELISA. Results No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups. Conclusion Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.

  14. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

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    Anna E. Maciag

    2013-01-01

    Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

  15. Improvement of oxidative stress tolerance in Saccharomyces cerevisiae through global transcription machinery engineering.

    Science.gov (United States)

    Zhao, Hongwei; Li, Jingyuan; Han, Beizhong; Li, Xuan; Chen, Jingyu

    2014-05-01

    Excessive oxidative stress poses significant damage to yeast cells during fermentation process, and finally affects fermentation efficiency and the quality of products. In this paper, global transcription machinery engineering was employed to elicit Saccharomyces cerevisiae phenotypes of higher tolerance against oxidative stress caused by H2O2. Two strains from two plasmid-based mutagenesis libraries (Spt15 and Taf25), which exhibited significant increases in oxidative stress tolerance, were successfully isolated. At moderate H2O2 shock (≤3.5 mM), a positive correlation was found between the outperformance in cell growth of the oxidation-tolerate strains and H2O2 concentration. Several mutations were observed in the native transcription factors, which resulted in a different transcriptional profile compared with the control. Catalase and superoxide dismutase activities of the two mutants increased under H2O2 stress conditions. Fermentation experiments revealed that the mutant strain taf25-3 has a shorter lag phase compared to the control one, indicating that taf25-3 had improved adaptation ability to H2O2-induced oxidative stress and higher fermentation efficiency. Our study demonstrated that several amino acid substitutions in general transcription factors (Spt15 and Taf25) could modify the cellular oxidation defense systems and improve the anti-oxidation ability of S. cerevisiae. It could make the industrial ethanol fermentation more efficient and cost-effective by using the strain of higher stress tolerance. PMID:24633583

  16. Oxidative stress and antioxidant vitamins in leprosy

    Directory of Open Access Journals (Sweden)

    Sangeeta B. Trimbake

    2013-06-01

    Full Text Available Background: Leprosy is a disease of great antiquity and it still continues to be a significant public health problem in few countries including India .Of the various mechanisms that influence the pathogenesis of leprosy, oxidative stress is important which occurs due to derangement in the balance between ROS and natural antioxidants. Hence this study attempted to assess the oxidative stress and antioxidant status in terms of MDA and vitamin E, vitamin C respectively in leprosy. Methods: Hundred untreated leprosy patients (50 PB and 50 MB were studied and compared with 50 healthy controls. Serum Malondialdehyde (MDA and vitamin E, vitamin C was measured by spectrophotometric method. Serum malondialdehyde (MDA was measured as an indicator of lipid peroxidation and antioxidant status was assessed by estimating serum vitamin E and vitamin C levels. Results: Significant rise in serum MDA (P <0.001 in both PB and MB leprosy was seen when compared with controls. The vitamin E level was significantly decreased in both PB and MB leprosy patients as compared to controls. The vitamin C level was significantly decrease (P<0.001 in MB leprosy patients as compared to controls. Conclusions: Elevated MDA levels indicate oxidative stress in leprosy patients, denoting its crucial involvement in the pathogenesis and tissue damage in leprosy. Hence MDA levels can be used to monitor prognosis, treatment and control of leprosy. Decreased vitamin E, C levels in leprosy can be improved by oral vitamin E, C supplementation. [Int J Res Med Sci 2013; 1(3.000: 226-229

  17. Urinary biopyrrins: A new marker of oxidative stress in psoriasis

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    Ola Ahmed Bakry

    2016-01-01

    Full Text Available Background: Psoriasis is a common chronic, relapsing, immune-mediated disease involving skin and joints of genetically predisposed individuals. Oxidative stress has been found to play many important roles in cellular damage and loss of function in a number of tissues and organs and is believed to contribute to the pathogenesis of a variety of diseases. Urinary biopyrrin levels have gained attention as an indicator of oxidative stress. Aim and Objective: To measure urinary biopyrrins excretion as a marker of oxidative stress in psoriasis. Patients and Methods: This case–control study was carried out on 85 subjects; 55 cases with chronic plaque psoriasis and 30 age, gender and body mass index-matched normal subjects as a control group. Urinary biopyrrin levels were measured using enzyme immunoassay. Results: There was a highly significant difference between cases and controls regarding urinary biopyrrins level (P < 0.001. There was significant positive correlation between biopyrrins level and both the age of cases (r = 0.28, P = 0.01 and psoriasis area and severity index score (r = 0.99, P < 0.001. Conclusion: Urinary biopyrrins are increased in patients with psoriasis, and the level is correlated with disease severity. Further large-scale studies involving different ages and different clinical varieties of the disease are needed to expand and validate current findings. The clinical usefulness of antioxidants in psoriasis treatment needs to be evaluated in future research. Furthermore, the value of biopyrrins as biomarkers for monitoring response to therapy needs to be evaluated.

  18. Oxidative stress and antioxidants: Distress or eustress?

    Science.gov (United States)

    Niki, Etsuo

    2016-04-01

    There is a growing consensus that reactive oxygen species (ROS) are not just associated with various pathologies, but that they act as physiological redox signaling messenger with important regulatory functions. It is sometimes stated that "if ROS is a physiological signaling messenger, then removal of ROS by antioxidants such as vitamins E and C may not be good for human health." However, it should be noted that ROS acting as physiological signaling messenger and ROS removed by antioxidants are not the same. The lipid peroxidation products of polyunsaturated fatty acids and cholesterol induce adaptive response and enhance defense capacity against subsequent oxidative insults, but it is unlikely that these lipid peroxidation products are physiological signaling messenger produced on purpose. The removal of ROS and inhibition of lipid peroxidation by antioxidants should be beneficial for human health, although it has to be noted also that they may not be an effective inhibitor of oxidative damage mediated by non-radical oxidants. The term ROS is vague and, as there are many ROS and antioxidants which are different in chemistry, it is imperative to explicitly specify ROS and antioxidant to understand the effects and role of oxidative stress and antioxidants properly.

  19. New Insights for Oxidative Stress and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Kenneth Maiese

    2015-01-01

    Full Text Available The release of reactive oxygen species (ROS and the generation of oxidative stress are considered critical factors for the pathogenesis of diabetes mellitus (DM, a disorder that is growing in prevalence and results in significant economic loss. New therapeutic directions that address the detrimental effects of oxidative stress may be especially warranted to develop effective care for the millions of individuals that currently suffer from DM. The mechanistic target of rapamycin (mTOR, silent mating type information regulation 2 homolog 1 (S. cerevisiae (SIRT1, and Wnt1 inducible signaling pathway protein 1 (WISP1 are especially justified to be considered treatment targets for DM since these pathways can address the complex relationship between stem cells, trophic factors, impaired glucose tolerance, programmed cell death pathways of apoptosis and autophagy, tissue remodeling, cellular energy homeostasis, and vascular biology that greatly impact the biology and disease progression of DM. The translation and development of these pathways into viable therapies will require detailed understanding of their proliferative nature to maximize clinical efficacy and limit adverse effects that have the potential to lead to unintended consequences.

  20. New Insights for Oxidative Stress and Diabetes Mellitus.

    Science.gov (United States)

    Maiese, Kenneth

    2015-01-01

    The release of reactive oxygen species (ROS) and the generation of oxidative stress are considered critical factors for the pathogenesis of diabetes mellitus (DM), a disorder that is growing in prevalence and results in significant economic loss. New therapeutic directions that address the detrimental effects of oxidative stress may be especially warranted to develop effective care for the millions of individuals that currently suffer from DM. The mechanistic target of rapamycin (mTOR), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), and Wnt1 inducible signaling pathway protein 1 (WISP1) are especially justified to be considered treatment targets for DM since these pathways can address the complex relationship between stem cells, trophic factors, impaired glucose tolerance, programmed cell death pathways of apoptosis and autophagy, tissue remodeling, cellular energy homeostasis, and vascular biology that greatly impact the biology and disease progression of DM. The translation and development of these pathways into viable therapies will require detailed understanding of their proliferative nature to maximize clinical efficacy and limit adverse effects that have the potential to lead to unintended consequences.

  1. 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.

  2. Leveraging oxidative stress questions in vivo: Implications and limitations

    Science.gov (United States)

    Arteel, Gavin E.

    2016-01-01

    The elegance of Helmut Sies’ original definition of oxidative stress belies the complexity of the reactions that are potentially involved. This is by no means a criticism of the author, but rather how the words have been used to oversimplify the concept by some. Reactive oxygen and nitrogen species (ROS and RNS, respectively) can be products of a myriad of events within the living body. Indeed, it is now understood that ROS/RNS are critical for normal cellular metabolism and have beneficial effects (e.g., cytotoxicity against invading bacteria). A general problem of studying prooxidants in vivo is that, due to their inherent reactivity, they generally cannot be measured directly. This indirect detection of ‘footprints’ leaves a very large black box that we are to this day only beginning to understand. This manuscript will summarize some considerations that are of utmost importance when translating oxidative stress into in vivo research. Helmut has been a key thought leader, researcher and mentor whose contributions to this field are immeasurable. PMID:27095213

  3. Leveraging oxidative stress questions in vivo: Implications and limitations.

    Science.gov (United States)

    Arteel, Gavin E

    2016-04-01

    The elegance of Helmut Sies' original definition of oxidative stress belies the complexity of the reactions that are potentially involved. This is by no means a criticism of the author, but rather how the words have been used to oversimplify the concept by some. Reactive oxygen and nitrogen species (ROS and RNS, respectively) can be products of a myriad of events within the living body. Indeed, it is now understood that ROS/RNS are critical for normal cellular metabolism and have beneficial effects (e.g., cytotoxicity against invading bacteria). A general problem of studying prooxidants in vivo is that, due to their inherent reactivity, they generally cannot be measured directly. This indirect detection of 'footprints' leaves a very large black box that we are to this day only beginning to understand. This manuscript will summarize some considerations that are of utmost importance when translating oxidative stress into in vivo research. Helmut has been a key thought leader, researcher and mentor whose contributions to this field are immeasurable. PMID:27095213

  4. Oxidative stress in secondary osteoarthritis: from cartilage destruction to clinical presentation?

    Science.gov (United States)

    Ziskoven, Christoph; Jäger, Marcus; Zilkens, Christoph; Bloch, Wilhelm; Brixius, Klara; Krauspe, Rüdiger

    2010-09-23

    Due to an increasing life expectance, osteoarthritis (OA) is one of the most common chronic diseases. Although strong efforts have been made to regenerate degenerated joint cartilage, OA is a progressive and irreversible disease up to date. Among other factors the dysbalance between free radical burden and cellular scavenging mechanisms defined as oxidative stress is a relevant part of OA pathogenesis. Here, only little data are available about the mediation and interaction between different joint compartments. The article provides a review of the current literature regarding the influence of oxidative stress on cellular aging, senescence and apoptosis in different joint compartments (cartilage, synovial tissue and subchondral bone). Free radical exposure is known to promote cellular senescence and apoptosis. Radical oxygen species (ROS) involvement in inflammation, fibrosis control and pain nociception has been proven. The data from literature indicates a link between free radical burden and OA pathogenesis mediating local tissue reactions between the joint compartments. Hence, oxidative stress is likely not only to promote cartilage destruction but also to be involved in inflammative transformation, promoting the transition from clinically silent cartilage destruction to apparent OA. ROS induced by exogenous factors such as overload, trauma, local intraarticular lesion and consecutive synovial inflammation cause cartilage degradation. In the affected joint, free radicals mediate disease progression. The interrelationship between oxidative stress and OA etiology might provide a novel approach to the comprehension and therefore modification of disease progression and symptom control.

  5. Oxidative stress in secondary osteoarthritis: from cartilage destruction to clinical presentation?

    Directory of Open Access Journals (Sweden)

    Christoph Ziskoven

    2010-12-01

    Full Text Available Due to an increasing life expectance, osteoarthritis (OA is one of the most common chronic diseases. Although strong efforts have been made to regenerate degenerated joint cartilage, OA is a progressive and irreversible disease up to date. Among other factors the dysbalance between free radical burden and cellular scavenging mechanisms defined as oxidative stress is a relevant part of OA pathogenesis. Here, only little data are available about the mediation and interaction between different joint compartments. The article provides a review of the current literature regarding the influence of oxidative stress on cellular aging, senescence and apoptosis in different joint compartments (cartilage, synovial tissue and subchondral bone. Free radical exposure is known to promote cellular senescence and apoptosis. Radical oxygen species (ROS involvement in inflammation, fibrosis control and pain nociception has been proven. The data from literature indicates a link between free radical burden and OA pathogenesis mediating local tissue reactions between the joint compartments. Hence, oxidative stress is likely not only to promote cartilage destruction but also to be involved in inflammative transformation, promoting the transition from clinically silent cartilage destruction to apparent OA. ROS induced by exogenous factors such as overload, trauma, local intraarticular lesion and consecutive synovial inflammation cause cartilage degradation. In the affected joint, free radicals mediate disease progression. The interrelationship between oxidative stress and OA etiology might provide a novel approach to the comprehension and therefore modification of disease progression and symptom control.

  6. Oxidative stress is a mediator for increased lipid accumulation in a newly isolated Dunaliella salina strain.

    Science.gov (United States)

    Yilancioglu, Kaan; Cokol, Murat; Pastirmaci, Inanc; Erman, Batu; Cetiner, Selim

    2014-01-01

    Green algae offer sustainable, clean and eco-friendly energy resource. However, production efficiency needs to be improved. Increasing cellular lipid levels by nitrogen depletion is one of the most studied strategies. Despite this, the underlying physiological and biochemical mechanisms of this response have not been well defined. Algae species adapted to hypersaline conditions can be cultivated in salty waters which are not useful for agriculture or consumption. Due to their inherent extreme cultivation conditions, use of hypersaline algae species is better suited for avoiding culture contamination issues. In this study, we identified a new halophilic Dunaliella salina strain by using 18S ribosomal RNA gene sequencing. We found that growth and biomass productivities of this strain were directly related to nitrogen levels, as the highest biomass concentration under 0.05 mM or 5 mM nitrogen regimes were 495 mg/l and 1409 mg/l, respectively. We also confirmed that nitrogen limitation increased cellular lipid content up to 35% under 0.05 mM nitrogen concentration. In order to gain insight into the mechanisms of this phenomenon, we applied fluorometric, flow cytometric and spectrophotometric methods to measure oxidative stress and enzymatic defence mechanisms. Under nitrogen depleted cultivation conditions, we observed increased lipid peroxidation by measuring an important oxidative stress marker, malondialdehyde and enhanced activation of catalase, ascorbate peroxidase and superoxide dismutase antioxidant enzymes. These observations indicated that oxidative stress is accompanied by increased lipid content in the green alga. In addition, we also showed that at optimum cultivation conditions, inducing oxidative stress by application of exogenous H2O2 leads to increased cellular lipid content up to 44% when compared with non-treated control groups. Our results support that oxidative stress and lipid overproduction are linked. Importantly, these results also suggest that

  7. 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.

  8. 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.

  9. 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

    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...

  10. C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.

    Science.gov (United States)

    Huggins, Christopher J; Mayekar, Manasi K; Martin, Nancy; Saylor, Karen L; Gonit, Mesfin; Jailwala, Parthav; Kasoji, Manjula; Haines, Diana C; Quiñones, Octavio A; Johnson, Peter F

    2015-12-14

    The integrated stress response (ISR) controls cellular adaptations to nutrient deprivation, redox imbalances, and endoplasmic reticulum (ER) stress. ISR genes are upregulated in stressed cells, primarily by the bZIP transcription factor ATF4 through its recruitment to cis-regulatory C/EBP:ATF response elements (CAREs) together with a dimeric partner of uncertain identity. Here, we show that C/EBPγ:ATF4 heterodimers, but not C/EBPβ:ATF4 dimers, are the predominant CARE-binding species in stressed cells. C/EBPγ and ATF4 associate with genomic CAREs in a mutually dependent manner and coregulate many ISR genes. In contrast, the C/EBP family members C/EBPβ and C/EBP homologous protein (CHOP) were largely dispensable for induction of stress genes. Cebpg(-/-) mouse embryonic fibroblasts (MEFs) proliferate poorly and exhibit oxidative stress due to reduced glutathione levels and impaired expression of several glutathione biosynthesis pathway genes. Cebpg(-/-) mice (C57BL/6 background) display reduced body size and microphthalmia, similar to ATF4-null animals. In addition, C/EBPγ-deficient newborns die from atelectasis and respiratory failure, which can be mitigated by in utero exposure to the antioxidant, N-acetyl-cysteine. Cebpg(-/-) mice on a mixed strain background showed improved viability but, upon aging, developed significantly fewer malignant solid tumors than WT animals. Our findings identify C/EBPγ as a novel antioxidant regulator and an obligatory ATF4 partner that controls redox homeostasis in normal and cancerous cells.

  11. 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

  12. Melamine Induces Oxidative Stress in Mouse Ovary.

    Directory of Open Access Journals (Sweden)

    Xiao-Xin Dai

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

  13. Nutritionally Mediated Oxidative Stress and Inflammation

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    Alexandra Muñoz

    2013-01-01

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

  14. Vascular oxidant stress and inflammation in hyperhomocysteinemia.

    Science.gov (United States)

    Papatheodorou, Louisa; Weiss, Norbert

    2007-11-01

    Elevated plasma levels of homocysteine are a metabolic risk factor for atherosclerotic vascular disease, as shown in numerous clinical studies that linked elevated homocysteine levels to de novo and recurrent cardiovascular events. High levels of homocysteine promote oxidant stress in vascular cells and tissue because of the formation of reactive oxygen species (ROS), which have been strongly implicated in the development of atherosclerosis. In particular, ROS have been shown to cause endothelial injury, dysfunction, and activation. Elevated homocysteine stimulates proinflammatory pathways in vascular cells, resulting in leukocyte recruitment to the vessel wall, mediated by the expression of adhesion molecules on endothelial cells and circulating monocytes and neutrophils, in the infiltration of leukocytes into the arterial wall mediated by increased secretion of chemokines, and in the differentiation of monocytes into cholesterol-scavenging macrophages. Furthermore, it stimulates the proliferation of vascular smooth muscle cells followed by the production of extracellular matrix. Many of these events involve redox-sensitive signaling events, which are promoted by elevated homocysteine, and result in the formation of atherosclerotic lesions. In this article, we review current knowledge about the role of homocysteine on oxidant stress-mediated vascular inflammation during the development of atherosclerosis.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    María Muriach

    2014-01-01

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

  18. 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.

  19. The malfunction of peroxisome has an impact on the oxidative stress sensitivity in Candida albicans.

    Science.gov (United States)

    Chen, Yulu; Yu, Qilin; Wang, Honggang; Dong, Yijie; Jia, Chang; Zhang, Bing; Xiao, Chenpeng; Zhang, Biao; Xing, Laijun; Li, Mingchun

    2016-10-01

    The peroxisome plays an essential role in eukaryotic cellular metabolism, including β-oxidation of fatty acids and detoxification of hydrogen peroxide. However, its functions in the important fungal pathogen, C. albicans, remain to be investigated. In this study, we identified a homologue of Saccharomyces cerevisiae peroxisomal protein Pex1 in this pathogen, and explored its functions in stress tolerance. Fluorescence observation revealed that C. albicans Pex1 was localized in the peroxisomes, and its loss led to the defect in peroxisome formation. Interestingly, the pex1Δ/Δ mutant had increased tolerance to oxidative stress, which was neither associated with the Cap1 pathway, nor related to the altered distribution of catalase. However, under oxidative stress, the pex1Δ/Δ mutant showed increased expression of autophagy-related genes, with enhanced cytoplasm-to-vacuole transport and degradation of the autophagy markers Atg8 and Lap41. Moreover, the double mutants pex1Δ/Δatg8Δ/Δ and pex1Δ/Δatg1Δ/Δ, both of which were defective in autophagy and peroxisome formation, showed remarkable attenuated tolerance to oxidative stress. These results indicated that autophagy is involved in resistance to oxidative stress in pex1Δ/Δ mutant. Taken together, this study provides evidence that the peroxisomal protein Pex1 regulates oxidative stress tolerance in an autophagy-dependent manner in C. albicans. PMID:27473887

  20. 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...

  1. Reduced resistance to oxidative stress during reproduction as a cost of early-life stress

    OpenAIRE

    Zimmer, C; Spencer, K A

    2015-01-01

    This study was funded by a BBSRC David Phillips Research Fellowship to K.A. Spencer. Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underly...

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

    International Nuclear Information System (INIS)

    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 (H2O2) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H2O2 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

  3. 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.

  4. Vitamin E and C supplementation reduces oxidative stress, improves antioxidant enzymes and positive muscle work in chronically loaded muscles of aged rats

    OpenAIRE

    Ryan, Michael J.; Dudash, Holly J.; Docherty, Megan; Geronilla, Kenneth B.; Baker, Brent A.; Haff, G. Gregory; Cutlip, Robert G; Alway, Stephen E.

    2010-01-01

    Aging is associated with increased oxidative stress. Muscle levels of oxidative stress are further elevated with exercise. The purpose of this study was to determine if dietary antioxidant supplementation would improve muscle function and cellular markers of oxidative stress in response to chronic repetitive loading in aging. The dorsiflexors of the left limb of aged and young adult Fischer 344 Brown x Norway rats were loaded 3 times weekly for 4.5 weeks using 80 maximal stretch-shortening co...

  5. Identification of the cellular mechanisms undelying the contribution of stress and glucocorticoids to Alzheimer's disease pathology

    OpenAIRE

    Sotiropoulos, Ioannis

    2006-01-01

    Clinical evidence suggests the involvement of stress and glucocorticoids (GC) in the etiopathogenesis of Alzheimer’s disease (AD), a disease marked by severe memory impairments as well as alterations in mood and emotional state. The experiments described in this dissertation represent an attempt to establish the cellular mechanisms through which stress and GC may impact on the development of AD. These studies focused on the hippocampus and prefrontal cortex (PFC), brain areas that are severel...

  6. Endomembrane Ca2+-AtPases play a significant role in virus-induced adaptation to oxidative stress

    DEFF Research Database (Denmark)

    Shabala, Sergey; Bækgaard, Lone; Shabala, Lana;

    2011-01-01

    in adaptive responses to oxidative stress by removing excessive Ca2+ from the cytosol, and that their functional expression is significantly altered in PVX-inoculated plants. These findings highlight the crucial role of Ca2+ efflux systems in acquired tolerance to oxidative stress and open up prospects...... for practical applications in agriculture, after in-depth comprehension of the fundamental mechanisms involved in common responses to environmental factors at the genomic, cellular and organismal levels....

  7. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL

    Science.gov (United States)

    Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R.; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment. PMID:27636901

  8. Endoplasmic Reticulum Stress Links Oxidative Stress to Impaired Pancreatic Beta-Cell Function Caused by Human Oxidized LDL.

    Science.gov (United States)

    Plaisance, Valérie; Brajkovic, Saška; Tenenbaum, Mathie; Favre, Dimitri; Ezanno, Hélène; Bonnefond, Amélie; Bonner, Caroline; Gmyr, Valéry; Kerr-Conte, Julie; Gauthier, Benoit R; Widmann, Christian; Waeber, Gérard; Pattou, François; Froguel, Philippe; Abderrahmani, Amar

    2016-01-01

    Elevated plasma concentration of the pro-atherogenic oxidized low density lipoprotein cholesterol (LDL) triggers adverse effects in pancreatic beta-cells and is associated with type 2 diabetes. Here, we investigated whether the endoplasmic reticulum (ER) stress is a key player coupling oxidative stress to beta-cell dysfunction and death elicited by human oxidized LDL. We found that human oxidized LDL activates ER stress as evidenced by the activation of the inositol requiring 1α, and the elevated expression of both DDIT3 (also called CHOP) and DNAJC3 (also called P58IPK) ER stress markers in isolated human islets and the mouse insulin secreting MIN6 cells. Silencing of Chop and inhibition of ER stress markers by the chemical chaperone phenyl butyric acid (PBA) prevented cell death caused by oxidized LDL. Finally, we found that oxidative stress accounts for activation of ER stress markers induced by oxidized LDL. Induction of Chop/CHOP and p58IPK/P58IPK by oxidized LDL was mimicked by hydrogen peroxide and was blocked by co-treatment with the N-acetylcystein antioxidant. As a conclusion, the harmful effects of oxidized LDL in beta-cells requires ER stress activation in a manner that involves oxidative stress. This mechanism may account for impaired beta-cell function in diabetes and can be reversed by antioxidant treatment. PMID:27636901

  9. Melanocytes as Instigators and Victims of Oxidative Stress

    OpenAIRE

    Denat, L.; Kadekaro, A.L.; Marrot, L; Leachman, S; Abdel-Malek, Z.A.

    2014-01-01

    Epidermal melanocytes are particularly vulnerable to oxidative stress due to the pro-oxidant state generated during melanin synthesis, and to intrinsic antioxidant defences that are compromised in pathologic conditions. Melanoma is thought to be oxidative stress-driven, and melanocyte death in vitiligo is thought to be instigated by a highly pro-oxidant state in the epidermis. We review the current knowledge about melanin and the redox state of melanocytes, how paracrine factors help countera...

  10. Oxidative stress response pathways: Fission yeast as archetype

    DEFF Research Database (Denmark)

    Papadakis, Manos A.; Workman, Christopher

    2015-01-01

    Schizosaccharomyces pombe is a popular model eukaryotic organism to study diverse aspects of mammalian biology, including responses to cellular stress triggered by redox imbalances within its compartments. The review considers the current knowledge on the signaling pathways that govern the...

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

    OpenAIRE

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

    2009-01-01

    The oxidative stress theory of aging predicts that manipulations that alter oxidative stress/damage will alter aging. The gold standard for determining whether aging is altered is lifespan, i.e., does altering oxidative stress/damage change lifespan? Mice with genetic manipulations in the antioxidant defense system designed to directly address this prediction have, with few exceptions, shown no change in lifespan. However, when these transgenic/knockout mice are tested using models that devel...

  12. Impact of Oxidative Stress on Exercising Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Peter Steinbacher

    2015-04-01

    Full Text Available 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.

  13. Permethrin-induced oxidative stress and toxicity and metabolism. A review.

    Science.gov (United States)

    Wang, Xu; Martínez, María-Aránzazu; Dai, Menghong; Chen, Dongmei; Ares, Irma; Romero, Alejandro; Castellano, Victor; Martínez, Marta; Rodríguez, José Luis; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Yuan, Zonghui

    2016-08-01

    Permethrin (PER), the most frequently used synthetic Type I pyrethroid insecticide, is widely used in the world because of its high activity as an insecticide and its low mammalian toxicity. It was originally believed that PER exhibited low toxicity on untargeted animals. However, as its use became more extensive worldwide, increasing evidence suggested that PER might have a variety of toxic effects on animals and humans alike, such as neurotoxicity, immunotoxicity, cardiotoxicity, hepatotoxicity, reproductive, genotoxic, and haematotoxic effects, digestive system toxicity, and cytotoxicity. A growing number of studies indicate that oxidative stress played critical roles in the various toxicities associated with PER. To date, almost no review has addressed the toxicity of PER correlated with oxidative stress. The focus of this article is primarily to summarise advances in the research associated with oxidative stress as a potential mechanism for PER-induced toxicity as well as its metabolism. This review summarises the research conducted over the past decade into the reactive oxygen species (ROS) generation and oxidative stress as a consequence of PER treatments, and ultimately their correlation with the toxicity and the metabolism of PER. The metabolism of PER involves various CYP450 enzymes, alcohol or aldehyde dehydrogenases for oxidation and the carboxylesterases for hydrolysis, through which oxidative stress might occur, and such metabolic factors are also reviewed. The protection of a variety of antioxidants against PER-induced toxicity is also discussed, in order to further understand the role of oxidative stress in PER-induced toxicity. This review will throw new light on the critical roles of oxidative stress in PER-induced toxicity, as well as on the blind spots that still exist in the understanding of PER metabolism, the cellular effects in terms of apoptosis and cell signaling pathways, and finally strategies to help to protect against its oxidative

  14. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    Full Text Available

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

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

  15. Thyroid Hormones, Oxidative Stress, and Inflammation

    Directory of Open Access Journals (Sweden)

    Antonio Mancini

    2016-01-01

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

  16. Thyroid Hormones, Oxidative Stress, and Inflammation.

    Science.gov (United States)

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

    2016-01-01

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

  17. Oxidative stress, free radicals and protein peroxides.

    Science.gov (United States)

    Gebicki, Janusz M

    2016-04-01

    Primary free radicals generated under oxidative stress in cells and tissues produce a cascade of reactive secondary radicals, which attack biomolecules with efficiency determined by the reaction rate constants and target concentration. Proteins are prominent targets because they constitute the bulk of the organic content of cells and tissues and react readily with many of the secondary radicals. The reactions commonly lead to the formation of carbon-centered radicals, which generally convert in vivo to peroxyl radicals and finally to semistable hydroperoxides. All of these intermediates can initiate biological damage. This article outlines the advantages of the application of ionizing radiations to studies of radicals, with particular reference to the generation of desired radicals, studies of the kinetics of their reactions and correlating the results with events in biological systems. In one such application, formation of protein hydroperoxides in irradiated cells was inhibited by the intracellular ascorbate and glutathione.

  18. Role of oxidative stress in cocaine-induced cardiotoxicity and cocaine-related death.

    Science.gov (United States)

    Cerretani, D; Fineschi, V; Bello, S; Riezzo, I; Turillazzi, E; Neri, M

    2012-01-01

    Cocaine-induced cardiovascular disorders such as hypertension, thrombosis, myocardial dysfunction, cardiac dysrhythmias and endocarditis have received widespread attention in the context of cocaine abuse. The number of sudden deaths from cardiac causes, including myocardial infarction, ventricular tachyarrhythmia or aortic dissection, is also increasing. This manuscript will highlight the recent employment of study about cocaine cardiotoxicity and oxidative stress. Evidence has revealed that cardiac oxidative stress is a prominent early event of cocaine administration, which severely compromises the cardiac antioxidant cellular system and causes cardiac antioxidant cellular system injuries. Oxidative damage such as peroxidation of membrane phospholipids and depletion of nonenzymatic antioxidants such as glutathione have been found in the myocardium of chronic cocaine-treated animals and in patients. The data indicate that cocaine administration compromised the heart's antioxidant defense system. About the mechanisms involved in the cellular damage, the evidence that cocaine causes apoptosis in the heart comes from in vivo study. In animals model after short-term and long term-cocaine administration, the investigators demonstrates the role of Reactive Oxygen Species as a trigger of cardiac injury induced by cocaine. Cocaine also increased infiltration of inflammatory cells in the heart, and apoptotic cells were predominantly found near inflammatory cells. The role of oxidative stress in cocaine-induced apoptosis in the heart is wide studied and documented. PMID:22856662

  19. Strategies for Reducing or Preventing the Generation of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    B. Poljsak

    2011-01-01

    Full Text Available The reduction of oxidative stress could be achieved in three levels: by lowering exposure to environmental pollutants with oxidizing properties, by increasing levels of endogenous and exogenous antioxidants, or by lowering the generation of oxidative stress by stabilizing mitochondrial energy production and efficiency. Endogenous oxidative stress could be influenced in two ways: by prevention of ROS formation or by quenching of ROS with antioxidants. However, the results of epidemiological studies where people were treated with synthetic antioxidants are inconclusive and contradictory. Recent evidence suggests that antioxidant supplements (although highly recommended by the pharmaceutical industry and taken by many individuals do not offer sufficient protection against oxidative stress, oxidative damage or increase the lifespan. The key to the future success of decreasing oxidative-stress-induced damage should thus be the suppression of oxidative damage without disrupting the wellintegrated antioxidant defense network. Approach to neutralize free radicals with antioxidants should be changed into prevention of free radical formation. Thus, this paper addresses oxidative stress and strategies to reduce it with the focus on nutritional and psychosocial interventions of oxidative stress prevention, that is, methods to stabilize mitochondria structure and energy efficiency, or approaches which would increase endogenous antioxidative protection and repair systems.

  20. 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.

  1. [Carbonyl stress and oxidatively modified proteins in chronic renal failure].

    Science.gov (United States)

    Bargnoux, A-S; Morena, M; Badiou, S; Dupuy, A-M; Canaud, B; Cristol, J-P

    2009-01-01

    Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis. PMID:19297289

  2. A signature microRNA expression profile for the cellular response to thermal stress

    Science.gov (United States)

    Wilmink, Gerald J.; Roth, Caleb C.; Ketchum, Norma; Ibey, Bennett L.; Waterworth, Angela; Suarez, Maria; Roach, William P.

    2009-02-01

    Recently, an extensive layer of intra-cellular signals was discovered that was previously undetected by genetic radar. It is now known that this layer consists primarily of a class of short noncoding RNA species that are referred to as microRNAs (miRNAs). MiRNAs regulate protein synthesis at the post-transcriptional level, and studies have shown that they are involved in many fundamental cellular processes. In this study, we hypothesized that miRNAs may be involved in cellular stress response mechanisms, and that cells exposed to thermal stress may exhibit a signature miRNA expression profile indicative of their functional involvement in such mechanisms. To test our hypothesis, human dermal fibroblasts were exposed to an established hyperthermic protocol, and the ensuing miRNA expression levels were evaluated 4 hr post-exposure using microRNA microarray gene chips. The microarray data shows that 123 miRNAs were differentially expressed in cells exposed to thermal stress. We collectively refer to these miRNAs as thermalregulated microRNAs (TRMs). Since miRNA research is in its infancy, it is interesting to note that only 27 of the 123 TRMs are currently annotated in the Sanger miRNA registry. Prior to publication, we plan to submit the remaining novel 96 miRNA gene sequences for proper naming. Computational and thermodynamic modeling algorithms were employed to identify putative mRNA targets for the TRMs, and these studies predict that TRMs regulate the mRNA expression of various proteins that are involved in the cellular stress response. Future empirical studies will be conducted to validate these theoretical predictions, and to further examine the specific role that TRMs play in the cellular stress response.

  3. Embryo as an active granular fluid: stress-coordinated cellular constriction chains

    Science.gov (United States)

    Gao, Guo-Jie Jason; Holcomb, Michael C.; Thomas, Jeffrey H.; Blawzdziewicz, Jerzy

    2016-10-01

    Mechanical stress plays an intricate role in gene expression in individual cells and sculpting of developing tissues. However, systematic methods of studying how mechanical stress and feedback help to harmonize cellular activities within a tissue have yet to be developed. Motivated by our observation of the cellular constriction chains (CCCs) during the initial phase of ventral furrow formation in the Drosophila melanogaster embryo, we propose an active granular fluid (AGF) model that provides valuable insights into cellular coordination in the apical constriction process. In our model, cells are treated as circular particles connected by a predefined force network, and they undergo a random constriction process in which the particle constriction probability P is a function of the stress exerted on the particle by its neighbors. We find that when P favors tensile stress, constricted particles tend to form chain-like structures. In contrast, constricted particles tend to form compact clusters when P favors compression. A remarkable similarity of constricted-particle chains and CCCs observed in vivo provides indirect evidence that tensile-stress feedback coordinates the apical constriction activity. Our particle-based AGF model will be useful in analyzing mechanical feedback effects in a wide variety of morphogenesis and organogenesis phenomena.

  4. Hormonal Regulation of Response to Oxidative Stress in Insects-An Update.

    Science.gov (United States)

    Kodrík, Dalibor; Bednářová, Andrea; Zemanová, Milada; Krishnan, Natraj

    2015-10-27

    Insects, like other organisms, must deal with a wide variety of potentially challenging environmental factors during the course of their life. An important example of such a challenge is the phenomenon of oxidative stress. This review summarizes the current knowledge on the role of adipokinetic hormones (AKH) as principal stress responsive hormones in insects involved in activation of anti-oxidative stress response pathways. Emphasis is placed on an analysis of oxidative stress experimentally induced by various stressors and monitored by suitable biomarkers, and on detailed characterization of AKH's role in the anti-stress reactions. These reactions are characterized by a significant increase of AKH levels in the insect body, and by effective reversal of the markers-disturbed by the stressors-after co-application of the stressor with AKH. A plausible mechanism of AKH action in the anti-oxidative stress response is discussed as well: this probably involves simultaneous employment of both protein kinase C and cyclic adenosine 3',5'-monophosphate pathways in the presence of extra and intra-cellular Ca(2+) stores, with the possible involvement of the FoxO transcription factors. The role of other insect hormones in the anti-oxidative defense reactions is also discussed.

  5. The link between radiofrequencies emitted from wireless technologies and oxidative stress.

    Science.gov (United States)

    Dasdag, Suleyman; Akdag, Mehmet Zulkuf

    2016-09-01

    Wireless communication such as cellular telephones and other types of handheld phones working with frequencies of 900MHz, 1800MHz, 2100MHz, 2450MHz have been increasing rapidly. Therefore, public opinion concern about the potential human health hazards of short and long-term effect of exposure to radiofrequency (RF) radiation. Oxidative stress is a biochemical condition, which is defined by the imbalance between reactive oxygen species (ROS) and the anti-oxidative defense. In this review, we evaluated available in vitro and in vivo studies carried out on the relation between RF emitted from mobile phones and oxidative stress. The results of the studies we reviewed here indicated that mobile phones and similar equipment or radars can be thought as a factor, which cause oxidative stress. Even some of them claimed that oxidative stress originated from radiofrequencies can be resulted with DNA damage. For this reason one of the points to think on is relation between mobile phones and oxidative stress. However, more performance is necessary especially on human exposure studies.

  6. The link between radiofrequencies emitted from wireless technologies and oxidative stress.

    Science.gov (United States)

    Dasdag, Suleyman; Akdag, Mehmet Zulkuf

    2016-09-01

    Wireless communication such as cellular telephones and other types of handheld phones working with frequencies of 900MHz, 1800MHz, 2100MHz, 2450MHz have been increasing rapidly. Therefore, public opinion concern about the potential human health hazards of short and long-term effect of exposure to radiofrequency (RF) radiation. Oxidative stress is a biochemical condition, which is defined by the imbalance between reactive oxygen species (ROS) and the anti-oxidative defense. In this review, we evaluated available in vitro and in vivo studies carried out on the relation between RF emitted from mobile phones and oxidative stress. The results of the studies we reviewed here indicated that mobile phones and similar equipment or radars can be thought as a factor, which cause oxidative stress. Even some of them claimed that oxidative stress originated from radiofrequencies can be resulted with DNA damage. For this reason one of the points to think on is relation between mobile phones and oxidative stress. However, more performance is necessary especially on human exposure studies. PMID:26371078

  7. 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

  8. Oxidative stress and cardiovascular complications in polycystic ovarian syndrome.

    Science.gov (United States)

    Hyderali, Barkath Nisha; Mala, Kanchana

    2015-08-01

    Polycystic ovarian syndrome (PCOS) is a complex endocrine condition which is associated with metabolic and cardiovascular complications. It is elevated to a metabolic disorder with significant long term health ramification due to the high prevalence of insulin resistance (IR), impaired glucose tolerance, type 2 diabetes (T2D), dyslipidemia and numerous cardiovascular risk factors in PCOS women. This article concentrates on the recent developments in the regulation of oxidative stress (OS) in PCOS and on the association between PCOS and CVD outcomes. The prognostic events that define the severity of PCOS and involvement of cardiovascular risk in PCOS include endothelial dysfunction (ED) and impaired cardiac structure. Fact is that, in PCOS women, the circulating biomarkers of OS are in abnormal levels that are independent of overweight, which depicts the participation of OS in the pathophysiology of this common derangement. In addition, hyperglycemia (HG) per se, promotes reactive oxygen species (ROS) generation in PCOS. When the destructive ROS outbalances the concentration of physiological antioxidants, OS occurs. The resultant OS, directly stimulates hyperandrogenism and causes extensive cellular injury, DNA damage and/or cell apoptosis. To further the burden, the total serum antioxidant level in PCOS women is compromised, which diminishes the body's defense against an oxidative milieu. Thus, it is evident that OS regulates several cellular mechanisms in PCOS. Improving our understanding about the regulation of OS, critical role of ROS and protein biomarkers in PCOS should lead to novel therapeutic strategies in addressing PCOS-induced CVD. Besides, it is possible that the beneficial effects of dietary or therapeutic antioxidants have significant clinical relevance in PCOS.

  9. Oma1 Links Mitochondrial Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses.

    Science.gov (United States)

    Bohovych, Iryna; Kastora, Stavroula; Christianson, Sara; Topil, Danelle; Kim, Heejeong; Fangman, Teresa; Zhou, You J; Barrientos, Antoni; Lee, Jaekwon; Brown, Alistair J P; Khalimonchuk, Oleh

    2016-09-01

    A network of conserved proteases known as the intramitochondrial quality control (IMQC) system is central to mitochondrial protein homeostasis and cellular health. IMQC proteases also appear to participate in establishment of signaling cues for mitochondrion-to-nucleus communication. However, little is known about this process. Here, we show that in Saccharomyces cerevisiae, inactivation of the membrane-bound IMQC protease Oma1 interferes with oxidative-stress responses through enhanced production of reactive oxygen species (ROS) during logarithmic growth and reduced stress signaling via the TORC1-Rim15-Msn2/Msn4 axis. Pharmacological or genetic prevention of ROS accumulation in Oma1-deficient cells restores this defective TOR signaling. Additionally, inactivation of the Oma1 ortholog in the human fungal pathogen Candida albicans also alters TOR signaling and, unexpectedly, leads to increased resistance to neutrophil killing and virulence in the invertebrate animal model Galleria mellonella Our findings reveal a novel and evolutionarily conserved link between IMQC and TOR-mediated signaling that regulates physiological plasticity and pancellular oxidative-stress responses.

  10. Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity?

    Science.gov (United States)

    Xie, Heng; Zhou, Fubo; Liu, Ling; Zhu, Guannan; Li, Qiang; Li, Chunying; Gao, Tianwen

    2016-01-01

    Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes. These factors synergistically contribute to the accumulation of ROS in melanocytes, finally leading to melanocyte damage and the production of autoantigens through the following ways: apoptosis, accumulation of misfolded peptides and cytokines induced by endoplasmic reticulum stress as well as the sustained unfolded protein response, and an 'eat me' signal for phagocytic cells triggered by calreticulin. Subsequently, autoantigens presentation and dendritic cells maturation occurred mediated by the release of antigen-containing exosomes, adenosine triphosphate and melanosomal autophagy. With the involvement of inducible heat shock protein 70, cellular immunity targeting autoantigens takes the essential place in the destruction of melanocytes, which eventually results in vitiligo. Several treatments, such as narrow band ultraviolet, quercetin and α-melanophore-stimulating hormone, are reported to be able to lower ROS thereby achieving repigmentation in vitiligo. In therapies targeting autoimmunity, restore of regulatory T cells is absorbing attention, in which narrow band ultraviolet also plays a role.

  11. Temporal evolution of the Arabidopsis oxidative stress response.

    Science.gov (United States)

    Mahalingam, Ramamurthy; Shah, Nigam; Scrymgeour, Alexandra; Fedoroff, Nina

    2005-03-01

    We have carried out a detailed analysis of the changes in gene expression levels in Arabidopsis thaliana ecotype Columbia (Col-0) plants during and for 6 h after exposure to ozone (O3) at 350 parts per billion (ppb) for 6 h. This O3 exposure is sufficient to induce a marked transcriptional response and an oxidative burst, but not to cause substantial tissue damage in Col-0 wild-type plants and is within the range encountered in some major metropolitan areas. We have developed analytical and visualization tools to automate the identification of expression profile groups with common gene ontology (GO) annotations based on the sub-cellular localization and function of the proteins encoded by the genes, as well as to automate promoter analysis for such gene groups. We describe application of these methods to identify stress-induced genes whose transcript abundance is likely to be controlled by common regulatory mechanisms and summarized our findings in a temporal model of the stress response. PMID:15988565

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

    Science.gov (United States)

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

  13. Curcumin alleviates oxidative stress and mitochondrial dysfunction in astrocytes.

    Science.gov (United States)

    Daverey, Amita; Agrawal, Sandeep K

    2016-10-01

    Oxidative stress plays a critical role in various neurodegenerative diseases, thus alleviating oxidative stress is a potential strategy for therapeutic intervention and/or prevention of neurodegenerative diseases. In the present study, alleviation of oxidative stress through curcumin is investigated in A172 (human glioblastoma cell line) and HA-sp (human astrocytes cell line derived from the spinal cord) astrocytes. H2O2 was used to induce oxidative stress in astrocytes (A172 and HA-sp). Data show that H2O2 induces activation of astrocytes in dose- and time-dependent manner as evident by increased expression of GFAP in A172 and HA-sp cells after 24 and 12h respectively. An upregulation of Prdx6 was also observed in A172 and HA-sp cells after 24h of H2O2 treatment as compared to untreated control. Our data also showed that curcumin inhibits oxidative stress-induced cytoskeleton disarrangement, and impedes the activation of astrocytes by inhibiting upregulation of GFAP, vimentin and Prdx6. In addition, we observed an inhibition of oxidative stress-induced inflammation, apoptosis and mitochondria fragmentation after curcumin treatment. Therefore, our results suggest that curcumin not only protects astrocytes from H2O2-induced oxidative stress but also reverses the mitochondrial damage and dysfunction induced by oxidative stress. This study also provides evidence for protective role of curcumin on astrocytes by showing its effects on attenuating reactive astrogliosis and inhibiting apoptosis. PMID:27423629

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

    Directory of Open Access Journals (Sweden)

    Rajendra Upadhya

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

  15. Mitochondria are targets for peroxisome-derived oxidative stress in cultured mammalian cells.

    Science.gov (United States)

    Wang, Bo; Van Veldhoven, Paul P; Brees, Chantal; Rubio, Noemí; Nordgren, Marcus; Apanasets, Oksana; Kunze, Markus; Baes, Myriam; Agostinis, Patrizia; Fransen, Marc

    2013-12-01

    Many cellular processes are driven by spatially and temporally regulated redox-dependent signaling events. Although mounting evidence indicates that organelles such as the endoplasmic reticulum and mitochondria can function as signaling platforms for oxidative stress-regulated pathways, little is known about the role of peroxisomes in these processes. In this study, we employ targeted variants of the genetically encoded photosensitizer KillerRed to gain a better insight into the interplay between peroxisomes and cellular oxidative stress. We show that the phototoxic effects of peroxisomal KillerRed induce mitochondria-mediated cell death and that this process can be counteracted by targeted overexpression of a select set of antioxidant enzymes, including peroxisomal glutathione S-transferase kappa 1, superoxide dismutase 1, and mitochondrial catalase. We also present evidence that peroxisomal disease cell lines deficient in plasmalogen biosynthesis or peroxisome assembly are more sensitive to KillerRed-induced oxidative stress than control cells. Collectively, these findings confirm and extend previous observations suggesting that disturbances in peroxisomal redox control and metabolism can sensitize cells to oxidative stress. In addition, they lend strong support to the ideas that peroxisomes and mitochondria share a redox-sensitive relationship and that the redox communication between these organelles is not only mediated by diffusion of reactive oxygen species from one compartment to the other. Finally, these findings indicate that mitochondria may act as dynamic receivers, integrators, and transmitters of peroxisome-derived mediators of oxidative stress, and this may have profound implications for our views on cellular aging and age-related diseases.

  16. Eckol inhibits ultraviolet B-induced cell damage in human keratinocytes via a decrease in oxidative stress

    International Nuclear Information System (INIS)

    In previous reports, the antioxidant effects of eckol were shown to protect cells against hydrogen peroxide- and gamma ray-induced oxidative stress. In this study, the role of eckol in protecting human skin keratinocytes (HaCaT) against UVB-induced oxidative cell damage was investigated. Also, triphlorethol-A, one of the chemical components in Ecklonia cava, and quercetin a well known antioxidant, were compared with eckol in terms of antioxidant activity based on chemical structure. Eckol decreased UVB-induced intracellular reactive oxygen species (ROS), decreased injury to cellular components resulting from UVB-induced oxidative stress, and restored cell viability. In addition, eckol reduced UVB-induced apoptosis by inhibiting the disruption of mitochondrial membranes. These results suggest that eckol protects human keratinocytes against UVB-induced oxidative stress by scavenging ROS, thereby lessening injury to cellular components. (author)

  17. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    Science.gov (United States)

    2016-01-01

    Mesenchymal stromal/stem cells (MSCs) are multipotent stem cells present in most fetal and adult tissues. Ex vivo culture-expanded MSCs are being investigated for tissue repair and immune modulation, but their full clinical potential is far from realization. Here we review the role of oxidative stress in MSC biology, as their longevity and functions are affected by oxidative stress. In general, increased reactive oxygen species (ROS) inhibit MSC proliferation, increase senescence, enhance adipogenic but reduce osteogenic differentiation, and inhibit MSC immunomodulation. Furthermore, aging, senescence, and oxidative stress reduce their ex vivo expansion, which is critical for their clinical applications. Modulation of sirtuin expression and activity may represent a method to reduce oxidative stress in MSCs. These findings have important implications in the clinical utility of MSCs for degenerative and immunological based conditions. Further study of oxidative stress in MSCs is imperative in order to enhance MSC ex vivo expansion and in vivo engraftment, function, and longevity. PMID:27413419

  18. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    International Nuclear Information System (INIS)

    Highlights: ► Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. ► Oxidative stress induces complete mitochondrial fragmentation in Δyfh1 cells. ► Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. ► Inhibition of mitochondrial fission in Δyfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron–sulfur cluster assembly. Yeast cells lacking frataxin (Δyfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in Δyfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  19. 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.

  20. Nanoparticles, lung injury, and the role of oxidant stress.

    Science.gov (United States)

    Madl, Amy K; Plummer, Laurel E; Carosino, Christopher; Pinkerton, Kent E

    2014-01-01

    The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion. PMID:24215442

  1. PtdIns5P and Pin1 in oxidative stress signaling.

    Science.gov (United States)

    Keune, Willem-Jan; Jones, David R; Divecha, Nullin

    2013-05-01

    Oxidative signaling is important in cellular health, involved in aging and contributes to the development of several diseases such as cancer, neurodegeneration and diabetes. Correct management of reactive oxygen species (ROS) prevents oxidative stress within cells and is imperative for cellular wellbeing. A key pathway that is regulated by oxidative stress is the activation of proline-directed stress kinases (p38, JNK). Phosphorylation induced by these kinases is often translated into cellular outcome through the recruitment of the prolyl-isomerase Pin1. Pin1 binds to phosphorylated substrates using its WW-domain and can induce conformational changes in the target protein through its prolyl-isomerase activity. We show that exposure of cells to UV irradiation or hydrogen peroxide (H₂O₂), induces the synthesis of the phosphoinositide second messenger PtdIns5P in part by inducing the interaction between phosphatidylinositol-5-phosphate 4-kinase (PIP4K) enzymes that remove PtdIns5P, with Pin1. In response to H₂O₂ exposure, Murine Embryonic Fibroblasts (MEFs) derived from Pin1⁻/⁻ mice showed increased cell viability and an increased abundance of PtdIns5P compared to wild-type MEFs. Decreasing the levels of PtdIns5P in Pin1⁻/⁻ MEFs decreased both their viability in response to H₂O₂ exposure and the expression of genes required for cellular ROS management. The decrease in the expression of these genes manifested itself in the increased accumulation of cellular ROS. These data strongly argue that PtdIns5P acts as a stress-induced second messenger that can calibrate how cells manage ROS.

  2. The role of oxidative stress in alcoholic liver injury

    Directory of Open Access Journals (Sweden)

    Radosavljević Tatjana

    2009-01-01

    Full Text Available Introduction. Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. Role of cytochrome P4502E1 in ethanol-induced oxidative stress. Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in alcohol-induced oxidative stress. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanolfed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. Role of Kupffer cells in alcohol-induced liver injury. Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. Role of neutrophils in alcohol-induced liver injury. Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. Role of nitric oxide in alcohol-induced oxidative stress. High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. Role of antioxidants in ethanol-induced oxidative stress. Chronic ethanol consumption is associated with reduced liver glutathione and α-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity. Conclusion. Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.

  3. Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases.

    Science.gov (United States)

    Piechota-Polanczyk, Aleksandra; Fichna, Jakub

    2014-07-01

    In this review, we focus on the role of oxidative stress in the aetiology of inflammatory bowel diseases (IBD) and colitis-associated colorectal cancer and discuss free radicals and free radical-stimulated pathways as pharmacological targets for anti-IBD drugs. We also suggest novel anti-oxidative agents, which may become effective and less-toxic alternatives in IBD and colitis-associated colorectal cancer treatment. A Medline search was performed to identify relevant bibliography using search terms including: 'free radicals,' 'antioxidants,' 'oxidative stress,' 'colon cancer,' 'ulcerative colitis,' 'Crohn's disease,' 'inflammatory bowel disease.' Several therapeutics commonly used in IBD treatment, among which are immunosuppressants, corticosteroids and anti-TNF-α antibodies, could also affect the IBD progression by interfering with cellular oxidative stress and cytokine production. Experimental data shows that these drugs may effectively scavenge free radicals, increase anti-oxidative capacity of cells, influence multiple signalling pathways, e.g. MAPK and NF-kB, and inhibit pro-oxidative enzyme and cytokine concentration. However, their anti-oxidative and anti-inflammatory effectiveness still needs further investigation. A highly specific antioxidative activity may be important for the clinical treatment and relapse of IBD. In the future, a combination of currently used pharmaceutics, together with natural and synthetic anti-oxidative compounds, like lipoic acid or curcumine, could be taken into account in the design of novel anti-IBD therapies. PMID:24798211

  4. Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential

    OpenAIRE

    Patil, Swanand; Sandberg, Amanda; Heckert, Eric; Self, William; Seal, Sudipta

    2007-01-01

    The surface chemistry of biomaterials can have a significant impact on their performance in biological applications. Our recent work suggests that cerium oxide nanoparticles are potent antioxidants in cell culture models and we have evaluated several therapeutic applications of these nanoparticles in different biological systems. Knowledge of protein adsorption and cellular uptake will be very useful in improving the beneficial effects of cerium oxide nanoparticles in biology. In the present ...

  5. Oxidative stress and psychological functioning among medical students

    OpenAIRE

    Rani Srivastava; Jyoti Batra

    2014-01-01

    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 fro...

  6. Diaphragmatic Breathing Reduces Exercise-Induced Oxidative Stress

    OpenAIRE

    Daniele Martarelli; Mario Cocchioni; Stefania Scuri; Pierluigi Pompei

    2011-01-01

    Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxid...

  7. Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS

    OpenAIRE

    Susanne Petri; Sonja Körner; Mahmoud Kiaei

    2012-01-01

    Nrf2 (nuclear erythroid 2-related factor 2) is a basic region leucine-zipper transcription factor which binds to the antioxidant response element (ARE) and thereby regulates the expression of a large battery of genes involved in the cellular antioxidant and anti-inflammatory defence as well as mitochondrial protection. As oxidative stress, inflammation and mitochondrial dysfunctions have been identified as important pathomechanisms in amyotrophic lateral sclerosis (ALS), this signaling cascad...

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

    OpenAIRE

    Mary Carmen Vázquez; Elisa Balboa; Alvarez, Alejandra R.; Silvana Zanlungo

    2012-01-01

    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 ...

  9. Increased Serum Oxidative Stress Markers in Women with Uterine Leiomyoma

    OpenAIRE

    Santulli, Pietro; Borghese, Bruno; Lemaréchal, Herve; Leconte, Mahaut; Millischer, Anne-Elodie; Batteux, Frédéric; Chapron, Charles; Borderie, Didier

    2013-01-01

    Background Uterine leiomyomas (fibroids) are the most common gynaecological benign tumors in premenopausal women. Evidences support the role of oxidative stress in the development of uterine leiomyoma. We have analysed oxidative stress markers (thiols, advanced oxidized protein products (AOPP), protein carbonyls and nitrates/nitrites) in preoperative sera from women with histologically proven uterine leiomyoma. Methodology/Principal Findings We conducted a laboratory study in a tertiary-care ...

  10. Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons.

    Science.gov (United States)

    Bartelt-Kirbach, Britta; Golenhofen, Nikola

    2014-01-01

    Upregulation of small heat-shock proteins (sHsps) in response to cellular stress is one mechanism to increase cell viability.We previously described that cultured rat hippocampal neurons express five of the 11 family members but only upregulate two of them (HspB1 and HspB5) at the protein level after heat stress. Since neurons have to cope with many other pathological conditions, we investigated in this study the expression of all five expressed sHsps on mRNA and protein level after sublethal sodium arsenite and oxidative and hyperosmotic stress. Under all three conditions, HspB1, HspB5, HspB6, and HspB8 but not HspB11 were consistently upregulated but showed differences in the time course of upregulation. The increase of sHsps always occurred earlier on mRNA level compared with protein levels. We conclude from our data that these four upregulated sHsps (HspB1, HspB5, HspB6, HspB8) act together in different proportions in the protection of neurons from various stress conditions.

  11. Acute Activation of Oxidative Pentose Phosphate Pathway as First-Line Response to Oxidative Stress in Human Skin Cells.

    Science.gov (United States)

    Kuehne, Andreas; Emmert, Hila; Soehle, Joern; Winnefeld, Marc; Fischer, Frank; Wenck, Horst; Gallinat, Stefan; Terstegen, Lara; Lucius, Ralph; Hildebrand, Janosch; Zamboni, Nicola

    2015-08-01

    Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure. In time-resolved metabolomics experiments, we observed that within seconds after stress induction, glucose catabolism is routed to the oxidative pentose phosphate pathway (PPP) and nucleotide synthesis independent of previously postulated blocks in glycolysis (i.e., of GAPDH or PKM2). Through ultra-short (13)C labeling experiments, we provide evidence for multiple cycling of carbon backbones in the oxidative PPP, potentially maximizing NADPH reduction. The identified metabolic rerouting in oxidative and non-oxidative PPP has important physiological roles in stabilization of the redox balance and ROS clearance.

  12. Oxidative stress induces itch via activation of transient receptor potential subtype ankyrin 1 in mice

    Institute of Scientific and Technical Information of China (English)

    Tong Liu; Ru-Rong Ji

    2012-01-01

    Objective To investigate the role of oxidative stress in itch-indicative scratching behavior in mice,and furthermore,to define the cellular and molecular mechanisms underlying oxidative stress-mediated itch.Methods Scratching behavior was induced by intradermal injection of the oxidants hydrogen peroxide (H2O2) or tert-butylhydroperoxide (tBHP) into the nape of the neck in mice.The mice were observed for 30 min.Results Intradermal H2O2 (0.03%-1%) or tBHP (1-30 μmol) elicited robust scratching behavior,displaying an inverted U-shaped dose-response curve.Naloxone,an opioid receptor antagonist,but not morphine,largely suppressed the oxidant-induced scratching.Chlorpheniramine,a histamine H 1 receptor antagonist,blocked histamine-but not oxidant-induced scratching,indicating the involvement of a histamine-independent mechanism in oxidant-evoked itch.Further,resiniferatoxin treatment abolished oxidant-induced scratching,suggesting an essential role of C-fibers.Notably,blockade of transient receptor potential subtype ankyrin 1 (TRPA1) with the selective TRPA1 antagonist HC-030031,or genetic deletion of Trpal but not Trpvl (subfamily V,member 1) resulted in a profound reduction in H2O2-evoked scratching.Finally,systemic administration of the antioxidant Nacety1-L-cysteine or trolox (a water-soluble vitamin E analog) attenuated scratching induced by the oxidants.Conclusion Oxidative stress by different oxidants induces profound scratching behavior,which is largely histamine-and TRPV1-independent but TRPA1-dependent.Antioxidants and TRPA1 antagonists may be used to treat human itch conditions associated with oxidative stress.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background 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. Methods 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. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions 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.

  15. OSTEOPOROSIS AND ALZHEIMER PATHOLOGY: ROLE OF CELLULAR STRESS RESPONSE AND HORMETIC REDOX SIGNALING IN AGING AND BONE REMODELING

    Directory of Open Access Journals (Sweden)

    Vittorio eCalabrese

    2014-06-01

    Full Text Available Alzheimer’s disease (AD as well as osteoporosis are multifactorial progressive degenerative disorders characterized by low parenchymal density and microarchitectural deterioration of tissue. Though not referred to as one of the major complications of AD, osteoporosis and hip fracture are commonly observed in patients with AD, however, the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS are generally recognized as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-kB ligand (RANKL-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. ROS formation, which is positively implicated in cellular stress response mechanisms, is a highly regulated process controlled by a complex network of intracellular signaling pathways which regulate life span across species including vitagenes which are genes involved in preserving cellular homeostasis during stressful conditions. Vitagenes encode for heat shock proteins (Hsp Hsp32, Hsp70, the thioredoxin and the sirtuin protein systems. Dietary antioxidants, have recently been demonstrated to be neuroprotective through the activation of hormetic pathways, including vitagenes. The hormetic dose–response, has the potential to affect significantly the design of pre-clinical studies and clinical trials as well as strategies for optimal patient dosing in the treatment of numerous diseases. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing stress responses. Here we focus on possible signaling mechanisms involved in bone remodeling and activation of vitagenes resulting in enhanced defense against energy and stress resistance homeostasis dysruption with consequent impact on

  16. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    Science.gov (United States)

    Liu, Fu-Wei; Liu, Fu-Chao; Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system. PMID:26637174

  17. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    Directory of Open Access Journals (Sweden)

    Fu-Wei Liu

    Full Text Available Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system.

  18. Acrolein cytotoxicity in hepatocytes involves endoplasmic reticulum stress, mitochondrial dysfunction and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Mohammad, Mohammad K. [Department of Medicine, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Avila, Diana [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Zhang, Jingwen [Department of Medicine, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Barve, Shirish [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Arteel, Gavin [Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); McClain, Craig [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States); Robley Rex VAMC, Louisville, KY (United States); Joshi-Barve, Swati, E-mail: s0josh01@louisville.edu [Department of Medicine, University of Louisville (United States); Department of Pharmacology and Toxicology, University of Louisville (United States); Alcohol Research Center, University of Louisville (United States)

    2012-11-15

    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. -- Highlights: ► Human primary hepatocytes and cultured cell lines are used. ► Multiple cell death signaling pathways are activated by acrolein. ► Novel finding of

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

    Lee-Wen Chang; Chin-Chen Chu; Heuy-Ling Chu; Horng-Cherng Wu; Pin-Der Duh

    2015-01-01

    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), againsttert-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 int-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 whileTTLO andICM were in the middle andSolanum indicum andClinacanthus nutans had relatively low activity. In cellular model systems,SPRB,BMDC, andTTLO showed higher protective effects againstt-BHP-induced oxidative stress.BMDC,ICM, andTTLO displayed higher inhibitory effects on reactive oxygen species generation int-BHP-induced Clone 9 cells. In addition,SPRB,MRM, andBMDC 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 selected herbs may play a crucial role in

  1. Aldose reductase, oxidative stress and diabetic mellitus

    Directory of Open Access Journals (Sweden)

    Waiho eTang

    2012-05-01

    Full Text Available Diabetes mellitus (DM is a complex metabolic disorder arising from lack of insulin production or insulin resistance 1. DM is a leading cause of morbidity and mortality in the developed world, particularly from vascular complications such as atherothrombosis in the coronary vessels. Aldose reductase (AR [ALR2; EC 1.1.1.21], a key enzyme in the polyol pathway, catalyzes NADPH-dependent reduction of glucose to sorbitol, leading to excessive accumulation of intracellular reactive oxygen species (ROS in various tissues of DM including the heart, vasculature, neurons, eyes and kidneys. As an example, hyperglycemia through such polyol pathway induced oxidative stress, may have dual heart actions, on coronary blood vessel (atherothrombosis and myocardium (heart failure leading to severe morbidity and mortality (reviewed in 2. In cells cultured under high glucose conditions, many studies have demonstrated similar AR-dependent increases in ROS production, confirming AR as an important factor for the pathogenesis of many diabetic complications. Moreover, recent studies have shown that AR inhibitors may be able to prevent or delay the onset of cardiovascular complications such as ischemia/reperfusion injury, atherosclerosis and atherothrombosis. In this review, we will focus on describing pivotal roles of AR in the pathogenesis of cardiovascular diseases as well as other diabetic complications, and the potential use of AR inhibitors as an emerging therapeutic strategy in preventing DM complications.

  2. Computer diagnosis in cardiology: Oxidative stress hypothesis

    Directory of Open Access Journals (Sweden)

    Ezekiel Uba Nwose

    2009-01-01

    Full Text Available Background : Virtual scanning is one of the emerging technologies in complementary medicine practice. The diagnostic principle is hinged on perception and ultra weak light emission, while the treatment options associated with it includes diet, flash light, exercise and relaxation. However, a mechanism that links the diagnostic and treatment principles has yet to be elucidated. Aims: The objective here is to further explanation of oxidative stress concept as the biochemical basis of the technology. Materials and Methods: Using available literature and basic science textbook, the function of the hypothalamus-pituitary-adrenalin axis as neuro-endocrine physiological system that is strongly linked to the rate of alterations in biochemical processes through to cardiovascular complications is articulated. Results: The hypothesis brings to fore the potential of using the alterations in biochemical processes associated with cognition as tool to validate the Virtual Scanning technology for possible incorporation into clinical practice. Or vice versa to use Virtual Scanning technology to determine the chemiluminescence-related biochemical changes resulting from pathologies that could benefit from relaxation, light therapy, exercise and antioxidant nutrition. Conclusions: This article advances the applicability of cognitive test procedure for indication of the disease(s affecting heart function. The implication for some laboratory indices that are already available in clinical practice is highlighted. Investigation of this hypothesis will help provide clear link between plausible mechanism and the theory proposed.

  3. Computer diagnosis in cardiology: Oxidative stress hypothesis

    Directory of Open Access Journals (Sweden)

    Ezekiel Uba Nwose

    2009-10-01

    Full Text Available Background: Virtual scanning is one of the emerging technologies in complementary medicine practice. The diagnostic principle is hinged on perception and ultra weak light emission, while the treatment options associated with it includes diet, flash light, exercise and relaxation. However, a mechanism that links the diagnostic and treatment principles has yet to be elucidated. Aims: The objective here is to further explanation of oxidative stress concept as the biochemical basis of the technology. Materials and Methods: Using available literature and basic science textbook, the function of the hypothalamus-pituitary-adrenalin axis as neuro-endocrine physiological system that is strongly linked to the rate of alterations in biochemical processes through to cardiovascular complications is articulated. Results: The hypothesis brings to fore the potential of using the alterations in biochemical processes associated with cognition as tool to validate the Virtual Scanning technology for possible incorporation into clinical practice. Or vice versa to use Virtual Scanning technology to determine the chemiluminescence-related biochemical changes resulting from pathologies that could benefit from relaxation, light therapy, exercise and antioxidant nutrition. Conclusions: This article advances the applicability of cognitive test procedure for indication of the disease(s affecting heart function. The implication for some laboratory indices that are already available in clinical practice is highlighted. Investigation of this hypothesis will help provide clear link between plausible mechanism and the theory proposed.

  4. The CK1 family: contribution to cellular stress response and its role in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Uwe eKnippschild

    2014-05-01

    Full Text Available Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key regulatory proteins and signal integration molecules and is tightly connected to the regulation of β-catenin, p53- and MDM2-specific functions and degradation. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, effort has enormously increased (i to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review we summarize the current knowledge regarding the regulation, functions, and interactions of CK1 family members with cellular proteins playing central roles in cellular stress-responses and carcinogenesis.

  5. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  6. Early-life Stress Impacts the Developing Hippocampus and Primes Seizure Occurrence: cellular, molecular, and epigenetic mechanisms

    OpenAIRE

    Li-Tung eHuang

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures...

  7. Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

    OpenAIRE

    Huang, Li-Tung

    2014-01-01

    Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures...

  8. Impact of oxidative stress on pregnancy outcome in albino rats

    Directory of Open Access Journals (Sweden)

    R.S. Al-Naemi

    2012-01-01

    Full Text Available Accumulative reports documented that oxidative stress is implicated in many human and animal diseases. However, the reports concerning the effect of oxidative stress on pregnancy outcome are limited and scarce. The objective of this study was to determine the impact of oxidative stress on pregnancy outcome and to assess the antioxidant effect of vitamin C and E on oxidative stress parameters in blood and placental tissue samples in experimental pregnant animals model exposed to oxidative stress. Wister Albino rats were used in this work to investigate the effects of oxidative stress exposure (addition of H2O2 to the drinking water on pregnancy outcome. Rats were divided into 5 groups, as follows: Group I (included 7 normal pregnant rats which served as control group. Group II (exposed to 1 % H2O2 included 7 pregnant rats, the rats were allowed to become pregnant and received (1% H2O2 in drinking water from day 7th till the day 19th of pregnancy. Group III (exposed to 3% H2O2 included 8 pregnant rats. Same as group 2, but the rats were exposed to a higher concentration of H2O2 (3% in drinking water. Group IV (included 8 pregnant rats. Pregnant rats received vitamins C and E without induction of oxidative stress. Group V (included 8 pregnant rats.induction of oxidative stress by 1% H2O2 with vitamins supplementation in the pregnant rats. Serum total antioxidants capacity (TAC, serum and placental tissue oxidative stress biomarker; 8-iso prostaglandin F2α (8-Isoprostane were measured using specific ELISA kits. Also placental tissues of pregnant rats were isolated and put directly in 10% formalin prepared for histopathological examination. Results revealed a significant decrease in the median values of the body weight and total serum antioxidants capacity (TAC in groups II and III of rats compared with the control group. A significant higher median value of TAC obtained in the groups IV and V when compared with the control group. Significant higher

  9. Protein Methionine Sulfoxide Dynamics in Arabidopsis thaliana under Oxidative Stress.

    Science.gov (United States)

    Jacques, Silke; Ghesquière, Bart; De Bock, Pieter-Jan; Demol, Hans; Wahni, Khadija; Willems, Patrick; Messens, Joris; Van Breusegem, Frank; Gevaert, Kris

    2015-05-01

    Reactive oxygen species such as hydrogen peroxide can modify proteins via direct oxidation of their sulfur-containing amino acids, cysteine and methionine. Methionine oxidation, studied here, is a reversible posttranslational modification that is emerging as a mechanism by which proteins perceive oxidative stress and function in redox signaling. Identification of proteins with oxidized methionines is the first prerequisite toward understanding the functional effect of methionine oxidation on proteins and the biological processes in which they are involved. Here, we describe a proteome-wide study of in vivo protein-bound methionine oxidation in plants upon oxidative stress using Arabidopsis thaliana catalase 2 knock-out plants as a model system. We identified over 500 sites of oxidation in about 400 proteins and quantified the differences in oxidation between wild-type and catalase 2 knock-out plants. We show that the activity of two plant-specific glutathione S-transferases, GSTF9 and GSTT23, is significantly reduced upon oxidation. And, by sampling over time, we mapped the dynamics of methionine oxidation and gained new insights into this complex and dynamic landscape of a part of the plant proteome that is sculpted by oxidative stress.

  10. Elevated copper and oxidative stress in cancer cells as a target for cancer treatment.

    Science.gov (United States)

    Gupte, Anshul; Mumper, Russell J

    2009-02-01

    As we gain a better understanding of the factors affecting cancer etiology, we can design improved treatment strategies. Over the past three to four decades, there have been numerous successful efforts in recognizing important cellular proteins essential in cancer growth and therefore these proteins have been targeted for cancer treatment. However, studies have shown that targeting one or two proteins in the complex cancer cascade may not be sufficient in controlling and/or inhibiting cancer growth. Therefore, there is a need to examine features which are potentially involved in multiple facets of cancer development. In this review we discuss the targeting of the elevated copper (both in serum and tumor) and oxidative stress levels in cancer with the aid of a copper chelator d-penicillamine (d-pen) for potential cancer treatment. Numerous studies in the literature have reported that both the serum and tumor copper levels are elevated in a variety of malignancies, including both solid tumor and blood cancer. Further, the elevated copper levels have been shown to be directly correlated to cancer progression. Enhanced levels of intrinsic oxidative stress has been shown in variety of tumors, possibly due to the combination of factors such as elevated active metabolism, mitochondrial mutation, cytokines, and inflammation. The cancer cells under sustained ROS stress tend to heavily utilize adaptation mechanisms and may exhaust cellular ROS-buffering capacity. Therefore, the elevated copper levels and increased oxidative stress in cancer cells provide for a prospect of selective cancer treatment.

  11. 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

  12. Skin aging and oxidative stress: Equol's anti-aging effects via biochemical and molecular mechanisms.

    Science.gov (United States)

    Lephart, Edwin D

    2016-11-01

    Oxygen in biology is essential for life. It comes at a cost during normal cellular function, where reactive oxygen species (ROS) are generated by oxidative metabolism. Human skin exposed to solar ultra-violet radiation (UVR) dramatically increases ROS production/oxidative stress. It is important to understand the characteristics of human skin and how chronological (intrinsic) aging and photo-aging (extrinsic aging) occur via the impact of ROS production by cascade signaling pathways. The goal is to oppose or neutralize ROS insults to maintain good dermal health. Botanicals, as active ingredients, represent one of the largest categories used in dermatology and cosmeceuticals to combat skin aging. An emerging botanical is equol, a polyphenolic/isoflavonoid molecule found in plants and food products and via gastrointestinal metabolism from precursor compounds. Introductory sections cover oxygen, free radicals (ROS), oxidative stress, antioxidants, human skin aging, cellular/molecular ROS events in skin, steroid enzymes/receptors/hormonal actions and genetic factors in aging skin. The main focus of this review covers the characteristics of equol (phytoestrogenic, antioxidant and enhancement of extracellular matrix properties) to reduce skin aging along with its anti-aging skin influences via reducing oxidative stress cascade events by a variety of biochemical/molecular actions and mechanisms to enhance human dermal health. PMID:27521253

  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. PMID:27413258

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

    Directory of Open Access Journals (Sweden)

    María Elena Soto

    2016-01-01

    Full Text Available 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.

  15. 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.

  16. Chemically-induced oxidative stress increases the vulnerability of PC12 cells to rotenone-induced toxicity

    NARCIS (Netherlands)

    de Groot, Martje W G D M; Westerink, Remco H S

    2014-01-01

    In vitro models, including the widely used PC12 cell line, can increase insight into cellular and molecular mechanisms underlying neurodegenerative processes. An important determinant for the vulnerability of cells for chemical insults may be the endogenous level of oxidative stress. To test this hy

  17. A meta-analysis of oxidative stress markers in schizophrenia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Oxidative stress has been identified as a possible element in the neuropathological processes of schizophrenia(SCZ).Alteration of oxidative stress markers has been reported in SCZ studies,but with inconsistent results.To evaluate the risk of oxidative stress to schizophrenia,a meta-analysis was conducted,including five markers of oxidative stress [thiobarbituric reactive substances(TBARS),nitric oxide(NO),catalase(CAT),glutathione peroxidase(GP) and superoxide dismutase(SOD)] in SCZ patients versus healthy controls.This study showed that TBARS and NO significantly increased in SCZ,while SOD activity significantly decreased in the disorganized type of SCZ patients.No significant effect size was found for the activities of GP and CAT in SCZ patients(P>0.05).Egger’s regression test observed no significant publication bias across the oxidative stress markers,but found high heterogeneities in all the 5 markers.The subgroup analysis suggested that the ethnicity,sample size of patients and sample sources may contribute to the heterogeneity of the results for TBARS,NO and SOD.The result further demonstrated the involvement of oxidative stress in the pathophysiology of schizophrenia.

  18. The effects of tea polyphenol on the oxidative stress and cellular apoptosis of testic-ular tissues in rat varicocele%茶多酚对精索静脉曲张大鼠睾丸组织氧化应激和细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    柯鑫文; 武政华; 冯少勇; 张利; 武进峰; 程伟; 成建军; 张建东; 张雁钢

    2015-01-01

    目的 通过研究茶多酚对精索静脉曲张大鼠睾丸组织氧化应激和细胞凋亡的影响 ,探讨茶多酚是否对精索静脉曲张大鼠生精功能具有保护作用 ,为临床上应用茶多酚治疗精索静脉曲张提供理论依据和实验基础.方法 32只雄性青春期Wistar大鼠随机分为4组 ,每组8只.其中第Ⅰ组为假手术组(仅游离左肾静脉 ,不结扎);第Ⅱ组为模型组(建立精索静脉曲张模型);第Ⅲ 、Ⅳ组为茶多酚干预组(先建立精索静脉曲张模型 ,然后分别给予不同浓度的茶多酚干预).造模4周后 ,第Ⅰ组及第Ⅱ组均给予生理盐水1 mL/100 g ,第Ⅲ组给予茶多酚10 mg/kg [即 :(1 mL盐水+1 mg茶多酚)/100 g ] ,第Ⅳ组给予茶多酚40 mg/kg [即 :(1 mL盐水+4 mg茶多酚)/100 g];1次/d ,灌胃 ,持续4周.4周后4组大鼠均处死取左侧睾丸组织 ,分别测定超氧化物歧化酶(SOD)活力、丙二醛(malondialdehyde ,MDA)含量及检测凋亡指数(apoptosis index ,AI).结果 第Ⅰ组SOD活力最高 ,第Ⅱ组低于第Ⅲ组和第Ⅳ组 ,差异有统计学意义(P<0 .05);第Ⅰ组MDA含量最低 ,第Ⅲ 、Ⅳ组低于第Ⅱ组 ,差异有统计学意义(P<0 .05);第Ⅰ组AI最低 ,第Ⅲ 、Ⅳ组AI低于第Ⅱ组 ,差异有统计学意义(P<0 .05).结论 茶多酚能显著降低精索静脉曲张大鼠睾丸组织的氧化应激和细胞凋亡 ,间接改善精索静脉曲张大鼠睾丸的生精功能.%Objective To explore the protective role of tea polyphenol on the oxidative stress and cellular apoptosis of testicular tissues in experimentally-induced varicocele rat models .Methods A total of 32 male prepubertal Wistar rats were randomly divided into 4 groups ,with 8 rats in each group .Group I was the sham operation group .Group Ⅱ was the varicocele model group .Group Ⅲ and Ⅳ were the tea polyphenol groups ,in which the varicocele models were treated with tea polyphe-nol of different concentrations .Four weeks after the models were

  19. Pharmacological models and approaches for pathophysiological conditions associated with hypoxia and oxidative stress.

    Science.gov (United States)

    Farías, Jorge G; Herrera, Emilio A; Carrasco-Pozo, Catalina; Sotomayor-Zárate, Ramón; Cruz, Gonzalo; Morales, Paola; Castillo, Rodrigo L

    2016-02-01

    Hypoxia is the failure of oxygenation at the tissue level, where the reduced oxygen delivered is not enough to satisfy tissue demands. Metabolic depression is the physiological adaptation associated with reduced oxygen consumption, which evidently does not cause any harm to organs that are exposed to acute and short hypoxic insults. Oxidative stress (OS) refers to the imbalance between the generation of reactive oxygen species (ROS) and the ability of endogenous antioxidant systems to scavenge ROS, where ROS overwhelms the antioxidant capacity. Oxidative stress plays a crucial role in the pathogenesis of diseases related to hypoxia during intrauterine development and postnatal life. Thus, excessive ROS are implicated in the irreversible damage to cell membranes, DNA, and other cellular structures by oxidizing lipids, proteins, and nucleic acids. Here, we describe several pathophysiological conditions and in vivo and ex vivo models developed for the study of hypoxic and oxidative stress injury. We reviewed existing literature on the responses to hypoxia and oxidative stress of the cardiovascular, renal, reproductive, and central nervous systems, and discussed paradigms of chronic and intermittent hypobaric hypoxia. This systematic review is a critical analysis of the advantages in the application of some experimental strategies and their contributions leading to novel pharmacological therapies. PMID:26617218

  20. The protective effect of lipoic acid on selected cardiovascular diseases caused by age-related oxidative stress.

    Science.gov (United States)

    Skibska, Beata; Goraca, Anna

    2015-01-01

    Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

  1. Heart disease link to fetal hypoxia and oxidative stress.

    Science.gov (United States)

    Giussani, Dino A; Niu, Youguo; Herrera, Emilio A; Richter, Hans G; Camm, Emily J; Thakor, Avnesh S; Kane, Andrew D; Hansell, Jeremy A; Brain, Kirsty L; Skeffington, Katie L; Itani, Nozomi; Wooding, F B Peter; Cross, Christine M; Allison, Beth J

    2014-01-01

    The quality of the intrauterine environment interacts with our genetic makeup to shape the risk of developing disease in later life. Fetal chronic hypoxia is a common complication of pregnancy. This chapter reviews how fetal chronic hypoxia programmes cardiac and endothelial dysfunction in the offspring in adult life and discusses the mechanisms via which this may occur. Using an integrative approach in large and small animal models at the in vivo, isolated organ, cellular and molecular levels, our programmes of work have raised the hypothesis that oxidative stress in the fetal heart and vasculature underlies the mechanism via which prenatal hypoxia programmes cardiovascular dysfunction in later life. Developmental hypoxia independent of changes in maternal nutrition promotes fetal growth restriction and induces changes in the cardiovascular, metabolic and endocrine systems of the adult offspring, which are normally associated with disease states during ageing. Treatment with antioxidants of animal pregnancies complicated with reduced oxygen delivery to the fetus prevents the alterations in fetal growth, and the cardiovascular, metabolic and endocrine dysfunction in the fetal and adult offspring. The work reviewed offers both insight into mechanisms and possible therapeutic targets for clinical intervention against the early origin of cardiometabolic disease in pregnancy complicated by fetal chronic hypoxia.

  2. High glucose-mediated oxidative stress impairs cell migration.

    Directory of Open Access Journals (Sweden)

    Marcelo L Lamers

    Full Text Available Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM D-glucose (low glucose, LG, 25 mM D-glucose (high glucose, HG or 25 mM L-glucose medium (osmotic control--OC, we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-Acetyl-Cysteine (NAC. We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients.

  3. Oxidative Stress, Sarcopenia, Antioxidant Strategies and Exercise: Molecular Aspects.

    Science.gov (United States)

    Brioche, Thomas; Lemoine-Morel, Sophie

    2016-01-01

    Sarcopenia could be currently defined as a geriatric syndrome initially characterized by a decrease in muscle mass that will get worse causing deterioration in strength and physical performance. A negative protein turnover, impaired mitochondrial dynamics and functions, a decreased muscle regeneration capacity, as well as an exacerbation of apoptosis are usually considered to be cellular mechanisms involved in muscle atrophy leading to sarcopenia. In this review, we first present that muscle overproduction of reactive oxygen and nitrogen species (RONS) and oxidative stress observed during aging are associated with sarcopenia, and then discuss how RONS are involved in redox-sensitive signaling pathways leading to sarcopenia. The identification of cost-effectiveness interventions to maintain muscle mass and physical functions in the elderly is one of the most important public health challenges. Here, we also discuss about the efficiency of different kind of antioxidant strategies against sarcopenia. Since exercise is the best strategy to prevent and reverse sarcopenia, we also highlight that exercise acts as an antioxidant. PMID:26891808

  4. In vitro evaluation of the cellular effect of indium tin oxide nanoparticles using the human lung adenocarcinoma A549 cells.

    Science.gov (United States)

    Tabei, Yosuke; Sonoda, Akinari; Nakajima, Yoshihiro; Biju, Vasudevanpillai; Makita, Yoji; Yoshida, Yasukazu; Horie, Masanori

    2015-05-01

    Indium tin oxide (ITO) is widely used in liquid crystal displays (LCDs) or plasma and mobile phone displays. Elevated production and usage of ITO in such displays have led to increased concerns over the safety of industrial workers exposed to particulate aerosols produced during cutting, grinding and polishing of these materials. However, the cellular effects of ITO nanoparticles (NPs) are still unclear, although it has been reported that micro-scale ITO particles induce cytotoxicity. The aim of this study was to examine the potential of ITO NPs to induce cytotoxicity, oxidative stress, and DNA damage using human lung adenocarcinoma A549 cells. Here, stable dispersions of a medium containing ITO NPs were obtained using pre-adsorption and centrifugal fractionation methods, and the A549 cells were incubated in this medium. The ITO NPs showed low cytotoxic effects as shown by the WST-1 and LDH assays. Transmission electron microscopy observations showed the cellular uptake of ITO NPs. The ITO NPs increased the intracellular level of reactive oxygen species and the expression of the heme oxygenase 1 gene. Further, the results of alkaline comet assays showed that ITO NPs induced DNA damage. Thus, these results suggest that ITO NPs possess a genotoxic potential on human lung adenocarcinoma A549 cells.

  5. Analysis of cellular responses of macrophages to zinc ions and zinc oxide nanoparticles: a combined targeted and proteomic approach

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Armand, Lucie; Gerdil, Adèle; Diemer, Hélène; Proamer, Fabienne; Collin-Faure, Véronique; Habert, Aurélie; Strub, Jean-Marc; Hanau, Daniel; Herlin, Nathalie; Carrière, Marie; van Dorsselaer, Alain; Rabilloud, Thierry

    2014-05-01

    Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate catabolism and proteasome are critical determinants of sensitivity to zinc, which also induces DNA damage. Conversely, glutathione levels and phagocytosis appear unaffected at moderately toxic zinc concentrations.Two different zinc oxide nanoparticles, as well as zinc ions, are used to study the cellular responses of the RAW 264 macrophage cell line. A proteomic screen is used to provide a wide view of the molecular effects of zinc, and the most prominent results are cross-validated by targeted studies. Furthermore, the alteration of important macrophage functions (e.g. phagocytosis) by zinc is also investigated. The intracellular dissolution/uptake of zinc is also studied to further characterize zinc toxicity. Zinc oxide nanoparticles dissolve readily in the cells, leading to high intracellular zinc concentrations, mostly as protein-bound zinc. The proteomic screen reveals a rather weak response in the oxidative stress response pathway, but a strong response both in the central metabolism and in the proteasomal protein degradation pathway. Targeted experiments confirm that carbohydrate

  6. Neuroendocrine Profile in a Rat Model of Psychosocial Stress: Relation to Oxidative Stress

    OpenAIRE

    Colaianna, Marilena; Schiavone, Stefania; Zotti, Margherita; Tucci, Paolo; Morgese, Maria Grazia; Bäckdahl, Liselotte; Holmdahl, Rikard; Krause, Karl-Heinz; Cuomo, Vincenzo; Trabace, Luigia

    2013-01-01

    Aims: Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine altera...

  7. Cellular oxidative damage is more sensitive to biosynthetic rate than to metabolic rate: A test of the theoretical model on hornworms (Manduca sexta larvae).

    Science.gov (United States)

    Amunugama, Kaushalya; Jiao, Lihong; Olbricht, Gayla R; Walker, Chance; Huang, Yue-Wern; Nam, Paul K; Hou, Chen

    2016-09-01

    We develop a theoretical model from an energetic viewpoint for unraveling the entangled effects of metabolic and biosynthetic rates on oxidative cellular damage accumulation during animal's growth, and test the model by experiments in hornworms. The theoretical consideration suggests that most of the cellular damages caused by the oxidative metabolism can be repaired by the efficient maintenance mechanisms, if the energy required by repair is unlimited. However, during growth a considerable amount of energy is allocated to the biosynthesis, which entails tradeoffs with the requirements of repair. Thus, the model predicts that cellular damage is more influenced by the biosynthetic rate than the metabolic rate. To test the prediction, we induced broad variations in metabolic and biosynthetic rates in hornworms, and assayed the lipid peroxidation and protein carbonyl. We found that the increase in the cellular damage was mainly caused by the increase in biosynthetic rate, and the variations in metabolic rate had negligible effect. The oxidative stress hypothesis of aging suggests that high metabolism leads to high cellular damage and short lifespan. However, some empirical studies showed that varying biosynthetic rate, rather than metabolic rate, changes animal's lifespan. The conflicts between the empirical evidence and the hypothesis are reconciled by this study. PMID:27296440

  8. Alzheimer's disease: Cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies

    NARCIS (Netherlands)

    M.W. Marlatt; P.J. Lucassen; G. Perry; M.A. Smith; X. Zhu

    2008-01-01

    Many lines of independent research have provided convergent evidence regarding oxidative stress, cerebrovascular disease, dementia, and Alzheimer's disease (AD). Clinical studies spurred by these findings engage basic and clinical communities with tangible results regarding molecular targets and pat

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

    Science.gov (United States)

    Rebbani, Khadija; Tsukiyama-Kohara, Kyoko

    2016-01-01

    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. PMID:27293514

  10. Thioredoxin Binding Protein-2 Regulates Autophagy of Human Lens Epithelial Cells under Oxidative Stress via Inhibition of Akt Phosphorylation

    Science.gov (United States)

    Yao, Ke; Zhang, Yidong; Chen, Guangdi; Lai, Kairan; Yin, Houfa

    2016-01-01

    Oxidative stress plays an essential role in the development of age-related cataract. Thioredoxin binding protein-2 (TBP-2) is a negative regulator of thioredoxin (Trx), which deteriorates cellular antioxidant system. Our study focused on the autophagy-regulating effect of TBP-2 under oxidative stress in human lens epithelial cells (LECs). Human lens epithelial cells were used for cell culture and treatment. Lentiviral-based transfection system was used for overexpression of TBP-2. Cytotoxicity assay, western blot analysis, GFP/mCherry-fused LC3 plasmid, immunofluorescence, and transmission electronic microscopy were performed. The results showed that autophagic response of LECs with increased LC3-II, p62, and GFP/mCherry-LC3 puncta (P < 0.01) was induced by oxidative stress. Overexpression of TBP-2 further strengthens this response and worsens the cell viability (P < 0.01). Knockdown of TBP-2 attenuates the autophagic response and cell viability loss induced by oxidative stress. TBP-2 mainly regulates autophagy in the initiation stage, which is mTOR-independent and probably caused by the dephosphorylation of Akt under oxidative stress. These findings suggest a novel role of TBP-2 in human LECs under oxidative stress. Oxidative stress can cause cell injury and autophagy in LECs, and TBP-2 regulates this response. Hence, this study provides evidence regarding the role of TBP-2 in lens and the possible mechanism of cataract development. PMID:27656263

  11. The Effect of Cellular Stress on T and B Cell Memory Pathways in Immunized and Unimmunized BALB/c Mice*

    Science.gov (United States)

    Wang, Yufei; Rahman, Durdana; Mistry, Mukesh; Lehner, Thomas

    2016-01-01

    Immunological memory is a fundamental function of vaccination. The antigenic breakdown products of the vaccine may not persist, and undefined tonic stimulation has been proposed to maintain the specific memory. We have suggested that cellular stress agents to which the immune cells are constantly exposed may be responsible for tonic stimulation. Here we have studied four stress agents: sodium arsenite, an oxidative agent; Gramicidin, eliciting K+ efflux and calcium influx; dithiocarbamate, a metal ionophore; and aluminum hydroxide (alum), an immunological adjuvant. The aims of this study are to extend these investigations to T and B cell responses of unimmunized and ovalbumin (OVA)-immunized BALB/c mice, and furthermore, to ascertain whether stress is involved in optimal expression of memory B cells, as demonstrated in CD4+ T cells. Examination of the homeostatic pathway defined by IL-15/IL-15R (IL-15 receptor) interaction and the inflammasome pathway defined by the IL-1-IL-1R interaction between dendritic cells (DC) and CD4+ T cells suggests that both pathways are involved in the development of optimal expression of CD4+CD45RO+ memory T cells in unimmunized and OVA-immunized BALB/c mice. Furthermore, significant direct correlation was found between CD4+CD44+ memory T cells and both IL-15 of the homeostatic and IL-1β of the inflammasome pathways. However, CD19+CD27+ memory B cells in vivo seem to utilize only the IL-15/IL-15R homeostatic pathway, although the proliferative responses are enhanced by the stress agents. Altogether, stress agents may up-regulate unimmunized and OVA-immunized CD4+CD44+ memory T cells by the homeostatic and inflammasome pathways. However, the CD19+CD27+ memory B cells utilize only the homeostatic pathway. PMID:27502276

  12. Food-Derived Bioactive Peptides on Inflammation and Oxidative Stress

    OpenAIRE

    Subhadeep Chakrabarti; Forough Jahandideh; Jianping Wu

    2014-01-01

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

  13. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

    OpenAIRE

    Roya Naderi; Gisou Mohaddes; Mustafa Mohammadi; Rana Ghaznavi; Rafigheh Ghyasi; Amir Mansour Vatankhah

    2015-01-01

    Purpose: Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. Methods: 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were sub...

  14. Ageing, oxidative stress and cancer: paradigms in parallax

    OpenAIRE

    Benz, Christopher C.; Yau, Christina

    2008-01-01

    Two paradigms central to geroscience research are that aging is associated with increased oxidative stress and increased cancer risk. Therefore, it could be deduced that cancers arising with ageing will show evidence of increased oxidative stress. Recent studies of gene expression in age-controlled breast cancer cases indicate that this deduction is false, posing parallax views of these two paradigms, and highlighting the unanswered question: does ageing cause or simply permit cancer developm...

  15. Mycotoxin-Containing Diet Causes Oxidative Stress in the Mouse

    OpenAIRE

    Hou, Yan-Jun; Zhao, Yong-yan; Xiong, Bo; Cui, Xiang-Shun; Kim, Nam-Hyung; Xu, Yin-xue; Sun, Shao-Chen

    2013-01-01

    Mycotoxins which mainly consist of Aflatoxin (AF), Zearalenone (ZEN) and Deoxynivalenol (DON) are commonly found in many food commodities. Although each component has been shown to cause liver toxicity and oxidative stress in several species, there is no evidence regarding the effect of naturally contained multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the present study, mycotoxins-contaminated maize (AF 597 µg/kg, ZEN 729 µg/kg, DON 3.1 mg/kg maize) was incorporated ...

  16. Introduction to Oxidative Stress in Biomedical and Biological Research

    OpenAIRE

    Michael Breitenbach; Peter Eckl

    2015-01-01

    Oxidative stress is now a well-researched area with thousands of new articles appearing every year. We want to give the reader here an overview of the topics in biomedical and basic oxidative stress research which are covered by the authors of this thematic issue. We also want to give the newcomer a short introduction into some of the basic concepts, definitions and analytical procedures used in this field.

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

    OpenAIRE

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

    2015-01-01

    Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melo...

  18. An Antioxidant Phytotherapy to Rescue Neuronal Oxidative Stress

    OpenAIRE

    Pingniang Shen; Boyang Yu; Qiujuan Wang; Yongqing Yan; Danni Zhu; Zhihong Lin; Kefeng Ruan

    2011-01-01

    Oxidative stress is involved in the pathogenesis of ischemic neuronal injury. A Chinese herbal formula composed of Poria cocos (Chinese name: Fu Ling), Atractylodes macrocephala (Chinese name: Bai Zhu) and Angelica sinensis (Chinese names: Danggui, Dong quai, Donggui; Korean name: Danggwi) (FBD), has been proved to be beneficial in the treatment of cerebral ischemia/reperfusion (I/R).This study was carried out to evaluate the protective effect of FBD against neuronal oxidative stress in vivo ...

  19. Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration

    OpenAIRE

    R. C. Patra; Amiya K. Rautray; D. Swarup

    2011-01-01

    Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthrop...

  20. [Regulatory role of mechanical stress response in cellular function: development of new drugs and tissue engineering].

    Science.gov (United States)

    Momose, Kazutaka; Matsuda, Takehisa; Oike, Masahiro; Obara, Kazuo; Laher, Ismail; Sugiura, Seiryo; Ohata, Hisayuki; Nakayama, Koichi

    2003-02-01

    The investigation of mechanotransduction in the cardiovascular system is essentially important for elucidating the cellular and molecular mechanisms involved in not only the maintenance of hemodynamic homeostasis but also etiology of cardiovascular diseases including arteriosclerosis. The present review summarizes the latest research performed by six academic groups, and presented at the 75th Annual Meeting of the Japanese Pharmacological Society. Technology of cellular biomechanics is also required for research and clinical application of a vascular hybrid tissue responding to pulsatile stress. 1) Vascular tissue engineering: Design of pulsatile stress-responsive scaffold and in vivo vascular wall reconstruction (T. Matsuda); 2) Cellular mechanisms of mechanosensitive calcium transients in vascular endothelium (M. Oike et al.); 3) Cross-talk of stimulation with fluid flow and lysophosphatidic acid in vascular endothelial cells (K. Momose et al.); 4) Mechanotransduction of vascular smooth muscles: Rate-dependent stretch-induced protein phosphorylations and contractile activation (K. Obara et al.); 5) Lipid mediators in vascular myogenic tone (I. Laher et al.); and 6) Caldiomyocyte regulates its mechanical output in response to mechanical load (S. Sugiura et al.).

  1. Morphological and migratory alterations in retinal Müller cells during early stages of hypoxia and oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Xiaohui Zhang; Zhaohui Feng; Chunhua Li; Yuping Zheng

    2012-01-01

    In the present study, retinal Müller cells were cultured in vitro and treated with hydrogen peroxide (oxidative stressor) and cobalt chloride (hypoxic injury). Following 24 hours of culture, compensatory hypertrophy was observed and cellular apoptosis increased. Hypoxia enhanced the migration ability of retinal Müller cells and induced the expression of α-smooth muscle actin. Oxidative stress altered the morphology of Müller cells when compared with hypoxia treatment.

  2. Mycotoxin-containing diet causes oxidative stress in the mouse.

    Directory of Open Access Journals (Sweden)

    Yan-Jun Hou

    Full Text Available Mycotoxins which mainly consist of Aflatoxin (AF, Zearalenone (ZEN and Deoxynivalenol (DON are commonly found in many food commodities. Although each component has been shown to cause liver toxicity and oxidative stress in several species, there is no evidence regarding the effect of naturally contained multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the present study, mycotoxins-contaminated maize (AF 597 µg/kg, ZEN 729 µg/kg, DON 3.1 mg/kg maize was incorporated into the diet at three different doses (0, 5 and 20% to feed the mice, and blood and tissue samples were collected to examine the oxidative stress related indexes. The results showed that the indexes of liver, kidney and spleen were all increased and the liver and kidney morphologies changed in the mycotoxin-treated mice. Also, the treatment resulted in the elevated glutathione peroxidase (GPx activity and malondialdehyde (MDA level in the serum and liver, indicating the presence of the oxidative stress. Moreover, the decrease of catalase (CAT activity in the serum, liver and kidney as well as superoxide dismutase (SOD activity in the liver and kidney tissue further confirmed the occurrence of oxidative stress. In conclusion, our data indicate that the naturally contained mycotoxins are toxic in vivo and able to induce the oxidant stress in the mouse.

  3. Regulation of oxidative stress response by CosR, an essential response regulator in Campylobacter jejuni.

    Directory of Open Access Journals (Sweden)

    Sunyoung Hwang

    Full Text Available CosR (Campylobacter oxidative stress regulator; Cj0355c is an OmpR-type response regulator essential for the viability of Campylobacter jejuni, a leading foodborne pathogen causing human gastroenteritis worldwide. Despite importance, the function of CosR remains completely unknown mainly because of cell death caused by its knockout mutation. To overcome this technical limitation, in this study, antisense technology was used to investigate the regulatory function of CosR by modulating the level of CosR expression. Two-dimensional gel electrophoresis (2DGE was performed to identify the CosR regulon either by suppressing CosR expression with antisense peptide nucleic acid (PNA or by overexpressing CosR in C. jejuni. According to the results of 2DGE, CosR regulated 32 proteins involved in various cellular processes. Notably, CosR negatively regulated a few key proteins of the oxidative stress response of C. jejuni, such as SodB, Dps, Rrc and LuxS, whereas CosR positively controlled AhpC. Electrophoretic mobility shift assay showed that CosR directly bound to the promoter region of the oxidative stress genes. DNase I footprinting assays identified 21-bp CosR binding sequences in the sodB and ahpC promoters, suggesting CosR specifically recognizes and binds to the regulated genes. Interestingly, the level of CosR protein was significantly reduced by paraquat (a superoxide generator but not by hydrogen peroxide. Consistent with the overall negative regulation of oxidative stress defense proteins by CosR, the CosR knockdown by antisense rendered C. jejuni more resistant to oxidative stress compared to the wild type. Overall, this study reveals the important role played by the essential response regulator CosR in the oxidative stress defense of C. jejuni.

  4. Early-life Stress Impacts the Developing Hippocampus and Primes Seizure Occurrence: cellular, molecular, and epigenetic mechanisms

    Directory of Open Access Journals (Sweden)

    Li-Tung eHuang

    2014-02-01

    Full Text Available Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed.

  5. Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide.

    Science.gov (United States)

    Ozgocmen, Salih; Ozyurt, Huseyin; Sogut, Sadik; Akyol, Omer

    2006-05-01

    Fibromyalgia (FM) is a common chronic pain syndrome with an unknown etiology. Recent years added new information to our understanding of FM pathophysiology. Researches on genetics, biogenic amines, neurotransmitters, hypothalamic-pituitary-adrenal axis hormones, oxidative stress, and mechanisms of pain modulation, central sensitization, and autonomic functions in FM revealed various abnormalities indicating that multiple factors and mechanisms are involved in the pathogenesis of FM. Oxidative stress and nitric oxide may play an important role in FM pathophysiology, however it is still not clear whether oxidative stress abnormalities documented in FM are the cause or the effect. This should encourage further researches evaluating the potential role of oxidative stress and nitric oxide in the pathophysiology of FM and the efficacy of antioxidant treatments (omega-3 and -6 fatty acids, vitamins and others) in double blind and placebo controlled trials. These future researches will enhance our understanding of the complex pathophysiology of this disorder. PMID:16328420

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

    Science.gov (United States)

    Wang, Jing; Yang, Xin; Zhang, Jingjing

    2016-08-01

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

  7. Oxidative Stress: A Potential Recipe For Anxiety, Hypertension and Insulin Resistance

    OpenAIRE

    Salim, Samina; Asghar, Mohammad; Chugh, Gaurav; Taneja, Manish; Xia, Zhilian; Saha, Kaustav

    2010-01-01

    We recently reported involvement of oxidative stress in anxiety-like behavior of rats. Others in separate studies have demonstrated a link between oxidative stress and hypertension as well as with type 2 diabetes/insulin resistance. In the present study, we have tested a putative role of oxidative stress in anxiety-like behavior, hypertension and insulin resistance using a rat model of oxidative stress. Oxidative stress in rats was produced by xanthine (0.1%; drinking water) and xanthine oxid...

  8. 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.

  9. 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.

  10. Analysis of deposition stresses in sputtered metal oxides

    International Nuclear Information System (INIS)

    The intrinsic stress has been measured for various metal oxides including ZnOx, ZrOx, NbOx, MoOx, and TaOx. The measurements have been performed using both ex- and in-situ wafer curvature methods. The wafer curvature method utilises the change of curvature in a film-substrate combination upon changing stress in the film. Our analysis shows that the stresses arising during reactive sputter deposition depend on the oxygen flow, the total pressure during deposition and the deposited material itself. Stresses in these oxides can easily reach the order of GPa. These stresses have e.g. been observed in ZnO, where the maximum state of stress reached 1.4 GPa for low total pressure. (Authors)

  11. Modulation of early stress-related biomarkers in cytoplasm by the antioxidants silymarin and quercetin using a cellular model of acute arsenic poisoning.

    Science.gov (United States)

    Soria, Elio A; Eynard, Aldo R; Bongiovanni, Guillermina A

    2010-12-01

    Several pathologies (e.g. cancer and diabetes) are increased in arsenic-exposed populations, with oxidative stress being a major toxicological mechanism. Since the flavonoids silymarin (S) and quercetin (Q) are antioxidants and may protect cells, it would be valuable to develop a model which allows assessing the potential of xenobiotic against arsenic cytotoxicity in an efficient and rapid way. Thus, the oxidant production [e.g. reactive oxygen species and reactive nitrogen species (RNS)], the molecular parameters of biological response [e.g. plasma membrane composition, actin microfilaments and activated diphosphorilated c-Jun N-terminal kinase (JNK)] and cellular viability were determined in CHO-K1 cells treated with arsenite (As), S and Q. Arsenic caused loss of the cellular viability in a time-dependent manner. This effect was accompanied by a lipid hydroperoxide (LHP) formation, with no RNS induction or ganglioside content changes being found. Both flavonoids counteracted oxidative damage. Despite all treatments had unspecific responses on nitrite cellular release along the time, there was no relation between them and the cellular viability. Arsenic induced cytoplasmic microfilament rearrangement (tight perinuclear distribution with projections, stress fibres and pseudopodia) which was reversed by S. Also, activated JNK showed a similar distribution to actin. Contrarily, Q caused a dysmorphic granular pattern, thus behaving as a toxic agent. Summing up, toxic levels of arsenic disturb the redox homeostasis with LHP induction and early triggering of stress responses in cytoskeleton and cell signalling. Using the proposed model, only S showed to protect cells from arsenical cytotoxicity without own toxic properties. Thus, S might be considered for modulation of the human arsenic susceptibility.

  12. Infrared Dielectric Properties of Low-Stress Silicon Oxide

    Science.gov (United States)

    Cataldo, Giuseppe; Wollack, Edward J.; Brown, Ari D.; Miller, Kevin H.

    2016-01-01

    Silicon oxide thin films play an important role in the realization of optical coatings and high-performance electrical circuits. Estimates of the dielectric function in the far- and mid-infrared regime are derived from the observed transmittance spectrum for a commonly employed low-stress silicon oxide formulation. The experimental, modeling, and numerical methods used to extract the dielectric function are presented.

  13. CONCENTRATED AMBIENT AIR POLLUTION CREATES OXIDATIVE STRESS IN CNS MICROGLIA.

    Science.gov (United States)

    Nanometer size particles carry free radical activity on their surface and can produce oxidative stress (OS)-mediated damage upon impact to target cells. The initiating event of phage cell activation (i.e., the oxidative burst) is unknown, although many proximal events have been i...

  14. ELECTROSTATIC CHARGE STIMULATES OXIDATIVE STRESS IN CNS MICROGLIA.

    Science.gov (United States)

    Nanometer size particles carry free radical activity on their surface and can create oxidative stress (OS)-mediated inflammatory changes upon impact. The oxidative burst signals the activation of phage-lineage cells such as peripheral macrophages, Kupffer cells and CNS microgl...

  15. Infrared dielectric properties of low-stress silicon oxide

    CERN Document Server

    Cataldo, Giuseppe; Brown, Ari D; Miller, Kevin H

    2016-01-01

    Silicon oxide thin films play an important role in the realization of optical coatings and high-performance electrical circuits. Estimates of the dielectric function in the far- and mid-infrared regime are derived from the observed transmittance spectrum for a commonly employed low-stress silicon oxide formulation. The experimental, modeling, and numerical methods used to extract the dielectric function are presented.

  16. Oxidative stress and antioxidant indices of marine alga Porphyra vietnamensis

    Digital Repository Service at National Institute of Oceanography (India)

    Pise, N.M.; Gaikwad, D.K.; Jagtap, T.G.

    Oxidative stress and antioxidant defence systems were assessed in a marine red alga Porphyra vietnamensis Tanaka et Pham-Hoang Ho, from India. Lipid peroxidation (LPX) and hydrogen peroxide (H2O2) were measured as oxidative...

  17. Residual stress distribution in oxide films formed on Zircaloy-2

    Science.gov (United States)

    Sawabe, T.; Sonoda, T.; Furuya, M.; Kitajima, S.; Takano, H.

    2015-11-01

    In order to evaluate residual the stress distribution in oxides formed on zirconium alloys, synchrotron X-ray diffraction (XRD) was performed on the oxides formed on Zircaloy-2 after autoclave treatment at a temperature of 360° C in pure water. The use of a micro-beam XRD and a micro-sized cross-sectional sample achieved the detailed local characterization of the oxides. The oxide microstructure was observed by TEM following the micro-beam XRD measurements. The residual compressive stress increased in the vicinity of the oxide/metal interface of the pre-transition oxide. Highly oriented columnar grains of a monoclinic phase were observed in that region. Furthermore, at the interface of the post-first transition oxide, there was only a small increase in the residual compressive stress and the columnar grains had a more random orientation. The volume fraction of the tetragonal phase increased with the residual compressive stress. The results are discussed in terms of the formation and transition of the protective oxide.

  18. Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

    Directory of Open Access Journals (Sweden)

    Yoo-hwan Lee

    2016-03-01

    Full Text Available Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL against oxidative stress (hydrogen peroxide, H2O2 and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS generation and deoxyribonucleic acid (DNA damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and H2O2 in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2-specific small interfering ribonucleic acid (siRNA was conducted to understand the relationship between Nrf2 expression and H2O2-induced growth inhibition. Results: The results showed that EGL effectively inhibited H2O2-induced growth and the generation of ROS. EGL markedly suppressed H2O2-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 (p-γH2AX, a widely used marker of DNA damage, suggesting that EGL prevented H2O2-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1, with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against H2O2-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL

  19. Salivary Nitric Oxide, a Biomarker for Stress and Anxiety?

    OpenAIRE

    Gammoh, Omar Salem; Al-Smadi, Ahmed Mohammad; Ashour, Ala Fawzi; Al-Awaida, Wajdy

    2016-01-01

    Objective To investigate if salivary nitrate correlates to the daily psychological stress and anxiety in a group of human subjects. Methods The convenient sample recruitment method was employed; data from seventy three subjects were analyzed. The Perceived Stress Scale (PSS) and Hamilton Anxiety Rating Scale (HAM-A) inventories were used to determine stress and anxiety scores respectively. Salivary nitric oxide was measured through nitrate (NOx) levels using the Griess reaction method. Result...

  20. Influence of Endodontic Treatment on Systemic Oxidative Stress

    OpenAIRE

    Inchingolo, Francesco; Marrelli, Massimo; Annibali, Susanna; Cristalli, Maria Paola; Dipalma, Gianna; Inchingolo, Alessio Danilo; Palladino, Antonio; Inchingolo, Angelo Michele; Gargari, Marco; Tatullo, Marco

    2013-01-01

    Introduction: An increased production of oxidizing species related to reactive oral diseases, such as chronic apical periodontitis, could have systemic implications such as an increase in cardiovascular morbidity. Based on this consideration, we conducted a prospective study to assess whether subjects affected by chronic periodontitis presented with higher values of oxidative stress than reference values before endodontic treatment, and whether endodontic treatment can reduce the oxidative im...

  1. Does reproduction cause oxidative stress? An open question

    OpenAIRE

    Metcalfe, N.B.; Monaghan, P.

    2013-01-01

    There has been substantial recent interest in the possible role of oxidative stress as a mechanism underlying life-history trade-offs, particularly with regard to reproductive costs. Several recent papers have found no evidence that reproduction increases oxidative damage and so have questioned the basis of the hypothesis that oxidative damage mediates the reproduction–lifespan trade-off. However, we suggest here that the absence of the predicted relationships could be due to a fundamental pr...

  2. β-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes.

    Science.gov (United States)

    Nagao, Manabu; Toh, Ryuji; Irino, Yasuhiro; Mori, Takeshige; Nakajima, Hideto; Hara, Tetsuya; Honjo, Tomoyuki; Satomi-Kobayashi, Seimi; Shinke, Toshiro; Tanaka, Hidekazu; Ishida, Tatsuro; Hirata, Ken-Ichi

    2016-07-01

    Recent studies have shown that the ketone body β-hydroxybutyrate (βOHB) acts not only as a carrier of energy but also as a signaling molecule that has a role in diverse cellular functions. Circulating levels of ketone bodies have been previously reported to be increased in patients with congestive heart failure (HF). In this study, we investigated regulatory mechanism and pathophysiological role of βOHB in HF. First, we revealed that βOHB level was elevated in failing hearts, but not in blood, using pressure-overloaded mice. We also measured cellular βOHB levels in both cardiomyocytes and non-cardiomyocytes stimulated with or without H2O2 and revealed that increased myocardial βOHB was derived from cardiomyocytes but not non-cardiomyocytes under pathological states. Next, we sought to elucidate the mechanisms of myocardial βOHB elevation and its implication under pathological states. The gene and protein expression levels of CoA transferase (SCOT), a key enzyme involved in ketone body oxidation, was decreased in failing hearts. In cardiomyocytes, H2O2 stimulation caused βOHB accumulation concomitantly with SCOT downregulation, implying that the accumulation of myocardial βOHB occurs because of the decline in its utilization. Finally, we checked the effects of βOHB on cardiomyocytes under oxidative stress. We found that βOHB induced FOXO3a, an oxidative stress resistance gene, and its target enzyme, SOD2 and catalase. Consequently, βOHB attenuated reactive oxygen species production and alleviated apoptosis induced by oxidative stress. It has been reported that hyperadrenergic state in HF boost lipolysis and result in elevation of circulating free fatty acids, which can lead hepatic ketogenesis for energy metabolism alteration. The present findings suggest that the accumulation of βOHB also occurs as a compensatory response against oxidative stress in failing hearts. PMID:27216458

  3. Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism.

    Science.gov (United States)

    Fletcher, Marianne E; Boshier, Piers R; Wakabayashi, Kenji; Keun, Hector C; Smolenski, Ryszard T; Kirkham, Paul A; Adcock, Ian M; Barton, Paul J; Takata, Masao; Marczin, Nandor

    2015-06-15

    Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications. PMID:26078397

  4. Influence of glutathione-S-transferase (GST) inhibition on lung epithelial cell injury: role of oxidative stress and metabolism.

    Science.gov (United States)

    Fletcher, Marianne E; Boshier, Piers R; Wakabayashi, Kenji; Keun, Hector C; Smolenski, Ryszard T; Kirkham, Paul A; Adcock, Ian M; Barton, Paul J; Takata, Masao; Marczin, Nandor

    2015-06-15

    Oxidant-mediated tissue injury is key to the pathogenesis of acute lung injury. Glutathione-S-transferases (GSTs) are important detoxifying enzymes that catalyze the conjugation of glutathione with toxic oxidant compounds and are associated with acute and chronic inflammatory lung diseases. We hypothesized that attenuation of cellular GST enzymes would augment intracellular oxidative and metabolic stress and induce lung cell injury. Treatment of murine lung epithelial cells with GST inhibitors, ethacrynic acid (EA), and caffeic acid compromised lung epithelial cell viability in a concentration-dependent manner. These inhibitors also potentiated cell injury induced by hydrogen peroxide (H2O2), tert-butyl-hydroperoxide, and hypoxia and reoxygenation (HR). SiRNA-mediated attenuation of GST-π but not GST-μ expression reduced cell viability and significantly enhanced stress (H2O2/HR)-induced injury. GST inhibitors also induced intracellular oxidative stress (measured by dihydrorhodamine 123 and dichlorofluorescein fluorescence), caused alterations in overall intracellular redox status (as evidenced by NAD(+)/NADH ratios), and increased protein carbonyl formation. Furthermore, the antioxidant N-acetylcysteine completely prevented EA-induced oxidative stress and cytotoxicity. Whereas EA had no effect on mitochondrial energetics, it significantly altered cellular metabolic profile. To explore the physiological impact of these cellular events, we used an ex vivo mouse-isolated perfused lung model. Supplementation of perfusate with EA markedly affected lung mechanics and significantly increased lung permeability. The results of our combined genetic, pharmacological, and metabolic studies on multiple platforms suggest the importance of GST enzymes, specifically GST-π, in the cellular and whole lung response to acute oxidative and metabolic stress. These may have important clinical implications.

  5. Persisting in papyrus: size, oxidative stress, and fitness in freshwater organisms adapted to sustained hypoxia.

    Science.gov (United States)

    Joyner-Matos, Joanna; Chapman, Lauren J

    2013-08-01

    Aquatic hypoxia is generally viewed as stressful for aerobic organisms. However, hypoxia may also benefit organisms by decreasing cellular stress, particularly that related to free radicals. Thus, an ideal habitat may have the minimum O2 necessary to both sustain aerobic metabolism and reduce the need to scavenge free radicals and repair free radical damage. The ability of aquatic organisms to sustain aerobic metabolism relates in part to the ability to maximize gas diffusion, which can be facilitated by small body size when O2 uptake occurs across the body surface, by a large gill surface area, or by the ability to use atmospheric air. We use water-breathing organisms in chronically hypoxic papyrus (Cyperus papyrus) swamps of East Africa to test the hypothesis that cellular-level benefits of hypoxia may translate into increased fitness, especially for small organisms. A review of recent studies of fingernail clams (Sphaerium sp.) shows that clams living in sustained hypoxia have minimized oxidative stress and that these cellular-level benefits may lead to increased fitness. We suggest that organisms in the extreme conditions in the papyrus swamps provide a unique opportunity to challenge the conventional classification of hypoxic habitats as 'stressful' and normoxic habitats as 'optimal.' PMID:23558301

  6. Effects of physicochemical properties of zinc oxide nanoparticles on cellular uptake

    Science.gov (United States)

    Yu, J.; Baek, M.; Chung, H. E.; Choi, S. J.

    2011-07-01

    Zinc oxide (ZnO) nanoparticles have been used as a source of zinc, an essential trace element in food industry and also widely applied to various cosmetic products. However, there are few researches demonstrating that the cellular uptake behaviours of ZnO with respect to the physicochemical characteristics such as particle size and surface charge in human cells. In this study, we evaluated the cellular uptake of ZnO with two different sizes (20 and 70 nm) and different charges (positive and negative). Human lung epithelial cells were exposed to ZnO for a given time, and then the uptake amount of ZnO was measured with inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The results showed that the smaller sized ZnO could more easily enter the cells than the larger sized ZnO. In terms of surface charge, positively charged ZnO showed high cellular uptake compared to ZnO with negative charge. The internalization pathway of positively charged ZnO nanoparticles was determined to be primarily related to the energy-dependent endocytosis. It is, therefore, concluded that the particle size and surface charge of ZnO nanoparticles are critical factors influencing on their cellular uptake. Understanding the cellular uptake behaviours of nanoparticles with respect to physicochemical properties may be important to predict their toxicity potential on human.

  7. Change of immune indexes and oxidative stress state of children with recurrent respiratory tract infection

    Institute of Scientific and Technical Information of China (English)

    Wei-Qing Wu; Shu-Ping Liao; Xiao-Lan Lin; Qiong-Fang Huang

    2015-01-01

    Objective:To observe and analyze the change situation of immune indexes and oxidative stress state of children with recurrent respiratory tract infection.Methods:75 children with recurrent respiratory tract infection in our hospital from January 2014 to June 2015 were selected as observation group, 75 healthy children with health examination at the same time were selected as control group, then the immune indexes and oxidative stress state related serum indexes of two groups were detected,and the detection results of observation group with boys and girls, mild, moderate and severe disease were compared.Results: The cellular immune and erythrocyte immune and oxidative stress state related serum indexes of observation group were all worse than those of control group,and the detection results of observation group with mild, moderate and severe disease had obvious differences too, allP0.05.Conclusion:The change of immune indexes and oxidative stress state of children with recurrent respiratory tract infection are obvious,and the differences of children with mild, moderate and severe disease are obvious too,while the differences of boys and girls are not obvious.

  8. 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.

  9. 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.

  10. Thiopurines Induce Oxidative Stress in T-Lymphocytes: A Proteomic Approach

    Directory of Open Access Journals (Sweden)

    Misbah Misdaq

    2015-01-01

    Full Text Available Thiopurines are extensively used immunosuppressants for the treatment of inflammatory bowel disease (IBD. The polymorphism of thiopurine S-methyltransferase (TPMT influences thiopurine metabolism and therapy outcome. We used a TPMT knockdown (kd model of human Jurkat T-lymphocytes cells to study the effects of treatment with 6-mercaptopurine (6-MP and 6-thioguanine (6-TG on proteome and phosphoproteome. We identified thirteen proteins with altered expression and nine proteins with altered phosphorylation signals. Three proteins (THIO, TXD17, and GSTM3 with putative functions in cellular oxidative stress responses were altered by 6-TG treatment and another protein PRDX3 was differentially phosphorylated in TPMT kd cells. Furthermore, reactive oxygen species (ROS assay results were consistent with a significant induction of oxidative stress by both TPMT knockdown and thiopurine treatments. Immunoblot analyses showed treatment altered expression of key antioxidant enzymes (i.e., SOD2 and catalase in both wt and kd groups, while SOD1 was downregulated by 6-TG treatment and TPMT knockdown. Collectively, increased oxidative stress might be a mechanism involved in thiopurine induced cytotoxicity and adverse effects (i.e., hepatotoxicity and an antioxidant cotherapy might help to combat this. Results highlight the significance of oxidative stress in thiopurines’ actions and could have important implications for the treatment of IBD patients.

  11. Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer's disease.

    Science.gov (United States)

    Mota, Sandra I; Costa, Rui O; Ferreira, Ildete L; Santana, Isabel; Caldeira, Gladys L; Padovano, Carmela; Fonseca, Ana C; Baldeiras, Inês; Cunha, Catarina; Letra, Liliana; Oliveira, Catarina R; Pereira, Cláudia M F; Rego, Ana Cristina

    2015-07-01

    Oxidative stress and endoplasmic reticulum (ER) stress have been associated with Alzheimer's disease (AD) progression. In this study we analyzed whether oxidative stress involving changes in Nrf2 and ER stress may constitute early events in AD pathogenesis by using human peripheral blood cells and an AD transgenic mouse model at different disease stages. Increased oxidative stress and increased phosphorylated Nrf2 (p(Ser40)Nrf2) were observed in human peripheral blood mononuclear cells (PBMCs) isolated from individuals with mild cognitive impairment (MCI). Moreover, we observed impaired ER Ca2+ homeostasis and increased ER stress markers in PBMCs from MCI individuals and mild AD patients. Evidence of early oxidative stress defense mechanisms in AD was substantiated by increased p(Ser40)Nrf2 in 3month-old 3xTg-AD male mice PBMCs, and also with increased nuclear Nrf2 levels in brain cortex. However, SOD1 protein levels were decreased in human MCI PBMCs and in 3xTg-AD mice brain cortex; the latter further correlated with reduced SOD1 mRNA levels. Increased ER stress was also detected in the brain cortex of young female and old male 3xTg-AD mice. We demonstrate oxidative stress and early Nrf2 activation in AD human and mouse models, which fails to regulate some of its targets, leading to repressed expression of antioxidant defenses (e.g., SOD-1), and extending to ER stress. Results suggest markers of prodromal AD linked to oxidative stress associated with Nrf2 activation and ER stress that may be followed in human peripheral blood mononuclear cells.

  12. Salivary markers of oxidative stress in oral diseases

    Directory of Open Access Journals (Sweden)

    Ľubomíra eTóthová

    2015-10-01

    Full Text Available Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis.

  13. An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans

    Science.gov (United States)

    Kato, Masaomi; Kashem, Mohammed Abul; Cheng, Chao

    2016-01-01

    Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic – a mild and long-term – oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. PMID:27623524

  14. Signaling Pathways and Molecular Mechanisms of Oxidative Stress in Skeletal Muscle

    Institute of Scientific and Technical Information of China (English)

    Haibing HU; Wenjing LI; Zhi FANG; Bo XUE; Longzhou LIU; Ye YANG

    2015-01-01

    Oxidative stress is a major factor affecting animal health and production performance. This paper briefly introduced the signaling pathways(i.e. NF-κB signal-ing pathway, MAPK, AP-1 and PGC-1α) of oxidative stress and the main genes regulating the signals of oxidative stress in skeletal muscle, providing a theoretical basis for reducing oxidative stress damage.

  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. Oxidative stress treatment for clinical trials in neurodegenerative diseases.

    Science.gov (United States)

    Ienco, Elena Caldarazzo; LoGerfo, Annalisa; Carlesi, Cecilia; Orsucci, Daniele; Ricci, Giulia; Mancuso, Michelangelo; Siciliano, Gabriele

    2011-01-01

    Oxidative stress is a metabolic condition arising from imbalance between the production of potentially reactive oxygen species and the scavenging activities. Mitochondria are the main providers but also the main scavengers of cell oxidative stress. The role of mitochondrial dysfunction and oxidative stress in the pathogenesis of neurodegenerative diseases is well documented. Therefore, therapeutic approaches targeting mitochondrial dysfunction and oxidative damage hold great promise in neurodegenerative diseases. Despite this evidence, human experience with antioxidant neuroprotectants has generally been negative with regards to the clinical progress of disease, with unclear results in biochemical assays. Here we review the antioxidant approaches performed so far in neurodegenerative diseases and the future challenges in modern medicine. PMID:21422516

  17. Retinopathy of prematurity: an oxidative stress neonatal disease.

    Science.gov (United States)

    Stone, William L; Shah, Darshan; Hollinger, Shawn M

    2016-01-01

    Proteomics is the global study of proteins in an organism or a tissue/fluid and is clinically relevant since most disease states are accompanied by specific alterations in an organism's proteome. This review focuses on the application of proteomics to neonatology with particular emphasis on retinopathy of prematurity (ROP), which is a disease in which oxidative stress plays a key pathophysiological role. Oxidative stress is a physiologically relevant redox imbalance caused by an excess of reactive oxygen (ROS) or reactive nitrogen oxide species (RNOS). A major conclusion of this review is that proteomics may be the optimal technology for studying neonatal diseases such as ROP, particularly in the setting of a neonatal intensive care unit (NICU). Proteomics has already identified a number of ROP serum biomarkers. This review will also suggest novel therapeutic approaches to ROP and other neonatal oxidative stress diseases (NOSDs) based on a systems medicine approach. PMID:26709767

  18. Markers of Oxidative Stress and Neuroprogression in Depression Disorder.

    Science.gov (United States)

    Vaváková, Magdaléna; Ďuračková, Zdeňka; Trebatická, Jana

    2015-01-01

    Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed.

  19. [The development of therapeutics targeting oxidative stress in prostate cancer].

    Science.gov (United States)

    Shiota, Masaki; Yokomizo, Akira; Naito, Seiji

    2014-12-01

    Oxidative stress is caused by increased reactive-oxygen species (ROS) due to augmented ROS production and impaired anti-oxidative capacity. Recently, oxidative stress has been revealed to promote castration resistance via androgen receptor(AR)-dependent pathway such as AR overexpression, AR cofactor, and AR post-translational modification as well as AR-independent pathway, leading to the emergence of castration-resistant prostate cancer (CRPC). Therefore, antioxidants therapy using natural and chemical ROS scavengers and inhibitors of ROS production seems to be a promising therapy for CRPC as well as preventing castration resistance. However, at present, the application to therapeutics is limited. Therefore, further research on oxidative stress in prostate cancer, as well as on the development for clinical application would be needed.

  20. The Myoblast C2C12 Transfected with Mutant Valosin-Containing Protein Exhibits Delayed Stress Granule Resolution on Oxidative Stress.

    Science.gov (United States)

    Rodriguez-Ortiz, Carlos J; Flores, Julio C; Valenzuela, Joanna A; Rodriguez, Gema J; Zumkehr, Joannee; Tran, Diana N; Kimonis, Virginia E; Kitazawa, Masashi

    2016-06-01

    Valosin-containing protein (VCP) mutations cause inclusion body myopathy with Paget disease and frontotemporal dementia. However, the mechanisms by which mutant VCP triggers degeneration remain unknown. Here, we investigated the role of VCP in cellular stress and found that the oxidative stressor arsenite and heat shock-activated stress responses evident by T-intracellular antigen-1-positive granules in C2C12 myoblasts. Granules also contained phosphorylated transactive response DNA-binding protein 43, ubiquitin, microtubule-associated protein 1A/1B light chains 3, and lysosome-associated membrane protein 2. Mutant VCP produced more T-intracellular antigen-1-positive granules than wild-type in the postarsenite exposure period. Similar results were observed for other granule components, indicating that mutant VCP delayed clearance of stress granules. Furthermore, stress granule resolution was impaired on differentiated C2C12 cells expressing mutant VCP. To address whether mutant VCP triggers dysregulation of the stress granule pathway in vivo, we analyzed skeletal muscle of aged VCPR155H-knockin mice. We found significant increments in oxidated proteins but observed the stress granule markers RasGAP SH3-binding protein and phosphorylated eukaryotic translation initiation factor 2α unchanged. The mixed results indicate that mutant VCP together with aging lead to higher oxidative stress in skeletal muscle but were insufficient to disrupt the stress granule pathway. Our findings support that deficiencies in recovery from stressors may result in attenuated tolerance to stress that could trigger muscle degeneration. PMID:27106764

  1. Oxidative stress response in neural stem cells exposed to different superparamagnetic iron oxide nanoparticles

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    Pongrac IM

    2016-04-01

    Full Text Available Igor M Pongrac,1 Ivan Pavičić,2 Mirta Milić,2 Lada Brkič Ahmed,1 Michal Babič,3 Daniel Horák,3 Ivana Vinković Vrček,2 Srećko Gajović1 1School of Medicine, Croatian Institute for Brain Research, University of Zagreb, 2Institute for Medical Research and Occupational Health, Zagreb, Croatia; 3Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic Abstract: Biocompatibility, safety, and risk assessments of superparamagnetic iron oxide nanoparticles (SPIONs are of the highest priority in researching their application in biomedicine. One improvement in the biological properties of SPIONs may be achieved by different functionalization and surface modifications. This study aims to investigate how a different surface functionalization of SPIONs – uncoated, coated with D-mannose, or coated with poly-L-lysine – affects biocompatibility. We sought to investigate murine neural stem cells (NSCs as important model system for regenerative medicine. To reveal the possible mechanism of toxicity of SPIONs on NSCs, levels of reactive oxygen species, intracellular glutathione, mitochondrial membrane potential, cell-membrane potential, DNA damage, and activities of SOD and GPx were examined. Even in cases where reactive oxygen species levels were significantly lowered in NSCs exposed to SPIONs, we found depleted intracellular glutathione levels, altered activities of SOD and GPx, hyperpolarization of the mitochondrial membrane, dissipated cell-membrane potential, and increased DNA damage, irrespective of the surface coating applied for SPION stabilization. Although surface coating should prevent the toxic effects of SPIONs, our results showed that all of the tested SPION types affected the NSCs similarly, indicating that mitochondrial homeostasis is their major cellular target. Despite the claimed biomedical benefits of SPIONs, the refined determination of their effects on various cellular functions

  2. Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity.

    Science.gov (United States)

    Calabrese, Vittorio; Cornelius, Carolin; Mancuso, Cesare; Pennisi, Giovanni; Calafato, Stella; Bellia, Francesco; Bates, Timothy E; Giuffrida Stella, Anna Maria; Schapira, Tony; Dinkova Kostova, Albena T; Rizzarelli, Enrico

    2008-12-01

    The predominant molecular symptom of aging is the accumulation of altered gene products. Moreover, several conditions including protein, lipid or glucose oxidation disrupt redox homeostasis and lead to accumulation of unfolded or misfolded proteins in the aging brain. Alzheimer's and Parkinson's diseases or Friedreich ataxia are neurological diseases sharing, as a common denominator, production of abnormal proteins, mitochondrial dysfunction and oxidative stress, which contribute to the pathogenesis of these so called "protein conformational diseases". The central nervous system has evolved the conserved mechanism of unfolded protein response to cope with the accumulation of misfolded proteins. As one of the main intracellular redox systems involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins (Hsp) Hsp70 and heme oxygenase-1, as well as thioredoxin reductase and sirtuins. Nutritional studies show that ageing in animals can be significantly influenced by dietary restriction. Thus, the impact of dietary factors on health and longevity is an increasingly appreciated area of research. Reducing energy intake by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against disease. Genetics has revealed that ageing may be controlled by changes in intracellular NAD/NADH ratio regulating sirtuin, a group of proteins linked to aging, metabolism and stress tolerance in several organisms. Recent findings suggest that several phytochemicals exhibit biphasic dose responses on cells with low doses activating signaling pathways that result in increased expression of vitagenes encoding survival proteins, as in the case of the Keap1/Nrf2/ARE pathway activated by curcumin and NAD/NADH-sirtuin-1 activated by resveratrol. Consistently, the neuroprotective roles of dietary antioxidants including

  3. Evaluation of parameters of oxidative stress after in vitro exposure to FMCW- and CDMA-modulated radiofrequency radiation fields.

    Science.gov (United States)

    Hook, Graham J; Spitz, Douglas R; Sim, Julia E; Higashikubo, Ryuji; Baty, Jack D; Moros, Eduardo G; Roti Roti, Joseph L

    2004-11-01

    The goal of this study was to determine whether radiofrequency (RF) radiation is capable of inducing oxidative stress or affecting the response to oxidative stress in cultured mammalian cells. The two types of RF radiation investigated were frequency-modulated continuous-wave with a carrier frequency of 835.62 MHz (FMCW) and code division multiple access centered on 847.74 MHz (CDMA). To evaluate the effect of RF radiation on oxidative stress, J774.16 mouse macrophage cells were stimulated with gamma-interferon (IFN) and bacterial lipopolysaccharide (LPS) prior to exposure. Cell cultures were exposed for 20-22 h to a specific absorption rate of 0.8 W/kg at a temperature of 37.0 +/- 0.3 degrees C. Oxidative stress was evaluated by measuring oxidant levels, antioxidant levels, oxidative damage and nitric oxide production. Oxidation of thiols was measured by monitoring the accumulation of glutathione disulfide (GSSG). Cellular antioxidant defenses were evaluated by measuring superoxide dismutase activity (CuZnSOD and MnSOD) as well as catalase and glutathione peroxidase activity. The trypan blue dye exclusion assay was used to measure any changes in viability. The results of these studies indicated that FMCW- and CDMA-modulated RF radiation did not alter parameters indicative of oxidative stress in J774.16 cells. FMCW- and CDMA-modulated fields did not alter the level of intracellular oxidants, accumulation of GSSG or induction of antioxidant defenses in IFN/LPS-stimulated cells. Consistent with the lack of an effect on oxidative stress parameters, no change in toxicity was observed in J774.16 cells after either optimal (with or without inhibitors of nitric oxide synthase) or suboptimal stimulation. PMID:15624304

  4. Characterization of RNA damage under oxidative stress in Escherichia coli

    Science.gov (United States)

    Liu, Min; Gong, Xin; Alluri, Ravi Kumar; Wu, Jinhua; Sablo, Tene’; Li, Zhongwei

    2012-01-01

    We have examined the level of 8-hydroxyguanosine (8-oxo-G), an oxidized form of guanosine, in RNA in Escherichia coli under normal and oxidative stress conditions. The level of 8-oxo-G in RNA rises rapidly and remains high for hours in response to hydrogen peroxide (H2O2) challenge in a dose-dependent manner. H2O2 induced elevation of 8-oxo-G content is much higher in RNA than that of 8-hydroxydeoxyguanosine (8-oxo-dG) in DNA. Under normal conditions, the 8-oxo-G level is low in RNA isolated from the ribosome and it is nearly three times higher in non-ribosomal RNAs. In contrast, 8-oxo-G generated by a short exposure to H2O2 is almost equally distributed in various RNA species, suggesting that although ribosomal RNAs are normally less oxidized, they are not protected against exogenous H2O2. Interestingly, highly folded RNA is not protected from oxidation because 8-oxo-G generated by H2O2 treatment in vitro increases to approximately the same levels in tRNA and rRNA in both native and denatured forms. Lastly, increased RNA oxidation is closely associated with cell death by oxidative stress. Our data suggests that RNA is a primary target for reactive oxygen species and RNA oxidation is part of the paradox that cells have to deal with under oxidative stress. PMID:22718628

  5. Selenium-Dependent Regulation of Oxidative Stress and Immunity in Periparturient Dairy Cattle

    Directory of Open Access Journals (Sweden)

    Lorraine M. Sordillo

    2013-01-01

    Full Text Available Uncontrolled or impaired immune and inflammatory responses in periparturient dairy cows are associated with increased incidence and severity of infectious diseases. The progressive development of oxidative stress during the transition from late gestation to peak lactation is thought to be a significant underlying factor leading to dysfunctional immune cell responses. Certain trace minerals, such as selenium (Se, can ameliorate oxidative stress and reduce the severity of several economically important diseases in dairy cattle including mastitis and metritis. Many of the health benefits of Se can be attributed to the antioxidant functions of selenoproteins. Changes in selenoprotein activity as a consequence of Se nutritional status can directly alter a number of critical cellular functions involved in the inflammatory response. A better understanding of how Se can optimize immune cell responses may facilitate the design of nutritional regimes that will reduce health disorders during the periparturient period.

  6. Altered Gene Expression, Mitochondrial Damage and Oxidative Stress: Converging Routes in Motor Neuron Degeneration

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    Luisa Rossi

    2012-01-01

    Full Text Available Motor neuron diseases (MNDs are a rather heterogeneous group of diseases, with either sporadic or genetic origin or both, all characterized by the progressive degeneration of motor neurons. At the cellular level, MNDs share features such as protein misfolding and aggregation, mitochondrial damage and energy deficit, and excitotoxicity and calcium mishandling. This is particularly well demonstrated in ALS, where both sporadic and familial forms share the same symptoms and pathological phenotype, with a prominent role for mitochondrial damage and resulting oxidative stress. Based on recent data, however, altered control of gene expression seems to be a most relevant, and previously overlooked, player in MNDs. Here we discuss which may be the links that make pathways apparently as different as altered gene expression, mitochondrial damage, and oxidative stress converge to generate a similar motoneuron-toxic phenotype.

  7. Nitric Oxide Signaling in Plant Responses to Abiotic Stresses

    Institute of Scientific and Technical Information of China (English)

    Weihua Qiao; LiuMin Fan

    2008-01-01

    Nitric oxide (NO) plays important roles in diverse physiological processes In plants. NO can provoke both beneficial and harmful effects, which depend on the concentration and location of NO in plant cells. This review is focused on NO synthesis and the functions of NO in plant responses to abiotic environmental stresses. Abiotic stresses mostly induce NO production in plants. NO alleviates the harmfulness of reactive oxygen species, and reacts with other target molecules, and regulates the expression of stress responsive genes under various stress conditions.

  8. Evaluation of protein and lipid oxidative stress in the patients with postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Banu Çavdaroğlu

    2014-03-01

    Full Text Available Objective: Oxidative stress may change cellular function in multiple pathological conditions, including osteoporosis. We aimed to determine malondialdehyde (MDA levels, advanced oxidation protein pruducts (AOPP, levels end products of protein oxidation, thiol as known antioxidant, serum paraoxonase 1 (PON1 activities as known lipid antioxidant, induced by reactive oxygen species (ROS for evaluating oxidative stress in osteoporotic patients. Methods: 59 patients diagnosed with postmenopaual osteoporosis were included in the study and compared with 21 healthy controls. Serum AOPP, MDA, thiol levels and PON1 activity were measured according to an enzymatic spectrophotometric method. Results: The serum MDA, AOPP, and thiol levels was significantly higher in the patient group than controls (p<0.05. PON1 activity was found lower in the patients group than the control group. Conclusion: Increased ROS levels in osteoporotic patients may result in a pro-oxidation environment, which in turn could result in increased MDA, AOPP. As a result, lipid peroxidation and protein oxidation may have a role in the pathogenesis of the osteoporotic patients.

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

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    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.

  10. [Oxidative stress and inflammation: hypothesis for the mechanism of aging].

    Science.gov (United States)

    Tsubota, Kazuo

    2007-03-01

    Oxidative stress due to free radicals is related to the pathogenesis of many chronic disorders including cancer, inflammation, and neurological diseases. Oxidative stress such as aging and light exposure is also considered to be associated with age-related macular degeneration and cataract. The ocular surface is chronically exposed to oxidative stress including ultraviolet light, the oxygen in air, and changes in oxygen pressure due to blinking. We demonstrated that a rat dry eye model with a jogging board showed corneal epithelial disoders and elevated levels of oxidative stress, suggesting that the pathogenesis of epithelial disorders in dry eye with low frequency of blinking is related to oxidative stress. Next, using a model of laser-induced choroidal neovascularization (CNV), we showed that angiotensin receptormediated inflammation is required for the development of CNV. We also demonstrated that mice deficient in superoxide dismutase (SOD) showed typical clinical features of AMD. Finally, we proposed our thoughts about regenerative medicine, that is, to maintain quiescent stem cells, we have to regulate the aging of stem cells. PMID:17402562

  11. A study of oxidative stress in paucibacillary and multibacillary leprosy

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    Jyothi P

    2008-01-01

    Full Text Available Background: The study and assessment of oxidative stress plays a significant role in the arena of leprosy treatment. Once the presence of oxidative stress is proved, antioxidant supplements can be provided to reduce tissue injury and deformity. Aim: To study oxidative stress in paucibacillary (PB and multibacillary (MB leprosy and to compare it with that in a control group. Methods: Fifty-eight untreated leprosy patients (23 PB and 35 MB cases were studied and compared with 58 healthy controls. Superoxide dismutase (SOD level as a measure of antioxidant status; malondialdehyde (MDA level, an indicator of lipid peroxidation; and MDA/SOD ratio, an index of oxidative stress were estimated in the serum. Results: The SOD level was decreased in leprosy patients, especially in MB leprosy. The MDA level was increased in PB and MB leprosy. The MDA/SOD ratio was significantly elevated in MB patients. There was a steady increase in this ratio along the spectrum from tuberculoid to lepromatous leprosy (LL. Conclusion: There is increased oxidative stress in MB leprosy, especially in LL. This warrants antioxidant supplements to prevent tissue injury.

  12. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  13. Relationship of oxidative stress with male infertility in sulfur mustard-exposed injuries

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    Eisa Tahmasbpour Marzony

    2016-03-01

    Full Text Available Sulfur mustard (SM is a cytotoxic and chemical agent that targets different tissues such as reproductive system. SM causes a wide variety of pathological effects on reproductive system such as disturbance in reproductive hormones, testis atrophy, spermatogenesis deficiency, low quality of sperm and fertility problem. However, molecular and cellular mechanisms of its adverse effects are still not well known. General events such as tissue damage, inflammation, DNA alkylation, cell membrane defects, apoptosis and cell death are observed frequently in SM-exposed subjects. Oxidative stress (OS and antioxidants depletion induced by SM seem to be one of the main factors that lead to low sperm quality and male infertility among exposed patients. It is believed that SM can trigger several molecular and cellular pathways linked to OS and inflammation in reproductive system that can cause impaired spermatogenesis, sperm apoptosis and poor sperm quality as well as loss of tissue structure and function. Identification of these signaling pathways and molecules gives us valuable information regarding the mechanisms of SM effect on reproductive dysfunction and the way for developing a better clinical treatment. Therefore, in this review we aimed to discuss the proposed cellular and molecular mechanisms of SM effect on reproductive system, the significance of oxidative stress and the mechanisms by which SM induces OS and antioxidants depletion in SM exposed men.

  14. Diaphragmatic Breathing Reduces Exercise-Induced Oxidative Stress

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    Daniele Martarelli

    2011-01-01

    Full Text Available Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1 h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals.

  15. Causes and consequences of oxidative stress in spermatozoa.

    Science.gov (United States)

    Aitken, Robert John; Gibb, Zamira; Baker, Mark A; Drevet, Joel; Gharagozloo, Parviz

    2015-02-01

    Spermatozoa are highly vulnerable to oxidative attack because they lack significant antioxidant protection due to the limited volume and restricted distribution of cytoplasmic space in which to house an appropriate armoury of defensive enzymes. In particular, sperm membrane lipids are susceptible to oxidative stress because they abound in significant amounts of polyunsaturated fatty acids. Susceptibility to oxidative attack is further exacerbated by the fact that these cells actively generate reactive oxygen species (ROS) in order to drive the increase in tyrosine phosphorylation associated with sperm capacitation. However, this positive role for ROS is reversed when spermatozoa are stressed. Under these conditions, they default to an intrinsic apoptotic pathway characterised by mitochondrial ROS generation, loss of mitochondrial membrane potential, caspase activation, phosphatidylserine exposure and oxidative DNA damage. In responding to oxidative stress, spermatozoa only possess the first enzyme in the base excision repair pathway, 8-oxoguanine DNA glycosylase. This enzyme catalyses the formation of abasic sites, thereby destabilising the DNA backbone and generating strand breaks. Because oxidative damage to sperm DNA is associated with both miscarriage and developmental abnormalities in the offspring, strategies for the amelioration of such stress, including the development of effective antioxidant formulations, are becoming increasingly urgent. PMID:27062870

  16. Evaluation of Oxidative Stress in Colorectal Cancer Patients

    Institute of Scientific and Technical Information of China (English)

    DONG CHANG; FAN WANG; YA-SHUANG ZHAO; HONG-ZHI PAN

    2008-01-01

    To evaluate the oxidative stress in patients with colorectal cancer and to investigate the relationship between oxidative stress and colorectal cancer. Methods Seventy-six subjects were divided into two groups (36 colorectal cancerpatients as the study group and 40 normal healthy individuals as the control group). Their protein oxidation, DNA damage, lipid peroxidation and antioxidants, vitamin C, vitamin E, glutathione (GSH), and antioxidative enzymes in serum were detected. Results The levels of protein carbonyl and advanced oxidation protein products (AOPP) were significantly higher in the study group than in the control group (P<0.01). Serum 8-OHdG was significantly increased in the study group compared to the control group (P<0.01). However, the mean serum level of MDA and conjugated diene was lower in the study group than in the control group (P<0.01). The activity of antioxidative enzymes was significantly decreased in the study group compared to the control group (P<0.01). Serum vitamins C and E concentrations were significantly reduced in the study group compared to the control group (P<0.01). Conclusion Colorectal cancer is associated with oxidative stress, and assessment of oxidative stress and given antioxidants is important for the treatment and prevention of colorectal cancer.

  17. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    Directory of Open Access Journals (Sweden)

    Giovanna Romano

    Full Text Available Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms.

  18. Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus.

    Science.gov (United States)

    Romano, Giovanna; Costantini, Maria; Buttino, Isabella; Ianora, Adrianna; Palumbo, Anna

    2011-01-01

    Diatoms are ubiquitous and abundant primary producers that have been traditionally considered as a beneficial food source for grazers and for the transfer of carbon through marine food webs. However, many diatom species produce polyunsaturated aldehydes that disrupt development in the offspring of grazers that feed on these unicellular algae. Here we provide evidence that production of the physiological messenger nitric oxide increases after treatment with the polyunsaturated aldehyde decadienal in embryos of the sea urchin Paracentrotus lividus. At high decadienal concentrations, nitric oxide mediates initial apoptotic events leading to loss of mitochondrial functionality through the generation of peroxynitrite. At low decadienal concentrations, nitric oxide contributes to the activation of hsp70 gene expression thereby protecting embryos against the toxic effects of this aldehyde. When nitric oxide levels were lowered by inhibiting nitric oxide synthase activity, the expression of hsp70 in swimming blastula decreased and the proportion of abnormal plutei increased. However, in later pluteus stages nitric oxide was no longer able to exert this protective function: hsp70 and nitric oxide synthase expression decreased with a consequent increase in the expression of caspase-8. Our findings that nitric oxide production increases rapidly in response to a toxic exogenous stimulus opens new perspectives on the possible role of this gas as an important messenger to environmental stress in sea urchins and for understanding the cellular mechanisms underlying toxicity during diatom blooms. PMID:22022485

  19. 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. PMID:26596837

  20. The role of nanosecond electric pulse-induced mechanical stress in cellular nanoporation

    Science.gov (United States)

    Roth, Caleb C.

    Background: Exposures of cells to very short (less than 1 microsecond) electric pulses in the megavolt/meter range have been shown to cause a multitude of effects, both physical and molecular in nature. Physically, nanosecond electrical pulse exposure can disrupt the plasma membrane, leading to a phenomenon known as nanoporation. Nanoporation is the production of nanometer sized holes (less than 2 nanometers in diameter) that can persist for up to fifteen minutes, allowing the flow of ions into and out of the cell. Nanoporation can lead to secondary physical effects, such as cellular swelling, shrinking and blebbing. Molecularly, nanosecond electrical pulses have been shown to activate signaling pathways, produce oxidative stress, stimulate hormone secretion and induce both apoptotic and necrotic death. The mechanism by which nanosecond electrical pulses cause molecular changes is unknown; however, it is thought the flow of ions, such as calcium, into the cell via nanopores, could be a major cause. The ability of nanosecond electrical pulses to cause membranes to become permeable and to induce apoptosis makes the technology a desirable modality for cancer research; however, the lack of understanding regarding the mechanisms by which nanosecond electrical pulses cause nanoporation impedes further development of this technology. This dissertation documents the genomic and proteomic responses of cells exposed to nanosecond electrical pulses and describes in detail the biophysical effects of these electrical pulses, including the demonstration for the first time of the generation of acoustic pressure transients capable of disrupting plasma membranes and possibly contributing to nanoporation. Methods: Jurkat, clone E6-1 (human lymphocytic cell line), U937 (human lymphocytic cell line), Chinese hamster ovarian cells and adult primary human dermal fibroblasts exposed to nanosecond electrical pulses were subjected to a variety of molecular assays, including flow cytometry

  1. Administration with Bushenkangshuai Tang alleviates UV irradiation- and oxidative stress-induced lifespan defects in nematode Caenorhabditis elegans

    Institute of Scientific and Technical Information of China (English)

    Qi RUI; Qin LU; Dayong WANG

    2009-01-01

    During normal metabolism, oxidative bypro-ducts will inevitably generate and damage molecules thereby impairing their biological functions, including the is a traditional Chinese medicine widely used for clini-cally treating premature ovarian failure. In the present study, BT administration at high concentrations signifi-cantly increased lifespan, slowed aging-related decline, and delayed accumulation of aging-related cellular damage in wild-type Caenorhabditis elegans. BT admin-istration could further largely alleviate the aging defects induced by UV and oxidative stresses, and BT administra-tion at different concentrations could largely rescue the aging defects in mev-1 mutant animals. The protective effects of BT administration on aging process were at least partially dependent on the Ins/IGF-like signaling pathway. Moreover, BT administration at different concentrations obviously altered the expression patterns of antioxidant genes and suppressed the severe stress responses induced by UV and oxidative stresses, suggesting that BT-induced tolerance to UV or oxidative stress might result from reactive oxygen species scavenging. BT administration during development was not necessarily a requirement for UV and oxidative stress resistance, and the concentrations of administrated BT examined were not toxic for nematodes. Therefore, BT administration could effectively retrieve the aging defects induced by UV irradiation and oxidative stress in Caenorhabditis elegans.

  2. Feedbacks and tipping points in organismal response to oxidative stress.

    Science.gov (United States)

    Klanjscek, Tin; Muller, Erik B; Nisbet, Roger M

    2016-09-01

    Biological feedbacks play a crucial role in determining effects of toxicants, radiation, and other environmental stressors on organisms. Focusing on reactive oxygen species (ROS) that are increasingly recognized as a crucial mediator of many stressor effects, we investigate how feedback strength affects the ability of organisms to control negative effects of exposure. We do this by developing a general theoretical framework for describing effects of a wide range of stressors and species. The framework accounts for positive and negative feedbacks representing cellular processes: (i) production of ROS due to metabolism and the stressor, (ii) ROS reactions with cellular compounds that cause damage, and (iii) cellular control of both ROS and damage. We suggest functional forms that capture generic properties of cellular control mechanisms constituting the feedbacks, assess stability of equilibrium states in the resulting models, and investigate tipping points at which cellular control breaks down causing unregulated increase of ROS and damage. Depending on the chosen functional forms, the models can have zero, one, or two positive steady states; except in one singular case, the steady state with lowest values of ROS and damage is locally stable. We found two types of tipping points: those induced by changes in the parameters (including the stressor intensity), and those induced by the history of exposure, i.e. ROS and damage levels. The relatively simple models effectively describe several patterns of cellular responses to stress, such as the covariation of ROS and damage, the break-down of cellular control leading to explosion of ROS and/or damage, increase in damage even when ROS is (near)-constant, and the effects of exposure history on the ability of the cell to handle additional stress. The models quantify dynamics of cellular control, and could therefore be used to estimate the metabolic costs of stress and help integrate them into models that use energetic

  3. Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease.

    Science.gov (United States)

    Sung, Chih-Chien; Hsu, Yu-Chuan; Chen, Chun-Chi; Lin, Yuh-Feng; Wu, Chia-Chao

    2013-01-01

    Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

  4. Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Chih-Chien Sung

    2013-01-01

    Full Text Available Patients with chronic kidney disease (CKD have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate, deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  7. Development and in vitro assay of oxidative stress modifying formulations for wound healing promotion.

    Science.gov (United States)

    Atrux-Tallau, Nicolas; Callejon, Sylvie; Migdal, Camille; Padois, Karine; Bertholle, Valérie; Denis, Alain; Chavagnac-Bonneville, Marlène; Haftek, Marek; Falson, Françoise; Pirot, Fabrice

    2011-05-01

    Often presented as metabolism byproducts, reactive oxygen species are linked to detrimental effects such as chronic wound, mutagenesis, cancer and skin ageing. However, recent in vitro and in vivo observations suggest that ROS, and mainly hydrogen peroxide, interfere with cell signaling acting like second messenger and inducing adaptive responses. This is particularly observed in skin wound healing where cells are exposed to H₂O₂ following injury. In this study, we developed and characterized an innovative formulation producing H₂O₂ at low concentrations, in order to mimic physiological inflammation phase. Then, this pro-oxidative formulation (CAM-GOx) was assayed in vitro on keratinocytes cell culture, compared to the blank formulation (CAM) and the anti-oxidative formulation (CAM-CAT) to assess whether oxidative stress was implied or not in cellular responses.

  8. 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.

  9. 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.

  10. Fluorescence studies on radiation oxidative damage to membranes with implications to cellular radiosensitivity

    Indian Academy of Sciences (India)

    K P Mishra

    2002-12-01

    Radiation oxidative damage to plasma membrane and its consequences to cellular radiosensitivity have received increasing attention in the past few years. This review gives a brief account of radiation oxidative damage in model and cellular membranes with particular emphasis on results from our laboratory. Fluorescence and ESR spin probes have been employed to investigate the structural and functional alterations in membranes after g-irradiation. Changes in the lipid bilayer in irradiated unilamellar liposomes prepared from egg yolk lecithin (EYL) were measured by using diphenylhexatriene (DPH) as a probe. The observed increase in DPH polarization and decrease in fluorescence intensity after g-irradiation of liposomes imply radiationinduced decrease in bilayer fluidity. Inclusion of cholesterol in liposome was found to protect lipids against radiation damage, possibly by modulation of bilayer organization e.g. lipid packing. Measurements on dipalmitoyl phosphatidylcholine (DPPC) liposomes loaded with 6-carboxyfluorescein (CF) showed radiation dose-dependent release of the probe indicating radiation-induced increased permeability. Changes in plasma membrane permeability of thymocytes were monitored by fluorescein diacetate (FDA) and induced intracellular reactive oxygen species (ROS) were determined by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA). Results suggest a correlation between ROS generation and membrane permeability changes induced by radiation within therapeutic doses (0-10 Gy). It is concluded that increase in membrane permeability was the result of ROS-mediated oxidative reactions, which might trigger processes leading to apoptotic cell death after radiation exposure.

  11. Inflammation and Oxidative Stress in Obesity-Related Glomerulopathy

    Directory of Open Access Journals (Sweden)

    Jinhua Tang

    2012-01-01

    Full Text Available Obesity-related glomerulopathy is an increasing cause of end-stage renal disease. Obesity has been considered a state of chronic low-grade systemic inflammation and chronic oxidative stress. Augmented inflammation in adipose and kidney tissues promotes the progression of kidney damage in obesity. Adipose tissue, which is accumulated in obesity, is a key endocrine organ that produces multiple biologically active molecules, including leptin, adiponectin, resistin, that affect inflammation, and subsequent deregulation of cell function in renal glomeruli that leads to pathological changes. Oxidative stress is also associated with obesity-related renal diseases and may trigger the initiation or progression of renal damage in obesity. In this paper, we focus on inflammation and oxidative stress in the progression of obesity-related glomerulopathy and possible interventions to prevent kidney injury in obesity.

  12. Impacts of Oxidative Stress and Antioxidants on Semen Functions

    Directory of Open Access Journals (Sweden)

    Amrit Kaur Bansal

    2011-01-01

    Full Text Available Oxidative stress (OS has been considered a major contributory factor to the infertility. Oxidative stress is the result of imbalance between the reactive oxygen species (ROS and antioxidants in the body which can lead to sperm damage, deformity, and eventually male infertility. Although high concentrations of the ROS cause sperm pathology (ATP depletion leading to insufficient axonemal phosphorylation, lipid peroxidation, and loss of motility and viability but, many evidences demonstrate that low and controlled concentrations of these ROS play an important role in sperm physiological processes such as capacitation, acrosome reaction, and signaling processes to ensure fertilization. The supplementation of a cryopreservation extender with antioxidant has been shown to provide a cryoprotective effect on mammalian sperm quality. This paper reviews the impacts of oxidative stress and reactive oxygen species on spermatozoa functions, causes of ROS generation, and antioxidative strategies to reduce OS. In addition, we also highlight the emerging concept of utilizing OS as a tool of contraception.

  13. Engrailed Homeoprotein Protects Mesencephalic Dopaminergic Neurons from Oxidative Stress

    Science.gov (United States)

    Rekaik, Hocine; Blaudin de Thé, François-Xavier; Fuchs, Julia; Massiani-Beaudoin, Olivia; Prochiantz, Alain; Joshi, Rajiv L.

    2016-01-01

    Summary Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress, and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed1 heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks, and protects dopaminergic neurons against apoptosis. PMID:26411690

  14. Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats

    Science.gov (United States)

    Naderi, Roya; Mohaddes, Gisou; Mohammadi, Mustafa; Ghaznavi, Rana; Ghyasi, Rafigheh; Vatankhah, Amir Mansour

    2015-01-01

    Purpose: Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. Methods: 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were subjected to voluntary running wheel exercise for 6 weeks. At the end of six weeks blood and heart tissue samples were collected and used for determination of antioxidant enzymes (including SOD, GPX and CAT activities) and MDA level. Results: Exercise significantly reduced MDA levels both in the heart tissue (pdiabetic rats. It also accentuates activities of SOD, GPX and CAT. Therefore, it may be considered a useful tool for the reduction of oxidative stress in diabetes. PMID:26236662

  15. Markers of oxidative stress in hepatopancreas of crayfish (Orconectes limosus, raf) experimentally exposed to nanosilver.

    Science.gov (United States)

    Strużyński, Witold; Dąbrowska-Bouta, Beata; Grygorowicz, Tomasz; Ziemińska, Elżbieta; Strużyńska, Lidia

    2014-11-01

    Silver nanoparticles, chemically neutral particles in the size range of 1-100 nm, express strong antimicrobial activity and therefore have a broad range of applications. The increased use of consumer products with nanosilver (nanoAg) may result in its release into the environment, and may particularly affect aquatic systems. The mechanisms of the harmful effects of nanoAg against aquatic organisms are unclear. Therefore, in the present study we investigate the pro-oxidative potential of these nanoparticles in experimentally exposed crayfish Orconectes limosus. Markers of oxidative stress and parameters of the antioxidant cell defense system such as total glutathione, glutathione reductase and the level of sulfhydryl groups were examined in the hepatopancreas of both sexes of O. limosus collected seasonally from Białe Lake (Poland) and subsequently exposed to nanoAg particles for 2 weeks. Exposure to nanoAg led to a high concentration-dependent increase in the rate of lipid peroxidation and a decrease of protein-bound SH groups which indicates protein oxidation. These markers of oxidative stress were accompanied by decreased levels of thiols and reduced activity of glutathione reductase. These results indicate a deficiency of reduced glutathione and suggest that the exposed organisms have less efficient antioxidative mechanisms available to counter ROS-mediated cellular stress. Furthermore, we find that confocal microscopy is of limited utility in monitoring the presence of silver nanoparticles in tissues of exposed crayfish.

  16. Cooperative function of antioxidant and redox systems against oxidative stress in male reproductive tissues

    Institute of Scientific and Technical Information of China (English)

    JunichiFujii; YoshihitoIuchi; ShingoMatsuki; TatsuyaIshii

    2003-01-01

    Reactive oxygen species (ROS) are produced under oxidative stress, such as high oxygen concentration and during the metabolic consumption of oxygen molecules. Male reproductive tissues appear to be continuously exposed to ROS produced by active metabolism. In addition, spermatozoa must pass through a high oxygen environ-ment during the mating process. Thus, to maintain viable reproductive ability, a protective mechanism against oxida-tive stress is of importance. Here, we overview our current understanding of the cooperative function of antioxidative and redox systems that are involved in male fertility. Superoxide dismutase and glutathione peroxidase are major enzymes that scavenge harmful ROS in male reproductive organs. In turn, glutathione and thioredoxin systems constitute the main redox systems that repair oxidized and damaged molecules and also play a role in regulating a variety of cellular functions. While glutathione functions as an antioxidant by donating electrons to glutathione peroxidase and thioredoxin donates electrons to peroxiredoxin as a counterpart of glutathione peroxidase. In addition,aldo-keto reductases, which detoxify carbonyl compounds produced by oxidative stress, are present at high levels in the epithelia of the genital tract and Sertoli cells of the testis. Since these systems are involved in cross-talk, a comprehensive understanding will be required to maintain the physiological functions of male reproductive system.( Asian J Andro12003 Sep; 5: 231-242)

  17. Tobacco smoking and oxidative stress to DNA

    DEFF Research Database (Denmark)

    Ellegaard, Pernille K; Poulsen, Henrik E

    2016-01-01

    studies on 3668 persons using ELISA methodology showed a non-significant effect of 8.7% [95% CL -1.2;18.6]. Tobacco smoke induces oxidative damage to DNA; however, this is not detected with ELISA methodology. Currently, the use of existing ELISA methodology to measure urinary excretion of 8-oxo-7...

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

    Directory of Open Access Journals (Sweden)

    Taysa Ribeiro Schalcher

    2013-09-01

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

  19. Selective induction of oxidative stress in cancer cells via synergistic combinations of agents targeting redox homeostasis.

    Science.gov (United States)

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2015-07-01

    Cancer cell resistance to chemotherapy is still a heavy burden that impairs the response of many cancer patients to conventional chemotherapy. Using drug combinations is one therapeutic approach to overcome the developing resistance to any one drug. Oxidative stress is now a generally regarded hallmark of cancer that can be one approach to selectively target cancer cells while sparing normal cells. With the aim of increasing oxidative stress in cancer cells to a lethal set point, we have generated and combined several series of redox active compounds that act at different points of the cellular oxidative cascade. The premise of such combinations is to deplete of endogenous antioxidant defence proteins (e.g., Glutathione) while concomitantly increasing the generation of ROS via metal redox recycling and Fenton chemistry which eventually leads to the disruption of cellular redox homeostasis and induction of cell death. Through this approach, we have identified highly synergistic combinations of two distinctive classes of compounds (Azines and Copper(II) complexes of 2-pyridyl ketone thiosemicarbazones) which are capable of eliminating cancer cells without concomitant increase in toxicity toward normal cells. In one of our most potent combinations, a combination index (CI) value of 0.056 was observed, representing a 17 fold enhancement in activity beyond additive effects. Such new combination regimen of redox active compounds can be one step closer to potentially safer low dose chemotherapy. PMID:26022081

  20. Work at high altitude and oxidative stress: antioxidant nutrients.

    Science.gov (United States)

    Askew, E W

    2002-11-15

    A significant portion of the world's geography lies above 10,000 feet elevation, an arbitrary designation that separates moderate and high altitude. Although the number of indigenous people living at these elevations is relatively small, many people travel to high altitude for work or recreation, exposing themselves to chronic or intermittent hypoxia and the associated risk of acute mountain sickness (AMS) and less frequently, high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The symptoms of AMS (headache, nausea, anorexia, fatigue, lassitude) occur in those who travel too high, too fast. Some investigators have linked the development of these symptoms with the condition of altered blood-brain barrier permeability, possibly related to hypoxia induced free radical formation. The burden of oxidative stress increases during the time spent at altitude and may even persist for some time upon return to sea level. The physiological and medical consequences of increased oxidative stress engendered by altitude is unclear; indeed, hypoxia is believed to be the trigger for the cascade of signaling events that ultimately leads to adaptation to altitude. These signaling events include the generation of reactive oxygen species (ROS) that may elicit important adaptive responses. If produced in excess, however, these ROS may contribute to impaired muscle function and reduced capillary perfusion at altitude or may even play a role in precipitating more serious neurological and pulmonary crisis. Oxidative stress can be observed at altitude without strenuous physical exertion; however, environmental factors other than hypoxia, such as exercise, UV light exposure and cold exposure, can also contribute to the burden. Providing antioxidant nutrients via the diet or supplements to the diet can reduce oxidative stress secondary to altitude exposure. In summary, the significant unanswered question concerning altitude exposure and antioxidant supplementation is

  1. Oxidized phosphatidylcholines in membrane-level cellular signaling: from biophysics to physiology and molecular pathology.

    Science.gov (United States)

    Volinsky, Roman; Kinnunen, Paavo K J

    2013-06-01

    The oxidation of lipids has been shown to impact virtually all cellular processes. The paradigm has been that this involvement is due to interference with the functions of membrane-associated proteins. It is only recently that methodological advances in molecular-level detection and identification have begun to provide insights into oxidative lipid modification and its involvement in cell signaling as well as in major diseases and inflammation. Extensive evidence suggests a correlation between lipid peroxidation and degenerative neurological diseases such as Parkinson's and Alzheimer's, as well as type 2 diabetes and cancer. Despite the obvious relevance of understanding the molecular basis of the above ailments, the exact modes of action of oxidized lipids have remained elusive. In this minireview, we summarize recent findings on the biophysical characteristics of biomembranes following oxidative derivatization of their lipids, and how these altered properties are involved in both physiological processes and major pathological conditions. Lipid-bearing, oxidatively truncated and functionalized acyl chains are known to modify membrane bulk physical properties, such as thermal phase behavior, bilayer thickness, hydration and polarity profiles, as manifest in the altered structural dynamics of lipid bilayers, leading to augmented membrane permeability, fast lipid transbilayer diffusion (flip-flop), loss of lipid asymmetry (scrambling) and phase segregation (the formation of 'rafts'). These changes, together with the generated reactive lipid derivatives, can be further expected to interfere with lipid-protein interactions, influencing metabolic pathways, causing inflammation, the execution phase in apoptosis and initiating pathological processes. PMID:23506295

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

    Science.gov (United States)

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked: considerable variation in oxidative stress resistance exists among and within species and ...

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

    Directory of Open Access Journals (Sweden)

    Masaaki Adachi

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

  4. Increased DNA damage and oxidative stress among silver jewelry workers.

    Science.gov (United States)

    Aktepe, Necmettin; Kocyigit, Abdurrahim; Yukselten, Yunus; Taskin, Abdullah; Keskin, Cumali; Celik, Hakim

    2015-04-01

    Silver has long been valued as a precious metal, and it is used to make ornaments, jewelry, high-value tableware, utensils, and currency coins. Human exposures to silver and silver compounds can occur oral, dermal, or by inhalation. In this study, we investigated genotoxic and oxidative effects of silver exposure among silver jewelry workers. DNA damage in peripheral mononuclear leukocytes was measured by using the comet assay. Serum total antioxidative status (TAS), total oxidative status (TOS), total thiol contents, and ceruloplasmin levels were measured by using colorimetric methods among silver jewelry workers. Moreover, oxidative stress index (OSI) was calculated. Results were compared with non-exposed healthy subjects. The mean values of mononuclear leukocyte DNA damage were significantly higher than control subjects (p jewelry workers caused oxidative stress and accumulation of severe DNA damage.

  5. Food-Derived Bioactive Peptides on Inflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Subhadeep Chakrabarti

    2014-01-01

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

  6. Chronic Kidney Disease—Effect of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Subha Palaneeswari Meenakshi Sundaram

    2014-01-01

    Full Text Available Chronic kidney disease (CKD is a growing health problem with increasing incidence. The annual mortality of end-stage renal disease patients is about 9%, which is 10–20 fold higher than the general population, approximately 50% of these deaths are due to cardiovascular (CV disease. CV risk factors, such as diabetes, hypertension, and hyperlipidemia, are strongly associated with poor outcome. Many other nontraditional risk factors such as inflammation, infection, oxidative stress, anemia, and malnutrition are also present. In this review we will focus on the role of oxidative stress in chronic kidney disease.

  7. Is the oxidative stress theory of aging dead?

    Science.gov (United States)

    Pérez, Viviana I; Bokov, Alex; Van Remmen, Holly; Mele, James; Ran, Qitao; Ikeno, Yuji; Richardson, Arlan

    2009-10-01

    Currently, the oxidative stress (or free radical) theory of aging is the most popular explanation of how aging occurs at the molecular level. While data from studies in invertebrates (e.g., C. elegans and Drosophila) and rodents show a correlation between increased lifespan and resistance to oxidative stress (and in some cases reduced oxidative damage to macromolecules), direct evidence showing that alterations in oxidative damage/stress play a role in aging are limited to a few studies with transgenic Drosophila that overexpress antioxidant enzymes. Over the past eight years, our laboratory has conducted an exhaustive study on the effect of under- or overexpressing a large number and wide variety of genes coding for antioxidant enzymes. In this review, we present the survival data from these studies together. Because only one (the deletion of the Sod1 gene) of the 18 genetic manipulations we studied had an effect on lifespan, our data calls into serious question the hypothesis that alterations in oxidative damage/stress play a role in the longevity of mice.

  8. OXIDATIVE STRESS INDUCED ULCER PROTECTED BY NATURAL ANTIOXIDANTS: A REVIEW

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    Gupta Priya

    2012-05-01

    Full Text Available Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates, which ultimately leads to oxidative deterioration of protein, lipid and DNA. In humans, oxidative stress is involved in pathology of many diseases, such as atherosclerosis, Parkinson’s disease, heart failure, myocardial infarction, and chronic fatigue syndrome. Reactive oxygen species (ROS can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. To counteract oxidative stress, the body produces an armory of antioxidants to defend itself. It's the job of antioxidants to neutralize free radicals that can harm the cells. Body's internal production of antioxidants is not enough to neutralize all the free radicals. It’s a well-known fact that ROS are involved in the aetio-pathogenesis of the inflammatory and ulcerative lesions of the gastrointestinal tract. The present review focuses on the studies where oxidative damage due to stress has been linked causally to loss of cell integrity mainly in peptic ulcer cured by natural antioxidants.

  9. Metal dyshomeostasis and oxidative stress in Alzheimer's disease.

    Science.gov (United States)

    Greenough, Mark A; Camakaris, James; Bush, Ashley I

    2013-04-01

    Alzheimer's disease is the leading cause of dementia in the elderly and is defined by two pathological hallmarks; the accumulation of aggregated amyloid beta and excessively phosphorylated Tau proteins. The etiology of Alzheimer's disease progression is still debated, however, increased oxidative stress is an early and sustained event that underlies much of the neurotoxicity and consequent neuronal loss. Amyloid beta is a metal binding protein and copper, zinc and iron promote amyloid beta oligomer formation. Additionally, copper and iron are redox active and can generate reactive oxygen species via Fenton (and Fenton-like chemistry) and the Haber-Weiss reaction. Copper, zinc and iron are naturally abundant in the brain but Alzheimer's disease brain contains elevated concentrations of these metals in areas of amyloid plaque pathology. Amyloid beta can become pro-oxidant and when complexed to copper or iron it can generate hydrogen peroxide. Accumulating evidence suggests that copper, zinc, and iron homeostasis may become perturbed in Alzheimer's disease and could underlie an increased oxidative stress burden. In this review we discuss oxidative/nitrosative stress in Alzheimer's disease with a focus on the role that metals play in this process. Recent studies have started to elucidate molecular links with oxidative/nitrosative stress and Alzheimer's disease. Finally, we discuss metal binding compounds that are designed to cross the blood brain barrier and restore metal homeostasis as potential Alzheimer's disease therapeutics.

  10. Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin.

    Science.gov (United States)

    Muñoz-Castañeda, Juan Rafael; Muntané, Jordi; Herencia, Carmen; Muñoz, Maria C; Bujalance, Inmaculada; Montilla, Pedro; Túnez, Issac

    2006-02-01

    Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.

  11. Fungicide prochloraz induces oxidative stress and DNA damage in vitro.

    Science.gov (United States)

    Lundqvist, J; Hellman, B; Oskarsson, A

    2016-05-01

    Prochloraz is widely used in horticulture and agriculture, e.g. as a post-harvest anti-mold treatment. Prochloraz is a known endocrine disruptor causing developmental toxicity with multiple mechanisms of action. However, data are scarce concerning other toxic effects. Since oxidative stress response, with formation of reactive oxygen species (ROS), is a common mechanism for different toxic endpoints, e.g. genotoxicity, carcinogenicity and teratogenicity, the aim of this study was to investigate if prochloraz can induce oxidative stress and/or DNA damage in human cells. A cell culture based in vitro model was used to study oxidative stress response by prochloraz, as measured by the activity of the nuclear factor erythroid 2-related factor 2 (Nrf2), a key molecule in oxidative defense mechanisms. It was observed that prochloraz induced oxidative stress in cultured human adrenocortical H295R and hepatoma HepG2 cells at non-toxic concentrations. Further, we used Comet assay to investigate the DNA damaging potential of prochloraz, and found that non-toxic concentrations of prochloraz induced DNA damage in HepG2 cells. These are novel findings, contradicting previous studies in the field of prochloraz and genotoxicity. This study reports a new mechanism by which prochloraz may exert toxicity. Our findings suggest that prochloraz might have genotoxic properties. PMID:26945613

  12. Stress dependent oxidation of sputtered niobium and effects on superconductivity

    International Nuclear Information System (INIS)

    We report on the suppression of room temperature oxidation of DC sputtered niobium films and the effects upon the superconductive transition temperature, Tc. Niobium was sputter-deposited on silicon dioxide coated 150 mm wafers and permitted to oxidize at room temperature and pressure for up to two years. Resistivity and stress measurements indicate that tensile films greater than 400 MPa resist bulk oxidation with measurements using transmission electron microscope, electron dispersive X-ray spectroscopy, x-ray photoelectric spectroscopy, and secondary ion mass spectrometry confirming this result. Although a surface oxide, Nb2O5, consumed the top 6–10 nm, we measure less than 1 at. % oxygen and nitrogen in the bulk of the films after the oxidation period. Tc measurements using a SQUID magnetometer indicate that the tensile films maintained a Tc approaching the dirty superconductive limit of 8.4 K after two years of oxidation while maintaining room temperature sheet resistance. This work demonstrates that control over niobium film stress during deposition can prevent bulk oxidation by limiting the vertical grain boundaries ability to oxidize, prolonging the superconductive properties of sputtered niobium when exposed to atmosphere

  13. Stress dependent oxidation of sputtered niobium and effects on superconductivity

    Science.gov (United States)

    David Henry, M.; Wolfley, Steve; Monson, Todd; Clark, Blythe G.; Shaner, Eric; Jarecki, Robert

    2014-02-01

    We report on the suppression of room temperature oxidation of DC sputtered niobium films and the effects upon the superconductive transition temperature, Tc. Niobium was sputter-deposited on silicon dioxide coated 150 mm wafers and permitted to oxidize at room temperature and pressure for up to two years. Resistivity and stress measurements indicate that tensile films greater than 400 MPa resist bulk oxidation with measurements using transmission electron microscope, electron dispersive X-ray spectroscopy, x-ray photoelectric spectroscopy, and secondary ion mass spectrometry confirming this result. Although a surface oxide, Nb2O5, consumed the top 6-10 nm, we measure less than 1 at. % oxygen and nitrogen in the bulk of the films after the oxidation period. Tc measurements using a SQUID magnetometer indicate that the tensile films maintained a Tc approaching the dirty superconductive limit of 8.4 K after two years of oxidation while maintaining room temperature sheet resistance. This work demonstrates that control over niobium film stress during deposition can prevent bulk oxidation by limiting the vertical grain boundaries ability to oxidize, prolonging the superconductive properties of sputtered niobium when exposed to atmosphere.

  14. KSR2 Mutations Are Associated with Obesity, Insulin Resistance, and Impaired Cellular Fuel Oxidation

    OpenAIRE

    Pearce, Laura R.; Atanassova, Neli; Banton, Matthew C.; Bottomley, Bill; van der Klaauw, Agatha A.; Revelli, Jean-Pierre; Hendricks, Audrey; Keogh, Julia M.; Henning, Elana; Doree, Deon; Jeter-Jones, Sabrina; Garg, Sumedha; Bochukova, Elena G.; Bounds, Rebecca; Ashford, Sofie

    2013-01-01

    Summary Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEK-ERK pathway and impair cellular fatty acid oxidation and glucose oxida...

  15. Oxidative stress in MeHg-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

    2011-11-15

    Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

  16. Oxidative Stress and DNA Methylation in Prostate Cancer

    OpenAIRE

    Krishna Vanaja Donkena; Young, Charles Y. F.; Tindall, Donald J.

    2010-01-01

    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 al...

  17. Mitochondria and Oxidative Stress in the Cardiorenal Metabolic Syndrome

    OpenAIRE

    Aroor, Annayya R.; Mandavia, Chirag; Ren, Jun; Sowers, James R.; Pulakat, Lakshmi

    2012-01-01

    Mitochondria play a fundamental role in the maintenance of normal structure, function, and survival of tissues. There is considerable evidence for mitochondrial dysfunction in association with metabolic diseases including insulin resistance, obesity, diabetes, and the cardiorenal metabolic syndrome. The phenomenon of reactive oxygen species (ROS)-induced ROS release through interactions between cytosolic and mitochondrial oxidative stress contributes to a vicious cycle of enhanced oxidative s...

  18. Novel Approaches to Treat Oxidative Stress and Cardiovascular Diseases

    OpenAIRE

    Berk, Bradford C.

    2007-01-01

    Reduction-oxidation (redox) reactions that generate reactive oxygen species (ROS) such as hydrogen peroxide and superoxide have been identified as important chemical processes that regulate signal transduction. The findings of increased ROS in association with endothelial dysfunction has given rise to the “antioxidant hypothesis”: since ROS are increased in hypertension, atherosclerosis and vascular injury, then inhibiting oxidative stress with antioxidants should decrease cardiovascular even...

  19. Nitric Oxide(NO)and Plant Stress

    Institute of Scientific and Technical Information of China (English)

    CHENG Shun-chang; REN Xiao-Lin; GUAN Qing-mei

    2005-01-01

    In depth study of NO reveals that NO is a bioactive molecule that exerts a number of roles in many physiological and pathological process.NO is produced in response to drought,salinity,temperature shock and pathogen attack.NO rapidly reacts with ROS,ABA and other hormones and directly or indirectly regulate ethylene biosynthesis.The authors review the response of between plant NO and kinds of stresses,and possible mechanism was discussed.

  20. Oxidative Stress and Skin Cancer: An Overview

    OpenAIRE

    Narendhirakannan, R. T.; Hannah, M. Angeline Christie

    2012-01-01

    Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, it is a major target for toxic insult by a broad spectrum of physical and chemical agents that are capable of altering its structure and function. There are a large number of dietary contaminants and drugs can manifest their toxicity in skin. These environmental toxicants or their metabolites are inherent oxidants and/or directl...

  1. 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.

  2. Statins Decrease Oxidative Stress and ICD Therapies

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    Heather L. Bloom

    2010-01-01

    Full Text Available Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs and interleukin-6 (IL-6. Results. Subjects included 252 (83% men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r=0.12, P=.02. Subjects on statins had lower hsCRP (5.2 versus 6.3; P=.05 and DROM levels (373 versus 397; P=.03. Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation.

  3. Oxidative Stress in Lead and Cadmium Toxicity and Its Amelioration

    Directory of Open Access Journals (Sweden)

    R. C. Patra

    2011-01-01

    Full Text Available Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthropogenic sources including mining, smelting, and other industrial processes are responsible for human and animal exposure. These pollutants, many a times, are copollutants leading to concurrent exposure to living beings and resultant synergistic deleterious health effects. Several mechanisms have been explained for the damaging effects on the body system. Of late, oxidative stress has been implicated in the pathogenesis of the lead- and cadmium-induced pathotoxicity. Several ameliorative measures to counteract the oxidative damage to the body system aftermath or during exposure to these toxicants have been assessed with the use of antioxidants. The present review focuses on mechanism of lead- and cadmium-induced oxidate damages and the ameliorative measures to counteract the oxidative damage and pathotoxicity with the use of supplemented antioxidants for their beneficial effects.

  4. Tyrosine can protect against oxidative stress through ferryl hemoglobin reduction.

    Science.gov (United States)

    Lu, Naihao; He, Yingjie; Chen, Chao; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

    2014-08-01

    The toxic mechanism of hemoglobin (Hb) under oxidative stress is linked to the formations of highly cytotoxic ferryl species and subsequently heme-to-protein cross-linked derivative of Hb (Hb-X). In this study, we have examined the effects of free tyrosine and its analogues (3-chlorotyrosine, phenylalanine) on the stability of ferryl hemoglobin and the formation of Hb-X. The results showed that free tyrosine (not phenylalanine, 10-500 μM) was an efficient reducing agent of ferryl species and also effective at preventing the formation of cytotoxic Hb-X. Meanwhile, the dimeric tyrosine was formed as the oxidation product of tyrosine during Hb redox reaction. Compared with free tyrosine, 3-chlorotyrosine, an oxidation product of tyrosine and a proposed biomarker for hypochlorous acid (HOCl) in vivo, exhibited stronger antioxidant properties in Hb-induced oxidative stress, which was consistent with its more efficient ability in the reduction of ferryl species. These results showed that the presence of tyrosine and its derivative in vivo and vitro could ameliorate oxidative damage through ferryl heme reduction. The antioxidant ability, therefore, may provide new insights into the nutritional and physiological significance of free tyrosine with redox active heme proteins-related oxidative stress.

  5. Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

    OpenAIRE

    B. Poljsak; Milisav, I.; Lampe, T.; Ostan, I.

    2011-01-01

    High levels of reactive oxygen species (ROS) compared to antioxidant defenses are considered to play a major role in diverse chronic age-related diseases and aging. Here we present an attempt to synthesize information about proximate oxidative processes in aging (relevant to free radical or oxidative damage hypotheses of aging) with an evolutionary scenario (credited here to Dawkins hypotheses) involving tradeoffs between the costs and benefits of oxidative stress to reproducing organisms. Ox...

  6. The plant Apolipoprotein D ortholog protects Arabidopsis against oxidative stress

    Directory of Open Access Journals (Sweden)

    Houde Mario

    2008-07-01

    Full Text Available Abstract Background Lipocalins are a large and diverse family of small, mostly extracellular proteins implicated in many important functions. This family has been studied in bacteria, invertebrate and vertebrate animals but little is known about these proteins in plants. We recently reported the identification and molecular characterization of the first true lipocalins from plants, including the Apolipoprotein D ortholog AtTIL identified in the plant model Arabidopsis thaliana. This study aimed to determine its physiological role in planta. Results Our results demonstrate that the AtTIL lipocalin is involved in modulating tolerance to oxidative stress. AtTIL knock-out plants are very sensitive to sudden drops in temperature and paraquat treatment, and dark-grown plants die shortly after transfer to light. These plants accumulate a high level of hydrogen peroxide and other ROS, which causes an oxidative stress that is associated with a reduction in hypocotyl growth and sensitivity to light. Complementation of the knock-out plants with the AtTIL cDNA restores the normal phenotype. On the other hand, overexpression enhances tolerance to stress caused by freezing, paraquat and light. Moreover, this overexpression delays flowering and maintains leaf greenness. Microarray analyses identified several differentially-regulated genes encoding components of oxidative stress and energy balance. Conclusion This study provides the first functional evidence that a plant lipocalin is involved in modulating tolerance to oxidative stress. These findings are in agreement with recently published data showing that overexpression of ApoD enhances tolerance to oxidative stress and increases life span in mice and Drosophila. Together, the three papers strongly support a similar function of lipocalins in these evolutionary-distant species.

  7. Osmotic stress stimulates phosphorylation and cellular expression of heat shock proteins in rhesus macaque sperm.

    Science.gov (United States)

    Cole, Julie A; Meyers, Stuart A

    2011-01-01

    The cryosurvival of sperm requires cell signaling mechanisms to adapt to anisotonic conditions during the freezing and thawing process. Chaperone proteins heat shock protein 70 (HSP 70) and heat shock protein 90 (HSP 90; recently renamed HSPA and HSPC, respectively) facilitate some of these cell signaling events in somatic cells. Sperm were evaluated for their cellular expression and levels of phosphorylation of both HSP 70 and HSP 90 under anisotonic conditions as a potential model for cell signaling during the cryopreservation of macaque spermatozoa. In order to monitor the level of stress, the motility and viability parameters were evaluated at various time points. Cells were then either prepared for phosphoprotein enrichment or indirect immunocytochemistry. As controls, the phosphoserine, phosphothreonine, and phosphotyrosine levels were measured under capacitation and cryopreservation conditions and were compared with the phosphoprotein levels expressed under osmotic conditions. As expected, there was an increase in the level of tyrosine phosphorylation under capacitation and cryopreservation conditions. There was also a significant increase in the level of all phosphoproteins under hyperosmotic conditions. There was no change in the level of expression of HSP 70 or 90 under osmotic stress conditions as measured by Western blot. The enrichment of phosphoproteins followed by Western immunoblotting revealed an increase in the phosphorylation of HSP 70 but not HSP 90 under osmotic stress conditions. Indirect immunofluorescence localized HSP 70 to the postacrosomal region of sperm, and the level of membrane expression of HSP 70 was significantly affected by anisotonic conditions, as measured by flow cytometry. Taken together, these results suggest a differential role for HSP 70 and HSP 90 during osmotic stress conditions in rhesus macaque sperm. PMID:21088232

  8. Artemisia annua increases resistance to heat and oxidative stresses, but has no effect on lifespan in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Seung-Il OH

    2016-01-01

    Full Text Available Abstract It is suggested that oxidative stress induced by cellular reactive oxygen species is one of the major causal factors of aging. The effect of dietary supplementation of anti-oxidants on response to environmental stressors and lifespan has been studied in various model organisms. In the present study, we examine the effect of Artemisia annua extract on resistance to oxidative, heat, and ultraviolet stresses in the nematode Caenorhabditis elegans. Artemisia annua significantly increases survival under oxidative and heat stresses, however has no effects in response to ultraviolet stress. Then, we measured the in vivo changes in expression of stress-responsive genes by Artemisia annua using green fluorescence protein. The expression of hsp-16.2, known to be involved in response to heat stress, is significantly increased by Artemisia annua supplementation. An anti-oxidant gene, sod-3, was also up-regulated by Artemisia annua. However, both mean and maximum lifespan of Caenorhabditis elegans was not altered by dietary supplementation of Artemisia annua. These findings indicate that Artemisia annua confers health-promoting effects through increasing the resistance to environmental stressors and has no effect on lifespan in C. elegans. Our study suggests that Artemisia annua can be used for the development of novel natural therapeutics for diseases caused by environmental stressors.

  9. Oxidative Stress and Heart Failure in Altered Thyroid States

    Directory of Open Access Journals (Sweden)

    Pallavi Mishra

    2012-01-01

    Full Text Available Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Hyperthyroidism and hypothyroidism represent opposite clinical conditions, albeit not mirror images. Recent experimental and clinical studies have suggested the involvement of ROS tissue damage under altered thyroid status. Altered-thyroid state-linked changes in heart modify their susceptibility to oxidants and the extent of the oxidative damage they suffer following oxidative challenge. Chronic increase in the cellular levels of ROS can lead to a catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS generation and cellular injury. Thus, these cellular events might play an important role in the development and progression of myocardial remodeling and heart failure in altered thyroid states (hypo- and hyper-thyroidism. The present review aims at elucidating the various signaling pathways mediated via ROS and their modulation under altered thyroid state and the possibility of antioxidant therapy.

  10. A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress.

    Directory of Open Access Journals (Sweden)

    Clement T Y Chan

    2010-12-01

    Full Text Available Decades of study have revealed more than 100 ribonucleoside structures incorporated as post-transcriptional modifications mainly in tRNA and rRNA, yet the larger functional dynamics of this conserved system are unclear. To this end, we developed a highly precise mass spectrometric method to quantify tRNA modifications in Saccharomyces cerevisiae. Our approach revealed several novel biosynthetic pathways for RNA modifications and led to the discovery of signature changes in the spectrum of tRNA modifications in the damage response to mechanistically different toxicants. This is illustrated with the RNA modifications Cm, m(5C, and m(2 (2G, which increase following hydrogen peroxide exposure but decrease or are unaffected by exposure to methylmethane sulfonate, arsenite, and hypochlorite. Cytotoxic hypersensitivity to hydrogen peroxide is conferred by loss of enzymes catalyzing the formation of Cm, m(5C, and m(2 (2G, which demonstrates that tRNA modifications are critical features of the cellular stress response. The results of our study support a general model of dynamic control of tRNA modifications in cellular response pathways and add to the growing repertoire of mechanisms controlling translational responses in cells.

  11. 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.

  12. Effect of electromagnetic fields at 2.45 GHz on the levels of cellular stress proteins HSP-90 and 70 in the rat thyroid

    International Nuclear Information System (INIS)

    In this study we analyzed the cellular stress levels achieved by heat shock proteins (HSP) 90 and 70 in rat thyroid tissue after exposure to radio waves in TWG experimental system. Parallel measurements of body stress in animals by rectal temperature probes allow us to determine whether there is any interaction between temperature increases and cellular stress.

  13. 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.

  14. Influence of Endodontic Treatment on Systemic Oxidative Stress

    Science.gov (United States)

    Inchingolo, Francesco; Marrelli, Massimo; Annibali, Susanna; Cristalli, Maria Paola; Dipalma, Gianna; Inchingolo, Alessio Danilo; Palladino, Antonio; Inchingolo, Angelo Michele; Gargari, Marco; Tatullo, Marco

    2014-01-01

    Introduction: An increased production of oxidizing species related to reactive oral diseases, such as chronic apical periodontitis, could have systemic implications such as an increase in cardiovascular morbidity. Based on this consideration, we conducted a prospective study to assess whether subjects affected by chronic periodontitis presented with higher values of oxidative stress than reference values before endodontic treatment, and whether endodontic treatment can reduce the oxidative imbalance and bring it back to normal in these subjects. Materials and methods: The authors recruited 2 groups of patients from private studies and dental clinics: these patients were recruited randomly. The oxidative balance in both patients with chronic apical periodontitis (CAP) and healthy control patients was determined by measuring the oxidant status, using an identification of the reactive oxygen metabolites (d-ROMs) test, while the antioxidant status in these patients was determined using a biological antioxidant potential (BAP) test. Both these tests were carried on plasma samples taken from enrolled patients. Values were measured both before the endodontic treatment of the patients with chronic apical periodontitis, and 30 and 90 days after treatment, and compared to those obtained from healthy control patients. Results: It was found that, on recruitment, the patients with chronic apical periodontitis exhibited significantly higher levels of oxidative stress than control patients, as determined by the d-ROMs and BAP tests. Furthermore, the d-ROMs test values were shown to decrease and the BAP test values to increase over time in patients with chronic apical periodontitis following endodontic therapy. As the levels of oxidative stress in these patients tended to reduce and return to normal by 90 days following treatment. Conclusions: This study has demonstrated a positive association between chronic apical periodontitis and oxidative stress. Subjects affected by chronic

  15. 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

  16. Oxidative stress and DNA damages induced by cadmium accumulation

    Institute of Scientific and Technical Information of China (English)

    LIN Ai-jun; ZHANG Xu-hong; CHEN Mei-mei; CAO Qing

    2007-01-01

    Experimental evidence shows that cadmium (Cd) could induce oxidative stress and then causes DNA damage in animal cells, however, whether such effect exists in plants is still unclear. In the present study, Vicia faba plants was exposed to 5 and 10 mg/L Cd for 4 d to investigate the distribution of Cd in plant, the metal effects on the cell lipids, antioxidative enzymes and DNA damages in leaves. Cd induced an increase in Cd concentrations in plants. An enhanced level of lipid peroxidation in leaves and an enhanced concentration of H2O2 in root tissues suggested that Cd caused oxidative stress in Vicia faba. Compared with control, Cd-induced enhancement in superoxide dismutase activity was significant at 5 mg/L than at 10 mg/kg in leaves, by contrast, catalase and peroxidaseactivities were significantly suppressed by Cd addition. DNA damage was detected by neutral/neutral, alkaline/neutral and alkaline/alkaline Comet assay. Increased levels of DNA damages induced by Cd occurred with reference to oxidative stress in leaves, therefore, oxidative stress induced by Cd accumulation in plants contributed to DNA damages and was possibly an important mechanism of Cd-phytotoxicity in Vicia faba plants.

  17. Fatty acids and oxidative stress in psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Tonello Lucio

    2008-04-01

    Full Text Available 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 categories: mental retardation; autistic disorder; Rett's disorder; attention-deficit hyperactivity disorder; delirium; dementia; amnestic disorders; alcohol-related disorders; amphetamine (or amphetamine-like-related disorders; hallucinogen-related disorders; nicotine-related disorders; opioid-related disorders; schizophrenia and other psychotic disorders; mood disorders; anxiety disorders; sexual dysfunctions; eating disorders; and sleep disorders. Conclusion Most psychiatric disorders are associated with increased oxidative stress. Patients suffering from that subgroup of these psychiatric disorders in which there is increased lipid peroxidation might therefore benefit from fatty acid supplementation (preferably with the inclusion of an antioxidant-rich diet while patients suffering from all these psychiatric disorders might benefit from a change to a whole-food plant-based diet devoid of refined carbohydrate products.

  18. Pneumococcal Gene Complex Involved in Resistance to Extracellular Oxidative Stress

    NARCIS (Netherlands)

    Andisi, Vahid Farshchi; Hinojosa, Cecilia A.; de Jong, Anne; Kuipers, Oscar P.; Orihuela, Carlos J.; Bijlsma, Jetta J. E.; Weiser, J.N.

    2012-01-01

    Streptococcus pneumoniae is a Gram-positive bacterium which is a member of the normal human nasopharyngeal flora but can also cause serious disease such as pneumonia, bacteremia, and meningitis. Throughout its life cycle, S. pneumoniae is exposed to significant oxidative stress derived from endogeno

  19. Thoracic radiography and oxidative stress indices in heartworm affected dogs

    Directory of Open Access Journals (Sweden)

    P. K. Rath

    2014-09-01

    Full Te