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Sample records for aging oxidative stress

  1. Oxidative stress and the ageing endocrine system.

    PubMed

    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.

  2. [Mitochondria, oxidative stress and aging].

    PubMed

    Szarka, András; Bánhegyi, Gábor; Sümegi, Balázs

    2014-03-23

    The free radical theory of aging was defined in the 1950s. On the base of this theory, the reactive oxygen species formed in the metabolic pathways can play pivotal role in ageing. The theory was modified by defining the mitochondrial respiration as the major cellular source of reactive oxygen species and got the new name mitochondrial theory of aging. Later on the existence of a "vicious cycle" was proposed, in which the reactive oxygen species formed in the mitochondrial respiration impair the mitochondrial DNA and its functions. The formation of reactive oxygen species are elevated due to mitochondrial dysfunction. The formation of mitochondrial DNA mutations can be accelerated by this "vicious cycle", which can lead to accelerated aging. The exonuclease activity of DNA polymerase γ, the polymerase responsible for the replication of mitochondrial DNA was impaired in mtDNA mutator mouse recently. The rate of somatic mutations in mitochondrial DNA was elevated and an aging phenotype could have been observed in these mice. Surprisingly, no oxidative impairment neither elevated reactive oxygen species formation could have been observed in the mtDNA mutator mice, which may question the existence of the "vicious cycle".

  3. [Mitochondria, oxidative stress and aging].

    PubMed

    Szarka, András; Bánhegyi, Gábor; Sümegi, Balázs

    2014-03-23

    The free radical theory of aging was defined in the 1950s. On the base of this theory, the reactive oxygen species formed in the metabolic pathways can play pivotal role in ageing. The theory was modified by defining the mitochondrial respiration as the major cellular source of reactive oxygen species and got the new name mitochondrial theory of aging. Later on the existence of a "vicious cycle" was proposed, in which the reactive oxygen species formed in the mitochondrial respiration impair the mitochondrial DNA and its functions. The formation of reactive oxygen species are elevated due to mitochondrial dysfunction. The formation of mitochondrial DNA mutations can be accelerated by this "vicious cycle", which can lead to accelerated aging. The exonuclease activity of DNA polymerase γ, the polymerase responsible for the replication of mitochondrial DNA was impaired in mtDNA mutator mouse recently. The rate of somatic mutations in mitochondrial DNA was elevated and an aging phenotype could have been observed in these mice. Surprisingly, no oxidative impairment neither elevated reactive oxygen species formation could have been observed in the mtDNA mutator mice, which may question the existence of the "vicious cycle". PMID:24631932

  4. Oxidative stress in aging human skin.

    PubMed

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

    2015-04-21

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

  5. Oxidative Stress in Aging Human Skin

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    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. Multimarker Screening of Oxidative Stress in Aging

    PubMed Central

    Syslová, Kamila; Böhmová, Adéla; Kuzma, Marek; Pelclová, Daniela; Kačer, Petr

    2014-01-01

    Aging is a complex process of organism decline in physiological functions. There is no clear theory explaining this phenomenon, but the most accepted one is the oxidative stress theory of aging. Biomarkers of oxidative stress, substances, which are formed during oxidative damage of phospholipids, proteins, and nucleic acids, are present in body fluids of diseased people as well as the healthy ones (in a physiological concentration). 8-iso prostaglandin F2α is the most prominent biomarker of phospholipid oxidative damage, o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine are biomarkers of protein oxidative damage, and 8-hydroxy-2′-deoxyguanosine and 8-hydroxyguanosine are biomarkers of oxidative damage of nucleic acids. It is thought that the concentration of biomarkers increases as the age of people increases. However, the concentration of biomarkers in body fluids is very low and, therefore, it is necessary to use a sensitive analytical method. A combination of HPLC and MS was chosen to determine biomarker concentration in three groups of healthy people of a different age (twenty, forty, and sixty years) in order to find a difference among the groups. PMID:25147595

  8. Chrononutrition against Oxidative Stress in Aging

    PubMed Central

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

    2013-01-01

    Free radicals and oxidative stress have been recognized as important factors in the biology of aging and in many age-associated degenerative diseases. Antioxidant systems deteriorate during aging. It is, thus, considered that one way to reduce the rate of aging and the risk of chronic disease is to avoid the formation of free radicals and reduce oxidative stress by strengthening antioxidant defences. Phytochemicals present in fruits, vegetables, grains, and other foodstuffs have been linked to reducing the risk of major oxidative stress-induced diseases. Some dietary components of foods possess biological activities which influence circadian rhythms in humans. Chrononutrition studies have shown that not only the content of food, but also the time of ingestion contributes to the natural functioning of the circadian system. Dietary interventions with antioxidant-enriched foods taking into account the principles of chrononutrition are of particular interest for the elderly since they may help amplify the already powerful benefits of phytochemicals as natural instruments with which to prevent or delay the onset of common age-related diseases. PMID:23861994

  9. Oxidative Stress in Ageing of Hair

    PubMed Central

    Trüeb, Ralph M

    2009-01-01

    Experimental evidence supports the hypothesis that oxidative stress plays a major role in the ageing process. Reactive oxygen species are generated by a multitude of endogenous and environmental challenges. Reactive oxygen species or free radicals are highly reactive molecules that can directly damage cellular structural membranes, lipids, proteins, and DNA. The body possesses endogenous defence mechanisms, such as antioxidative enzymes and non-enzymatic antioxidative molecules, protecting it from free radicals by reducing and neutralizing them. With age, the production of free radicals increases, while the endogenous defence mechanisms decrease. This imbalance leads to the progressive damage of cellular structures, presumably resulting in the ageing phenotype. Ageing of hair manifests as decrease of melanocyte function or graying, and decrease in hair production or alopecia. There is circumstantial evidence that oxidative stress may be a pivotal mechanism contributing to hair graying and hair loss. New insights into the role and prevention of oxidative stress could open new strategies for intervention and reversal of the hair graying process and age-dependent alopecia. PMID:20805969

  10. Mitochondrial oxidative stress in aging and healthspan

    PubMed Central

    2014-01-01

    The free radical theory of aging proposes that reactive oxygen species (ROS)-induced accumulation of damage to cellular macromolecules is a primary driving force of aging and a major determinant of lifespan. Although this theory is one of the most popular explanations for the cause of aging, several experimental rodent models of antioxidant manipulation have failed to affect lifespan. Moreover, antioxidant supplementation clinical trials have been largely disappointing. The mitochondrial theory of aging specifies more particularly that mitochondria are both the primary sources of ROS and the primary targets of ROS damage. In addition to effects on lifespan and aging, mitochondrial ROS have been shown to play a central role in healthspan of many vital organ systems. In this article we review the evidence supporting the role of mitochondrial oxidative stress, mitochondrial damage and dysfunction in aging and healthspan, including cardiac aging, age-dependent cardiovascular diseases, skeletal muscle aging, neurodegenerative diseases, insulin resistance and diabetes as well as age-related cancers. The crosstalk of mitochondrial ROS, redox, and other cellular signaling is briefly presented. Potential therapeutic strategies to improve mitochondrial function in aging and healthspan are reviewed, with a focus on mitochondrial protective drugs, such as the mitochondrial antioxidants MitoQ, SkQ1, and the mitochondrial protective peptide SS-31. PMID:24860647

  11. Role of oxidative stress on platelet hyperreactivity during aging.

    PubMed

    Fuentes, Eduardo; Palomo, Iván

    2016-03-01

    Thrombotic events are common causes of morbidity and mortality in the elderly. Age-accelerated vascular injury is commonly considered to result from increased oxidative stress. There is abundant evidence that oxidative stress regulate several components of thrombotic processes, including platelet activation. Thus oxidative stress can trigger platelet hyperreactivity by decreasing nitric oxide bioavailability. Therefore oxidative stress measurement may help in the early identification of asymptomatic subjects at risk of thrombosis. In addition, oxidative stress inhibitors and platelet-derived nitric oxide may represent a novel anti-aggregation/-activation approach. In this article the relative contribution of oxidative stress and platelet activation in aging is explored.

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

    PubMed

    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.

  13. Oxidative stress response and Nrf2 signaling in aging

    PubMed Central

    Zhang, Hongqiao; Davies, Kelvin J. A.; Forman, Henry Jay

    2015-01-01

    Increasing oxidative stress, a major characteristic of aging, has been implicated in variety of age-related pathologies. In aging, oxidant production from several sources is increased while antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins also declines. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels including transcription, post-translation, and interaction with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the change of Nrf2 regulatory mechanisms with aging. PMID:26066302

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2010-04-01

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

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

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

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

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

    PubMed

    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

  18. The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

    PubMed Central

    Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Sun, Tao

    2014-01-01

    Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol. PMID:25143940

  19. The role of oxidative stress and inflammation in cardiovascular aging.

    PubMed

    Wu, Junzhen; Xia, Shijin; Kalionis, Bill; Wan, Wenbin; Sun, Tao

    2014-01-01

    Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66(Shc), and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

  20. Oxidative stress and ageing of the post-ovulatory oocyte.

    PubMed

    Lord, Tessa; Aitken, R John

    2013-12-01

    With extended periods of time following ovulation, the metaphase II stage oocyte experiences deterioration in quality referred to as post-ovulatory oocyte ageing. Post-ovulatory ageing occurs both in vivo and in vitro and has been associated with reduced fertilization rates, poor embryo quality, post-implantation errors and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been established, the molecular mechanisms controlling this process are not well defined. This review analyses the relationships between biochemical changes exhibited by the ageing oocyte and the symptoms associated with the ageing phenotype. We also discuss molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We propose that oxidative stress may act as the initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to cause a decline in levels of critical cell cycle factors such as maturation-promoting factor, impair calcium homoeostasis, induce mitochondrial dysfunction and directly damage multiple intracellular components of the oocyte such as lipids, proteins and DNA. Finally, this review addresses current strategies for delaying post-ovulatory oocyte ageing with a particular focus on the potential use of compounds such as caffeine or selected antioxidants in the development of more refined media for the preservation of oocyte integrity during IVF procedures.

  1. [Oxidative stress, antioxydants and the ageing process].

    PubMed

    Pincemail, J; Ricour, C; Defraigne, J O; Petermans, J

    2014-01-01

    Antioxidant supplementation in the form of pills is thought to slow down the aging process through the "free radical" scavenger activity of these compounds. The idea arose from the "Free Radical Theory of Ageing" (FRTA), initially developed by Harman in 1956. In the present paper, we present some arguments against this theory. One of the most pertinent is that "free radicals", more properly renamed as reactive oxygen species (ROS), play important biological roles in defense mechanisms of the organism as illustrated, in particular, by the hormesis phenomenon. Surprisingly, a moderate production of ROS has been shown to extend the life span in animals. PMID:25065231

  2. Is the oxidative stress theory of aging dead?

    PubMed

    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.

  3. Age-related Oxidative Stress Compromises Endosomal Proteostasis

    PubMed Central

    Cannizzo, Elvira S.; Clement, Cristina C.; Morozova, Kateryna; Valdor, Rut; Kaushik, Susmita; Almeida, Larissa N.; Follo, Carlo; Sahu, Ranjit; Cuervo, Ana Maria; Macian, Fernando; Santambrogio, Laura

    2012-01-01

    A hallmark of aging is an imbalance between production and clearance of reactive oxygen species and increased levels of oxidatively damaged biomolecules. Herein we demonstrate that splenic and nodal antigen presenting cells purified from old mice accumulate oxidatively modified proteins with side chain carbonylation, advanced glycation end products and lipid peroxidation. We show further that the endosomal accumulation of oxidatively modified proteins interferes with the efficient processing of exogenous antigens and degradation of macroautophagy-delivered proteins. In support of a causative role for oxidized products in the inefficient immune response, a decrease in oxidative stress improved the adaptive immune response to immunizing antigens. These findings underscore a previously unrecognized negative effect of age-dependent changes in cellular proteostasis on the immune response. PMID:22840404

  4. Positive oxidative stress in aging and aging-related disease tolerance.

    PubMed

    Yan, Liang-Jun

    2014-01-01

    It is now well established that reactive oxygen species (ROS), reactive nitrogen species (RNS), and a basal level of oxidative stress are essential for cell survival. It is also well known that while severe oxidative stress often leads to widespread oxidative damage and cell death, a moderate level of oxidative stress, induced by a variety of stressors, can yield great beneficial effects on adaptive cellular responses to pathological challenges in aging and aging-associated disease tolerance such as ischemia tolerance. Here in this review, I term this moderate level of oxidative stress as positive oxidative stress, which usually involves imprinting molecular signatures on lipids and proteins via formation of lipid peroxidation by-products and protein oxidation adducts. As ROS/RNS are short-lived molecules, these molecular signatures can thus execute the ultimate function of ROS/RNS. Representative examples of lipid peroxidation products and protein oxidation adducts are presented to illustrate the role of positive oxidative stress in a variety of pathological settings, demonstrating that positive oxidative stress could be a valuable prophylactic and/or therapeutic approach targeting aging and aging-associated diseases.

  5. A mitochondrial superoxide theory for oxidative stress diseases and aging.

    PubMed

    Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J

    2015-01-01

    Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.

  6. Oxidative Stress in Aging: Advances in Proteomic Approaches

    PubMed Central

    Ortuño-Sahagún, Daniel; Pallàs, Mercè; Rojas-Mayorquín, Argelia E.

    2014-01-01

    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. PMID:24688629

  7. Oxidative stress in aging: advances in proteomic approaches.

    PubMed

    Ortuño-Sahagún, Daniel; Pallàs, Mercè; Rojas-Mayorquín, Argelia E

    2014-01-01

    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.

  8. Mitochondrial oxidative stress in aortic stiffening with age: the role of smooth muscle cell function.

    EPA Science Inventory

    OBJECTIVE: Age-related aortic stiffness is an independent risk factor for cardiovascular diseases. Although oxidative stress is implicated in aortic stiffness, the underlying molecular mechanisms remain unelucidated. Here, we examined the source of oxidative stress in aging and i...

  9. The sirtuins, oxidative stress and aging: an emerging link.

    PubMed

    Merksamer, Philip I; Liu, Yufei; He, Wenjuan; Hirschey, Matthew D; Chen, Danica; Verdin, Eric

    2013-03-01

    Reactive oxygen species (ROS) are a family of compounds that can oxidatively damage cellular macromolecules and may influence lifespan. Sirtuins are a conserved family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases that regulate lifespan in many model organisms including yeast and mice. Recent work suggests that sirtuins can modulate ROS levels notably during a dietary regimen known as calorie restriction which enhances lifespan for several organisms. Although both sirtuins and ROS have been implicated in the aging process, their precise roles remain unknown. In this review, we summarize current thinking about the oxidative stress theory of aging, discuss some of the compelling data linking the sirtuins to ROS and aging, and propose a conceptual model placing the sirtuins into an ROS-driven mitochondria-mediated hormetic response.

  10. Iron accumulation with age, oxidative stress and functional decline.

    PubMed

    Xu, Jinze; Knutson, Mitchell D; Carter, Christy S; Leeuwenburgh, Christiaan

    2008-01-01

    Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age) at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects.

  11. Iron Accumulation with Age, Oxidative Stress and Functional Decline

    PubMed Central

    Xu, Jinze; Knutson, Mitchell D.; Carter, Christy S.; Leeuwenburgh, Christiaan

    2008-01-01

    Identification of biological mediators in sarcopenia is pertinent to the development of targeted interventions to alleviate this condition. Iron is recognized as a potent pro-oxidant and a catalyst for the formation of reactive oxygen species in biological systems. It is well accepted that iron accumulates with senescence in several organs, but little is known about iron accumulation in muscle and how it may affect muscle function. In addition, it is unclear if interventions which reduced age-related loss of muscle quality, such as calorie restriction, impact iron accumulation. We investigated non-heme iron concentration, oxidative stress to nucleic acids in gastrocnemius muscle and key indices of sarcopenia (muscle mass and grip strength) in male Fischer 344 X Brown Norway rats fed ad libitum (AL) or a calorie restricted diet (60% of ad libitum food intake starting at 4 months of age) at 8, 18, 29 and 37 months of age. Total non-heme iron levels in the gastrocnemius muscle of AL rats increased progressively with age. Between 29 and 37 months of age, the non-heme iron concentration increased by approximately 200% in AL-fed rats. Most importantly, the levels of oxidized RNA in gastrocnemius muscle of AL rats were significantly increased as well. The striking age-associated increase in non-heme iron and oxidized RNA levels and decrease in sarcopenia indices were all attenuated in the calorie restriction (CR) rats. These findings strongly suggest that the age-related iron accumulation in muscle contributes to increased oxidative damage and sarcopenia, and that CR effectively attenuates these negative effects. PMID:18682742

  12. Oxidative stress and its downstream signaling in aging eyes

    PubMed Central

    Pinazo-Durán, María Dolores; Gallego-Pinazo, Roberto; García-Medina, Jose Javier; Zanón-Moreno, Vicente; Nucci, Carlo; Dolz-Marco, Rosa; Martínez-Castillo, Sebastián; Galbis-Estrada, Carmen; Marco-Ramírez, Carla; López-Gálvez, Maria Isabel; Galarreta, David J; Díaz-Llópis, Manuel

    2014-01-01

    Background Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. Objective We reviewed the role of OS and its downstream signaling in aging eyes. Methods A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Results Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. Conclusion OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases. PMID:24748782

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

    PubMed

    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

  14. Astaxanthin affects oxidative stress and hyposalivation in aging mice

    PubMed Central

    Kuraji, Manatsu; Matsuno, Tomonori; Satoh, Tazuko

    2016-01-01

    Oral dryness, a serious problem for the aging Japanese society, is induced by aging-related hyposalivation and causes dysphagia, dysgeusia, inadaptation of dentures, and growth of oral Candida albicans. Oxidative stress clearly plays a role in decreasing saliva secretion and treatment with antioxidants such astaxanthin supplements may be beneficial. Therefore, we evaluated the effects of astaxanthin on the oral saliva secretory function of aging mice. The saliva flow increased in astaxanthin-treated mice 72 weeks after administration while that of the control decreased by half. The plasma d-ROMs values of the control but not astaxanthin-treated group measured before and 72 weeks after treatment increased. The diacron-reactive oxygen metabolites (d-ROMs) value of astaxanthin-treated mice 72 weeks after treatment was significantly lower than that of the control group was. The plasma biological antioxidative potential (BAP) values of the control but not astaxanthin-treated mice before and 72 weeks after treatment decreased. Moreover, the BAP value of the astaxanthin-treated group 72 weeks after treatment was significantly higher than that of the control was. Furthermore, the submandibular glands of astaxanthin-treated mice had fewer inflammatory cells than the control did. Specifically, immunofluorescence revealed a significantly large aquaporin-5 positive cells in astaxanthin-treated mice. Our results suggest that astaxanthin treatment may prevent age-related decreased saliva secretion. PMID:27698533

  15. Astaxanthin affects oxidative stress and hyposalivation in aging mice

    PubMed Central

    Kuraji, Manatsu; Matsuno, Tomonori; Satoh, Tazuko

    2016-01-01

    Oral dryness, a serious problem for the aging Japanese society, is induced by aging-related hyposalivation and causes dysphagia, dysgeusia, inadaptation of dentures, and growth of oral Candida albicans. Oxidative stress clearly plays a role in decreasing saliva secretion and treatment with antioxidants such astaxanthin supplements may be beneficial. Therefore, we evaluated the effects of astaxanthin on the oral saliva secretory function of aging mice. The saliva flow increased in astaxanthin-treated mice 72 weeks after administration while that of the control decreased by half. The plasma d-ROMs values of the control but not astaxanthin-treated group measured before and 72 weeks after treatment increased. The diacron-reactive oxygen metabolites (d-ROMs) value of astaxanthin-treated mice 72 weeks after treatment was significantly lower than that of the control group was. The plasma biological antioxidative potential (BAP) values of the control but not astaxanthin-treated mice before and 72 weeks after treatment decreased. Moreover, the BAP value of the astaxanthin-treated group 72 weeks after treatment was significantly higher than that of the control was. Furthermore, the submandibular glands of astaxanthin-treated mice had fewer inflammatory cells than the control did. Specifically, immunofluorescence revealed a significantly large aquaporin-5 positive cells in astaxanthin-treated mice. Our results suggest that astaxanthin treatment may prevent age-related decreased saliva secretion.

  16. Metabolic Syndrome, Aging and Involvement of Oxidative Stress

    PubMed Central

    Bonomini, Francesca; Rodella, Luigi Fabrizio; Rezzani, Rita

    2015-01-01

    The prevalence of the metabolic syndrome, a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder consists of a cluster of metabolic conditions, such as hypertriglyceridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that-in combination with genetic susceptibility and abdominal obesity-are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart diseases. One of the defects in metabolic syndrome and its associated diseases is excess of reactive oxygen species. Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process. In this article we review current understandings of oxidative stress in metabolic syndrome related disease and its possible contribution to accelerated senescence. PMID:25821639

  17. The Immunoproteasome in oxidative stress, aging, and disease.

    PubMed

    Johnston-Carey, Helen K; Pomatto, Laura C D; Davies, Kelvin J A

    2015-01-01

    The Immunoproteasome has traditionally been viewed primarily for its role in peptide production for antigen presentation by the major histocompatibility complex, which is critical for immunity. However, recent research has shown that the Immunoproteasome is also very important for the clearance of oxidatively damaged proteins in homeostasis, and especially during stress and disease. The importance of the Immunoproteasome in protein degradation has become more evident as diseases characterized by protein aggregates have also been linked to deficiencies of the Immunoproteasome. Additionally, there are now diseases defined by mutations or polymorphisms within Immunoproteasome-specific subunit genes, further suggesting its crucial role in cytokine signaling and protein homeostasis (or "proteostasis"). The purpose of this review is to highlight our growing understanding of the importance of the Immunoproteasome in the management of protein quality control, and the detrimental impact of its dysregulation during disease and aging. PMID:27098648

  18. Oxidative stress, innate immunity, and age-related macular degeneration

    PubMed Central

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  19. Oxidative stress in the etiology of age-associated decline in glucose metabolism.

    PubMed

    Salmon, Adam B

    2012-01-01

    One of the most common pathologies in aging humans is the development of glucose metabolism dysfunction. The high incidence of metabolic dysfunction, in particular type 2 diabetes mellitus, is a significant health and economic burden on the aging population. However, the mechanisms that regulate this age-related physiological decline, and thus potential preventative treatments, remain elusive. Even after accounting for age-related changes in adiposity, lean mass, blood lipids, etc., aging is an independent factor for reduced glucose tolerance and increased insulin resistance. Oxidative stress has been shown to have significant detrimental impacts on the regulation of glucose homeostasis in vitro and in vivo. Furthermore, oxidative stress has been shown to be modulated by age and diet in several model systems. This review provides an overview of these data and addresses whether increases in oxidative stress with aging may be a primary determinant of age-related metabolic dysfunction.

  20. Mouse Models of Oxidative Stress Indicate a Role for Modulating Healthy Aging

    PubMed Central

    Hamilton, Ryan T.; Walsh, Michael E.; Van Remmen, Holly

    2013-01-01

    Aging is a complex process that affects every major system at the molecular, cellular and organ levels. Although the exact cause of aging is unknown, there is significant evidence that oxidative stress plays a major role in the aging process. The basis of the oxidative stress hypothesis is that aging occurs as a result of an imbalance between oxidants and antioxidants, which leads to the accrual of damaged proteins, lipids and DNA macromolecules with age. Age-dependent increases in protein oxidation and aggregates, lipofuscin, and DNA mutations contribute to age-related pathologies. Many transgenic/knockout mouse models over expressing or deficient in key antioxidant enzymes have been generated to examine the effect of oxidative stress on aging and age-related diseases. Based on currently reported lifespan studies using mice with altered antioxidant defense, there is little evidence that oxidative stress plays a role in determining lifespan. However, mice deficient in antioxidant enzymes are often more susceptible to age-related disease while mice overexpressing antioxidant enzymes often have an increase in the amount of time spent without disease, i.e., healthspan. Thus, by understanding the mechanisms that affect healthy aging, we may discover potential therapeutic targets to extend human healthspan. PMID:25300955

  1. Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster.

    PubMed

    Landis, Gary; Shen, Jie; Tower, John

    2012-11-01

    Gene expression changes in response to aging, heat stress, hyperoxia, hydrogen peroxide, and ionizing radiation were compared using microarrays. A set of 18 genes were up-regulated across all conditions, indicating a general stress response shared with aging, including the heat shock protein (Hsp) genes Hsp70, Hsp83 and l(2)efl, the glutathione-S-transferase gene GstD2, and the mitochondrial unfolded protein response (mUPR) gene ref(2)P. Selected gene expression changes were confirmed using quantitative PCR, Northern analysis and GstD-GFP reporter constructs. Certain genes were altered in only a subset of the conditions, for example, up-regulation of numerous developmental pathway and signaling genes in response to hydrogen peroxide. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hyperoxia, hydrogen peroxide, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.

  2. Gene expression changes in response to aging compared to heat stress, oxidative stress and ionizing radiation in Drosophila melanogaster.

    PubMed

    Landis, Gary; Shen, Jie; Tower, John

    2012-11-01

    Gene expression changes in response to aging, heat stress, hyperoxia, hydrogen peroxide, and ionizing radiation were compared using microarrays. A set of 18 genes were up-regulated across all conditions, indicating a general stress response shared with aging, including the heat shock protein (Hsp) genes Hsp70, Hsp83 and l(2)efl, the glutathione-S-transferase gene GstD2, and the mitochondrial unfolded protein response (mUPR) gene ref(2)P. Selected gene expression changes were confirmed using quantitative PCR, Northern analysis and GstD-GFP reporter constructs. Certain genes were altered in only a subset of the conditions, for example, up-regulation of numerous developmental pathway and signaling genes in response to hydrogen peroxide. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hyperoxia, hydrogen peroxide, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging. PMID:23211361

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

    PubMed

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

    2016-03-25

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

  4. Treadmill Exercise Attenuates Retinal Oxidative Stress in Naturally-Aged Mice: An Immunohistochemical Study.

    PubMed

    Kim, Chan-Sik; Park, Sok; Chun, Yoonseok; Song, Wook; Kim, Hee-Jae; Kim, Junghyun

    2015-01-01

    In the retina, a number of degenerative diseases, including glaucoma, diabetic retinopathy, and age-related macular degeneration, may occur as a result of aging. Oxidative damage is believed to contribute to the pathogenesis of aging as well as to age-related retinal disease. Although physiological exercise has been shown to reduce oxidative stress in rats and mice, it is not known whether it has a similar effect in retinal tissues. The aim of this study was to evaluate retinal oxidative stress in naturally-aged mice. In addition, we evaluated the effects of aerobic training on retinal oxidative stress by immunohistochemically evaluating oxidative stress markers. A group of twelve-week-old male mice were not exercised (young control). Two groups of twenty-two-month-old male mice were created: an old control group and a treadmill exercise group. The old control group mice were not exercised. The treadmill exercise group mice ran on a treadmill (5 to 12 m/min, 30 to 60 min/day, 3 days/week for 12 weeks). The retinal thickness and number of cells in the ganglion cell layer of the naturally-aged mice were reduced compared to those in the young control mice. However, treadmill exercise reversed these morphological changes in the retinas. We evaluated retinal expression of carboxymethyllysine (CML), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine. The retinas from the aged mice showed increased CML, 8-OHdG, and nitrotyrosine immunostaining intensities compared to young control mice. The exercise group exhibited significantly lower CML levels and nitro-oxidative stress than the old control group. These results suggest that regular exercise can reduce retinal oxidative stress and that physiological exercise may be distinctly advantageous in reducing retinal oxidative stress. PMID:26404251

  5. Beyond and behind the fingerprints of oxidative stress in age-related diseases: Secrets of successful aging.

    PubMed

    Polidori, M Cristina; Scholtes, Marlies

    2016-04-01

    Several years after the first publication of the definition of oxidative stress by Helmut Sies, this topic is still focus of a large body of attention and research in the field of aging, neurodegeneration and disease prevention. The conduction of clinical and epidemiological research without a solid biochemical rationale has led to largely frustrating results without being able to disprove the oxidative stress hypothesis. The present work is dedicated to Helmut Sies and describes the successful scientific approach to bench-to-bedside (-to-behavior) oxidative stress clinical research. PMID:27095215

  6. EFFECTS OF TOLUENE ON BRAIN OXIDATIVE STRESS PARAMETERS IN AGING BROWN NORWAY RATS

    EPA Science Inventory

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  7. Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys

    PubMed Central

    Castro, María del R.; Suarez, Edu; Kraiselburd, Edmundo; Isidro, Angel; Paz, José; Ferder, León; Ayala-Torres, Sylvette

    2013-01-01

    While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging. PMID:22027539

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

    PubMed Central

    Numan, Mohamed Saber; Brown, Jacques P.; Michou, Laëtitia

    2015-01-01

    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. PMID:25690002

  9. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    PubMed Central

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients. PMID:27095931

  10. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    PubMed

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan; Shirzad, Hedayatolah

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.

  11. Oxidative Stress and Adipocyte Biology: Focus on the Role of AGEs

    PubMed Central

    Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M. Faadiel

    2015-01-01

    Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression. PMID:25878764

  12. AGE-INDEPENDENT, GREY-MATTER-LOCALIZED, BRAIN ENHANCED OXIDATIVE STRESS IN MALE FISCHER 344 RATS,1,2

    EPA Science Inventory

    While studies showed that aging is accompanied by increased exposure of the brain to oxidative stress, others have not detected any age-correlated differences in levels of markers of oxidative stress. Use of conventional markers of oxidative damage in vivo, which may be formed ex...

  13. The role of oxidative and nitrosative stress in accelerated aging and major depressive disorder.

    PubMed

    Maurya, Pawan Kumar; Noto, Cristiano; Rizzo, Lucas B; Rios, Adiel C; Nunes, Sandra O V; Barbosa, Décio Sabbatini; Sethi, Sumit; Zeni, Maiara; Mansur, Rodrigo B; Maes, Michael; Brietzke, Elisa

    2016-02-01

    Major depressive disorder (MDD) affects millions of individuals and is highly comorbid with many age associated diseases such as diabetes mellitus, immune-inflammatory dysregulation and cardiovascular diseases. Oxidative/nitrosative stress plays a fundamental role in aging, as well as in the pathogenesis of neurodegenerative/neuropsychiatric disorders including MDD. In this review, we critically review the evidence for an involvement of oxidative/nitrosative stress in acceleration of aging process in MDD. There are evidence of the association between MDD and changes in molecular mechanisms involved in aging. There is a significant association between telomere length, enzymatic antioxidant activities (SOD, CAT, GPx), glutathione (GSH), lipid peroxidation (MDA), nuclear factor κB, inflammatory cytokines with MDD. Major depression also is characterized by significantly lower concentration of antioxidants (zinc, coenzyme Q10, PON1). Since, aging and MDD share a common biological base in their pathophysiology, the potential therapeutic use of antioxidants and anti-aging molecules in MDD could be promising.

  14. Oxidative stress induces age-dependent changes in lymphocyte protein synthesis and second messenger levels.

    PubMed

    Lopez-Hellin, J; Garcia-Arumi, E; Schwartz, S

    1998-01-01

    Cumulative damage in cells from aged people could lead to a greater fragility against acute oxidative stress. The effects of acute oxidative stress on cell viability, cAMP and cGMP concentrations, and protein synthesis rates were studied in lymphocytes from 25 young and 26 elderly subjects. Lymphocytes were exposed to stress by hydrogen peroxide 25 micromol/l and incubated for 18 hours. Cell viability after stress was lower (p<0.0001, Student's t test) in cells from the elderly (63.4%) than in cells from the young donors (73.2%). The protein synthesis rate was also lower after stress (p<0.04, Mann-Whitney U test) in cells from the elderly (47.3% vs. non-stressed cells), than in cells from the young (82.19% vs. non-stressed cells). After oxidative stress, cAMP and cGMP concentrations showed no significant changes in cells from young subjects; there were, however, significant decreases in these cyclic nucleotides in cells from the elderly (p<0.008 for both nucleotides, paired Student's t test). There were no differences in basal cAMP or cGMP levels between the two groups. These results show that mortality and metabolic changes due to oxidative stress are greater in lymphocytes proceeding from elderly subjects than in those from young subjects.

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

    PubMed Central

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

    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 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. PMID:24002027

  16. Interrelation Between Oxidative Stress and Complement Activation in Models of Age-Related Macular Degeneration.

    PubMed

    Pujol-Lereis, Luciana M; Schäfer, Nicole; Kuhn, Laura B; Rohrer, Bärbel; Pauly, Diana

    2016-01-01

    Millions of individuals older than 50-years suffer from age-related macular degeneration (AMD). Associated with this multifactorial disease are polymorphisms of complement factor genes and a main environmental risk factor-oxidative stress. Until now the linkage between these risk factors for AMD has not been fully understood. Recent studies, integrating results on oxidative stress, complement activation, epidemiology and ocular pathology suggested the following sequence in AMD-etiology: initially, chronic oxidative stress results in modification of proteins and lipids in the posterior of the eye; these tissue alterations trigger chronic inflammation, involving the complement system; and finally, invasive immune cells facilitate pathology in the retina. Here, we summarize the results for animal studies which aim to elucidate this molecular interplay of oxidative events and tissue-specific complement activation in the eye.

  17. The role of intracellular zinc release in aging, oxidative stress, and Alzheimer’s disease

    PubMed Central

    McCord, Meghan C.; Aizenman, Elias

    2014-01-01

    Brain aging is marked by structural, chemical, and genetic changes leading to cognitive decline and impaired neural functioning. Further, aging itself is also a risk factor for a number of neurodegenerative disorders, most notably Alzheimer’s disease (AD). Many of the pathological changes associated with aging and aging-related disorders have been attributed in part to increased and unregulated production of reactive oxygen species (ROS) in the brain. ROS are produced as a physiological byproduct of various cellular processes, and are normally detoxified by enzymes and antioxidants to help maintain neuronal homeostasis. However, cellular injury can cause excessive ROS production, triggering a state of oxidative stress that can lead to neuronal cell death. ROS and intracellular zinc are intimately related, as ROS production can lead to oxidation of proteins that normally bind the metal, thereby causing the liberation of zinc in cytoplasmic compartments. Similarly, not only can zinc impair mitochondrial function, leading to excess ROS production, but it can also activate a variety of extra-mitochondrial ROS-generating signaling cascades. As such, numerous accounts of oxidative neuronal injury by ROS-producing sources appear to also require zinc. We suggest that zinc deregulation is a common, perhaps ubiquitous component of injurious oxidative processes in neurons. This review summarizes current findings on zinc dyshomeostasis-driven signaling cascades in oxidative stress and age-related neurodegeneration, with a focus on AD, in order to highlight the critical role of the intracellular liberation of the metal during oxidative neuronal injury. PMID:24860495

  18. Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

    PubMed Central

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

  19. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    PubMed

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  20. Age-induced hair greying - the multiple effects of oxidative stress.

    PubMed

    Seiberg, M

    2013-12-01

    An obvious sign of ageing is hair greying, or the loss of pigment production and deposition within the hair shafts. Numerous mechanisms, acting at different levels and follicular locations, contribute to hair greying, ranging from melanocyte stem cells defects to follicular melanocyte death. One key issue that is in common to these processes is oxidative damage. At the hair follicle stem cells niche, oxidative stress, accelerated by B-cell lymphoma 2 gene (BCL-2) depletion, leads to selective apoptosis and diminution of melanocyte stem cells, reducing the repopulation of newly formed anagen follicles. Melanotic bulbar melanocytes express high levels of BCL-2 to enable survival from melanogenesis- and ultraviolet A (UVA)-induced reactive oxygen species (ROS) attacks. With ageing, the bulbar melanocyte expression of anti-oxidant proteins such as BCL-2, and possibly TRP-2, is reduced, and the dedicated enzymatic anti-oxidant defence system throughout the follicle weakens, resulting in enhanced oxidative stress. A marked reduction in catalase expression and activity results in millimolar accumulation of hydrogen peroxide, contributing to bulbar melanocyte malfunction and death. Interestingly, amelanotic melanocytes at the outer root sheath (ORS) are somewhat less affected by these processes and survive for longer time even within the white, ageing hair follicles. Better understanding of the overtime susceptibility of melanocytes to oxidative stress at the different follicular locations might yield clues to possible therapies for the prevention and reversal of hair greying.

  1. [The role of oxidative stress in skin aging].

    PubMed

    Kozina, L S; Borzova, I V; Arutiunov, V A; Ryzhak, G A

    2012-01-01

    The review covers the literature proving that ROS formation in aging overbalances the antioxidant defense system potential of the skin structure (horny layer, epidermis and dermis). It has been shown that ROS are involved in the pathogenesis of inflammatory processes and allergic responses in the skin. The role of ROS and antioxidant systems in the cell-mediated responses associated with the MAP kinase activity in the skin is discussed. Special attention is paid to the ultraviolet irradiation exposure, which accounts for its genotoxic, immunosuppressive and carcinogenic effects on the skin.

  2. Effect of crocin on aged rat kidney through inhibition of oxidative stress and proinflammatory state.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Borji, Abasalt; Farkhondeh, Tahereh

    2016-08-01

    This study evaluated whether crocin, a bioactive component of saffron, has a protective effect on kidney through reducing the oxidative stress and inflammatory response in aged rats. In this study the changes in activities of antioxidant enzymes, lipid peroxidation, glutathione (GSH) levels and the expression of pro-inflammatory cytokines in the serum and renal tissue were evaluated by ELISA and RT-PCR, respectively. The middle and aged rats were given intraperitoneal injections of crocin (10, 20, 30 mg/kg/day) for 4 weeks. After 4 weeks, animals were anesthetized with diethyl ether. The kidney samples were taken for biochemical analysis. The results revealed the aging was associated with a significant decrease in the activities of antioxidant enzymes, and GSH content with increase in lipid peroxidation level in kidney of the aged rats (p < 0.001). The increased levels of serum renal functional parameter, oxidative parameters (p < 0.01) and also pro-inflammatory cytokine levels were significantly reduced by crocin administration (p < 0.05). The aged rats exhibited a dysregulation of the oxidative stress, and inflammation in the kidneys, but crocin treatment significantly reduced the expression of the inflammatory genes. These results provide pivotal documentation that crocin has a renoprotective effects against the development of oxidative stress and inflammation in the kidney of old rats. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27279282

  3. Cardiac Aging in Mice and Humans: the Role of Mitochondrial Oxidative Stress

    PubMed Central

    Dai, Dao-Fu; Rabinovitch, Peter S.

    2009-01-01

    Age is a major risk factor for cardiovascular diseases, not only because it prolongs exposure to several other cardiovascular risks, but also owing to intrinsic cardiac aging, which reduces cardiac functional reserve, predisposes the heart to stress and contributes to increased cardiovascular mortality in the elderly. Intrinsic cardiac aging in the murine model closely recapitulates age-related cardiac changes in humans, including left ventricular hypertrophy, fibrosis and diastolic dysfunction. Cardiac aging in mice is accompanied by accumulation of mitochondrial protein oxidation, increased mitochondrial DNA mutations, increased mitochondrial biogenesis, as well as decreased cardiac SERCA2 protein. All of these age-related changes are significantly attenuated in mice overexpressing catalase targeted to mitochondria (mCAT). These findings demonstrate the critical role of mitochondrial reactive oxygen species (ROS) in cardiac aging and support the potential application of mitochondrial antioxidants to cardiac aging and age-related cardiovascular diseases. PMID:20382344

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

    PubMed Central

    Salmon, Adam B.

    2016-01-01

    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. PMID:27438860

  5. Oxidative Stress and Salvia miltiorrhiza in Aging-Associated Cardiovascular Diseases

    PubMed Central

    Chang, Yu-Chun

    2016-01-01

    Aging-associated cardiovascular diseases (CVDs) have some risk factors that are closely related to oxidative stress. Salvia miltiorrhiza (SM) has been used commonly to treat CVDs for hundreds of years in the Chinese community. We aimed to explore the effects of SM on oxidative stress in aging-associated CVDs. Through literature searches using Medicine, PubMed, EMBASE, Cochrane library, CINAHL, and Scopus databases, we found that SM not only possesses antioxidant, antiapoptotic, and anti-inflammatory effects but also exerts angiogenic and cardioprotective activities. SM may reduce the production of reactive oxygen species by inhibiting oxidases, reducing the production of superoxide, inhibiting the oxidative modification of low-density lipoproteins, and ameliorating mitochondrial oxidative stress. SM also increases the activities of catalase, manganese superoxide dismutase, glutathione peroxidase, and coupled endothelial nitric oxide synthase. In addition, SM reduces the impact of ischemia/reperfusion injury, prevents cardiac fibrosis after myocardial infarction, preserves cardiac function in coronary disease, maintains the integrity of the blood-brain barrier, and promotes self-renewal and proliferation of neural stem/progenitor cells in stroke. However, future clinical well-designed and randomized control trials will be necessary to confirm the efficacy of SM in aging-associated CVDs. PMID:27807472

  6. Tadalafil enhances working memory, and reduces hippocampal oxidative stress in both young and aged mice.

    PubMed

    Al-Amin, Md Mamun; Hasan, S M Nageeb; Alam, Tanzir; Hasan, Ahmed Tasdid; Hossain, Imran; Didar, Rohini Rowshan; Alam, Md Ashraful; Rahman, Md Mahbubur

    2014-12-15

    Tadalafil, a type-5 phosphodiesterase enzyme inhibitor with long half-life used to treat erectile dysfunction. Recently it has been reported that tadalafil improves cognitive function. Here, we aimed to investigate the age dependent effects of tadalafil on memory, locomotor, behavior, and oxidative stress in the hippocampus. Tadalafil was orally administered everyday (5 mg/kg) to young (2 months) and old (16 months) healthy mice for 4 weeks. Control mice from each group received equal volume of 0.9% normal saline for the same duration. Memory and locomotor activity were tested using radial arm maze and open field test respectively. The level of malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) was analyzed and catalase activity was determined from the isolated hippocampus. Treatment with tadalafil in aged mice improves working memory than the corresponding tadalafil treated young mice in radial arm maze test. Tadalafil treated mice traveled less distance in the center and the mean speed of tadalafil treated aged mice was significantly lower than the tadalafil treated young mice in open field test. Tadalafil treatment elicited a decrease of MDA level in the hippocampus of aged mice than that of young mice. APOP level was decreased only in aged mice treated with tadalafil. Treatment with tadalafil decreased NO and increased catalase activity in both young and aged mice. On the basis of previous and our findings, we conclude that tadalafil treatment reduces oxidative stress while increased cGMP level in the hippocampus might be responsible for memory enhancement.

  7. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

    SciTech Connect

    Zana, Marianna . E-mail: mzana@freemail.hu; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Vetro, Agnes; Pakaski, Magdolna; Janka, Zoltan; Kalman, Janos; Szabo, Krisztina; Szucs, Peter; Varkonyi, Agnes; Boda, Krisztina; Rasko, Istvan

    2006-06-30

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults.

  8. Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

    PubMed Central

    Cencioni, Chiara; Spallotta, Francesco; Martelli, Fabio; Valente, Sergio; Mai, Antonello; Zeiher, Andreas M.; Gaetano, Carlo

    2013-01-01

    Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies. PMID:23989608

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

    PubMed Central

    Petersen, K. S.

    2016-01-01

    Advanced age is associated with increased incidence of a variety of chronic disease states which share oxidative stress and inflammation as causative role players. Furthermore, data point to a role for both cumulative oxidative stress and low grade inflammation in the normal ageing process, independently of disease. Therefore, arguably the best route with which to address premature ageing, as well as age-associated diseases such as diabetes, cardiovascular disease, and dementia, is preventative medicine aimed at modulation of these two responses, which are intricately interlinked. In this review, we provide a detailed account of the literature on the communication of these systems in the context of ageing, but with inclusion of relevant data obtained in other models. In doing so, we attempted to more clearly elucidate or identify the most probable cellular or molecular targets for preventative intervention. In addition, given the absence of a clear pharmaceutical solution in this context, together with the ever-increasing consumer bias for natural medicine, we provide an overview of the literature on grape (Vitis vinifera) derived products, for which beneficial effects are consistently reported in the context of both oxidative stress and inflammation. PMID:27034739

  10. Skeletal Involution by Age-associated Oxidative Stress and Its Acceleration by Loss of Sex Steroids*

    PubMed Central

    Almeida, Maria; Han, Li; Martin-Millan, Marta; Plotkin, Lilian I.; Stewart, Scott A.; Roberson, Paula K.; Kousteni, Stavroula; O’Brien, Charles A.; Bellido, Teresita; Parfitt, A. Michael; Weinstein, Robert S.; Jilka, Robert L.; Manolagas, Stavros C.

    2011-01-01

    Both aging and loss of sex steroids have adverse effects on skeletal homeostasis, but whether and how they may influence each others negative impact on bone remains unknown. We report herein that both female and male C57BL/6 mice progressively lost strength (as determined by load-to-failure measurements) and bone mineral density in the spine and femur between the ages of 4 and 31 months. These changes were temporally associated with decreased rate of remodeling as evidenced by decreased osteoblast and osteoclast numbers and decreased bone formation rate; as well as increased osteoblast and osteocyte apoptosis, increased reactive oxygen species levels, and decreased glutathione reductase activity and a corresponding increase in the phosphorylation of p53 and p66shc, two key components of a signaling cascade that are activated by reactive oxygen species and influences apoptosis and lifespan. Exactly the same changes in oxidative stress were acutely reproduced by gonadectomy in 5-month-old females or males and reversed by estrogens or androgens in vivo as well as in vitro.We conclude that the oxidative stress that underlies physiologic organismal aging in mice may be a pivotal pathogenetic mechanism of the age-related bone loss and strength. Loss of estrogens or androgens accelerates the effects of aging on bone by decreasing defense against oxidative stress. PMID:17623659

  11. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    PubMed Central

    Reinisalo, Mika; Kårlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O.

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer's disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2) mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed. PMID:26180583

  12. Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction.

    PubMed

    Guan, Lili; Feng, Haiyan; Gong, Dezheng; Zhao, Xu; Cai, Li; Wu, Qiong; Yuan, Bo; Yang, Mei; Zhao, Jie; Zou, Yuan

    2013-12-01

    Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial dysfunction are supposed to be major factors leading to age-related IR. Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of genipin on insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive intraperitoneal injections of either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the decreased glucose decay constant rate during insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced glycogen content. Hepatic malondialdehyde level and mitochondrial reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower as compared with the normal control rats. Administration of genipin ameliorated systemic and hepatic insulin resistance, alleviated hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved insulin sensitivity by promoting insulin-stimulated glucose consumption and glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of MMP and ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02 hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. PMID:24041487

  13. Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction

    PubMed Central

    Mikhed, Yuliya; Daiber, Andreas; Steven, Sebastian

    2015-01-01

    The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan. PMID:26184181

  14. Brain aging, memory impairment and oxidative stress: a study in Drosophila melanogaster.

    PubMed

    Haddadi, Mohammad; Jahromi, Samaneh Reiszadeh; Sagar, B K Chandrasekhar; Patil, Rajashekhar K; Shivanandappa, T; Ramesh, S R

    2014-02-01

    Memory impairment during aging is believed to be a consequence of decline in neuronal function and increase in neurodegeneration. Accumulation of oxidative damage and reduction of antioxidant defense system play a key role in organismal aging and functional senescence. In our study, we examined the age-related memory impairment (AMI) in relation to oxidative stress using Drosophila model. We observed a decline in cognitive function in old flies with respect to both short-lived and consolidated forms of olfactory memory. Light and electron microscopy of mushroom bodies revealed a reduction in the number of synapses and discernible architectural defects in mitochondria. An increase in neuronal apoptosis in Kenyon cells was also evident in aged flies. Biochemical investigations revealed a comparable age-associated decrease in the activity of antioxidant enzymes such as catalase and superoxide dismutase as well as the GSH level, accompanied by an increase in the level of lipid peroxidation and generation of reactive oxygen species in the brain. There was no significant difference in the activity level of AChE and BChE enzymes between different age groups while immunohistochemical studies showed a significant decrease in the level of ChAT in 50-day-old flies. RNAi-mediated silencing of cat and sod1 genes caused severe memory impairment in 15-day-old flies, whereas, over-expression of cat gene could partially rescue the memory loss in the old flies. We demonstrated that a Drosophila long-lived strain, possessing enhanced activity of antioxidant enzymes and higher rate of resistance to oxidative stress, shows lower extent of AMI compared to normal lifespan strain. Present study provides evidence for involvement of oxidative stress in AMI in Drosophila. PMID:24183945

  15. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain.

    PubMed

    Simpson, Tamara; Pase, Matthew; Stough, Con

    2015-01-01

    The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer's disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function.

  16. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

    PubMed Central

    Simpson, Tamara; Pase, Matthew; Stough, Con

    2015-01-01

    The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer's disease. The Indian herb Bacopa monnieri is a dietary antioxidant, with animal and in vitro studies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts of Bacopa monnieri improve cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies and in vivo evidence for Bacopa monnieri as a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant status in vivo cause improvements in cognitive function. PMID:26413126

  17. Fructose and glucose differentially affect aging and carbonyl/oxidative stress parameters in Saccharomyces cerevisiae cells.

    PubMed

    Semchyshyn, Halyna M; Lozinska, Liudmyla M; Miedzobrodzki, Jacek; Lushchak, Volodymyr I

    2011-05-15

    Fructose is commonly used as an industrial sweetener and has been excessively consumed in human diets in the last decades. High fructose intake is causative in the development of metabolic disorders, but the mechanisms underlying fructose-induced disturbances are under debate. Fructose compared to glucose has been found to be a more potent initiator of the glycation reaction. Therefore, we supposed that glucose and fructose might have different vital effects. Here we compare the effects of glucose and fructose on yeast cell viability and markers of carbonyl/oxidative stress. Analysis of the parameters in cells growing on glucose and fructose clearly reveals that yeast growing on fructose has higher levels of carbonyl groups in proteins, α-dicarbonyl compounds and reactive oxygen species. This may explain the observation that fructose-supplemented growth as compared with growth on glucose resulted in more pronounced age-related decline in yeast reproductive ability and higher cell mortality. The results are discussed from the point of view that fructose rather than glucose is more extensively involved in glycation and ROS generation in vivo, yeast aging and development of carbonyl/oxidative stress. It should be noted that carbohydrate restriction used in this study does not reveal a significant difference between markers of aging and carbonyl/oxidative stress in yeasts cultivated on glucose and fructose.

  18. Aging Exacerbates Pressure-Induced Mitochondrial Oxidative Stress in Mouse Cerebral Arteries.

    PubMed

    Springo, Zsolt; Tarantini, Stefano; Toth, Peter; Tucsek, Zsuzsanna; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-11-01

    Epidemiological studies demonstrate that in addition to the increased prevalence of hypertension in old patients, the deleterious cerebrovascular effects of hypertension (including atherosclerosis, stroke, and vascular cognitive impairment) are also exacerbated in elderly individuals. The cellular mechanisms by which aging and hypertension interact to promote cerebrovascular pathologies are not well understood. To test the hypothesis that aging exacerbates high pressure-induced mitochondrial oxidative stress, we exposed isolated segments of the middle cerebral arteries of young (3 months) and aged (24 months) C57BL/6 mice to 60 or 140 mmHg intraluminal pressure and assessed changes in mitochondrial reactive oxygen species production using a mitochondria-targeted redox-sensitive fluorescent indicator dye (MitoSox) by confocal microscopy. Perinuclear MitoSox fluorescence was significantly stronger in high pressure-exposed middle cerebral arteries compared with middle cerebral arteries of the same animals exposed to 60 mmHg, indicating that high pressure increases mitochondrial reactive oxygen species production in the smooth muscle cells of cerebral arteries. Comparison of young and aged middle cerebral arteries showed that aging exacerbates high pressure-induced mitochondrial reactive oxygen species production in cerebral arteries. We propose that increased mechanosensitive mitochondrial oxidative stress may potentially exacerbate cerebrovascular injury and vascular inflammation in aging.

  19. Oxidative Stress Is a Central Target for Physical Exercise Neuroprotection Against Pathological Brain Aging.

    PubMed

    García-Mesa, Yoelvis; Colie, Sandra; Corpas, Rubén; Cristòfol, Rosa; Comellas, Francesc; Nebreda, Angel R; Giménez-Llort, Lydia; Sanfeliu, Coral

    2016-01-01

    Physical exercise is suggested for preventing or delaying senescence and Alzheimer's disease (AD). We have examined its therapeutic value in the advanced stage of AD-like pathology in 3xTg-AD female mice through voluntary wheel running from 12 to 15 months of age. Mice submitted to exercise showed improved body fitness, immunorejuvenation, improvement of behavior and cognition, and reduced amyloid and tau pathology. Brain tissue analysis of aged 3xTg-AD mice showed high levels of oxidative damage. However, this damage was decreased by physical exercise through regulation of redox homeostasis. Network analyses showed that oxidative stress was a central event, which correlated with AD-like pathology and the AD-related behaviors of anxiety, apathy, and cognitive loss. This study corroborates the importance of redox mechanisms in the neuroprotective effect of physical exercise, and supports the theory of the crucial role of oxidative stress in the switch from normal brain aging to pathological aging and AD.

  20. The SODyssey: superoxide dismutases from biochemistry, through proteomics, to oxidative stress, aging and nutraceuticals.

    PubMed

    D'Alessandro, Angelo; Zolla, Lello

    2011-06-01

    A total of 40 years have already passed since the pioneering work of McCord and Fridovich on erythrocuprein superoxide dismutase (SOD) activity. This modern scientific 'Odyssey' has been accompanied by a series of successes in the fields of biochemistry, biomedicine and proteomics. In this article, we resume the main strides in these fields, mainly aiming at delivering an exhaustive portrait of SOD's involvement in several oxidative stress-triggered threats to human health, including neurodegenerative disorders (amyotrophic lateral sclerosis, Alzheimer's, Parkinson's and Huntington's diseases), cardiovascular diseases, cancer and aging. In parallel, food-derived chemical compounds appear to be intertwined with cellular redox poise modulation, as this increasingly emerges from clinical biochemical and proteomic investigations. Thus, we will also consider the involvement of these nutraceuticals in oxidative stress-triggered diseases and SOD activity modulation. Like a modern Ulysses, researchers know that the journey is not yet over. Nevertheless, much information has been gathered over the last four decades. PMID:21679120

  1. NOX4 NADPH Oxidase-Dependent Mitochondrial Oxidative Stress in Aging-Associated Cardiovascular Disease

    PubMed Central

    Vendrov, Aleksandr E.; Vendrov, Kimberly C.; Smith, Alberto; Yuan, Jinling; Sumida, Arihiro; Robidoux, Jacques; Madamanchi, Nageswara R.

    2015-01-01

    Abstract Aims: Increased oxidative stress and vascular inflammation are implicated in increased cardiovascular disease (CVD) incidence with age. We and others demonstrated that NOX1/2 NADPH oxidase inhibition, by genetic deletion of p47phox, in Apoe−/− mice decreases vascular reactive oxygen species (ROS) generation and atherosclerosis in young age. The present study examined whether NOX1/2 NADPH oxidases are also pivotal to aging-associated CVD. Results: Both aged (16 months) Apoe−/− and Apoe−/−/p47phox−/− mice had increased atherosclerotic lesion area, aortic stiffness, and systolic dysfunction compared with young (4 months) cohorts. Cellular and mitochondrial ROS (mtROS) levels were significantly higher in aortic wall and vascular smooth muscle cells (VSMCs) from aged wild-type and p47phox−/− mice. VSMCs from aged mice had increased mitochondrial protein oxidation and dysfunction and increased vascular cell adhesion molecule 1 expression, which was abrogated with (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) treatment. NOX4 expression was increased in the vasculature and mitochondria of aged mice and its suppression with shRNA in VSMCs from aged mice decreased mtROS levels and improved function. Increased mtROS levels were associated with enhanced mitochondrial NOX4 expression in aortic VSMCs from aged subjects, and NOX4 expression levels in arterial wall correlated with age and atherosclerotic severity. Aged Apoe−/− mice treated with MitoTEMPO and 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione had decreased vascular ROS levels and atherosclerosis and preserved vascular and cardiac function. Innovation and Conclusion: These data suggest that NOX4, but not NOX1/2, and mitochondrial oxidative stress are mediators of CVD in aging under hyperlipidemic conditions. Regulating NOX4 activity/expression and using mitochondrial antioxidants are

  2. Nitric oxide and cellular stress response in brain aging and neurodegenerative disorders: the role of vitagenes.

    PubMed

    Calabrese, Vittorio; Boyd-Kimball, Debra; Scapagnini, Giovanni; Butterfield, D Allan

    2004-01-01

    nitrosative stress. An amount of experimental evidence indicates that increased rate of free radical generation and decreased efficiency of the reparative/degradative mechanisms, such as proteolysis, are factors that primarily contribute to age-related elevation in the level of oxidative stress and brain damage. Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing such a response. These findings have led to new perspectives in medicine and pharmacology, as molecules inducing this defense mechanism appear to be possible candidates for novel, cytoprotective strategies. Particularly, manipulation of endogenous cellular defense mechanisms such as the heat shock response, through nutritional antioxidants or pharmacological compounds, represents an innovative approach to therapeutic intervention in diseases causing tissue damage, such as neurodegeneration. Consistent with this notion, maintenance or recovery of the activity of vitagenes may possibly delay the aging process and decrease the occurrence of age-related diseases with resulting prolongation of a healthy life span.

  3. [The correlations between aging of the human body, oxidative stress and reduced efficiency of repair systems].

    PubMed

    Michalak, Aleksandra; Krzeszowiak, Jakub; Markiewicz-Górka, Iwona

    2014-12-15

    The article presents an current knowledge overview about the importance of oxidative stress and reduced efficiency of repair processes during the aging process of the human body. Oxidative damage to cellular macromolecules (proteins, lipids, nucleic acids), are formed under the influence of reactive oxygen species (ROS). They are the part of important mechanism which is responsible for the process of aging and the development of many diseases. The most important effects result from DNA damage, due to the mutations formation, which can lead to the development of tumors. However, a well-functioning repair systems (i.a. homologous recombination) remove the damage and prevent harmful changes in the cells. Lipid peroxidation products also cause oxidative modification of nucleic acids (and proteins). Proteins and fats also have repair systems, but much simpler than those responsible for the repair of nucleic acids. Unfortunately, with increasing age, they are more weakened, which contributes to increase numbers of cell damage, and consequently development of diseases specific to old age: cancer, neurodegenerative diseases or atherosclerosis.

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

    PubMed

    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.

  5. The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

    PubMed Central

    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. PMID:25949771

  6. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

    PubMed

    Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-04-01

    D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats. PMID:26518192

  7. Carnosine and taurine treatments diminished brain oxidative stress and apoptosis in D-galactose aging model.

    PubMed

    Aydın, A Fatih; Çoban, Jale; Doğan-Ekici, Işın; Betül-Kalaz, Esra; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2016-04-01

    D-galactose (GAL) has been used as an animal model for brain aging and antiaging studies. GAL stimulates oxidative stress in several tissues including brain. Carnosine (CAR; β-alanil-L-histidine) and taurine (TAU; 2-aminoethanesulfonic acid) exhibit antioxidant properties. CAR and TAU have anti-aging and neuroprotective effects. We investigated the effect of CAR and TAU supplementations on oxidative stress and brain damage in GAL-treated rats. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with CAR (250 mg/kg/daily; i.p.; 5 days per week) or TAU (2.5% w/w; in rat chow) for 2 months. Brain malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione transferase (GST) and acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brains by immunohistochemistry. GAL treatment increased brain MDA and PC levels and AChE activities. It decreased significantly brain GSH levels, SOD and GSH-Px but not GST activities. GAL treatment caused histopathological changes and increased apoptosis. CAR and TAU significantly reduced brain AChE activities, MDA and PC levels and elevated GSH levels in GAL-treated rats. CAR, but not TAU, significantly increased low activities of SOD and GSH-Px. Both CAR and TAU diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. Our results indicate that CAR and TAU may be effective to prevent the development of oxidative stress, apoptosis and histopathological deterioration in the brain of GAL-treated rats.

  8. Impact of Oxidative Stress in Premature Aging and Iron Overload in Hemodialysis Patients

    PubMed Central

    Hernández Vázquez, Wendy Ivett; Solorio-Meza, Sergio; Albarrán-Tamayo, Froylán; Ramos-Rodríguez, Edna; Benítez- Bribiesca, Luis

    2016-01-01

    Background. Increased oxidative stress is a well described feature of patients in hemodialysis. Their need for multiple blood transfusions and supplemental iron causes a significant iron overload that has recently been associated with increased oxidation of polyunsaturated lipids and accelerated aging due to DNA damage caused by telomere shortening. Methods. A total of 70 patients were evaluated concomitantly, 35 volunteers with ferritin levels below 500 ng/mL (Group A) and 35 volunteers with ferritin levels higher than 500 ng/mL (Group B). A sample of venous blood was taken to extract DNA from leukocytes and to measure relative telomere length by real-time PCR. Results. Patients in Group B had significantly higher plasma TBARS (p = 0.008), carbonyls (p = 0.0004), and urea (p = 0.02) compared with those in Group A. Telomeres were significantly shorter in Group B, 0.66 (SD, 0.051), compared with 0.75 (SD, 0.155) in Group A (p = 0.0017). We observed a statistically significant association between relative telomere length and ferritin levels (r = −0.37, p = 0.001). Relative telomere length was inversely related to time on hemodialysis (r = −0.27, p = 0.02). Conclusions. Our findings demonstrate that iron overload was associated with increased levels of oxidative stress and shorter relative telomere length. PMID:27800120

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

    PubMed

    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.

  10. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice.

    PubMed

    de Picciotto, Natalie E; Gano, Lindsey B; Johnson, Lawrence C; Martens, Christopher R; Sindler, Amy L; Mills, Kathryn F; Imai, Shin-Ichiro; Seals, Douglas R

    2016-06-01

    We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD(+) intermediate, increases arterial SIRT1 activity and reverses age-associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium-dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)-mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age-associated impairment in EDD was restored in OC by the superoxide (O2-) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s(-1) vs. 337 ± 3 cm s(-1) ) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O2- production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen-I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO-mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s(-1) ) and EM (3694 ± 315 kPa), normalized O2- production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen-I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD(+) threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age-related arterial dysfunction by decreasing oxidative stress.

  11. Oxidative stress induces the decline of brain EPO expression in aging rats.

    PubMed

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    .699, p<0.01), EPO (r=-0.701, p<0.01) and the MDA level. These results indicated that aging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability. PMID:27452792

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

    PubMed

    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

  13. TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE AND SENESCENT BROWN NORWAY RATS

    EPA Science Inventory

    Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for tol...

  14. AGING AND LIFE-STAGE SUSCEPTIBILITY: TOLUENE EFFECTS ON BRAIN OXIDATIVE STRESS PARAMETERS IN BROWN NORWAY RATS.

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is poorly understood. The objectives of this study were to test whether oxidative stress (OS) is a potential toxicity pathway following toluene exposure and to determine if these effects are age-dependent. We ...

  15. Telomere protein RAP1 levels are affected by cellular aging and oxidative stress

    PubMed Central

    Swanson, Mark J.; Baribault, Michelle E.; Israel, Joanna N.; Bae, Nancy S.

    2016-01-01

    Telomeres are important for maintaining the integrity of the genome through the action of the shelterin complex. Previous studies indicted that the length of the telomere did not have an effect on the amount of the shelterin subunits; however, those experiments were performed using immortalized cells with stable telomere lengths. The interest of the present study was to observe how decreasing telomere lengths over successive generations would affect the shelterin subunits. As neonatal human dermal fibroblasts aged and their telomeres became shorter, the levels of the telomere-binding protein telomeric repeat factor 2 (TRF2) decreased significantly. By contrast, the levels of one of its binding partners, repressor/activator protein 1 (RAP1), decreased to a lesser extent than would be expected from the decrease in TRF2. Other subunits, TERF1-interacting nuclear factor 2 and protection of telomeres protein 1, remained stable. The decrease in RAP1 in the older cells occurred in the nuclear and cytoplasmic fractions. Hydrogen peroxide (H2O2) stress was used as an artificial means of aging in the cells, and this resulted in RAP1 levels decreasing, but the effect was only observed in the nuclear portion. Similar results were obtained using U251 glioblastoma cells treated with H2O2 or grown in serum-depleted medium. The present findings indicate that TRF2 and RAP1 levels decrease as fibroblasts naturally age. RAP1 remains more stable compared to TRF2. RAP1 also responds to oxidative stress, but the response is different to that observed in aging. PMID:27446538

  16. Impaired Transcriptional Activity of Nrf2 in Age-Related Myocardial Oxidative Stress Is Reversible by Moderate Exercise Training

    PubMed Central

    Gounder, Sellamuthu S.; Kannan, Sankaranarayanan; Devadoss, Dinesh; Miller, Corey J.; Whitehead, Kevin S.; Odelberg, Shannon J.; Firpo, Matthew A.; Paine, Robert; Hoidal, John R.; Abel, E. Dale; Rajasekaran, Namakkal S.

    2012-01-01

    Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS) in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2) through antioxidant response cis-elements (AREs) and are impaired in the aging heart. Whereas acute exercise stress (AES) activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (∼2 months), aging mouse (>23 months) hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES), but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day) for ∼6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases. PMID:23029187

  17. Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging.

    PubMed

    Ngo, Jenny K; Pomatto, Laura C D; Davies, Kelvin J A

    2013-02-09

    The elimination of oxidatively modified proteins is a crucial process in maintaining cellular homeostasis, especially during stress. Mitochondria are protein-dense, high traffic compartments, whose polypeptides are constantly exposed to superoxide, hydrogen peroxide, and other reactive species, generated by 'electron leakage' from the respiratory chain. The level of oxidative stress to mitochondrial proteins is not constant, but instead varies greatly with numerous metabolic and environmental factors. Oxidized mitochondrial proteins must be removed rapidly (by proteolytic degradation) or they will aggregate, cross-link, and cause toxicity. The Lon Protease is a key enzyme in the degradation of oxidized proteins within the mitochondrial matrix. Under conditions of acute stress Lon is highly inducible, possibly with the oxidant acting as the signal inducer, thereby providing increased protection. It seems that under chronic stress conditions, however, Lon levels actually decline. Lon levels also decline with age and with senescence, and senescent cells even lose the ability to induce Lon during acute stress. We propose that the regulation of Lon is biphasic, in that it is up-regulated during transient stress and down-regulated during chronic stress and aging, and we suggest that the loss of Lon responsiveness may be a significant factor in aging, and in age-related diseases.

  18. Habitually exercising older men do not demonstrate age-associated vascular endothelial oxidative stress.

    PubMed

    Pierce, Gary L; Donato, Anthony J; LaRocca, Thomas J; Eskurza, Iratxe; Silver, Annemarie E; Seals, Douglas R

    2011-12-01

    We tested the hypothesis that older men who perform habitual aerobic exercise do not demonstrate age-associated vascular endothelial oxidative stress compared with their sedentary peers. Older exercising men (n=13, 62±2 years) had higher (P<0.05) physical activity (79±7 vs. 30±6 MET hours per week) and maximal exercise oxygen consumption (42±1 vs. 29±1 mL kg(-1) per minute) vs. sedentary men (n=28, 63±1 years). Brachial artery flow-mediated dilation (FMD), a measure of vascular endothelial function, was greater (P<0.05) in the exercising vs. sedentary older men (6.3±0.5 vs. 4.9±0.4%Δ) and not different than young controls (n=20, 25±1 years, 7.1±0.5%Δ). In vascular endothelial cells sampled from the brachial artery, nitrotyrosine, a marker of oxidative stress, was 51% lower in the exercising vs. sedentary older men (0.38±0.06 vs. 0.77±0.10 AU). This was associated with lower endothelial expression of the oxidant enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47(phox) subunit, 0.33±0.05 vs. 0.61±0.09 AU) and the redox-sensitive transcription factor nuclear factor kappa B (NFκB) (p65 subunit, 0.36±0.05 vs. 0.72±0.09 AU). Expression of the antioxidant enzyme manganese superoxide dismutase (SOD) (0.57±0.13 vs. 0.30±0.04 AU) and activity of endothelium-bound extracellular SOD were greater (6.4±0.5 vs. 5.0±0.6 U mL(-1) per minute) in the exercising men (both P<0.05), but differences no longer were significant after correcting for adiposity and circulating metabolic factors. Overall, values for the young controls differed with those for the sedentary, but not the exercising older men. Older men who exercise regularly do not demonstrate vascular endothelial oxidative stress, and this may be a key molecular mechanism underlying their reduced risk of cardiovascular diseases.

  19. [Defects in TOR regulatory complexes retard aging and carbonyl/oxidative stress development in yeast Saccharomyces cerevisiae].

    PubMed

    Homza, B V; Vasyl'kovs'ka, R A; Semchyshyn, H M

    2014-01-01

    TOR signaling pathway first described in yeast S. cerevisiae is the highly conserved regulator of eukaryotic cell growth, aging and stress resistance. The effect of nitrogen sources, in particular amino acids, on the activity of TOR signaling pathway is well studied, however its relation to carbohydrates is poor understood. The aim of the present study is expanding of our understanding of potential role of TOR regulatory complexes in development of carbonyl/oxidative stress that can result from yeast cultivation on glucose and fructose. It has been shown that the level of alpha-dicarbonyl compounds and protein carbonyl groups increased with time of yeast cultivation and was higher in cells grown on fructose that demonstrated their accelerated aging and carbonyl/oxidative stress development as compared with cells grown on glucose. The strains defective in TOR proteins cultivated in the presence of glucose as well as fructose demonstrated lower markers of the stress and aging than parental strain. Thus these data confirmed the previous conclusion on fructose more potent ability to cause carbonyl/oxidative stress and accelerated aging in S. cerevisiae as compared with glucose. However, defects in TOR regulatory complexes retard aging and development of the stress in yeast independent on the type of carbohydrate in the cultivation medium.

  20. [Defects in TOR regulatory complexes retard aging and carbonyl/oxidative stress development in yeast Saccharomyces cerevisiae].

    PubMed

    Homza, B V; Vasyl'kovs'ka, R A; Semchyshyn, H M

    2014-01-01

    TOR signaling pathway first described in yeast S. cerevisiae is the highly conserved regulator of eukaryotic cell growth, aging and stress resistance. The effect of nitrogen sources, in particular amino acids, on the activity of TOR signaling pathway is well studied, however its relation to carbohydrates is poor understood. The aim of the present study is expanding of our understanding of potential role of TOR regulatory complexes in development of carbonyl/oxidative stress that can result from yeast cultivation on glucose and fructose. It has been shown that the level of alpha-dicarbonyl compounds and protein carbonyl groups increased with time of yeast cultivation and was higher in cells grown on fructose that demonstrated their accelerated aging and carbonyl/oxidative stress development as compared with cells grown on glucose. The strains defective in TOR proteins cultivated in the presence of glucose as well as fructose demonstrated lower markers of the stress and aging than parental strain. Thus these data confirmed the previous conclusion on fructose more potent ability to cause carbonyl/oxidative stress and accelerated aging in S. cerevisiae as compared with glucose. However, defects in TOR regulatory complexes retard aging and development of the stress in yeast independent on the type of carbohydrate in the cultivation medium. PMID:24834721

  1. Evolution of stress and deformations in high-temperature polymer matrix composites during thermo-oxidative aging

    NASA Astrophysics Data System (ADS)

    Pochiraju, K. V.; Tandon, G. P.; Schoeppner, G. A.

    2008-03-01

    This paper presents a model-based analysis of thermo-oxidative behavior in high-temperature polymer matrix composite (HTPMC) materials. The thermo-oxidative behavior of the composite differs from that of the constituents as the composite microstructure, the fiber/matrix interphase/interface behavior and damage mechanisms introduce anisotropy in the diffusion and oxidation behavior. Three-dimensional Galerkin finite element methods (GFEM) that model the thermo-oxidative layer growth with time are used together with homogenization techniques to analyze lamina-scale behavior using representative volume elements (RVEs). Thermo-oxidation-induced shrinkage is characterized from dimensional changes observed during aging in inert (argon) and oxidative (air) environments. Temperature-dependent macro-scale (bulk) mechanical testing and nano-indentation techniques are used for characterizing the effect of oxidative aging on modulus evolution. The stress and deformation fields in a single ply unidirectional lamina are studied using coupled oxidation evolution and non-linear elastic deformation analyses. Deformation and stress states are shown as a function of the aging time. While the thermo-oxidative processes are controlled by diffusion phenomenon in neat resin, the onset and propagation of damage determines the oxidative response of an HTPMC.

  2. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases.

    PubMed

    Sallam, Nada; Laher, Ismail

    2016-01-01

    Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential. PMID:26823952

  3. Exercise Modulates Oxidative Stress and Inflammation in Aging and Cardiovascular Diseases

    PubMed Central

    Sallam, Nada

    2016-01-01

    Despite the wealth of epidemiological and experimental studies indicating the protective role of regular physical activity/exercise training against the sequels of aging and cardiovascular diseases, the molecular transducers of exercise/physical activity benefits are not fully identified but should be further investigated in more integrative and innovative approaches, as they bear the potential for transformative discoveries of novel therapeutic targets. As aging and cardiovascular diseases are associated with a chronic state of oxidative stress and inflammation mediated via complex and interconnected pathways, we will focus in this review on the antioxidant and anti-inflammatory actions of exercise, mainly exerted on adipose tissue, skeletal muscles, immune system, and cardiovascular system by modulating anti-inflammatory/proinflammatory cytokines profile, redox-sensitive transcription factors such as nuclear factor kappa B, activator protein-1, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha, antioxidant and prooxidant enzymes, and repair proteins such as heat shock proteins, proteasome complex, oxoguanine DNA glycosylase, uracil DNA glycosylase, and telomerase. It is important to note that the effects of exercise vary depending on the type, intensity, frequency, and duration of exercise as well as on the individual's characteristics; therefore, the development of personalized exercise programs is essential. PMID:26823952

  4. Effect of Mitochondrial Oxidative Stress and Age on the Signaling Pathway of Ultrafine Particulate Matter Exposure in Murine Aorta

    EPA Science Inventory

    Epidemiological studies have linked ultrafine particulate matter (PM) exposure and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism contributing to the adverse short-term vascular effects of air pollution exposure. Advanced age is one ...

  5. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation1234

    PubMed Central

    Patel, Sanjeet G; Guthikonda, Anuradha P; Reid, Marvin; Balasubramanyam, Ashok; Taffet, George E; Jahoor, Farook

    2011-01-01

    Background: Aging is associated with oxidative stress, but underlying mechanisms remain poorly understood. Objective: We tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in aging and whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress. Design: Eight elderly and 8 younger subjects received stable-isotope infusions of [2H2]glycine, after which red blood cell (RBC) glutathione synthesis and concentrations, plasma oxidative stress, and markers of oxidant damage (eg, F2-isoprostanes) were measured. Elderly subjects were restudied after 2 wk of glutathione precursor supplementation. Results: Compared with younger control subjects, elderly subjects had markedly lower RBC concentrations of glycine (486.7 ± 28.3 compared with 218.0 ± 23.7 μmol/L; P < 0.01), cysteine (26.2 ± 1.4 compared with 19.8 ± 1.3 μmol/L; P < 0.05), and glutathione (2.08 ± 0.12 compared with 1.12 ± 0.18 mmol/L RBCs; P < 0.05); lower glutathione fractional (83.14 ± 6.43% compared with 45.80 ± 5.69%/d; P < 0.01) and absolute (1.73 ± 0.16 compared with 0.55 ± 0.12 mmol/L RBCs per day; P < 0.01) synthesis rates; and higher plasma oxidative stress (304 ± 16 compared with 346 ± 20 Carratelli units; P < 0.05) and plasma F2-isoprostanes (97.7 ± 8.3 compared with 136.3 ± 11.3 pg/mL; P < 0.05). Precursor supplementation in elderly subjects led to a 94.6% higher glutathione concentration, a 78.8% higher fractional synthesis rate, a 230.9% higher absolute synthesis rate, and significantly lower plasma oxidative stress and F2-isoprostanes. No differences in these measures were observed between younger subjects and supplemented elderly subjects. Conclusions: Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and

  6. The Effect of Aging on Mitochondrial Complex I and the Extent of Oxidative Stress in the Rat Brain Cortex.

    PubMed

    Tatarkova, Zuzana; Kovalska, Maria; Timkova, Veronika; Racay, Peter; Lehotsky, Jan; Kaplan, Peter

    2016-08-01

    One of the characteristic features of the aging is dysfunction of mitochondria. Its role in the regulation of metabolism and apoptosis suggests a possible link between these cellular processes. This study investigates the relationship of respiratory complex I with aging-related oxidative stress in the cerebral mitochondria. Deterioration of complex I seen in senescent (26-months old) mitochondria was accompanied by decline in total thiol group content, increase of HNE and HNE-protein adducts as well as decreased content of complex I subunits, GRIM-19 and NDUFV2. On the other hand, decline of complex I might be related with the mitochondrial apoptosis through increased Bax/Bcl-2 cascade in 15-month old animal brains. Higher amount of Bcl-2, Bcl-xL with the lower content of GRIM-19 could maintain to some extent elevated oxidative stress in mitochondria as seen in the senescent group. In the cortical M1 region increased presence of TUNEL+ cells and more than 20-times higher density of Fluoro-Jade C+ cells in 26-months old was observed, suggesting significant neurodegenerative effect of aging in the neuronal cells. Our study supports a scenario in which the age-related decline of complex I might sensitize neurons to the action of death agonists, such as Bax through lipid and protein oxidative stimuli in mitochondria. Although aging is associated with oxidative stress, these changes did not increase progressively with age, as similar extent of lesions was observed in oxidative stress markers of the both aged groups. PMID:27161369

  7. Brain Tissue Hypoxia and Oxidative Stress Induced by Obstructive Apneas is Different in Young and Aged Rats

    PubMed Central

    Dalmases, Mireia; Torres, Marta; Márquez-Kisinousky, Leonardo; Almendros, Isaac; Planas, Anna M.; Embid, Cristina; Martínez-Garcia, Miguel Ángel; Navajas, Daniel; Farré, Ramon; Montserrat, Josep Maria

    2014-01-01

    Study Objectives: To test the hypotheses that brain oxygen partial pressure (PtO2) in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress. Design: Prospective controlled animal study. Setting: University laboratory. Participants: Sixty-four male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo). Interventions: Protocol 1: Twenty-four animals were subjected to obstructive apneas (50 apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h. Measurements and Results: Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode. During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats (1.34 ± 0.17 nmol/mg of protein) compared to old ones (0.63 ± 0.03 nmol/mg), where a higher expression of antioxidant enzymes was observed. Conclusions: The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats. Citation: Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, Martínez-Garcia MA, Navajas D, Farré R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats. SLEEP 2014;37(7):1249-1256. PMID:25061253

  8. Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer.

    PubMed

    Pinti, Marcello; Gibellini, Lara; Liu, Yongzhang; Xu, Shan; Lu, Bin; Cossarizza, Andrea

    2015-12-01

    Lon protease is a nuclear DNA-encoded mitochondrial enzyme highly conserved throughout evolution, involved in the degradation of damaged and oxidized proteins of the mitochondrial matrix, in the correct folding of proteins imported in mitochondria, and in the maintenance of mitochondrial DNA. Lon expression is induced by various stimuli, including hypoxia and reactive oxygen species, and provides protection against cell stress. Lon down-regulation is associated with ageing and with cell senescence, while up-regulation is observed in tumour cells, and is correlated with a more aggressive phenotype of cancer. Lon up-regulation contributes to metabolic reprogramming observed in cancer, favours the switch from a respiratory to a glycolytic metabolism, helping cancer cell survival in the tumour microenvironment, and contributes to epithelial to mesenchymal transition. Silencing of Lon, or pharmacological inhibition of its activity, causes cell death in various cancer cells. Thus, Lon can be included in the growing class of proteins that are not responsible for oncogenic transformation, but that are essential for survival and proliferation of cancer cells, and that can be considered as a new target for development of anticancer drugs.

  9. Effects of carnosine plus vitamin E and betaine treatments on oxidative stress in some tissues of aged rats.

    PubMed

    Çoban, Jale; Bingül, Ilknur; Yesil-Mizrak, Kubra; Dogru-Abbasoglu, Semra; Oztezcan, Serdar; Uysal, Mujdat

    2013-07-01

    Oxidative stress plays an important role in aging. Effects of several antioxidants on age-related oxidative stress have been investigated. Carnosine (CAR) and betaine have antioxidant actions. The combination of CAR with vitamin E(CAR+E) increases its antioxidant efficiency. We investigated the effects of CAR+E and betaine treatments on oxidative and antioxidative status in liver, heart and brain tissues of aged rats. Experiments were carried out on young (5 months)and aged (22 months) male Wistar rats. Aged rats were given CAR (250 mg/kg; i.p.; 5 days per week) and vitamin E (200mg/kg; i.m.; twice per week) or betaine (1% w/v) for two months. Malondialdehyde (MDA) and diene conjugate (DC)levels and antioxidants were measured. MDA and DC levels were higher in tissues of aged rats than young rats. Glutathione(GSH) levels decreased in liver, but not heart and brain. There were no changes in vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in tissues of aged rats. CAR+E treatment was observed to decrease MDA and DC levels in tissues of aged rats. However, betaine decreased only hepatic MDA and DC levels. Both CAR+E and betaine increased hepatic GSH and vitamin E levels, but these treatments did not affect antioxidant enzyme activities. These results suggest that CAR+E treatment seems to be useful to decrease oxidative stress in liver, heart and brain tissues, but betaine is only effective in liver tissue of aged rats. PMID:23701646

  10. Aging-associated oxidative stress leads to decrease in IAS tone via RhoA/ROCK downregulation.

    PubMed

    Singh, Jagmohan; Kumar, Sumit; Krishna, Chadalavada Vijay; Rattan, Satish

    2014-06-01

    Internal anal sphincter (IAS) tone plays an important role in rectoanal incontinence (RI). IAS tone may be compromised during aging, leading to RI in certain patients. We examined the influence of oxidative stress in the aging-associated decrease in IAS tone (AADI). Using adult (4-6 mo old) and aging (24-30 mo old) rats, we determined the effect of oxidative stress on IAS tone and the regulatory RhoA/ROCK signal transduction cascade. We determined the effect of the oxidative stress inducer LY83583, which produces superoxide anions (O2 (·-)), on basal and stimulated IAS tone before and after treatment of intact smooth muscle strips and smooth muscle cells with the O2 (·-) scavenger SOD. Our data showed that AADI was associated with a decrease in RhoA/ROCK expression at the transcriptional and translational levels. Oxidative stress with a LY83583-mediated decrease in IAS tone and relaxation of IAS smooth muscle cells was associated with a decrease in RhoA/ROCK signal transduction, which was reversible by SOD. In addition, LY83583 caused a significant decrease in IAS contraction produced by the RhoA activator and a known RhoA/ROCK agonist, U46619, that was also reversible by SOD. The inhibitory effects of LY83583 and the ROCK inhibitor Y27632 on the U46619-induced increase in IAS tone were similar. We conclude that an increase in oxidative stress plays an important role in AADI in the elderly and may be one of the underlying mechanisms of RI in certain aging patients.

  11. Effects of Aging and Oxidative Stress on Spermatozoa of Superoxide-Dismutase 1- and Catalase-Null Mice.

    PubMed

    Selvaratnam, Johanna S; Robaire, Bernard

    2016-09-01

    Advanced paternal age is linked to complications in pregnancy and genetic diseases in offspring. Aging results in excess reactive oxygen species (ROS) and DNA damage in spermatozoa; this damage can be transmitted to progeny with detrimental consequences. Although there is a loss of antioxidants with aging, the impact on aging male germ cells of the complete absence of either catalase (CAT) or superoxide dismutase 1 (SOD1) has not been investigated. We used CAT-null (Cat(-/-)) and SOD1-null (Sod(-/-)) mice to determine whether loss of these antioxidants increases germ cell susceptibility to redox dysfunction with aging. Aging reduced fertility and the numbers of Sertoli and germ cells in all mice. Aged Sod(-/-) mice displayed an increased loss of fertility compared to aged wild-type mice. Treatment with the pro-oxidant SIN-10 increased ROS in spermatocytes of aged wild-type and Sod(-/-) mice, while aged Cat(-/-) mice were able to neutralize this ROS. The antioxidant peroxiredoxin 1 (PRDX1) increased with age in wild-type and Cat(-/-) mice but was consistently low in young and aged Sod(-/-) mice. DNA damage and repair markers (γ-H2AX and 53BP1) were reduced with aging and lower in young Sod(-/-) and Cat(-/-) mice. Colocalization of γ-H2AX and 53BP1 suggested active repair in young wild-type mice but reduced in young Cat(-/-) and in Sod(-/-) mice and with age. Oxidative DNA damage (8-oxodG) increased in young Sod(-/-) mice and with age in all mice. These studies show that aged Sod(-/-) mice display severe redox dysfunction, while wild-type and Cat(-/-) mice have compensatory mechanisms to partially alleviate oxidative stress and reduce age-related DNA damage in spermatozoa. Thus, SOD1 but not CAT is critical to the maintenance of germ cell quality with aging. PMID:27465136

  12. Protective role of vitamins E and C against oxidative stress caused by intermittent cold exposure in aging rat's frontoparietal cortex.

    PubMed

    Asha Devi, S; Manjula, K R; Subramanyam, M V V

    2012-11-01

    This study examined the role of vitamins E and C in combating oxidative stress (OS) caused by intermittent cold exposure (ICE) in the frontoparietal cortex (FPC) of adult (3 months), late-adult (12 months), middle-aged (18 months) and old (24 months) male Wistar rats. Each age group was divided into sub-groups, control (CON), cold-exposed at 5°C (C5), control supplementees (CON+S) and cold-exposed supplementees (C5+S). The supplement was a daily dose of 400mg vitamin C and 50I.U.of vitamin E/kg body weight. Cold exposure lasted 2h/day for 4 weeks. All age groups except the old showed an increase in the final body mass in the cold-exposed. The feeding efficiency was higher in the cold-exposed irrespective of age. OS as reflected in age-related increased levels of hydrogen peroxide, protein carbonyl, advanced oxidation protein products and malondialdehyde showed further increase with ICE in the FPC. However, vitamins E and C supplementation attenuated the ICE-induced OS. ICE depleted the levels of tissue vitamins E and C while supplementation resulted in increased levels. Further age emerged as a significant factor in ICE-induced stress and also the response to vitamins E and C supplementation. Behavioral studies are underway to examine the findings on ICE-induced oxidative injury in the FPC, and the prospects for using vitamins E and C in cold exposures in the aged.

  13. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Cutler, Roy G.; Kelly, Jeremiah; Storie, Kristin; Pedersen, Ward A.; Tammara, Anita; Hatanpaa, Kimmo; Troncoso, Juan C.; Mattson, Mark P.

    2004-02-01

    Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid -peptide (A) and degeneration of neurons in brain regions such as the hippocampus, resulting in progressive cognitive dysfunction. The pathogenesis of AD is tightly linked to A deposition and oxidative stress, but it remains unclear as to how these factors result in neuronal dysfunction and death. We report alterations in sphingolipid and cholesterol metabolism during normal brain aging and in the brains of AD patients that result in accumulation of long-chain ceramides and cholesterol. Membrane-associated oxidative stress occurs in association with the lipid alterations, and exposure of hippocampal neurons to A induces membrane oxidative stress and the accumulation of ceramide species and cholesterol. Treatment of neurons with -tocopherol or an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and cholesterol and protects them against death induced by A. Our findings suggest a sequence of events in the pathogenesis of AD in which A induces membrane-associated oxidative stress, resulting in perturbed ceramide and cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that leads to clinical disease. amyloid | apoptosis | hippocampus | lipid peroxidation | sphingomyelin

  14. Mitochondrial oxidative stress caused by Sod2 deficiency promotes cellular senescence and aging phenotypes in the skin.

    PubMed

    Velarde, Michael C; Flynn, James M; Day, Nicholas U; Melov, Simon; Campisi, Judith

    2012-01-01

    Cellular senescence arrests the proliferation of mammalian cells at risk for neoplastic transformation, and is also associated with aging. However, the factors that cause cellular senescence during aging are unclear. Excessive reactive oxygen species (ROS) have been shown to cause cellular senescence in culture, and accumulated molecular damage due to mitochondrial ROS has long been thought to drive aging phenotypesin vivo. Here, we test the hypothesis that mitochondrial oxidative stress can promote cellular senescence in vivo and contribute to aging phenotypes in vivo, specifically in the skin. We show that the number of senescent cells, as well as impaired mitochondrial (complex II) activity increase in naturally aged mouse skin. Using a mouse model of genetic Sod2 deficiency, we show that failure to express this important mitochondrial anti-oxidant enzyme also impairs mitochondrial complex II activity, causes nuclear DNA damage, and induces cellular senescence but not apoptosis in the epidermis. Sod2 deficiency also reduced the number of cells and thickness of the epidermis, while increasing terminal differentiation. Our results support the idea that mitochondrial oxidative stress and cellular senescence contribute to aging skin phenotypes in vivo.

  15. 8-oxo-7,8-dihydroguanine: Link to gene expression, aging and defense against oxidative stress

    PubMed Central

    Radak, Zsolt; Boldogh, Istvan

    2010-01-01

    The one-electron oxidation product of guanine 8-oxo-7,8-dihydroguanine (8-oxoG) is an abundant lesion in genomic, mitochondrial and telomeric DNA and RNA. It is considered to be a marker of oxidative stress that preferentially accumulates at the 5’ end of guanine strings in the DNA helix, guanine quadruplexes and in RNA molecules. 8-oxoG has a lower oxidation potential compared to guanine, thus it is susceptible to oxidation/reduction and along with its redox products, is traditionally considered to be a major genotoxic/mutagenic DNA base lesion. It does not change the architecture of the DNA double helix and it is specifically recognized and excised by 8-oxoguanine DNA glycosylase (OGG1) during the DNA base excision repair pathway. OGG1 null animals accumulate excess levels of 8-oxoG in their genome, while they do not have shorter lifespan, nor exhibit severe pathological symptoms including tumor formation. In fact they are increasingly resistant to inflammation. Here we address rarely considered significance of 8-oxoG such as its optimal level in the DNA and RNA in a given condition, essentiality for normal cellular physiology, evolutionary role, ability to soften the effects of oxidative stress in DNA, harmful consequences of its repair, as well as its importance in transcriptional initiation and chromatin relaxation. PMID:20483371

  16. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer

    PubMed Central

    Essick, Eric E

    2010-01-01

    Autophagy is a catalytic process of the bulk degradation of long-lived cellular components, ultimately resulting in lysosomal digestion within mature cytoplasmic compartments known as autophagolysosomes. Autophagy serves many functions in the cell, including maintaining cellular homeostasis, a means of cell survival during stress (e.g., nutrient deprivation or starvation) or conversely as a mechanism for cell death. Increased reactive oxygen species (ROS) production and the resulting oxidative cell stress that occurs in many disease states has been shown to induce autophagy. The following review focuses on the roles that autophagy plays in response to the ROS generated in several diseases. PMID:20716941

  17. Vascular aging: Chronic oxidative stress and impairment of redox signaling—consequences for vascular homeostasis and disease

    PubMed Central

    Bachschmid, Markus M.; Schildknecht, Stefan; Matsui, Reiko; Zee, Rebecca; Haeussler, Dagmar; Cohen, Richard A.; Pimental, David; van der Loo, Bernd

    2013-01-01

    Characteristic morphological and molecular alterations such as vessel wall thickening and reduction of nitric oxide occur in the aging vasculature leading to the gradual loss of vascular homeostasis. Consequently, the risk of developing acute and chronic cardiovascular diseases increases with age. Current research of the underlying molecular mechanisms of endothelial function demonstrates a duality of reactive oxygen and nitrogen species in contributing to vascular homeostasis or leading to detrimental effects when formed in excess. Furthermore, changes in function and redox status of vascular smooth muscle cells contribute to age-related vascular remodeling. The age-dependent increase in free radical formation causes deterioration of the nitric oxide signaling cascade, alters and activates prostaglandin metabolism, and promotes novel oxidative posttranslational protein modifications that interfere with vascular and cell signaling pathways. As a result, vascular dysfunction manifests. Compensatory mechanisms are initially activated to cope with age-induced oxidative stress, but become futile, which results in irreversible oxidative modifications of biological macromolecules. These findings support the ‘free radical theory of aging’ but also show that reactive oxygen and nitrogen species are essential signaling molecules, regulating vascular homeostasis. PMID:22380696

  18. Reduced serine racemase expression in aging rat cerebellum is associated with oxidative DNA stress and hypermethylation in the promoter.

    PubMed

    Zhang, He; Kuang, Xiu-Li; Chang, Yuhua; Lu, Jinfang; Jiang, Haiyan; Wu, Shengzhou

    2015-12-10

    Regulation of serine racemase (SR) occurs at transcriptional and translational levels; post-translational modification, cytosolic distribution as well as allosteric effect regulate SR activity. In this study, we report a new route of SR regulation, i.e. oxidative stress and hypermethylation of the srr (gene of SR) promoter correlate with its reduced transcription in aging rat cerebella. We first showed that the mRNA and protein level of srr were decreased in the homogenates of rat cerebellum at age 12 months compared with the counterparts from age 20 days. The reduction of SR protein level in aging cerebella was evidenced by decreased immunostaining observed in the cell body of granule cells or Purkinje cells. Staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress to DNA, was much stronger in granule cell or Purkinje cell nuclei from rat cerebella at 12 months compared with staining at 20 days. We further detected srr promoter hypermethylation at 12 months compared with that at 20 days by use of bisulfite sequencing PCR, coinciding with elevated protein levels of DNA methyltransferase 1 (DNMT1) in homogenates of aging cerebella. In vitro, we demonstrated that chronic treatment with the oxidant, menadione (VK3), reduced srr mRNA levels, which was reversed by the DNA demethylating agent 5-Aza-dC-2'-deoxycytidine (5-Aza-dC) in primary cerebellar granule cell cultures. Together, the in vivo and ex vivo results suggest that oxidative DNA stress and srr promoter hypermethylation are associated with reduced srr gene transcription and corresponding reduced protein expression in aging cerebella.

  19. Oxidative Stress in Cancer-Prone Genetic Diseases in Pediatric Age: The Role of Mitochondrial Dysfunction

    PubMed Central

    Longini, Mariangela; Buonocore, Giuseppe

    2016-01-01

    Oxidative stress is a distinctive sign in several genetic disorders characterized by cancer predisposition, such as Ataxia-Telangiectasia, Fanconi Anemia, Down syndrome, progeroid syndromes, Beckwith-Wiedemann syndrome, and Costello syndrome. Recent literature unveiled new molecular mechanisms linking oxidative stress to the pathogenesis of these conditions, with particular regard to mitochondrial dysfunction. Since mitochondria are one of the major sites of ROS production as well as one of the major targets of their action, this dysfunction is thought to be the cause of the prooxidant status. Deeper insight of the pathogenesis of the syndromes raises the possibility to identify new possible therapeutic targets. In particular, the use of mitochondrial-targeted agents seems to be an appropriate clinical strategy in order to improve the quality of life and the life span of the patients. PMID:27239251

  20. Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice

    PubMed Central

    Song, Chao; Peng, Wei; Yin, Songna; Zhao, Jiamin; Fu, Beibei; Zhang, Jingcheng; Mao, Tingchao; Wu, Haibo; Zhang, Yong

    2016-01-01

    Increasing evidence shows that melatonin protected against age-related mitochondrial oxidative damage. However, the protective effects of melatonin against ovarian aging has not been explored. Young Kunming females (aged 2–3 months) were fed with melatonin added to drinking water for 6 or 12 months (mo). We found that long-term (12 mo) melatonin treatment significantly reduced ovarian aging, as indicated by substantial increases in litter size, pool of follicles, and telomere length as well as oocyte quantity and quality. Melatonin treatment suppressed ovarian mitochondrial oxidative damage by decreasing mitochondrial reactive oxygen species (mROS) generation, inhibiting apoptosis, repressing collapse of mitochondrial membrane potential and preserving respiratory chain complex activities. Female mice fed with melatonin had enhanced mitochondrial antioxidant activities, thus reducing the risk of mitochondrial oxidative damage cause by free radicals. Notably, melatonin treatment enhanced SIRT3 activity but not the protein expression level, and increased the binding affinity of FoxO3a to the promoters of both superoxide dismutase 2 (SOD2) and catalase (CAT). In conclusion, melatonin exerted protection against aging-induced fertility decline and maintenance of mitochondrial redox balance. PMID:27731402

  1. The senescence-accelerated mouse (SAM): a higher oxidative stress and age-dependent degenerative diseases model.

    PubMed

    Chiba, Yoichi; Shimada, Atsuyoshi; Kumagai, Naoko; Yoshikawa, Keisuke; Ishii, Sanae; Furukawa, Ayako; Takei, Shiro; Sakura, Masaaki; Kawamura, Noriko; Hosokawa, Masanori

    2009-04-01

    The SAM strain of mice is actually a group of related inbred strains consisting of a series of SAMP (accelerated senescence-prone) and SAMR (accelerated senescence-resistant) strains. Compared with the SAMR strains, the SAMP strains show a more accelerated senescence process, a shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes similar to human geriatric disorders. The higher oxidative stress status observed in SAMP mice is partly caused by mitochondrial dysfunction, and may be a cause of this senescence acceleration and age-dependent alterations in cell structure and function. Based on our recent observations, we discuss a possible mechanism for mitochondrial dysfunction resulting in the excessive production of reactive oxygen species, and a role for the hyperoxidative stress status in neurodegeneration in SAMP mice. These SAM strains can serve as a useful tool to understand the cellular mechanisms of age-dependent degeneration, and to develop clinical interventions. PMID:18688709

  2. The effect of aging on the DNA damage and repair capacity in 2BS cells undergoing oxidative stress.

    PubMed

    Wang, Jin-Ling; Wang, Pei-Chang

    2012-01-01

    Aging is associated with a reduction in the DNA repair capacity under oxidative stress. However, whether the DNA damage and repair capacity can be a biomarker of aging remains controversial. In this study, we demonstrated two cause-and-effect relationships, the one is between the DNA damage and repair capacity and the cellular age, another is between DNA damage and repair capacity and the level of oxidative stress in human embryonic lung fibroblasts (2BS) exposed to different doses of hydrogen peroxide (H2O2). To clarify the mechanisms of the age-related reduction in DNA damage and repair capacity, we preliminarily evaluated the expressions of six kinds of pivotal enzymes involved in the two classical DNA repair pathways. The DNA repair capacity was observed in human fibroblasts cells using the comet assay; the age-related DNA repair enzymes were selected by RT-PCR and then verified by Western blot in vitro. Results showed that the DNA repair capacity was negatively and linearly correlated with (i) cumulative population doubling (PD) levels only in the group of low concentration of hydrogen peroxide treatment, (ii) with the level of oxidative stress only in the group of young PD cells. The mRNA expression of DNA polymerase δ1 decreased substantially in senescent cells and showed negative linear-correlation with PD levels; the protein expression level was well consistent with the mRNA level. Taken together, DNA damage and repair capacity can be a biomarker of aging. Reduced expression of DNA polymerase δ1 may be responsible for the decrease of DNA repair capacity in senescent cells.

  3. Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion.

    PubMed

    Mourmoura, Evangelia; Leguen, Marie; Dubouchaud, Hervé; Couturier, Karine; Vitiello, Damien; Lafond, Jean-Luc; Richardson, Melanie; Leverve, Xavier; Demaison, Luc

    2011-09-01

    Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10- or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H(2)O(2) release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H(2)O(2) when they oxidize FADH(2)-linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration of the coronary perfusion was explained by an increased mitochondrial ROS release related to the

  4. Triggers and Effectors of Oxidative Stress at Blood-Brain Barrier Level: Relevance for Brain Ageing and Neurodegeneration

    PubMed Central

    2013-01-01

    As fundamental research advances, it is becoming increasingly clear that a clinically expressed disease implies a mixture of intertwining molecular disturbances. Oxidative stress is one of such pathogenic pathways involved in virtually all central nervous system pathologies, infectious, inflammatory, or degenerative in nature. Since brain homeostasis largely depends on integrity of blood-brain barrier (BBB), many studies focused lately on BBB alteration in a wide spectrum of brain diseases. The proper two-way molecular transfer through BBB depends on several factors, including the functional status of its tight junction (TJ) complexes of proteins sealing neighbour endothelial cells. Although there is abundant experimental work showing that oxidative stress associates BBB permeability alteration, less is known about its implications, at molecular level, in TJ protein expression or TJ-related cell signalling. In this paper, oxidative stress is presented as a common pathway for different brain pathogenic mechanisms which lead to BBB dysregulation. We revise here oxidative-induced molecular mechanisms of BBB disruption and TJ protein expression alteration, in relation to ageing and neurodegeneration. PMID:23533687

  5. Reduced Metabolic Capacity in Aged Primary Retinal Pigment Epithelium (RPE) is Correlated with Increased Susceptibility to Oxidative Stress.

    PubMed

    Rohrer, Bärbel; Bandyopadhyay, Mausumi; Beeson, Craig

    2016-01-01

    One of the affected tissues in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), a tissue that consists of terminally differentiated cells and that accumulates damage over time. In all tissues, mitochondria (mt), which play an essential role in both cell health (energy) and death (initiator of apoptosis), undergo an aging process through the accumulation of mtDNA damage, changes in mitochondrial dynamics, a reduction in biogenesis, and mitophagy, leading to an overall reduction in mitochondrial energy production and other non-energy-related functions. Here we have compared energy metabolism in primary human RPE cells isolated from aborted fetus or aged donor eyes and grown as stable monolayers. H2O2 treatment resulted in the generation of reactive oxygen species and superoxide, an effect that was significantly augmented by age. Mitochondrial metabolism, as analyzed by Seahorse respirometry, revealed reduced mitochondrial oxygen consumption (ATP production) at baseline and a complete loss of reserve capacity in aged cells. Likewise, glycolysis was blunted in aged cells. Taken together, these studies showed that RPE cells derived from aged donor eyes are more susceptible to oxidative stress, and exhibit a loss in mitochondrial respiratory reserve capacity and a reduction in glycolysis. These data suggest that while old cells may have sufficient energy at rest, they cannot mount a stress response requiring additional ATP and reducing agents. In summary, these data support the hypothesis that mitochondria or energy metabolism is a valid target for therapy in AMD. PMID:26427491

  6. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    SciTech Connect

    Kodavanti, Prasada Rao S.; Royland, Joyce E.; Richards, Judy E.; Besas, Jonathan; MacPhail, Robert C.

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  7. Practicality of intermittent fasting in humans and its effect on oxidative stress and genes related to aging and metabolism.

    PubMed

    Wegman, Martin P; Guo, Michael H; Bennion, Douglas M; Shankar, Meena N; Chrzanowski, Stephen M; Goldberg, Leslie A; Xu, Jinze; Williams, Tiffany A; Lu, Xiaomin; Hsu, Stephen I; Anton, Stephen D; Leeuwenburgh, Christiaan; Brantly, Mark L

    2015-04-01

    Caloric restriction has consistently been shown to extend life span and ameliorate aging-related diseases. These effects may be due to diet-induced reactive oxygen species acting to up-regulate sirtuins and related protective pathways, which research suggests may be partially inhibited by dietary anti-oxidant supplementation. Because caloric restriction is not sustainable long term for most humans, we investigated an alternative dietary approach, intermittent fasting (IF), which is proposed to act on similar biological pathways. We hypothesized that a modified IF diet, where participants maintain overall energy balance by alternating between days of fasting (25% of normal caloric intake) and feasting (175% of normal), would increase expression of genes associated with aging and reduce oxidative stress and that these effects would be suppressed by anti-oxidant supplementation. To assess the tolerability of the diet and to explore effects on biological mechanisms related to aging and metabolism, we recruited a cohort of 24 healthy individuals in a double-crossover, double-blinded, randomized clinical trial. Study participants underwent two 3-week treatment periods-IF and IF with anti-oxidant (vitamins C and E) supplementation. We found strict adherence to study-provided diets and that participants found the diet tolerable, with no adverse clinical findings or weight change. We detected a marginal increase (2.7%) in SIRT3 expression due to the IF diet, but no change in expression of other genes or oxidative stress markers analyzed. We also found that IF decreased plasma insulin levels (1.01 μU/mL). Although our study suggests that the IF dieting paradigm is acceptable in healthy individuals, additional research is needed to further assess the potential benefits and risks. PMID:25546413

  8. Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

    PubMed Central

    Hermann, Petra M.; Watson, Shawn N.; Wildering, Willem C.

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain. PMID:25538730

  9. Oxidative stress associated with middle aging leads to sympathetic hyperactivity and downregulation of soluble guanylyl cyclase in corpus cavernosum.

    PubMed

    Silva, Fábio H; Lanaro, Carolina; Leiria, Luiz Osório; Rodrigues, Renata Lopes; Davel, Ana Paula; Claudino, Mário A; Toque, Haroldo A; Antunes, Edson

    2014-11-15

    Impairment of nitric oxide (NO)-mediated cavernosal relaxations in middle age contributes to erectile dysfunction. However, little information is available about the alterations of sympathetic neurotransmission and contraction in erectile tissue at middle age. This study aimed to evaluate the alterations of the contractile machinery associated with tyrosine hydroxylase (TH) in rat corpus cavernosum (RCC) at middle age, focusing on the role of superoxide anion. Male Wistar young (3.5-mo) and middle-aged (10-mo) rats were used. Electrical-field stimulation (EFS)- and phenylephrine-induced contractions were obtained in RCC strips. Levels of reactive-oxygen species (ROS) and TH mRNA expression, as well as protein expressions for α₁/β₁-subunits of soluble guanylyl cyclase (sGC), in RCC were evaluated. The neurogenic contractile responses elicited by EFS (4-32 Hz) were greater in RCC from the middle-aged group that was accompanied by elevated TH mRNA expression (P < 0.01). Phenylephrine-induced contractions were also greater in the middle-aged group. A 62% increase in ROS generation in RCC from middle-aged rats was observed. The mRNA expression for the α₁A-adrenoceptor remained unchanged among groups. Protein levels of α₁/β₁-sGC subunits were decreased in RCC from the middle-aged compared with young group. The NADPH oxidase inhibitor apocynin (85 mg·rat(-1)·day(-1), 4 wk) fully restored the enhanced ROS production, TH mRNA expressions, and α₁/β₁-subunit sGC expression, indicating that excess of superoxide anion plays a major role in the sympathetic hyperactivity and hypercontractility in erectile tissue at middle age. Reduction of oxidative stress by dietary antioxidants may be an interesting approach to treat erectile dysfunction in aging population.

  10. Curcumin Mitigates Accelerated Aging after Irradiation in Drosophila by Reducing Oxidative Stress

    PubMed Central

    Yu, Mira; Park, Sunhoo; Jin, Young Woo; Min, Kyung-Jin

    2015-01-01

    Curcumin, belonging to a class of natural phenol compounds, has been extensively studied due to its antioxidative, anticancer, anti-inflammatory, and antineurodegenerative effects. Recently, it has been shown to exert dual activities after irradiation, radioprotection, and radiosensitization. Here, we investigated the protective effect of curcumin against radiation damage using D. melanogaster. Pretreatment with curcumin (100 μM) recovered the shortened lifespan caused by irradiation and increased eclosion rate. Flies subjected to high-dose irradiation showed a mutant phenotype of outstretched wings, whereas curcumin pretreatment reduced incidence of the mutant phenotype. Protein carbonylation and formation of γH2Ax foci both increased following high-dose irradiation most likely due to generation of reactive oxygen species. Curcumin pretreatment reduced the amount of protein carbonylation as well as formation of γH2Ax foci. Therefore, we suggest that curcumin acts as an oxidative stress reducer as well as an effective protective agent against radiation damage. PMID:25815315

  11. Strawberry or blueberry supplementation may protect against increased oxidative stress vulnerability from both irradiation and aging

    NASA Astrophysics Data System (ADS)

    Joseph, J. A.; Shukitt-Hale, B.; Carey, A.; Rabin, B. M.

    In several studies we have now shown that there are some interesting parallels between aging and the effects of heavy particle irradiation (56Fe) in a rat model. Interestingly this research also has shown that, much as has been seen in aged animals, dietary supplementation with high antioxidant-strawberry (SB) or blueberry (BB) extracts (2% of the diet) reversed many of the age-related changes. Similarly, supplementing the diets of young rats with SBs or BBs (2% of diet as in the aged animals) for 8 weeks prior to being exposed to 56Fe (1 GeV/n), using the AGS or NSRL at Brookhaven National Laboratory, prevented the deleterious effects of the radiation exposure on the motor, cognitive and neuronal parameters described above. In the present experiment we examined whether striatal tissue obtained from BB- or SB-supplemented or control-fed, irradiated or non-radiated, young rats would show differential sensitivity (as assessed via decrements in mAChR stimulation of dopamine release) to hydrogen peroxide, a reactive oxygen species (ROS) generating agent. The results indicated that, just as we had seen previously with respect to radiation protection in the parameters described above, the tissue from the SB or BB-supplemented irradiated or non-radiated animals showed increased mAChR-stimulated DA release from the striatal tissue following hydrogen peroxide exposure compared to that seen in non-supplemented irradiated or non-radiated animals (e.g., DA rels. p moles/mg protein, rad + H202 non-supplemented = 90, SB = 260, BB = 360). These results show that aging and irradiation may produce similar decrements in dopamine release and that, much as we have seen previously with age, radiation enhances the vulnerability to oxidative stressors, but these are reduced with SB or BB supplementation. They are discussed in-terms of protection against the effects of exposure to heavy particles and aging via nutritional supplementation with foods that are high in antioxidant activity

  12. Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging

    PubMed Central

    Tatone, Carla; Vitti, Maurizio; Santini, Silvano; D'Alessandro, Anna Maria

    2015-01-01

    In search for strategies aimed at preventing oxidative threat to female fertility, a possible role of sirtuins has emerged. Sirtuins (silent information regulator 2 (Sir2) proteins), NAD+ dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity, are emerging as key antiaging molecules and regulators in many diseases. Recently, a crucial role for SIRT1 and SIRT3, the main components of sirtuin family, as sensors and guardians of the redox state in oocytes, granulosa cells, and early embryos has emerged. In this context, the aim of the present review is to summarize current knowledge from research papers on the role of sirtuins in female fertility with particular emphasis on the impairment of SIRT1 signalling with oocyte aging. On this basis, the authors wish to build up a framework to promote research on the possible role of sirtuins as targets for future strategies for female fertility preservation. PMID:26075037

  13. DECREASED OXIDATIVE STRESS AND GREATER BONE ANABOLISM IN THE AGED, AS COMPARED TO THE YOUNG, MURINE SKELETON BY PARATHYROID HORMONE

    PubMed Central

    Jilka, R.L.; Almeida, M.; Ambrogini, E.; Han, L.; Roberson, P. K.; Weinstein, R.S.; Manolagas, S.C.

    2010-01-01

    Summary Because of recent insights into the pathogenesis of age-related bone loss, we investigated whether intermittent parathyroid hormone (PTH) administration antagonizes the molecular mechanisms of the adverse effects of aging on bone. PTH produced a greater increase in vertebral trabecular bone mineral density and bone volume as well as a greater expansion of the endocortical bone surface in the femur of 26 as compared to 6 month old female C57BL/6 mice. Moreover, PTH increased trabecular connectivity in vertebrae and the toughness of both vertebrae and femora in old, but not young, mice. PTH also increased the rate of bone formation and reduced osteoblast apoptosis to a greater extent in the old mice. Most strikingly, PTH reduced reactive oxygen species (ROS), p66Shc phosphorylation and expression of the lipoxygenase Alox15; and it increased glutathione and stimulated Wnt signaling in bone of old mice. PTH also antagonized the effects of oxidative stress on p66Shc phosphorylation, FoxO transcriptional activity, osteoblast apoptosis, and Wnt signaling in vitro. In contrast, administration of the antioxidants N-acetyl cysteine or pegylated catalase reduced osteoblast progenitors, and attenuated proliferation and Wnt signaling. These results suggest that PTH has a greater bone anabolic efficacy in old age because in addition to its other positive actions on bone formation it antagonizes the age-associated increase in oxidative stress and its adverse effects on the birth and survival of osteoblasts. On the other hand, ordinary antioxidants cannot restore bone mass in old age because they slow remodeling and attenuate osteoblastogenesis by interfering with Wnt signaling. PMID:20698835

  14. Vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults.

    PubMed

    Kaplon, Rachelle E; Gano, Lindsey B; Seals, Douglas R

    2014-01-15

    We tested the hypothesis that vascular endothelial function and oxidative stress are related to dietary niacin intake among healthy middle-aged and older adults. In 127 men and women aged 48-77 yr, brachial artery flow-mediated dilation (FMD) was positively related to dietary niacin intake [%change (Δ): r = 0.20, P < 0.05; mmΔ: r = 0.25, P < 0.01]. In subjects with above-average dietary niacin intake (≥ 22 mg/day, NHANES III), FMD was 25% greater than in subjects with below-average intake (P < 0.05). Stepwise linear regression revealed that dietary niacin intake (above vs. below average) was an independent predictor of FMD (%Δ: β = 1.8; mmΔ: β = 0.05, both P < 0.05). Plasma oxidized low-density lipoprotein, a marker of systemic oxidative stress, was inversely related to niacin intake (r = -0.23, P < 0.05) and was lower in subjects with above- vs. below-average niacin intake (48 ± 2 vs. 57 ± 2 mg/dl, P < 0.01). Intravenous infusion of the antioxidant vitamin C improved brachial FMD in subjects with below-average niacin intake (P < 0.001, n = 33), but not above-average (P > 0.05, n = 20). In endothelial cells sampled from the brachial artery of a subgroup, dietary niacin intake was inversely related to nitrotyrosine, a marker of peroxynitrite-mediated oxidative damage (r = -0.30, P < 0.05, n = 55), and expression of the prooxidant enzyme, NADPH oxidase (r = -0.44, P < 0.01, n = 37), and these markers were lower in subjects with above- vs. below-average niacin intake [nitrotyrosine: 0.39 ± 0.05 vs. 0.56 ± 0.07; NADPH oxidase: 0.38 ± 0.05 vs. 0.53 ± 0.05 (ratio to human umbilical vein endothelial cell control), both P < 0.05]. Our findings support the hypothesis that higher dietary niacin intake is associated with greater vascular endothelial function related to lower systemic and vascular oxidative stress among healthy middle-aged and older adults.

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

    PubMed

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

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

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

    PubMed Central

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

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms (“proteostasis”) are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = –0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = –0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: –0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

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

    PubMed

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

    2010-11-01

    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×Norway rats were loaded 3 times weekly for 4.5 weeks using 80 maximal stretch-shortening contractions per session. The contra-lateral limb served as the intra-animal control. The rats were randomly assigned to a diet supplemented with Vitamin E and Vitamin C or normal non-supplemented rat chow. Biomarkers of oxidative stress were measured in the tibialis anterior muscle. Repetitive loading exercise increased maximal isometric force, negative work and positive work in the dorsiflexors of young adult rats. Only positive work increased in the aged animals that were supplemented with Vitamin E and C. Markers of oxidative stress (H(2)O(2), total GSH, GSH/GSSG ratio, malondialdehyde and 8-OHdG) increased in the tibialis anterior muscles from aged and young adult animals with repetitive loading, but Vitamin E and C supplements attenuated this increase. MnSOD activity increased with supplementation in the young adult animals. CuZnSOD and catalase activity increased with supplementation in young adult and aged animals and GPx activity increased with exercise in the non-supplemented young adult and aged animals. The increased levels of endogenous antioxidant enzymes after Vitamin E and C supplementation appear to be regulated by post-transcriptional modifications that are affected differently by age, exercise, and supplementation. These data suggest that antioxidant supplementation improves indices of oxidative stress associated with repetitive loading exercise and aging and improves the positive work output of muscles in aged rodents.

  18. Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice

    PubMed Central

    Banks, William A.; Morley, John E.; Farr, Susan A.; Price, Tulin O.; Ercal, Nuran; Vidaurre, Irving; Schally, Andrew V.

    2010-01-01

    Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with isolated GH deficiency such as Laron dwarfs show increased life span. Here, we determined the effects of treatment with the GH-releasing hormone (GHRH) receptor antagonist MZ-5-156 on aging in SAMP8 mice, a strain that develops with aging cognitive deficits and has a shortened life expectancy. Starting at age 10 mo, mice received daily s.c. injections of 10 μg/mouse of MZ-5-156. Mice treated for 4 mo with MZ-5-156 showed increased telomerase activity, improvement in some measures of oxidative stress in brain, and improved pole balance, but no change in muscle strength. MZ-5-156 improved cognition after 2 mo and 4 mo, but not after 7 mo of treatment (ages 12, 14 mo, and 17 mo, respectively). Mean life expectancy increased by 8 wk with no increase in maximal life span, and tumor incidence decreased from 10 to 1.7%. These results show that treatment with a GHRH antagonist has positive effects on some aspects of aging, including an increase in telomerase activity. PMID:21135231

  19. The Aging Stress Response

    PubMed Central

    Haigis, Marcia C.; Yankner, Bruce A.

    2010-01-01

    Aging is the outcome of a balance between damage and repair. The rate of aging and the appearance of age-related pathology are modulated by stress response and repair pathways that gradually decline, including the proteostasis and DNA damage repair networks and mitochondrial respiratory metabolism. Highly conserved insulin/IGF-1, TOR, and sirtuin signaling pathways in turn, control these critical cellular responses. The coordinated action of these signaling pathways maintains cellular and organismal homeostasis in the face of external perturbations, such as changes in nutrient availability, temperature and oxygen level, as well as internal perturbations, such as protein misfolding and DNA damage. Studies in model organisms suggest that changes in signaling can augment these critical stress response systems, increasing lifespan and reducing age-related pathology. The systems biology of stress response signaling thus provides a new approach to the understanding and potential treatment of age-related diseases. PMID:20965426

  20. The human tripeptide GHK-Cu in prevention of oxidative stress and degenerative conditions of aging: implications for cognitive health.

    PubMed

    Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna

    2012-01-01

    Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging-detrimental epigenetic modifications-has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline. PMID:22666519

  1. UV, stress and aging.

    PubMed

    Debacq-Chainiaux, Florence; Leduc, Cedric; Verbeke, Alix; Toussaint, Olivier

    2012-07-01

    Skin is a model of choice in studies on aging. Indeed, skin aging can be modulated by internal and external factors, reflecting its complexity. Two types of skin aging have been identified: intrinsic, mainly genetically determined and extrinsic-also called "photo-aging"-resulting on the impact of environmental stress and more precisely of UV rays. Simplified in vitro models, based on cellular senescence, have been developed to study the relationship between UV and aging. These models vary on the cell type (fibroblasts or keratinocytes, normal or immortalized) and the type of UV used (UVA or UVB). PMID:23467762

  2. UV, stress and aging.

    PubMed

    Debacq-Chainiaux, Florence; Leduc, Cedric; Verbeke, Alix; Toussaint, Olivier

    2012-07-01

    Skin is a model of choice in studies on aging. Indeed, skin aging can be modulated by internal and external factors, reflecting its complexity. Two types of skin aging have been identified: intrinsic, mainly genetically determined and extrinsic-also called "photo-aging"-resulting on the impact of environmental stress and more precisely of UV rays. Simplified in vitro models, based on cellular senescence, have been developed to study the relationship between UV and aging. These models vary on the cell type (fibroblasts or keratinocytes, normal or immortalized) and the type of UV used (UVA or UVB).

  3. Melatonin alleviates hyperthyroidism induced oxidative stress and neuronal cell death in hippocampus of aged female golden hamster, Mesocricetus auratus.

    PubMed

    Rao, Geeta; Verma, Rakesh; Mukherjee, Arun; Haldar, Chandana; Agrawal, Neeraj Kumar

    2016-09-01

    Oxidative stress is a well known phenomenon under hyperthyroid condition that induces various physiological and neural problems with a higher prevalence in females. We, therefore investigated the antioxidant potential of melatonin (Mel) on hyperthyroidism-induced oxidative stress and neuronal cell death in the hippocampus region of brain (cognition and memory centre) of aged female golden hamster, Mesocricetus auratus. Aged female hamsters were randomly divided into four experimental groups (n=7); group-I: control, group-II: Melatonin (5mgkg(-1)day(-1), i.p., for one week), group-III: Hyperthyroid (100μg kg(-1)day(-1), i.p., for two weeks) and group-IV- Hyper+Mel. Hormonal profiles (thyroid and melatonin), activity of antioxidant enzymes (SOD, CAT and GPX), lipid peroxidation level (TBARS) and the specific apoptotic markers (Bax/Bcl-2 ratio and Caspase-3) expression were evaluated. A significant increase in the profile of total thyroid hormone (tT3 and tT4) in hyperthyroidic group as compared to control while tT3 significantly decreased in melatonin treated hyperthyroidic group. However, Mel level significantly decreased in hyperthyroidic group but increased in melatonin treated hyperthyroidic group. Further, the number of immune-positive cells for thyroid hormone receptor-alpha (TR-α) decreased in the hippocampus of hyperthyroidic group and increased in melatonin treated hyperthyroidic group. Profiles of antioxidant enzymes showed a significant decrease in hyperthyroidic group with a simultaneous increase in lipid peroxidation (TBARS). Melatonin treatment to hyperthyroidic group lead to decreased TBARS level with a concomitant increase in antioxidant enzyme activity. Moreover, increased expression of Bax/Bcl-2 ratio and Caspase-3, in hyperthyroidic group had elevated neuronal cell death in hippocampal area and melatonin treatment reduced its expression in hyperthyroidic group. Our findings thus indicate that melatonin reduced the hyperthyroidism

  4. Today's oxidative stress markers.

    PubMed

    Czerska, Marta; Mikołajewska, Karolina; Zieliński, Marek; Gromadzińska, Jolanta; Wąsowicz, Wojciech

    2015-01-01

    Oxidative stress represents a situation where there is an imbalance between the reactive oxygen species (ROS) and the availability and the activity of antioxidants. This balance is disturbed by increased generation of free radicals or decreased antioxidant activity. It is very important to develop methods and find appropriate biomarkers that may be used to assess oxidative stress in vivo. It is significant because appropriate measurement of such stress is necessary in identifying its role in lifestyle-related diseases. Previously used markers of oxidative stress, such as thiobarbituric acid reactive substances (TBARS) or malondialdehyde (MDA), are progressively being supplemented by new ones, such as isoprostanes (IsoPs) and their metabolites or allantoin. This paper is focusing on the presentation of new ones, promising markers of oxidative stress (IsoPs, their metabolites and allantoin), taking into account the advantage of those markers over markers used previously. PMID:26325052

  5. [Stress and optimal ageing].

    PubMed

    Gogol, Manfred

    2015-08-01

    Stress is a stimulus or incident which has an exogenic or endogenic influence on an organism and leads to a biological and/or psychological adaptation from the organism by adaptation. Stressors can be differentiated by the temporal impact (e.g. acute, chronic or acute on chronic), strength and quality. The consequences of stress exposure and adaptation can be measured at the cellular level and as (sub) clinical manifestations, where this process can be biologically seen as a continuum. Over the course of life there is an accumulation of stress incidents resulting in a diminution of the capability for adaptation and repair mechanisms. By means of various interventions it is possible to improve the individual capability for adaptation but it is not currently definitively possible to disentangle alterations due to ageing and the development of diseases. As a consequence the term "healthy ageing" should be replaced by the concept of "optimal ageing". PMID:26208575

  6. The Human Tripeptide GHK-Cu in Prevention of Oxidative Stress and Degenerative Conditions of Aging: Implications for Cognitive Health

    PubMed Central

    Pickart, Loren; Vasquez-Soltero, Jessica Michelle; Margolina, Anna

    2012-01-01

    Oxidative stress, disrupted copper homeostasis, and neuroinflammation due to overproduction of proinflammatory cytokines are considered leading causative factors in development of age-associated neurodegenerative conditions. Recently, a new mechanism of aging—detrimental epigenetic modifications—has emerged. Thus, compounds that possess antioxidant, anti-inflammatory activity as well as compounds capable of restoring copper balance and proper gene functioning may be able to prevent age-associated cognitive decline and ward off many common neurodegenerative conditions. The aim of this paper is to bring attention to a compound with a long history of safe use in wound healing and antiaging skin care. The human tripeptide GHK was discovered in 1973 as an activity in human albumin that caused old human liver tissue to synthesize proteins like younger tissue. It has high affinity for copper ions and easily forms a copper complex or GHK-Cu. In addition, GHK possesses a plethora of other regenerative and protective actions including antioxidant, anti-inflammatory, and wound healing properties. Recent studies revealed its ability to up- and downregulate a large number of human genes including those that are critical for neuronal development and maintenance. We propose GHK tripeptide as a possible therapeutic agent against age-associated neurodegeneration and cognitive decline. PMID:22666519

  7. Nutritional Intervention in Brain Aging: Reducing the Effects of Inflammation and Oxidative Stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is estimated that by the year 2050 the elderly (aged 65 or older) population will double the population of children (aged 0 – 14) for the first time in history. The expansion of the elderly population has already taken a toll on health care systems. In order to alleviate the health care costs a...

  8. Changes in oxidative stress enzymes during artificial ageing in cotton (Gossypium hirsutum L.) seeds.

    PubMed

    Goel, Anuradha; Goel, Ajay Kumar; Sheoran, Inder Singh

    2003-09-01

    The present study was carried out to elucidate the mechanism of seed deterioration in two cotton (Gossypium hirsutum L.) cultivars (HS6 and H1098). The seeds were artificially aged at 40 +/- 1 degree C and 100% relative humidity for 4 days. In both cultivars, germinability decreased, whereas membrane deterioration, as assayed by electrical conductivity of the seed leachates, increased progressively with artificial ageing. The decrease in germinability was well correlated with increased accumulation of total peroxide and malondialdehyde content and decreased activities of antioxidant enzymes peroxidase, catalase, ascorbate peroxidase, glutathione reductase and superoxide dismutase. Hydropriming for 2 h and ascorbic acid priming for 12 h partially maintained germination and the activities of various antioxidant enzymes under artificial ageing and the accumulation of peroxide and MDA content was decreased. The results suggest that cotton seed deterioration during accelerated ageing is closely related to a decrease in activities of various peroxide scavenging enzymes and to lipid peroxidation.

  9. Inflammation and Oxidative Stress as Biomarkers of Premature Aging in Persons with Intellectual Disability

    ERIC Educational Resources Information Center

    Carmeli, Eli; Imam, Bita; Bachar, Asad; Merrick, Joav

    2012-01-01

    The decline in cognitive ability and physical performance in older adults with intellectual disabilities (ID) is accompanied by less participation in social activities and a sedentary lifestyle; however the pathogenesis is not clear yet. It was recently suggested that chronic disease, adverse drug reactions, and aging create a cascade of events…

  10. Mitigation of oxidative stress and inflammatory signaling by fruit and walnut polyphenols: implications for cognitive aging

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous epidemiological studies have indicated that individuals who consume a diet containing high amounts of fruits and vegetables exhibit fewer age-related diseases such as Alzheimer Disease (AD). A recent report has indicated that individuals who consumed a diet containing 2.5 servings of fruit ...

  11. Oxidative Stress in Atopic Dermatitis

    PubMed Central

    Ji, Hongxiu; Li, Xiao-Kang

    2016-01-01

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

  12. Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging

    PubMed Central

    Panich, Uraiwan; Sittithumcharee, Gunya; Rathviboon, Natwarath

    2016-01-01

    Skin is the largest human organ. Skin continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. Some areas of skin are continuously exposed to a variety of environmental stressors that can inflict direct and indirect damage to skin cell DNA. Skin homeostasis is maintained by mesenchymal stem cells in inner layer dermis and epidermal stem cells (ESCs) in the outer layer epidermis. Reduction of skin stem cell number and function has been linked to impaired skin homeostasis (e.g., skin premature aging and skin cancers). Skin stem cells, with self-renewal capability and multipotency, are frequently affected by environment. Ultraviolet radiation (UVR), a major cause of stem cell DNA damage, can contribute to depletion of stem cells (ESCs and mesenchymal stem cells) and damage of stem cell niche, eventually leading to photoinduced skin aging. In this review, we discuss the role of UV-induced DNA damage and oxidative stress in the skin stem cell aging in order to gain insights into the pathogenesis and develop a way to reduce photoaging of skin cells. PMID:27148370

  13. Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice

    PubMed Central

    Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Hao, Enkui

    2016-01-01

    Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin-light chains 1), cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF)), cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB) to nucleus and formation of LC3-II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP-1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy-oxidative stress-inflammation-cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly. PMID:27200146

  14. Staphylococcal response to oxidative stress

    PubMed Central

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

    2012-01-01

    Staphylococci are a versatile genus of bacteria that are capable of causing acute and chronic infections in diverse host species. The success of staphylococci as pathogens is due in part to their ability to mitigate endogenous and exogenous oxidative and nitrosative stress. Endogenous oxidative stress is a consequence of life in an aerobic environment; whereas, exogenous oxidative and nitrosative stress are often due to the bacteria's interaction with host immune systems. To overcome the deleterious effects of oxidative and nitrosative stress, staphylococci have evolved protection, detoxification, and repair mechanisms that are controlled by a network of regulators. In this review, we summarize the cellular targets of oxidative stress, the mechanisms by which staphylococci sense oxidative stress and damage, oxidative stress protection and repair mechanisms, and regulation of the oxidative stress response. When possible, special attention is given to how the oxidative stress defense mechanisms help staphylococci control oxidative stress in the host. PMID:22919625

  15. Stress, Aging and Thirst

    NASA Technical Reports Server (NTRS)

    Greenleaf, John E.

    1998-01-01

    After growth during adolesence, total body water decreases progressively with aging from 65% of body weight to about 53% of body weight in the 70th decade; a majority of the loss occurs from the extracellular volume, from 42% to about 25%, respectively. Cellular volume also reaches equilibrium in the 70th decade at about 25% of body weight. Various stresses such as exercise, heat and attitude exposure, ad prior dehydration attenuate voluntary fluid intake (involuntary dehydration). Voluntary fluid intake appears to decrease with aging (involuntary dehydration in this sense aging can be considered as a stress. Kidney function and muscle mass (80% water) decrease somewhat with aging, and voluntary fluid intake (thirst) is also attenuated. Thirst is stimulated by increasing osmolality (hypernatremia) of the extracellular fluid and by decreased extracellular volume (mainly plasma volume) which act to increase intracellular fluid volume osmolality to activiate drinking. The latter decreases fluid compartment osmolality which ' It terminates drinking. However, this drinking mechanism seems to be attenuated with aging such that increasing plasma osmolality no longer stimulates fluid intake appropriately. Hypernatremia in the elderly has been associated all too frequently with greater incidence of bacterial infection and increased mortality. Involuntary dehydration can be overcome in young men by acclimation to an intermittent exercise-in-heat training program. Perhaps exercise training in the elderly would also increase voluntary fluid intake and increase muscle mass to enhance retention of water.

  16. Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases.

    PubMed

    Callaway, Danielle A; Jiang, Jean X

    2015-07-01

    Osteoclasts are cells derived from bone marrow macrophages and are important in regulating bone resorption during bone homeostasis. Understanding what drives osteoclast differentiation and activity is important when studying diseases characterized by heightened bone resorption relative to formation, such as osteoporosis. In the last decade, studies have indicated that reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are crucial components that regulate the differentiation process of osteoclasts. However, there are still many unanswered questions that remain. This review will examine the mechanisms by which ROS can be produced in osteoclasts as well as how it may affect osteoclast differentiation and activity through its actions on osteoclastogenesis signaling pathways. In addition, the contribution of ROS to the aging-associated disease of osteoporosis will be addressed and how targeting ROS may lead to the development of novel therapeutic treatment options.

  17. Aging Exacerbates Obesity-Induced Oxidative Stress and Inflammation in Perivascular Adipose Tissue in Mice: A Paracrine Mechanism Contributing to Vascular Redox Dysregulation and Inflammation

    PubMed Central

    Bailey-Downs, Lora C.; Tucsek, Zsuzsanna; Toth, Peter

    2013-01-01

    Obesity in the elderly individuals is increasing at alarming rates and there is evidence suggesting that elderly individuals are more vulnerable to the deleterious cardiovascular effects of obesity than younger individuals. However, the specific mechanisms through which aging and obesity interact to promote the development of cardiovascular disease remain unclear. The present study was designed to test the hypothesis that aging exacerbates obesity-induced inflammation in perivascular adipose tissue, which contributes to increased vascular oxidative stress and inflammation in a paracrine manner. To test this hypothesis, we assessed changes in the secretome, reactive oxygen species production, and macrophage infiltration in periaortic adipose tissue of young (7 month old) and aged (24 month old) high-fat diet–fed obese C57BL/6 mice. High-fat diet–induced vascular reactive oxygen species generation significantly increased in aged mice, which was associated with exacerbation of endothelial dysfunction and vascular inflammation. In young animals, high-fat diet–induced obesity promoted oxidative stress in the perivascular adipose tissue, which was associated with a marked proinflammatory shift in the profile of secreted cytokines and chemokines. Aging exacerbated obesity-induced oxidative stress and inflammation and significantly increased macrophage infiltration in periaortic adipose tissue. Using cultured arteries isolated from young control mice, we found that inflammatory factors secreted from the perivascular fat tissue of obese aged mice promote significant prooxidative and proinflammatory phenotypic alterations in the vascular wall, mimicking the aging phenotype. Overall, our findings support an important role for localized perivascular adipose tissue inflammation in exacerbation of vascular oxidative stress and inflammation in aging, an effect that likely enhances the risk for development of cardiovascular diseases from obesity in the elderly individuals

  18. Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress.

    PubMed

    Tóbon-Velasco, Julio C; Cuevas, Elvis; Torres-Ramos, Mónica A

    2014-01-01

    Recently, it has been proposed that the receptor for advanced glycation end-products (RAGE) plays a crucial role in damaging cellular processes, such as neuroinflammation, neurodegeneration, excitotoxicity and oxidative stress. RAGE is a multiligand receptor belonging to the immunoglobulin superfamily of cell surface molecules acting as a counter-receptor for diverse molecules. Engagement of RAGE converts a brief pulse of cellular activation into sustained cellular dysfunction and tissue damage. Indeed, the involvement of RAGE in physiopathological processes has been demonstrated for several neurodegenerative diseases. It is the full-length form of RAGE the one constituting the cellular receptor which is able to activate intracellular signals. After the binding of ligands to RAGE, oxidative stress is increased; then, over-expression of RAGE produces vicious cycles that perpetuate oxidative stress and contribute to neuroinflammation by nuclear factor-kB (NF-kB) up-regulation. The NF-kB activation promotes the expression of proinflammatory cytokines, including RAGE expression, to induce a prolonged activation and promotion of signaling mechanisms for cell damage. Because inflammatory and oxidative events have been demonstrated to concertedly interact during neurodegenerative events, this review is aimed to discuss the role of RAGE as mediator of an interaction between inflammation and oxidative stress through NF-kB signaling pathway.

  19. The influence of gender, age and treatment time on brain oxidative stress and memory impairment induced by D-galactose in mice.

    PubMed

    Hao, Ling; Huang, Huang; Gao, Junying; Marshall, Charles; Chen, Yali; Xiao, Ming

    2014-06-13

    Chronic exposure to d-galactose (d-gal) serves as a model for age-related oxidative damage and cognitive dysfunction. However, methods used, including the dose and treatment time of d-gal as well as the gender, age and strain of animals used, vary greatly among published articles. In this study, we investigate the effect of gender, age and treatment time on brain oxidative stress and spatial memory deficits induced by d-gal in mice, respectively. Eight-week-old female mice injected with 100mg/kg d-gal per day, for 6 weeks, did not show spatial memory impairment or high levels of hydroxyl radical, protein carbonyl and malondialdehyde in brain homogenates, although brain reactive oxygen species were increased when compared with saline control mice. In contrast, both 8-week-old male mice and 24-week-old female mice receiving 100mg/kg d-gal for 6 weeks, or 8-week-old female mice receiving 100mg/kg d-gal for 10 weeks showed spatial memory deficits and significant increases in the above oxidative markers, compared with their corresponding controls. These results demonstrate that d-gal-induced brain oxidative stress and spatial memory impairment are dependent upon exposure time of d-gal, plus gender and age of the animals used. The findings can serve as a useful guide for successfully establishing d-gal induced age-related oxidative damage models.

  20. Increased macromolecular damage due to oxidative stress in the neocortex and hippocampus of WNIN/Ob, a novel rat model of premature aging.

    PubMed

    Sinha, J K; Ghosh, S; Swain, U; Giridharan, N V; Raghunath, M

    2014-06-01

    Wistar of the National Institute of Nutrition obese (WNIN/Ob) is a unique rat strain isolated and established at NIN, Hyderabad, India, in 1996, from its existing stock of Wistar rat colony (WNIN). This animal model exhibits all traits of metabolic syndrome and has a remarkably reduced lifespan (1.5 years as compared to 3 years in parental WNIN rats), albeit, the factors associated with premature aging are not well understood. Considering that oxidative stress and DNA damage are crucial players associated with senescence, we analyzed oxidative stress markers like lipid peroxidation and protein oxidation; DNA damage in terms of both single-stranded and double-stranded breaks and the activity of antioxidant enzymes: superoxide dismutase and catalase in brain regions of these animals. Our study revealed that the magnitude of oxidative stress and DNA damage in the neocortex and hippocampus of 3-month-old WNIN/Ob obese rats is as high as that seen in 15-month-old parental WNIN control rats. Concurrently, the antioxidant enzyme activity was significantly decreased. From these results, it can be concluded that increased oxidative stress-induced damage of macromolecules, probably due to reduced activity of antioxidant enzymes, is associated with premature aging in WNIN/Ob obese rats.

  1. Resveratrol Directly Binds to Mitochondrial Complex I and Increases Oxidative Stress in Brain Mitochondria of Aged Mice

    PubMed Central

    Chupin, Stéphanie; Baron, Stéphanie; Nivet-Antoine, Valérie; Vessières, Emilie; Ayer, Audrey; Henrion, Daniel; Lenaers, Guy; Reynier, Pascal; Procaccio, Vincent

    2015-01-01

    Resveratrol is often described as a promising therapeutic molecule for numerous diseases, especially in metabolic and neurodegenerative disorders. While the mechanism of action is still debated, an increasing literature reports that resveratrol regulates the mitochondrial respiratory chain function. In a recent study we have identified mitochondrial complex I as a direct target of this molecule. Nevertheless, the mechanisms and consequences of such an interaction still require further investigation. In this study, we identified in silico by docking study a binding site for resveratrol at the nucleotide pocket of complex I. In vitro, using solubilized complex I, we demonstrated a competition between NAD+ and resveratrol. At low doses (<5μM), resveratrol stimulated complex I activity, whereas at high dose (50 μM) it rather decreased it. In vivo, in brain mitochondria from resveratrol treated young mice, we showed that complex I activity was increased, whereas the respiration rate was not improved. Moreover, in old mice with low antioxidant defenses, we demonstrated that complex I activation by resveratrol led to oxidative stress. These results bring new insights into the mechanism of action of resveratrol on mitochondria and highlight the importance of the balance between pro- and antioxidant effects of resveratrol depending on its dose and age. These parameters should be taken into account when clinical trials using resveratrol or analogues have to be designed. PMID:26684010

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

    PubMed Central

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

    2014-01-01

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

  3. Effects of Acute Exercise on Some Respiratory, Circulatory and Oxidative Stress Parameters of School Boys Aged 15-17 Years

    ERIC Educational Resources Information Center

    Kurkcu, Recep; Gokhan, Ismail

    2013-01-01

    The purpose of this study was to evaluate the effects of acute exercise on respiratory functions, heart-beats, blood pressure, total antioxidative capacity (TAC), oxidative stress index (OSI), lipid hydro-peroxide (LOOHs) and Paraoxonase (PON) in school boys. A sample of 18 male amateur wrestlers are selected for this study. The participants…

  4. Biomarkers of oxidative stress and redox status in a short-term low-dosed multivitamin and mineral supplementation study in two human age groups.

    PubMed

    Jansen, Eugene; Beekhof, Piet; Tamosiunas, Abdonas; Luksiene, Dalia; Baceviciene, Migle

    2015-10-01

    A 60-day intervention study was conducted in which the participants took a low dose of a multivitamin and mineral supplement. The study consists of a final number of 66 volunteers (30 males and 36 females), divided into two age groups of 30-35 and 60-65 years. For 30 days they took a multivitamin and mineral supplement with 1× the recommended daily intake (RDI) followed by another 30 days with 2× the RDI. The aim of the study was to monitor oxidative stress and redox status of both young and old age groups. In serum, the expected increase of the water-soluble vitamins folate and vitamin B12 was observed with a concomitant decrease in homocysteine. Serum biomarkers of oxidative stress, the reactive oxygen metabolites, of the antioxidant status, the biological antioxidant potential did not change. However, the total thiol levels in serum, biomarker of the redox status, decreased significant, only in both groups of elderly after 60 days. In erythrocytes, there was a change in the glutathione metabolism as observed by an increase in glutathione reductase and to a lower extend in glutathione peroxidase, indicating an increase in oxidative stress in all groups. It is concluded that a low-dosed multivitamin and -mineral supplementation have different effects on the redox status in young versus old. It remained to explain why a low dose of a multivitamin and -mineral supplement cause increased oxidative stress.

  5. Activation of the Hog1p kinase in Isc1p-deficient yeast cells is associated with mitochondrial dysfunction, oxidative stress sensitivity and premature aging.

    PubMed

    Barbosa, António Daniel; Graça, João; Mendes, Vanda; Chaves, Susana Rodrigues; Amorim, Maria Amélia; Mendes, Marta Vaz; Moradas-Ferreira, Pedro; Côrte-Real, Manuela; Costa, Vítor

    2012-05-01

    The Saccharomyces cerevisiae Isc1p, an orthologue of mammalian neutral sphingomyelinase 2, plays a key role in mitochondrial function, oxidative stress resistance and chronological lifespan. Isc1p functions upstream of the ceramide-activated protein phosphatase Sit4p through the modulation of ceramide levels. Here, we show that both ceramide and loss of Isc1p lead to the activation of Hog1p, the MAPK of the high osmolarity glycerol (HOG) pathway that is functionally related to mammalian p38 and JNK. The hydrogen peroxide sensitivity and premature aging of isc1Δ cells was partially suppressed by HOG1 deletion. Notably, Hog1p activation mediated the mitochondrial dysfunction and catalase A deficiency associated with oxidative stress sensitivity and premature aging of isc1Δ cells. Downstream of Hog1p, Isc1p deficiency activated the cell wall integrity (CWI) pathway. Deletion of the SLT2 gene, which encodes for the MAPK of the CWI pathway, was lethal in isc1Δ cells and this mutant strain was hypersensitive to cell wall stress. However, the phenotypes of isc1Δ cells were not associated with cell wall defects. Our findings support a role for Hog1p in the regulation of mitochondrial function and suggest that constitutive activation of Hog1p is deleterious for isc1Δ cells under oxidative stress conditions and during chronological aging. PMID:22445853

  6. Targeted deletion of the murine Lgr4 gene decreases lens epithelial cell resistance to oxidative stress and induces age-related cataract formation.

    PubMed

    Zhu, Jun; Hou, Qiang; Dong, Xiang Da; Wang, Zhenlian; Chen, Xiaoyan; Zheng, Dandan; Zhou, Linglin; He, Chao; Liu, Mingyao; Tu, LiLi; Qu, Jia

    2015-01-01

    Oxidative stress contributes to the formation of cataracts. The leucine rich repeat containing G protein-coupled receptor 4 (LGR4, also known as GPR48), is important in many developmental processes. Since deletion of Lgr4 has previously been shown to lead to cataract formation in mice, we sought to determine the specific role that Lgr4 plays in the formation of cataracts. Initially, the lens opacities of Lgr4(-/-) mice at different ages without ocular anterior segment dysgenesis (ASD) were evaluated with slit-lamp biomicroscopy. Lenses from both Lgr4(-/-) and wild-type mice were subjected to oxidation induced protein denaturation to assess the ability of the lens to withstand oxidation. The expression of antioxidant enzymes was evaluated with real-time quantitative PCR. Phenotypically, Lgr4(-/-) mice showed earlier onset of lens opacification and higher incidence of cataract formation compared with wild-type mice of similar age. In addition, Lgr4(-/-) mice demonstrated increased sensitivity to environmental oxidative damage, as evidenced by altered protein expression. Real-time quantitative PCR showed that two prominent antioxidant defense enzymes, catalase (CAT) and superoxidase dismutase-1 (SOD1), were significantly decreased in the lens epithelial cells of Lgr4(-/-) mice. Our results suggest that the deletion of Lgr4 can lead to premature cataract formation, as well as progressive deterioration with aging. Oxidative stress and altered expression of several antioxidant defense enzymes contribute to the formation of cataracts. PMID:25811370

  7. NADPH oxidase 3-associated oxidative stress and caspase 3-dependent apoptosis in the cochleae of D-galactose-induced aged rats

    PubMed Central

    DU, ZHENGDE; LI, SHUO; LIU, LIN; YANG, QIONG; ZHANG, HONGWEI; GAO, CHUNSHENG

    2015-01-01

    Oxidative damage to mitochondrial DNA (mtDNA) and cell apoptosis are heavily implicated in aging. Our previous study established a mimetic rat model of aging in the cochleae using D-galactose (D-gal), and revealed that chronic injection of D-gal can increase oxidative stress and mtDNA common deletions (CD). The aim of the present study was to investigate the sources of reactive oxygen species and the occurrence of apoptosis in the cochleae of rats following 8 weeks of D-gal exposure. The results of the present study indicated that an elevated accumulation of the mtDNA CD and mitochondrial ultrastructural damage occurred in the cochleae of rats injected with D-gal for 8 weeks. In addition, the levels of 8-hydroxy-2-deoxyguanosine, NADPH oxidase (NOX) 3, P22phox and cleaved caspase 3, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end-labelling-positive cells were increased in the cochleae of D-gal-treated rats, compared with the controls. These findings suggested that nitric oxide synthase NOX3-associated oxidative stress may contribute to the accumulation of mtDNA mutations and activate a caspase 3-dependent apoptotic signalling pathway in the cochleae during aging. The present study also provided novel insights into the development of age-associated hearing loss, also termed presbycusis. PMID:26498835

  8. Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress

    PubMed Central

    Machi, Jacqueline Freire; Dias, Danielle da Silva; Freitas, Sarah Cristina; de Moraes, Oscar Albuquerque; da Silva, Maikon Barbosa; Cruz, Paula Lázara; Mostarda, Cristiano; Salemi, Vera M C; Morris, Mariana; De Angelis, Kátia; Irigoyen, Maria-Cláudia

    2016-01-01

    Objective The aim of this study was to evaluate the effects of aging on metabolic, cardiovascular, autonomic, inflammatory, and oxidative stress parameters after ovarian hormone deprivation (OVX). Methods Female Wistar rats (3 or 22 months old) were divided into: young controls, young ovariectomized, old controls, and old ovariectomized (bilateral ovaries removal). After a 9-week follow-up, physical capacity, metabolic parameters, and morphometric and cardiac functions were assessed. Subsequently, arterial pressure was recorded and cardiac autonomic control was evaluated. Oxidative stress was measured on the cardiac tissue, while inflammatory profile was assessed in the plasma. Results Aging or OVX caused an increase in body and fat weight and triglyceride concentration and a decrease in both insulin sensitivity and aerobic exercise capacity. Left ventricular diastolic dysfunction and increased cardiac overload (myocardial performance index) were reported in old groups when compared with young groups. Aging and OVX led to an increased sympathetic tonus, and vagal tonus was lower only for the old groups. Tumor necrosis factor-α and interleukin-6 were increased in old groups when compared with young groups. Glutathione redox balance (GSH/GSSG) was reduced in young ovariectomized, old controls, and old ovariectomized groups when compared with young controls, indicating an increased oxidative stress. A negative correlation was found between GSH/GSSG and tumor necrosis factor-α (r=−0.6, P<0.003). Correlations were found between interleukin-6 with adipose tissue (r=0.5, P<0.009) and vagal tonus (r=−0.7, P<0.0002); and among myocardial performance index with interleukin-6 (r=0.65, P<0.0002), sympathetic tonus (r=0.55, P<0.006), and physical capacity (r=−0.55, P<0.003). The findings in this trial showed that ovariectomy aggravated the impairment of cardiac and functional effects of aging in female rats, probably associated with exacerbated autonomic dysfunction

  9. The free-radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan.

    PubMed

    Speakman, John R; Selman, Colin

    2011-04-01

    Recent work on a small European cave salamander (Proteus anguinus) has revealed that it has exceptional longevity, yet it appears to have unexceptional defences against oxidative damage. This paper comes at the end of a string of other studies that are calling into question the free-radical damage theory of ageing. This theory rose to prominence in the 1990s as the dominant theory for why we age and die. Despite substantial correlative evidence to support it, studies in the last five years have raised doubts over its importance. In particular, these include studies of mice with the major antioxidant genes knocked out (both singly and in combination), which show the expected elevation in oxidative damage but no impact on lifespan. Combined, these findings raise fundamental questions over whether the free-radical damage theory remains useful for understanding the ageing process, and variation in lifespan and life histories.

  10. Cutaneous oxidative stress.

    PubMed

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

    2012-03-01

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

  11. Oxidative Stress in Malaria

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Oxidative stress in prostate cancer.

    PubMed

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

    2009-09-18

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

  14. Oxidative Stress in Myopia

    PubMed Central

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

    2015-01-01

    Myopia affected approximately 1.6 billion people worldwide in 2000, and it is expected to increase to 2.5 billion by 2020. Although optical problems can be corrected by optics or surgical procedures, normal myopia and high myopia are still an unsolved medical problem. They frequently predispose people who have them to suffer from other eye pathologies: retinal detachment, glaucoma, macular hemorrhage, cataracts, and so on being one of the main causes of visual deterioration and blindness. Genetic and environmental factors have been associated with myopia. Nevertheless, lack of knowledge in the underlying physiopathological molecular mechanisms has not permitted an adequate diagnosis, prevention, or treatment to be found. Nowadays several pieces of evidence indicate that oxidative stress may help explain the altered regulatory pathways in myopia and the appearance of associated eye diseases. On the one hand, oxidative damage associated with hypoxia myopic can alter the neuromodulation that nitric oxide and dopamine have in eye growth. On the other hand, radical superoxide or peroxynitrite production damage retina, vitreous, lens, and so on contributing to the appearance of retinopathies, retinal detachment, cataracts and so on. The objective of this review is to suggest that oxidative stress is one of the key pieces that can help solve this complex eye problem. PMID:25922643

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

    PubMed

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

    2011-11-01

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

  16. Testing the oxidative stress hypothesis of aging in primate fibroblasts: is there a correlation between species longevity and cellular ROS production?

    PubMed

    Csiszar, Anna; Podlutsky, Andrej; Podlutskaya, Natalia; Sonntag, William E; Merlin, Steven Z; Philipp, Eva E R; Doyle, Kristian; Davila, Antonio; Recchia, Fabio A; Ballabh, Praveen; Pinto, John T; Ungvari, Zoltan

    2012-08-01

    The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide (O2(·-)) generation, showed an inverse correlation between longevity and steady state or metabolic stress-induced mitochondrial O2(·-) production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H(2)O(2)-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity. PMID:22219516

  17. The effect of low-level laser therapy on oxidative stress and functional fitness in aged rats subjected to swimming: an aerobic exercise.

    PubMed

    Guaraldo, Simone A; Serra, Andrey Jorge; Amadio, Eliane Martins; Antônio, Ednei Luis; Silva, Flávio; Portes, Leslie Andrews; Tucci, Paulo José Ferreira; Leal-Junior, Ernesto Cesar Pinto; de Carvalho, Paulo de Tarso Camillo

    2016-07-01

    The aim of the present study was to determine whether low-level laser therapy (LLLT) in conjunction with aerobic training interferes with oxidative stress, thereby influencing the performance of old rats participating in swimming. Thirty Wistar rats (Norvegicus albinus) (24 aged and six young) were tested. The older animals were randomly divided into aged-control, aged-exercise, aged-LLLT, aged-LLLT/exercise, and young-control. Aerobic capacity (VO2max(0.75)) was analyzed before and after the training period. The exercise groups were trained for 6 weeks, and the LLLT was applied at 808 nm and 4 J energy. The rats were euthanized, and muscle tissue was collected to analyze the index of lipid peroxidation thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. VO2 (0.75)max values in the aged-LLLT/exercise group were significantly higher from those in the baseline older group (p <0.01) and the LLLT and exercise group (p <0.05). The results indicate that the activities of CAT, SOD, and GPx were higher and statistically significant (p <0.05) in the LLLT/exercise group than those in the LLLT and exercise groups. Young animals presented lesser and statistically significant activities of antioxidant enzymes compared to the aged group. The LLLT/exercise group and the LLLT and exercise group could also mitigate the concentration of TBARS (p > 0.05). Laser therapy in conjunction with aerobic training may reduce oxidative stress, as well as increase VO2 (0.75)max, indicating that an aerobic exercise such as swimming increases speed and improves performance in aged animals treated with LLLT. PMID:26861983

  18. Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community.

    PubMed

    Cui, Xiaoyi; Ohtsu, Mayumi; Mise, Nathan; Ikegami, Akihiko; Mizuno, Atsuko; Sakamoto, Takako; Ogawa, Masanori; Machida, Munehito; Kayama, Fujio

    2016-01-01

    This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard β of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging.

  19. Heavy metal exposure, in combination with physical activity and aging, is related with oxidative stress in Japanese women from a rural agricultural community.

    PubMed

    Cui, Xiaoyi; Ohtsu, Mayumi; Mise, Nathan; Ikegami, Akihiko; Mizuno, Atsuko; Sakamoto, Takako; Ogawa, Masanori; Machida, Munehito; Kayama, Fujio

    2016-01-01

    This study aimed to evaluate the relationships between oxidative stress and heavy metal exposure (lead [Pb] and cadmium [Cd]), as well as co-factors such as physical activity and age, in Japanese women. This study was conducted with female subjects from a rural agricultural community in Japan. Subjects were asked to complete lifestyle-related questionnaires and undergo a group health examination. Physical activity, alcohol consumption, body mass index, and other demographic information were collected. Blood and urine samples were collected to measure urinary 8-hydroxydeoxyguanosine (8-OHdG) levels and blood and urinary Cd and Pb concentrations. Urine samples were analyzed using high performance liquid chromatography and flameless atomic absorption spectrometry; blood samples were analyzed using inductively coupled plasma-mass spectrometry. Age, physical activity, and blood and urinary Cd and Pb concentrations were included in structural equation modeling analysis. Two latent factors for heavy metal exposure and physical activity were produced to predict the total influence of the variables. The final model was good: CMIN/DF = 0.775, CFI = 1.000, GFI = 0.975, AGFI = 0.954, RMSEA = 0.000. 8-OHdG levels were positively associated with heavy metal exposure, physical activity, and age (standard β of path analysis: 0.33, 0.38, and 0.20, respectively). Therefore, oxidative stress is associated with both, environmental and lifestyle factors, in combination with aging. PMID:27386333

  20. Peroxisomal metabolism and oxidative stress.

    PubMed

    Nordgren, Marcus; Fransen, Marc

    2014-03-01

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

  1. Peroxisomal metabolism and oxidative stress.

    PubMed

    Nordgren, Marcus; Fransen, Marc

    2014-03-01

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

  2. Oxidative stress by inorganic nanoparticles.

    PubMed

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

    2016-05-01

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

  3. Oxidative stress by inorganic nanoparticles.

    PubMed

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

    2016-05-01

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

  4. The effects of Ginkgo biloba extract on cognitive functions in aged female rats: the role of oxidative stress and brain-derived neurotrophic factor.

    PubMed

    Belviranlı, Muaz; Okudan, Nilsel

    2015-02-01

    The aim of this study was to investigate the effects of Ginkgo biloba extract (GBE) on cognitive functions as well as oxidative stress and brain-derived neurotrophic factor (BDNF) levels in aged female rats. Rats were divided into 4 groups according to age (young vs. aged) and treatment (GBE vs. vehicle). GBE or vehicle was given for 30 d, and a series of behavioral tests were performed. Following behavioral testing, blood samples and brain tissues were obtained for analysis of BDNF, malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and glutathione levels, and superoxide dismutase activity. Locomotor activity and anxiety levels were lower in the aged rats. Based on Morris water maze probe trial findings, GBE supplementation increased the number of platform crossings in the aged rats. MDA and 8-OHdG levels were lower in the brain tissue, and BDNF levels were higher in plasma in the rates treated with GBE. Based on these findings, we concluded that GBE supplementation improved cognitive functions by decreasing oxidative damage and increasing the BDNF level in aged female rats.

  5. [Vitamins and oxidative stress].

    PubMed

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

    2013-01-01

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

  6. Oxidative stress-induced premature senescence dysregulates VEGF and CFH expression in retinal pigment epithelial cells: Implications for Age-related Macular Degeneration

    PubMed Central

    Marazita, Mariela C.; Dugour, Andrea; Marquioni-Ramella, Melisa D.; Figueroa, Juan M.; Suburo, Angela M.

    2015-01-01

    Oxidative stress has a critical role in the pathogenesis of Age-related Macular Degeneration (AMD), a multifactorial disease that includes age, gene variants of complement regulatory proteins and smoking as the main risk factors. Stress-induced premature cellular senescence (SIPS) is postulated to contribute to this condition. In this study, we hypothesized that oxidative damage, promoted by endogenous or exogenous sources, could elicit a senescence response in RPE cells, which would in turn dysregulate the expression of major players in AMD pathogenic mechanisms. We showed that exposure of a human RPE cell line (ARPE-19) to a cigarette smoke concentrate (CSC), not only enhanced Reactive Oxygen Species (ROS) levels, but also induced 8-Hydroxydeoxyguanosine-immunoreactive (8-OHdG) DNA lesions and phosphorylated-Histone 2AX-immunoreactive (p-H2AX) nuclear foci. CSC-nuclear damage was followed by premature senescence as shown by positive senescence associated-β-galactosidase (SA-β-Gal) staining, and p16INK4a and p21Waf-Cip1 protein upregulation. N-acetylcysteine (NAC) treatment, a ROS scavenger, decreased senescence markers, thus supporting the role of oxidative damage in CSC-induced senescence activation. ARPE-19 senescent cultures were also established by exposure to hydrogen peroxide (H2O2), which is an endogenous stress source produced in the retina under photo-oxidation conditions. Senescent cells upregulated the proinflammatory cytokines IL-6 and IL-8, the main markers of the senescence-associated secretory phenotype (SASP). Most important, we show for the first time that senescent ARPE-19 cells upregulated vascular endothelial growth factor (VEGF) and simultaneously downregulated complement factor H (CFH) expression. Since both phenomena are involved in AMD pathogenesis, our results support the hypothesis that SIPS could be a principal player in the induction and progression of AMD. Moreover, they would also explain the striking association of this disease

  7. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally-aging mice

    PubMed Central

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Michelle Jennifer; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-01-01

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer’s disease and normal aging is understudied. In the present study we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer’s disease, by crossing APP/PSEN1+ bigenic mice with SVCT2+/− heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2+/− mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2+/− and APP/PSEN1+, mice, and the combination genotype SVCT2+/−APP/PSEN1+, were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2+/−) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2+/− mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2+/−APP/PSEN1+ mice compared to APP/PSEN1+ mice with normal brain vitamin C. The data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways. PMID:25642732

  8. Changes in Oxidative Stress and Inflammatory Biomarkers in Fragile Adults over Fifty Years of Age and in Elderly People Exclusively Fed Enteral Nutrition

    PubMed Central

    Mesa, Maria D.; Olza, Josune; Gonzalez-Anton, Carolina; Aguilera, Concepcion M.; Moreno-Torres, Rosario; Jimenez, Africa; Perez de la Cruz, Antonio; Ruperez, Azahara I.; Gil, Angel

    2016-01-01

    We aim to evaluate whether exclusive feeding of an enteral formula enriched with n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA) affects oxidative stress and the antioxidant defence system and may improve the levels of some relevant inflammatory, and cardiovascular biomarkers in frail adults over fifty years of age and in elderly subjects. Fifty-five patients were divided into two groups and were exclusively fed a newly designed normoproteic and isocaloric enteral formula enriched with eicosapentaenoic (98 mg/d) and docosahexaenoic acids (46 mg/d) (n = 26) or a reference enteral diet (n = 29). Oxidative, inflammatory and cardiovascular risk biomarkers and red blood cell fatty acid profiles were determined at the beginning and after 90 and 180 days of feeding. The n-3 LC-PUFA percentage tended to be higher (P = 0.053) in the experimental group than in the reference group. Administration of the n-3 LC-PUFA diet did not increase oxidative stress or modify plasma antioxidant capacity but decreased antioxidant enzymatic activities. MMP-9 plasma concentration decreased with both formulae, whereas tPAI-1 tended to decrease (P = 0.116) with the administration of the experimental formula. In conclusion, administration of the new n-3 LC-PUFA-enriched product for 6 months did not negatively alter the oxidative status and improved some cardiovascular risk biomarkers. PMID:26697137

  9. Testing predictions of the oxidative stress hypothesis of aging using a novel invertebrate model of longevity: the giant clam (Tridacna derasa).

    PubMed

    Ungvari, Zoltan; Csiszar, Anna; Sosnowska, Danuta; Philipp, Eva E; Campbell, Courtney M; McQuary, Philip R; Chow, Tracy T; Coelho, Miguel; Didier, Elizabeth S; Gelino, Sara; Holmbeck, Marissa A; Kim, Insil; Levy, Erik; Sonntag, William E; Whitby, Paul W; Austad, Steven N; Ridgway, Iain

    2013-04-01

    Bivalve species with exceptional longevity are newly introduced model systems in biogerontology to test evolutionarily conserved mechanisms of aging. Here, we tested predictions based on the oxidative stress hypothesis of aging using one of the tropical long-lived sessile giant clam species, the smooth giant clam (Tridacna derasa; predicted maximum life span: >100 years) and the short-lived Atlantic bay scallop (Argopecten irradians irradians; maximum life span: 2 years). The warm water-dwelling giant clams warrant attention because they challenge the commonly held view that the exceptional longevity of bivalves is a consequence of the cold water they reside in. No significant interspecific differences in production of H2O2 and O2- in the gills, heart, or adductor muscle were observed. Protein carbonyl content in gill and muscle tissues were similar in T derasa and A i irradians. In tissues of T derasa, neither basal antioxidant capacities nor superoxide dismutase and catalase activities were consistently greater than in A i irradians. We observed a positive association between longevity and resistance to mortality induced by exposure to tert-butyl hydroperoxide (TBHP). This finding is consistent with the prediction based on the oxidative stress hypothesis of aging. The findings that in tissues of T derasa, proteasome activities are significantly increased as compared with those in tissues of A i irradians warrant further studies to test the role of enhanced protein recycling activities in longevity of bivalves.

  10. The impact of oxidative stress on hair.

    PubMed

    Trüeb, R M

    2015-12-01

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

  11. The impact of oxidative stress on hair.

    PubMed

    Trüeb, R M

    2015-12-01

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

  12. Moderate swimming exercise and caffeine supplementation reduce the levels of inflammatory cytokines without causing oxidative stress in tissues of middle-aged rats.

    PubMed

    Cechella, José L; Leite, Marlon R; Dobrachinski, Fernando; da Rocha, Juliana T; Carvalho, Nelson R; Duarte, Marta M M F; Soares, Félix A A; Bresciani, Guilherme; Royes, Luiz F F; Zeni, Gilson

    2014-05-01

    The levels of circulatory inflammatory markers, including interleukin (IL) IL-1β, IL-6, tumor necrosis factor-α (TNF-α) and interferon (INF-γ), are known to increase associated to aging. Caffeine has been reported to produce many beneficial effects for health. Exercise is considered to be a safe medicine to attenuate inflammation and cellular senescence. The purpose of the present study was to investigate the effects of a moderate-intensity swimming exercise (3 % of body weight, 20 min per day, 4 weeks) and sub-chronic supplementation with caffeine (30 mg/kg, 4 weeks) on the serum cytokine levels in middle-aged (18 months) Wistar rats. The effects of swimming exercise and caffeine on oxidative stress in muscle and liver of middle-aged rats were also investigated. The two-way ANOVA of pro-inflammatory cytokine levels demonstrated a significant exercise x caffeine interaction for IL-1β (F (1, 16) = 9.5772; p = 0.0069), IL-6 (F (1, 16) = 8.0463; p = 0.0119) and INF-γ (F (1, 16) = 15.078; p = 0.0013). The two-way ANOVA of TNF-α levels revealed a significant exercise × caffeine interaction (F (1, 16) = 9.6881; p = 0.00670). Swimming exercise and caffeine supplementation increased the ratio of reduced glutathione/oxidized glutathione in the rat liver and gastrocnemius muscle. Hepatic and renal markers of damage were not modified. In conclusion, a moderate-intensity swimming exercise protocol and caffeine supplementation induced positive adaptations in modulating cytokine levels without causing oxidative stress in muscle and liver of middle-aged rats. PMID:24481487

  13. Impaired response to oxidative stress in senescent cells may lead to accumulation of DNA damage in mesothelial cells from aged donors

    SciTech Connect

    Ksiazek, Krzysztof Piatek, Katarzyna; Witowski, Janusz

    2008-08-22

    The accumulation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) exemplifies oxidative DNA injury, which is strongly implicated in ageing. We show that human peritoneal mesothelial cells (HPMCs) from donors >75 years have lower proliferative capacity but increased 8-OH-dG content compared with cells from individuals <25 years. We detected a positive relationship between the donor's age and the 8-OH-dG level in early-passage HPMCs, and an inverse relationship between those 8-OH-dG levels and subsequent replicative lifespan of HPMCs (n = 30). In early-passage cells from donors >75 years, the repair of oxidant-induced 8-OH-dG was delayed compared to cells from donors <25 years. This was coupled with prolonged removal of reactive oxygen species and faster decline in superoxide dismutase activity. Similar effects were observed in HPMCs rendered senescent in vitro. These results indicate that increased 8-OH-dG levels in HPMCs from aged individuals may reflect the in vivo presence of senescent cells with increased vulnerability to oxidative stress-induced DNA damage.

  14. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    PubMed

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  15. Endocrine disruption and oxidative stress in larvae of Chironomus dilutus following short-term exposure to fresh or aged oil sands process-affected water.

    PubMed

    Wiseman, S B; Anderson, J C; Liber, K; Giesy, J P

    2013-10-15

    Understanding the toxicity of oil sands process-affected water (OSPW) is a significant issue associated with the production of oil from the Alberta oil sands. OSPW is acutely and chronically toxic to organisms, including larvae of Chironomus dilutus. In this study, fresh OSPW ('WIP-OSPW') was collected from the West In-Pit settling pond and aged OSPW ('FE5-OSPW') was collected from the FE5 experimental reclamation pond, both of which are located on the Syncrude Canada Ltd. lease site near Fort McMurray, Alberta, Canada. Larvae of C. dilutus were exposed to a freshwater control, WIP-OSPW, or FE5-OSPW for 4 or 7 days and survival, growth, and markers of oxidative stress and endocrine disruption were assessed. Survival was not significantly different among treatment groups. Compared to masses of larvae exposed to freshwater, masses of larvae exposed to WIP-OSPW were 49% lesser on day 4 and 62% lesser on day 7. However, organisms exposed to FE5-OSPW did not have significantly lesser masses than controls. Abundances of transcripts of glutathione-s-transferase (gst), catalase (cat), and glutathione peroxidase (gpx), which are important for the response to oxidative stress, were significantly altered in larvae exposed to WIP-OSPW, but not FE5-OSPW, relative to controls. Peroxidation of lipids was greater in larvae exposed to WIP-OSPW, but not FE5-OSPW. Exposure to fresh OSPW might have caused endocrine disruption because abundances of transcripts of the steroid hormone receptors, ultraspiricle protein (usp), ecysteroid receptor (esr), and estrogen related receptor (err) were greater in larvae exposed to WIP-OSPW for 7 days, but not FE5-OSPW. These results suggest that lesser growth of larvae of C. dilutus exposed to fresh OSPW might be due to oxidative stress and disruption of endocrine processes, and that aging of OSPW attenuates these adverse effects. PMID:24096237

  16. Specific roles for Group V secretory PLA₂ in retinal iron-induced oxidative stress. Implications for age-related macular degeneration.

    PubMed

    Rodríguez Diez, G; Sánchez Campos, S; Giusto, N M; Salvador, G A

    2013-08-01

    Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its

  17. Transcriptome-Wide Mapping of Pea Seed Ageing Reveals a Pivotal Role for Genes Related to Oxidative Stress and Programmed Cell Death

    PubMed Central

    Colville, Louise; Lorenzo, Oscar; Graeber, Kai; Küster, Helge; Leubner-Metzger, Gerhard; Kranner, Ilse

    2013-01-01

    Understanding of seed ageing, which leads to viability loss during storage, is vital for ex situ plant conservation and agriculture alike. Yet the potential for regulation at the transcriptional level has not been fully investigated. Here, we studied the relationship between seed viability, gene expression and glutathione redox status during artificial ageing of pea (Pisum sativum) seeds. Transcriptome-wide analysis using microarrays was complemented with qRT-PCR analysis of selected genes and a multilevel analysis of the antioxidant glutathione. Partial degradation of DNA and RNA occurred from the onset of artificial ageing at 60% RH and 50°C, and transcriptome profiling showed that the expression of genes associated with programmed cell death, oxidative stress and protein ubiquitination were altered prior to any sign of viability loss. After 25 days of ageing viability started to decline in conjunction with progressively oxidising cellular conditions, as indicated by a shift of the glutathione redox state towards more positive values (>−190 mV). The unravelling of the molecular basis of seed ageing revealed that transcriptome reprogramming is a key component of the ageing process, which influences the progression of programmed cell death and decline in antioxidant capacity that ultimately lead to seed viability loss. PMID:24205239

  18. Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation.

    PubMed

    Imai, Rika; Asai, Kanae; Hanai, Jun-ichi; Takenaka, Masaru

    2015-07-01

    Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosisin vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A.

  19. Transgenic mice overexpressing glia maturation factor-β, an oxidative stress inducible gene, show premature aging due to Zmpste24 down-regulation

    PubMed Central

    Hanai, Jun-ichi; Takenaka, Masaru

    2015-01-01

    Glia Maturation Factor-β (GMF), a brain specific protein, is induced by proteinuria in renal tubules. Ectopic GMF overexpression causes apoptosis in vitro via cellular vulnerability to oxidative stress. In order to examine the roles of GMF in non-brain tissue, we constructed transgenic mice overexpressing GMF (GMF-TG). The GMF-TG mice exhibited appearance phenotypes associated with premature aging. The GMF-TG mice also demonstrated short lifespans and reduced hair regrowth, suggesting an accelerated aging process. The production of an abnormal lamin A, a nuclear envelope protein, plays a causal role in both normal aging and accelerated aging diseases, known as laminopathies. Importantly, we identified the abnormal lamin A (prelamin A), accompanied by a down-regulation of a lamin A processing enzyme (Zmpste24) in the kidney of the GMF-TG mice. The GMF-TG mice showed accelerated aging in the kidney, compared with wild-type mice, showing increased TGF-β1, CTGF gene and serum creatinine. The gene expression of p21/waf1 was increased at an earlier stage of life, at 10 weeks, which was in turn down-regulated at a later stage, at 60 weeks. In conclusion, we propose that GMF-TG mice might be a novel mouse model of accelerated aging, due to the abnormal lamin A. PMID:26232943

  20. Leaf Age-Dependent Photoprotective and Antioxidative Response Mechanisms to Paraquat-Induced Oxidative Stress in Arabidopsis thaliana

    PubMed Central

    Moustaka, Julietta; Tanou, Georgia; Adamakis, Ioannis-Dimosthenis; Eleftheriou, Eleftherios P.; Moustakas, Michael

    2015-01-01

    Exposure of Arabidopsis thaliana young and mature leaves to the herbicide paraquat (Pq) resulted in a localized increase of hydrogen peroxide (H2O2) in the leaf veins and the neighboring mesophyll cells, but this increase was not similar in the two leaf types. Increased H2O2 production was concomitant with closed reaction centers (qP). Thirty min after Pq exposure despite the induction of the photoprotective mechanism of non-photochemical quenching (NPQ) in mature leaves, H2O2 production was lower in young leaves mainly due to the higher increase activity of ascorbate peroxidase (APX). Later, 60 min after Pq exposure, the total antioxidant capacity of young leaves was not sufficient to scavenge the excess reactive oxygen species (ROS) that were formed, and thus, a higher H2O2 accumulation in young leaves occurred. The energy allocation of absorbed light in photosystem II (PSII) suggests the existence of a differential photoprotective regulatory mechanism in the two leaf types to the time-course Pq exposure accompanied by differential antioxidant protection mechanisms. It is concluded that tolerance to Pq-induced oxidative stress is related to the redox state of quinone A (QA). PMID:26096005

  1. Age associated oxidative damage in lymphocytes

    PubMed Central

    Gautam, Nandeslu; Das, Subhasis; Mahapatra, Santanu Kar; Chakraborty, Subhankari Prasad; Kundu, Pratip Kumar

    2010-01-01

    Lymphocytes are an important immunological cell and have been played a significant role in acquired immune system; hence, may play in pivotal role in immunosenescence. Oxidative stress has been reported to increase in elderly subjects, possibly arising from an uncontrolled production of free radicals with aging and decreased antioxidant defenses. This study was aimed to evaluate the level of lipid-protein damage and antioxidant status in lymphocytes of healthy individuals to correlate between oxidative damage with the aging process. Twenty healthy individuals of each age group (11–20; 21–30; 31–40; 41–50; and 51–60 years) were selected randomly. Blood samples were drawn by medical practitioner and lymphocytes were isolated from blood samples. Malondialdehyde (MDA), protein carbonyls (PC) level were evaluated to determine the lipid and protein damage in lymphocytes. Superoxide dismutase (SOD), catalase (CAT), glutathione and glutathione dependent enzymes were estimated to evaluate the antioxidant status in the lymphocytes. Increased MDA and PC levels strongly support the increased oxidative damage in elderly subject than young subjects. The results indicated that, balance of oxidant and antioxidant systems in lymphocytes shifts in favor of accelerated oxidative damage during aging. Thus oxidative stress in lymphocytes may particular interest in aging and may play important role in immunosenescence. PMID:20972374

  2. Obesity in Aging Exacerbates Blood–Brain Barrier Disruption, Neuroinflammation, and Oxidative Stress in the Mouse Hippocampus: Effects on Expression of Genes Involved in Beta-Amyloid Generation and Alzheimer’s Disease

    PubMed Central

    Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Szalai, Gabor; Sonntag, William E.; Csiszar, Anna

    2014-01-01

    There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet–fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflammation and blood–brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood–brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein–dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood–brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals. PMID:24269929

  3. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease.

    PubMed

    Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Szalai, Gabor; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2014-10-01

    There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet-fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflammation and blood-brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood-brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein-dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals.

  4. Testing the Oxidative Stress Hypothesis of Aging in Primate Fibroblasts: Is There a Correlation Between Species Longevity and Cellular ROS Production?

    PubMed Central

    Csiszar, Anna; Podlutsky, Andrej; Podlutskaya, Natalia; Sonntag, William E.; Merlin, Steven Z.; Philipp, Eva E. R.; Doyle, Kristian; Davila, Antonio; Recchia, Fabio A.; Ballabh, Praveen; Pinto, John T.

    2012-01-01

    The present study was conducted to test predictions of the oxidative stress theory of aging assessing reactive oxygen species production and oxidative stress resistance in cultured fibroblasts from 13 primate species ranging in body size from 0.25 to 120 kg and in longevity from 20 to 90 years. We assessed both basal and stress-induced reactive oxygen species production in fibroblasts from five great apes (human, chimpanzee, bonobo, gorilla, and orangutan), four Old World monkeys (baboon, rhesus and crested black macaques, and patas monkey), three New World monkeys (common marmoset, red-bellied tamarin, and woolly monkey), and one lemur (ring-tailed lemur). Measurements of cellular MitoSox fluorescence, an indicator of mitochondrial superoxide (O2·−) generation, showed an inverse correlation between longevity and steady state or metabolic stress–induced mitochondrial O2·− production, but this correlation was lost when the effects of body mass were removed, and the data were analyzed using phylogenetically independent contrasts. Fibroblasts from longer-lived primate species also exhibited superior resistance to H2O2-induced apoptotic cell death than cells from shorter-living primates. After correction for body mass and lack of phylogenetic independence, this correlation, although still discernible, fell short of significance by regression analysis. Thus, increased longevity in this sample of primates is not causally associated with low cellular reactive oxygen species generation, but further studies are warranted to test the association between increased cellular resistance to oxidative stressor and primate longevity. PMID:22219516

  5. Vascular oxidative stress, nitric oxide and atherosclerosis.

    PubMed

    Li, Huige; Horke, Sven; Förstermann, Ulrich

    2014-11-01

    In the vascular wall, reactive oxygen species (ROS) are produced by several enzyme systems including NADPH oxidase, xanthine oxidase, uncoupled endothelial nitric oxide synthase (eNOS) and the mitochondrial electron transport chain. On the other hand, the vasculature is protected by antioxidant enzyme systems, including superoxide dismutases, catalase, glutathione peroxidases and paraoxonases, which detoxify ROS. Cardiovascular risk factors such as hypercholesterolemia, hypertension, and diabetes mellitus enhance ROS generation, resulting in oxidative stress. This leads to oxidative modification of lipoproteins and phospholipids, mechanisms that contribute to atherogenesis. In addition, oxidation of tetrahydrobiopterin may cause eNOS uncoupling and thus potentiation of oxidative stress and reduction of eNOS-derived NO, which is a protective principle in the vasculature. This review summarizes the latest advances in the role of ROS-producing enzymes, antioxidative enzymes as well as NO synthases in the initiation and development of atherosclerosis.

  6. A Remarkable Age-Related Increase in SIRT1 Protein Expression against Oxidative Stress in Elderly: SIRT1 Gene Variants and Longevity in Human

    PubMed Central

    Kilic, Ulkan; Gok, Ozlem; Erenberk, Ufuk; Dundaroz, Mehmet Rusen; Torun, Emel; Kucukardali, Yasar; Elibol-Can, Birsen; Uysal, Omer; Dundar, Tolga

    2015-01-01

    Aging is defined as the accumulation of progressive organ dysfunction. Controlling the rate of aging by clarifying the complex pathways has a significant clinical importance. Nowadays, sirtuins have become famous molecules for slowing aging and decreasing age-related disorders. In the present study, we analyzed the SIRT1 gene polymorphisms (rs7895833 A>G, rs7069102 C>G and rs2273773 C>T) and its relation with levels of SIRT1, eNOS, PON-1, cholesterol, TAS, TOS, and OSI to demonstrate the association between genetic variation in SIRT1 and phenotype at different ages in humans. We observed a significant increase in the SIRT1 level in older people and found a significant positive correlation between SIRT1 level and age in the overall studied population. The oldest people carrying AG genotypes for rs7895833 have the highest SIRT1 level suggesting an association between rs7895833 SNP and lifespan longevity. Older people have lower PON-1 levels than those of adults and children which may explain the high levels of SIRT1 protein as a compensatory mechanism for oxidative stress in the elderly. The eNOS protein level was significantly decreased in older people as compared to adults. There was no significant difference in the eNOS level between older people and children. The current study is the first to demonstrate age-related changes in SIRT1 levels in humans and it is important for a much better molecular understanding of the role of the longevity gene SIRT1 and its protein product in aging. It is also the first study presenting the association between SIRT1 expression in older people and rs7895833 in SIRT1 gene. PMID:25785999

  7. Diabetes, Oxidative Stress and Physical Exercise

    PubMed Central

    Atalay, Mustafa; Laaksonen, David E.

    2002-01-01

    Oxidative stress, an imbalance between the generation of reactive oxygen species and antioxidant defense capacity of the body, is closely associated with aging and a number of diseases including cancer, cardiovascular diseases, diabetes and diabetic complications. Several mechanisms may cause oxidative insult in diabetes, although their exact contributions are not entirely clear. Accumulating evidence points to many interrelated mechanisms that increase production of reactive oxygen and nitrogen species or decrease antioxidant protection in diabetic patients. In modern medicine, regular physical exercise is an important tool in the prevention and treatment of diseases including diabetes. Although acute exhaustive exercise increases oxidative stress, exercise training has been shown to up regulate antioxidant protection. This review aims to summarize the mechanisms of increased oxidative stress in diabetes and with respect to acute and chronic exercise. PMID:24672266

  8. Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish--implication in neural tube defects and Alzheimer's diseases.

    PubMed

    Kao, Tseng-Ting; Chu, Chia-Yi; Lee, Gang-Hui; Hsiao, Tsun-Hsien; Cheng, Nai-Wei; Chang, Nan-Shan; Chen, Bing-Hung; Fu, Tzu-Fun

    2014-11-01

    Folate is a nutrient essential for the development, function and regeneration of nervous systems. Folate deficiency has been linked to many neurological disorders including neural tube defects in fetus and Alzheimer's diseases in the elderly. However, the etiology underlying these folate deficiency-associated diseases is not completely understood. In this study, zebrafish transgenic lines with timing and duration-controllable folate deficiency were developed by ectopically overexpressing a recombinant EGFP-γ-glutamyl hydrolase (γGH). Impeded neural crest cell migration was observed in the transgenic embryos when folate deficiency was induced in early stages, leading to defective neural tube closure and hematopoiesis. Adding reduced folate or N-acetylcysteine reversed the phenotypic anomalies, supporting the causal link between the increased oxidative stress and the folate deficiency-induced abnormalities. When folate deficiency was induced in aged fish accumulation of beta-amyloid and phosphorylated Tau protein were found in the fish brain cryo-sections. Increased autophagy and accumulation of acidic autolysosome were apparent in folate deficient neuroblastoma cells, which were reversed by reduced folate or N-acetylcysteine supplementation. Decreased expression of cathepsin B, a lysosomal protease, was also observed in cells and tissue with folate deficiency. We concluded that folate deficiency-induced oxidative stress contributed to the folate deficiency-associated neuropathogenesis in both early and late stages of life.

  9. The metabolomics of oxidative stress.

    PubMed

    Noctor, Graham; Lelarge-Trouverie, Caroline; Mhamdi, Amna

    2015-04-01

    Oxidative stress resulting from increased availability of reactive oxygen species (ROS) is a key component of many responses of plants to challenging environmental conditions. The consequences for plant metabolism are complex and manifold. We review data on small compounds involved in oxidative stress, including ROS themselves and antioxidants and redox buffers in the membrane and soluble phases, and we discuss the wider consequences for plant primary and secondary metabolism. While metabolomics has been exploited in many studies on stress, there have been relatively few non-targeted studies focused on how metabolite signatures respond specifically to oxidative stress. As part of the discussion, we present results and reanalyze published datasets on metabolite profiles in catalase-deficient plants, which can be considered to be model oxidative stress systems. We emphasize the roles of ROS-triggered changes in metabolites as potential oxidative signals, and discuss responses that might be useful as markers for oxidative stress. Particular attention is paid to lipid-derived compounds, the status of antioxidants and antioxidant breakdown products, altered metabolism of amino acids, and the roles of phytohormone pathways. PMID:25306398

  10. Poor maternal nutrition and accelerated postnatal growth induces an accelerated aging phenotype and oxidative stress in skeletal muscle of male rats

    PubMed Central

    Fernandez-Twinn, Denise S.; Chen, Jian Hua; Hargreaves, Iain P.; Neergheen, Viruna; Aiken, Catherine E.; Ozanne, Susan E.

    2016-01-01

    ABSTRACT ‘Developmental programming’, which occurs as a consequence of suboptimal in utero and early environments, can be associated with metabolic dysfunction in later life, including an increased incidence of cardiovascular disease and type 2 diabetes, and predisposition of older men to sarcopenia. However, the molecular mechanisms underpinning these associations are poorly understood. Many conditions associated with developmental programming are also known to be associated with the aging process. We therefore utilized our well-established rat model of low birth weight and accelerated postnatal catch-up growth (termed ‘recuperated’) in this study to establish the effects of suboptimal maternal nutrition on age-associated factors in skeletal muscle. We demonstrated accelerated telomere shortening (a robust marker of cellular aging) as evidenced by a reduced frequency of long telomeres (48.5-8.6 kb) and an increased frequency of short telomeres (4.2-1.3 kb) in vastus lateralis muscle from aged recuperated offspring compared to controls. This was associated with increased protein expression of the DNA-damage-repair marker 8-oxoguanine-glycosylase (OGG1) in recuperated offspring. Recuperated animals also demonstrated an oxidative stress phenotype, with decreased citrate synthase activity, increased electron-transport-complex activities of complex I, complex II-III and complex IV (all markers of functional mitochondria), and increased xanthine oxidase (XO), p67phox and nuclear-factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Recuperated offspring also demonstrated increased antioxidant defense capacity, with increased protein expression of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD), catalase and heme oxygenase-1 (HO1), all of which are known targets of NF-κB and can be upregulated as a consequence of oxidative stress. Recuperated offspring also had a pro-inflammatory phenotype, as evidenced by

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

    PubMed

    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 (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHd

  12. Good Stress, Bad Stress and Oxidative Stress: Insights from Anticipatory Cortisol Reactivity

    PubMed Central

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

    2014-01-01

    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 F2α (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 (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-OxoG and IsoP (but not

  13. Oxidative stress-elevated high gamma glutamyl transferase levels, and aging, intake of tropical food plants, migration and visual disability in Central Africans

    PubMed Central

    Longo-Mbenza, Benjamin; Muaka, Moïse Mvitu; Mokondjimobe, Etienne; Ndembe, Dalida Kibokela; Mona, Doris Tulomba; Buassabu-bu-Tsumbu, Baudouin

    2012-01-01

    AIM To investigate the independent pathogenic role of high serum gamma-glutamyl transferase (GGT) levels, sociodemographic data, dietary and environmental risk factors for visual disability (VD). METHODS This was a case-control study, run in 200 black Congolese patients managed in Saint Joseph Hospital Ophthalmology Division from Kinshasa town. Logistic regression model was used to identify determinants of VD (n=58) among sex, age, cigarette smoking, alcohol abuse, rural-urban migration, education levels, aging ≥60 years, intake of red Beans, Safou fruit and Taro leaves, lipid profile, residence, socioeconomic status, and GGT. RESULTS After adjusting for confounding factors, we identified migration (OR=3.7 95% CI: 1.2-11.3; P=0.023), low education level (OR=3.1 95% CI 1.1-8.5; P=0.026), no intake of Safou fruit (OR=34.2 95% CI 11.5-102; P<0.0001), age ≥ 60 years (OR=2.5 95% CI 1.01-6.5; P=0.049), and serum GGT ≥10 U/L (OR=3.6 95% CI 1.3-9.6; P=0.012) as the significant and independent determinants of VD. CONCLUSION VD appears as a major public health problem in Central Africa to be prevented or delayed by control of migration, lifestyle changes, antioxidant supplements, appropriate diet, nutrition education, and blocking of oxidative stress. PMID:22937512

  14. Pectinase-treated Panax ginseng ameliorates hydrogen peroxide-induced oxidative stress in GC-2 sperm cells and modulates testicular gene expression in aged rats

    PubMed Central

    Kopalli, Spandana Rajendra; Cha, Kyu-Min; Jeong, Min-Sik; Lee, Sang-Ho; Sung, Jong-Hwan; Seo, Seok-Kyo; Kim, Si-Kwan

    2015-01-01

    Background To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods Hydrogen peroxide (H2O2)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results GINST treatment (50 μg/mL, 100 μg/mL, and 200 μg/mL) significantly (p < 0.05) inhibited the H2O2-induced (200 μM) cytotoxicity in GC-2spd cells. Furthermore, GINST (50 μg/mL and 100 μg/mL) significantly (p < 0.05) ameliorated the H2O2-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-α, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated H2O2-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility. PMID:27158240

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Oxidative Stress Resistance in Deinococcus radiodurans†

    PubMed Central

    Slade, Dea; Radman, Miroslav

    2011-01-01

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

  18. Oral treatment with herbal formula B307 alleviates cardiac failure in aging R6/2 mice with Huntington's disease via suppressing oxidative stress, inflammation, and apoptosis.

    PubMed

    Lin, Ching-Lung; Wang, Sheue-Er; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Cardiac failure is often observed in aging patients with Huntington's disease (HD). However, conventional pharmacological treatments for cardiac failure in HD patients have rarely been studied. Chinese herbal medicines, especially combined herbal formulas, have been widely used to treat cardiac dysfunctions over the centuries. Thus, we assess whether oral treatment with herbal formula B307 can alleviate cardiac failure in transgenic mice with HD. After oral B307 or vehicle treatment for 2 weeks, cardiac function and cardiomyocytes in 12-week-old male R6/2 HD mice and their wild-type littermate controls (WT) were examined and then compared via echocardiography, immunohistochemistry, and Western blotting. We found that cardiac performance in aging R6/2 HD mice had significantly deteriorated in comparison with their WT (P<0.01). Cardiac expressions of superoxide dismutase 2 (SOD2) and B-cell lymphoma 2 (Bcl-2) in aging R6/2 HD mice were significantly lower than their WT (P<0.01), but cardiac expressions of tumor necrosis factor alpha (TNF-α), neurotrophin-3 (3-NT), 4-hydroxynonenal (4-HNE), Bcl-2-associated X protein (Bax), calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly higher than their WT (P<0.05). Furthermore, we found that cardiac performance in aging R6/2 HD mice had significantly improved under oral B307 treatment (P<0.05). Cardiac expressions of SOD2 and Bcl-2 of aging R6/2 HD mice were significantly higher under oral B307 treatment (P<0.01), but cardiac expressions of TNF-α, 3-NT, 4-HNE, Bax, calpain, caspase 12, caspase 9, and caspase 3 of aging R6/2 HD mice were significantly reduced under oral B307 treatment (P<0.05). Oral B307 treatment may briefly alleviate cardiac failure in aging HD R6/2 mice via suppressing cardiac oxidative stress, inflammation, and apoptosis. We suggested that the herbal formula B307 may be further developed as a potential health supplement for ameliorating cardiac failure associated with

  19. Role of mitochondria in toxic oxidative stress.

    PubMed

    Fariss, Marc W; Chan, Catherine B; Patel, Manisha; Van Houten, Bennett; Orrenius, Sten

    2005-04-01

    Oxidative stress and mitochondrial oxidative damage have been implicated in the etiology of numerous common diseases. The critical mitochondrial events responsible for oxidative stress-mediated cell death (toxic oxidative stress), however, have yet to be defined. Several oxidative events implicated in toxic oxidative stress include alterations in mitochondrial lipids (e.g., cardiolipin), mitochondrial DNA, and mitochondrial proteins (eg. aconitase and uncoupling protein 2). Furthermore, recent findings indicate the enrichment of mitochondrial membranes with vitamin E protects cells against the toxic effects of oxidative stress. This review briefly summarizes the role of these mitochondrial events in toxic oxidative stress, including: 1) the protective role of mitochondrial vitamin E in toxic oxidative stress, 2) the role of mitochondrial DNA in toxic oxidative stress, 3) the interaction between cardiolipin and cytochrome c in mitochondrial regulation of apoptosis, 4) the role of mitochondrial aconitase in oxidative neurodegeneration, and 5) the role of mitochondrial uncoupling protein 2 in the pathogenesis of type 2 diabetes. PMID:15821158

  20. Inorganic and methylmercury levels in plasma are differentially associated with age, gender, and oxidative stress markers in a population exposed to mercury through fish consumption.

    PubMed

    Carneiro, Maria Fernanda Hornos; Grotto, Denise; Barbosa, Fernando

    2014-01-01

    This study aimed to determine the concentrations of plasma methylmercury (Me-Hg) and inorganic mercury (I-Hg) in a population exposed to Me-Hg. In addition, associations between each form of mercury (Hg) and gender, age, plasma selenium (Se), and oxidative stress markers were also investigated. The mean plasma I-Hg level was 5.7 μg/L while the mean for plasma Me-Hg was 3.6 μg/L, representing approximately 59 and 41% of the total Hg in blood, respectively. However, several plasma samples contained higher percentages of Me-Hg. Age displayed a direct linkage with plasma I-Hg levels, whereas gender did not correlate with any of the Hg species. In addition, fish intake was only correlated with and a predictor of plasma Me-Hg, suggesting that plasma I-Hg levels originated endogenously through a demethylation reaction that needs to be verified. Further, plasma Me-Hg was markedly correlated with adverse effects to a greater extent than plasma I-Hg and may be considered a valuable, reliable internal dose biomarker for Hg in chronically Me-Hg- exposed individuals.

  1. [Oxidative stress in Crohn's disease].

    PubMed

    Moret, Inés; Cerrillo, Elena; Navarro-Puche, Ana; Iborra, Marisa; Rausell, Francisco; Tortosa, Luis; Beltrán, Belén

    2014-01-01

    Crohn's disease (CD) is characterized by transmural inflammation that is most frequently located in the region of the terminal ileum. Although the physiopathological mechanisms of the disease are not yet well defined, the unregulated immune response is associated with high production of reactive oxygen species (ROS). These elements are associated with complex systems known as antioxidant defenses, whose function is ROS regulation, thereby preventing the harmful effects of these elements. However, the presence of an imbalance between ROS production and ROS elimination by antioxidants has been widely described and leads to oxidative stress. In this article, we describe the most significant findings on oxidative stress in the intestinal mucosa and peripheral blood.

  2. Influence of different periods of the year and age on the parameters of antioxidative status and oxidative stress in the blood serum of breeding bulls.

    PubMed

    Žaja, Ivona Žura; Samardžija, Marko; Vince, Silvijo; Majić-Balić, Ivanka; Đuričić, Dražen; Milinković-Tur, Suzana

    2016-06-01

    The sources of variations that may cause physiological differences between blood serum biochemistry parameters of bulls have not been investigated in detail. Aim of the present study was to establish influence of different periods of the year and the age of breeding bulls on parameters of antioxidative status and oxidative stress in their serum and to correlate these monitored variables. Research was performed on two groups, each comprising 9 Simmental bulls: a younger group (YB) (aged 2-4 years) and older one (OB) (aged 5-10 years). Blood samples for biochemical analyses were collected from jugular vein in cold (CP) and warm periods (WP) of the year. Reduced glutathione (GSH), uric acid (UA), total protein (TP), albumin (ALB), thiobarbituric acid reactive substance (TBARS), and protein carbonyl content (PCC) serum concentration were determined, as well as activities of selenium-dependent glutathione peroxidase (Se-GSH-Px), total superoxide dismutase (TSOD), manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT). Serum values of SeGSH-Px, MnSOD, UA and TP in OB were significantly higher compared to those in YB during CP of the year. Significantly higher PCC concentration in serum of YB and OB were established in CP of the year than in WP. TBARS serum concentration in YB was significantly higher in comparison to that in OB during CP of the year. It can be concluded that both OB and YB show a great sensitivity to climate condition alterations during CP in comparison to WP of the year and that YB show even greater sensitivity.

  3. Role of oligomeric proanthocyanidins derived from an extract of persimmon fruits in the oxidative stress-related aging process.

    PubMed

    Yokozawa, Takako; Park, Chan Hum; Noh, Jeong Sook; Roh, Seong Soo

    2014-01-01

    Many researchers have focused on the oligomeric form of proanthocyanidins with a lower level of polymerization found in foodstuffs such as grape seeds and blackberries. The present study indicated that the oral administration of oligomers isolated from persimmon fruits extended the lifespan of senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence. On the other hand, oligomer-treated SAMP8 did not show stereotypical behavior. We also revealed that the oral administration of oligomers improved spatial and object recognition memory in SAMP8. The density of axons in the hippocampal CA1 was significantly increased by oligomer administration. Moreover, the administration of oligomers increased the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2 in the hippocampal CA3, hypothalamus, and choroid plexus. We speculate that memory improvement accompanied by histological changes may be induced directly in the hippocampus and indirectly in the hypothalamus and choroid plexus through VEGFR-2 signaling. In the present study, we elucidated the protective effect of oligomers against memory impairment with aging. VEGFR-2 signaling may provide a new insight into ways to protect against memory deficit in the aging brain.

  4. Oxidative Stress and Neurodegenerative Disorders

    PubMed Central

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

    2013-01-01

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

  5. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    PubMed Central

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

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

    PubMed

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

    2016-04-01

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

  7. PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species.

    PubMed

    Nelson, Valery M; Dancik, Chantée M; Pan, Weiying; Jiang, Zhi-Gang; Lebowitz, Michael S; Ghanbari, Hossein A

    2009-01-01

    Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells.

  8. Space flight and oxidative stress

    NASA Technical Reports Server (NTRS)

    Stein, T. P.

    2002-01-01

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

  9. Oxidative stress in marine environments: biochemistry and physiological ecology.

    PubMed

    Lesser, Michael P

    2006-01-01

    Oxidative stress-the production and accumulation of reduced oxygen intermediates such as superoxide radicals, singlet oxygen, hydrogen peroxide, and hydroxyl radicals-can damage lipids, proteins, and DNA. Many disease processes of clinical interest and the aging process involve oxidative stress in their underlying etiology. The production of reactive oxygen species is also prevalent in the world's oceans, and oxidative stress is an important component of the stress response in marine organisms exposed to a variety of insults as a result of changes in environmental conditions such as thermal stress, exposure to ultraviolet radiation, or exposure to pollution. As in the clinical setting, reactive oxygen species are also important signal transduction molecules and mediators of damage in cellular processes, such as apoptosis and cell necrosis, for marine organisms. This review brings together the voluminous literature on the biochemistry and physiology of oxidative stress from the clinical and plant physiology disciplines with the fast-increasing interest in oxidative stress in marine environments.

  10. Oxidative stress and reactive oxygen species.

    PubMed

    Galli, Francesco; Piroddi, Marta; Annetti, Claudia; Aisa, Cristina; Floridi, Emanuela; Floridi, Ardesio

    2005-01-01

    This article discusses different aspects concerning classification/nomenclature, biochemical properties and pathophysiological roles of reactive oxygen species (ROS) which are pivotal to interpret the concept of oxidative stress. In vitro studies in both the prokaryotes and eukaryotes clearly demonstrate that exogenous or constitutive and inducible endogenous sources of ROS together with cofactors such as transition metals can damage virtually all the biomolecules. This adverse chemistry is at the origin of structural and metabolic defects that ultimately may lead to cell dysfunction and death as underlying mechanisms in tissue degeneration processes. The same biomolecular interpretation of aging has been proposed to embodies an oxidative stress-based process and oxidative stress may virtually accompany all the inflammatory events. As a consequence, ROS have proposed to play several roles in the pathogenesis of chronic-degenerative conditions, such as athero-thrombotic events, neurodegeneration, cancer, some forms of anemia, auto-immune diseases, and the entire comorbidity of uremia and diabetes. Nowadays, the chance to investigate biochemical and toxicological aspects of ROS with advanced biomolecular tools has, if needed, still more emphasized the interest on this area of biomedicine. These technological advancements and the huge information available in literature represent in our time a challenge to further understand the clinical meaning of oxidative stress and to develop specific therapeutic strategies.

  11. Synergistic effect of high charge and energy particle radiation and chronological age on biomarkers of oxidative stress and tissue degeneration: a ground-based study using the vertebrate laboratory model organism Oryzias latipes.

    PubMed

    Zheng, Xuan; Zhang, Xinyan; Ding, Lingling; Lee, Jeffrey R; Weinberger, Paul M; Dynan, William S

    2014-01-01

    High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration. PMID:25375139

  12. Synergistic Effect of High Charge and Energy Particle Radiation and Chronological Age on Biomarkers of Oxidative Stress and Tissue Degeneration: A Ground-Based Study Using the Vertebrate Laboratory Model Organism Oryzias latipes

    PubMed Central

    Zheng, Xuan; Zhang, Xinyan; Ding, Lingling; Lee, Jeffrey R.; Weinberger, Paul M.; Dynan, William S.

    2014-01-01

    High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration. PMID:25375139

  13. Synergistic Effect of High Charge and Energy Particle Radiation and Chronological Age on Biomarkers of Oxidative Stress and Tissue Degeneration: A Ground-Based Study Using the Vertebrate Laboratory Model Organism Oryzias latipes

    SciTech Connect

    Zheng, Xuan; Zhang, Xinyan; Ding, Lingling; Lee, Jeffrey R.; Weinberger, Paul M.; Dynan, William S.

    2014-11-06

    High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZE particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration.

  14. Synergistic Effect of High Charge and Energy Particle Radiation and Chronological Age on Biomarkers of Oxidative Stress and Tissue Degeneration: A Ground-Based Study Using the Vertebrate Laboratory Model Organism Oryzias latipes

    DOE PAGES

    Zheng, Xuan; Zhang, Xinyan; Ding, Lingling; Lee, Jeffrey R.; Weinberger, Paul M.; Dynan, William S.

    2014-11-06

    High charge and energy (HZE) particles are a main hazard of the space radiation environment. Uncertainty regarding their health effects is a limiting factor in the design of human exploration-class space missions, that is, missions beyond low earth orbit. Previous work has shown that HZE exposure increases cancer risk and elicits other aging-like phenomena in animal models. Here, we investigate how a single exposure to HZE particle radiation, early in life, influences the subsequent age-dependent evolution of oxidative stress and appearance of degenerative tissue changes. Embryos of the laboratory model organism, Oryzias latipes (Japanese medaka fish), were exposed to HZEmore » particle radiation at doses overlapping the range of anticipated human exposure. A separate cohort was exposed to reference γ-radiation. Survival was monitored for 750 days, well beyond the median lifespan. The population was also sampled at intervals and liver tissue was subjected to histological and molecular analysis. HZE particle radiation dose and aging contributed synergistically to accumulation of lipid peroxidation products, which are a marker of chronic oxidative stress. This was mirrored by a decline in PPARGC1A mRNA, which encodes a transcriptional co-activator required for expression of oxidative stress defense genes and for mitochondrial maintenance. Consistent with chronic oxidative stress, mitochondria had an elongated and enlarged ultrastructure. Livers also had distinctive, cystic lesions. Depending on the endpoint, effects of γ-rays in the same dose range were either lesser or not detected. Results provide a quantitative and qualitative framework for understanding relative contributions of HZE particle radiation exposure and aging to chronic oxidative stress and tissue degeneration.« less

  15. Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: a link between surface-associated AGEs and diabetic complications.

    PubMed Central

    Wautier, J L; Wautier, M P; Schmidt, A M; Anderson, G M; Hori, O; Zoukourian, C; Capron, L; Chappey, O; Yan, S D; Brett, J

    1994-01-01

    Vascular complications are an important cause of morbidity and mortality in patients with diabetes. The extent of vascular complications has been linked statistically to enhanced adherence of diabetic erythrocytes to endothelial cells (ECs) and to the accumulation of a class of glycated proteins termed advanced glycation end products (AGEs). We hypothesized that formation of AGEs on the surface of diabetic erythrocytes could mediate their interaction with ECs leading to binding and induction of vascular dysfunction. Enhanced binding of diabetic erythrocytes to ECs was blocked by preincubation of erythrocytes with anti-AGE IgG or preincubation of ECs with antibodies to the receptor for AGE (RAGE). Immunoblotting of cultured human ECs and immunostaining of normal/diabetic human tissue confirmed the presence of RAGE in the vessel wall. Binding of diabetic erythrocytes to endothelium generated an oxidant stress, as measured by production of thiobarbituric acid-reactive substances (TBARS) and activation of the transcription factor NF-kappa B, both of which were blocked by probucol or anti-RAGE IgG. Erythrocytes from diabetic rats infused into normal rats had an accelerated, early phase of clearance that was prevented, in part, by antibody to RAGE. Liver tissue from rats infused with diabetic erythrocytes showed elevated levels of TBARS, which was prevented by pretreatment with anti-RAGE IgG or probucol. Thus, erythrocyte surface AGEs can function as ligands that interact with RAGE on endothelium. The extensive contact of diabetic erythrocytes bearing surface-associated AGEs with vessel wall RAGE could be important in the development of vascular complications. Images PMID:8052654

  16. Exposure to O-16 particle irradiation causes age-like decrements in rats through increased oxidative stress, inflammation and loss of autophagy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Exposing young rats to particles of high energy and charge (HZE particles) enhances indices of oxidative stress and inflammation, disrupts the functioning of neuronal communication, and alters cognitive behaviors. Even though exposure to these highly charged particles occurs at low fluence rates, p...

  17. Inflammatory and oxidative stress in rotavirus infection

    PubMed Central

    Guerrero, Carlos A; Acosta, Orlando

    2016-01-01

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

  18. [Oxidative stress in Crohn's disease].

    PubMed

    Moret, Inés; Cerrillo, Elena; Navarro-Puche, Ana; Iborra, Marisa; Rausell, Francisco; Tortosa, Luis; Beltrán, Belén

    2014-01-01

    Crohn's disease (CD) is characterized by transmural inflammation that is most frequently located in the region of the terminal ileum. Although the physiopathological mechanisms of the disease are not yet well defined, the unregulated immune response is associated with high production of reactive oxygen species (ROS). These elements are associated with complex systems known as antioxidant defenses, whose function is ROS regulation, thereby preventing the harmful effects of these elements. However, the presence of an imbalance between ROS production and ROS elimination by antioxidants has been widely described and leads to oxidative stress. In this article, we describe the most significant findings on oxidative stress in the intestinal mucosa and peripheral blood. PMID:23643278

  19. Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice.

    PubMed

    Martínez-Cisuelo, V; Gómez, J; García-Junceda, I; Naudí, A; Cabré, R; Mota-Martorell, N; López-Torres, M; González-Sánchez, M; Pamplona, R; Barja, G

    2016-10-01

    Rapamycin consistently increases longevity in mice although the mechanism of action of this drug is unknown. In the present investigation we studied the effect of rapamycin on mitochondrial oxidative stress at the same dose that is known to increase longevity in mice (14mgofrapamycin/kg of diet). Middle aged mice (16months old) showed significant age-related increases in mitochondrial ROS production at complex I, accumulation of mtDNA fragments inside nuclear DNA, mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young animals (4months old) in the liver. After 7weeks of dietary treatment all those increases were totally or partially (lipofuscin) abolished by rapamycin, middle aged rapamycin-treated animals showing similar levels in those parameters to young animals. The decrease in mitochondrial ROS production was due to qualitative instead of quantitative changes in complex I. The decrease in mitochondrial protein lipoxidation was not due to decreases in the amount of highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of RAPTOR (of mTOR complex) and increased the amounts of the PGC1-α and ATG13 proteins. The results are consistent with the possibility that rapamycin increases longevity in mice at least in part by lowering mitochondrial ROS production and increasing autophagy, decreasing the derived final forms of damage accumulated with age which are responsible for increased longevity. The decrease in lipofuscin accumulation induced by rapamycin adds to previous information suggesting that the increase in longevity induced by this drug can be due to a decrease in the rate of aging. PMID:27498120

  20. Rapamycin reverses age-related increases in mitochondrial ROS production at complex I, oxidative stress, accumulation of mtDNA fragments inside nuclear DNA, and lipofuscin level, and increases autophagy, in the liver of middle-aged mice.

    PubMed

    Martínez-Cisuelo, V; Gómez, J; García-Junceda, I; Naudí, A; Cabré, R; Mota-Martorell, N; López-Torres, M; González-Sánchez, M; Pamplona, R; Barja, G

    2016-10-01

    Rapamycin consistently increases longevity in mice although the mechanism of action of this drug is unknown. In the present investigation we studied the effect of rapamycin on mitochondrial oxidative stress at the same dose that is known to increase longevity in mice (14mgofrapamycin/kg of diet). Middle aged mice (16months old) showed significant age-related increases in mitochondrial ROS production at complex I, accumulation of mtDNA fragments inside nuclear DNA, mitochondrial protein lipoxidation, and lipofuscin accumulation compared to young animals (4months old) in the liver. After 7weeks of dietary treatment all those increases were totally or partially (lipofuscin) abolished by rapamycin, middle aged rapamycin-treated animals showing similar levels in those parameters to young animals. The decrease in mitochondrial ROS production was due to qualitative instead of quantitative changes in complex I. The decrease in mitochondrial protein lipoxidation was not due to decreases in the amount of highly oxidizable unsaturated fatty acids. Rapamycin also decreased the amount of RAPTOR (of mTOR complex) and increased the amounts of the PGC1-α and ATG13 proteins. The results are consistent with the possibility that rapamycin increases longevity in mice at least in part by lowering mitochondrial ROS production and increasing autophagy, decreasing the derived final forms of damage accumulated with age which are responsible for increased longevity. The decrease in lipofuscin accumulation induced by rapamycin adds to previous information suggesting that the increase in longevity induced by this drug can be due to a decrease in the rate of aging.

  1. Oxidative stress in industrial fungi.

    PubMed

    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

  2. Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis

    PubMed Central

    Iannaccone, Alessandro; Giorgianni, Francesco; New, David D.; Hollingsworth, T. J.; Umfress, Allison; Alhatem, Albert H.; Neeli, Indira; Lenchik, Nataliya I.; Jennings, Barbara J.; Calzada, Jorge I.; Satterfield, Suzanne; Mathews, Dennis; Diaz, Rocio I.; Harris, Tamara; Johnson, Karen C.; Charles, Steve; Kritchevsky, Stephen B.; Gerling, Ivan C.; Beranova-Giorgianni, Sarka; Radic, Marko Z.

    2015-01-01

    role of inflammation and the immune system in AMD pathogenesis, AAbs were identified in AMD sera, including early-stage disease. Identified targets may be mechanistically linked to AMD pathogenesis because the identified proteins are implicated in autophagy, immunomodulation, and protection from oxidative stress and apoptosis. In particular, a role in autophagy activation is shared by all five autoantigens, raising the possibility that the detected AAbs may play a role in AMD via autophagy compromise and downstream activation of the inflammasome. Thus, we propose that the detected AAbs provide further insight into AMD pathogenesis and have the potential to contribute to disease biogenesis and progression. PMID:26717306

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  4. Oxidative Stress and Periodontal Disease in Obesity.

    PubMed

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

    2016-03-01

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

  5. Oxidative Stress and Periodontal Disease in Obesity

    PubMed Central

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

    2016-01-01

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

  6. Management of multicellular senescence and oxidative stress

    PubMed Central

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

    2013-01-01

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

  7. [Does nitric oxide stress exist?].

    PubMed

    Torreilles, J; Guérin, M C

    1995-01-01

    Ten years ago, the term "oxidative stress" (sigma -O2) was created to define oxidative damage inflicted to the organism. This definition brings together processes involving reactive oxygen species production and action such as free radical production during univalent reduction of oxygen within mitochondria, activation of NADPH-dependent oxidase system on the membrane surface of neutrophils, flavoprotein-catalyzed redox cycling of xenobiotics and exposure to chemical and physical agents in the environment. Since the discovery of the nitric oxide biosynthetic pathway, the deleterious effects of uncontrolled nitric oxide generation are generally classified as oxidative stress. Indeed, products of the reaction of NO and superoxide lead to oxidants such as peroxinitrite, nitrogen dioxide and hydroxyl radical, which are involved in mechanisms of cell-mediated immune reactions and defence of the intracellular environment against microbiol invasion. However NO can also regulate many biological reactions and signal transduction pathways that lead to a variety of physiological responses such as blood pressure, neurotransmission, platelet aggregation, endothelin generation or smooth muscle cell proliferation. Then the uncontrolled NO production can lead to a variety of physiological and pathophysiological responses similar to a Nitric Oxide Stress: activation of guanylate cyclase and production of cGMP: overstimulation of the inducible L-arginine to L-citrulline and NO pathway by bactericidal endotoxins and cytokines has been shown to promote undesired increases in vasodilatation, which may account for hypotension in septic shock and cytokine therapy. stimulation of auto-ADP-ribosylation and modification of SH-groups of glyceraldehyde-3-phosphate dehydrogenase in a cGMP-independent mechanism: by this way, NO in excess can strongly inhibits this important glycolytic enzyme and reduce the cellular energy production. inhibition of ribonucleotide reductase: extensive inhibition

  8. Oxidative stress in neurodegenerative diseases.

    PubMed

    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. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology

    PubMed Central

    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

  10. Effects of Oxidative Stress on Mesenchymal Stem Cell Biology.

    PubMed

    Denu, Ryan A; Hematti, Peiman

    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

  11. Monitoring antioxidant defenses and free radical production in space-flight, aviation and railway engine operators, for the prevention and treatment of oxidative stress, immunological impairment, and pre-mature cell aging.

    PubMed

    De Luca, C; Deeva, I; Mariani, S; Maiani, G; Stancato, A; Korkina, L

    2009-01-01

    Degenerative diseases, immune impairment, and premature ageing commonly affect professional categories exposed to severe environmental and psychological stress. Among these, cosmonauts routinely experience extreme conditions due to microgravity, space radiation, altered oxygen supply, physical and mental fatigue during training, spaceflight, and post-flight. Long route aviation pilots display elevated oncogenic risk, connected with cosmic radiation overexposure, and high mortality rates for cardiovascular causes. Engine drivers, like pilots, are affected by health consequences of psycho-emotional stress, and burnout syndrome. The free radical (FR)/antioxidant (AO) imbalance is a common feature in all these pathological conditions. To assess the effective relevance of oxidative stress, we analyzed blood and urine reliable markers of FR production and AO defenses in 12 Russian cosmonauts, 55 airline pilots, 63 train engine drivers, and 50 age-matched controls by measuring the following: (a) lipophilic/hydrophilic low-molecular weight AO and AO enzyme activities, (b) nitric oxide, superoxide anion, hydroperoxide production, and (c) urinary catecholamine/serotonine metabolites and lipoperoxidation markers. Cosmonauts showed elevated granulocyte superoxide and nitric oxide production, increased erythrocyte superoxide dismutase activity and glutathione oxidation, and drastically decreased plasma/leucocyte lipophilic AO levels (P < 0.001-0.01). Aviation pilots, like train drivers, displayed a mild but constant oxidative stress, more pronounced in intercontinental routes pilots, and consistent with lymphocyte chromosomal alterations, DNA oxidation, and cardiovascular malfunction. Results obtained on these selected professionals operating under wearing conditions offer a solid molecular basis for advising the regular monitoring of clinical biochemistry laboratory markers of AO/FR status, to tailor individually specific AO supplementation and diet regimen, and monitor

  12. Management of oxidative stress by microalgae.

    PubMed

    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.

  13. Oxidative Stress in Cardiovascular Disease

    PubMed Central

    Csányi, Gábor; Miller, Francis J.

    2014-01-01

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

  14. Effect of Oxidative Stress in Hemodialysed Patients

    PubMed Central

    Peti, Attila; Csiky, Botond; Guth, Eszter; Kenyeres, Peter; Mezosi, Emese; Kovacs, Gabor L.

    2011-01-01

    Aims, subjects and methods Markers of oxidative stress and inflammatory activation of endothelium, as well as the adipose tissue secreted adipokines, e.g. adiponectin show altered pattern in renal failure. However, their internal relations have not been fully evaluated in this special patient population. In our cross sectional study, beside the routine clinical and biochemical parameters, plasma malondialdehyde, glutathione (GSH), catalase, total peroxidase, as well as serum E-selectin and adiponectin were measured in 70 hemodialysed (HD) patients. Results GSH showed negative correlations with systolic and diastolic blood pressure (BP) values, while a positive one with HDL-cholesterol level, as expected. Interestingly, the level of sE-selectin was inversely correlated only with the age. In multiple regression analyses where anthropometric, BP and laboratory parameters were included and sE-selectin was the dependent variable, the inverse association between the age and level of sE-Selectin turned out being an independent factor. Conclusions In HD kidney failure patients of the biochemical cardiovascular risk markers those related to oxidative stress, endothelial dysfunction, or altered adipokine homeostasis are not necessarily strongly associated. Larger studies may be needed to confirm our novel observation, a negative and independent correlation of age to sE-Selectin level.

  15. Hormetic modulation of aging and longevity by mild heat stress.

    PubMed

    Rattan, Suresh I S

    2006-05-22

    Aging is characterized by a stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. In a series of experimental studies we have shown that repetitive mild heat stress has anti-aging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These effects include the maintenance of stress protein profiles, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to ethanol, hydrogen peroxide and ultraviolet-B rays, and enhanced levels of various antioxidant enzymes. Anti-aging hormetic effects of mild heat shock appear to be facilitated by reducing protein damage and protein aggregation by activating internal antioxidant, repair and degradation processes.

  16. Etiologies of sperm oxidative stress

    PubMed Central

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

    2016-01-01

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

  17. Etiologies of sperm oxidative stress.

    PubMed

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

    2016-04-01

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

  18. Inflammation, Oxidative Stress, and Obesity

    PubMed Central

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

    2011-01-01

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

  19. Impact of Oxidative Stress in Fetal Programming

    PubMed Central

    Thompson, Loren P.; Al-Hasan, Yazan

    2012-01-01

    Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring. PMID:22848830

  20. Modification by acrolein, a component of tobacco smoke and age-related oxidative stress, mediates functional impairment of human apolipoprotein E.

    PubMed

    Tamamizu-Kato, Shiori; Wong, Jason Yiu; Jairam, Vikram; Uchida, Koji; Raussens, Vincent; Kato, Hiroyuki; Ruysschaert, Jean-Marie; Narayanaswami, Vasanthy

    2007-07-17

    Oxidative damage to proteins such as apolipoprotein B-100 increases the atherogenicity of low-density lipoproteins (LDL). However, little is known about the potential oxidative damage to apolipoprotein E (apoE), an exchangeable antiatherogenic apolipoprotein. ApoE plays an integral role in lipoprotein metabolism by regulating the plasma cholesterol and triglyceride levels. Hepatic uptake of lipoproteins is facilitated by apoE's ability to bind with cell surface heparan sulfate proteoglycans and to lipoprotein receptors via basic residues in its 22 kDa N-terminal domain (NT). We investigated the effect of acrolein, an aldehydic product of endogenous lipid peroxidation and a tobacco smoke component, on the conformation and function of recombinant human apoE3-NT. Acrolein caused oxidative modification of apoE3-NT as detected by Western blot with acrolein-lysine-specific antibodies, and tertiary conformational alterations. Acrolein modification impairs the ability of apoE3-NT to interact with heparin and the LDL receptor. Furthermore, acrolein-modified apoE3-NT displayed a 5-fold decrease in its ability to interact with lipid surfaces. Our data indicate that acrolein disrupts the functional integrity of apoE3, which likely interferes with its role in regulating plasma cholesterol homeostasis. These observations have implications regarding the role of apoE in the pathogenesis of smoking- and oxidative stress-mediated cardiovascular and cerebrovascular diseases.

  1. Oxidative stress induces senescence in human mesenchymal stem cells

    SciTech Connect

    Brandl, Anita; Meyer, Matthias; Bechmann, Volker; Nerlich, Michael; Angele, Peter

    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.

  2. Correlation of Zinc with Oxidative Stress Biomarkers

    PubMed Central

    Morales-Suárez-Varela, María; Llopis-González, Agustín; González-Albert, Verónica; López-Izquierdo, Raúl; González-Manzano, Isabel; Cháves, Javier; Huerta-Biosca, Vicente; Martin-Escudero, Juan C.

    2015-01-01

    Hypertension and smoking are related with oxidative stress (OS), which in turn reports on cellular aging. Zinc is an essential element involved in an individual’s physiology. The aim of this study was to evaluate the relation of zinc levels in serum and urine with OS and cellular aging and its effect on the development of hypertension. In a Spanish sample with 1500 individuals, subjects aged 20–59 years were selected, whose zinc intake levels fell within the recommended limits. These individuals were classified according to their smoking habits and hypertensive condition. A positive correlation was found (Pearson’s C = 0.639; p = 0.01) between Zn serum/urine quotient and oxidized glutathione levels (GSSG). Finally, risk of hypertension significantly increased when the GSSG levels exceeded the 75 percentile; OR = 2.80 (95%CI = 1.09–7.18) and AOR = 3.06 (95%CI = 0.96–9.71). Low zinc levels in serum were related with OS and cellular aging and were, in turn, to be a risk factor for hypertension.  PMID:25774936

  3. Oxidative stress, thyroid dysfunction & Down syndrome

    PubMed Central

    Campos, Carlos; Casado, Ángela

    2015-01-01

    Down syndrome (DS) is one of the most common chromosomal disorders, occurring in one out of 700-1000 live births, and the most common cause of mental retardation. Thyroid dysfunction is the most typical endocrine abnormality in patients with DS. It is well known that thyroid dysfunction is highly prevalent in children and adults with DS and that both hypothyroidism and hyperthyroidism are more common in patients with DS than in the general population. Increasing evidence has shown that DS individuals are under unusual increased oxidative stress, which may be involved in the higher prevalence and severity of a number of pathologies associated with the syndrome, as well as the accelerated ageing observed in these individuals. The gene for Cu/Zn superoxide dismutase (SOD1) is coded on chromosome 21 and it is overexpressed (~50%) resulting in an increase of reactive oxygen species (ROS) due to overproduction of hydrogen peroxide (H2O2). ROS leads to oxidative damage of DNA, proteins and lipids, therefore, oxidative stress may play an important role in the pathogenesis of DS. PMID:26354208

  4. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    PubMed Central

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

    2016-01-01

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

  5. Social support, stress and the aging brain.

    PubMed

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress. PMID:26060327

  6. Social support, stress and the aging brain.

    PubMed

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress.

  7. Oxidative stress responses in Escherichia coli and Salmonella typhimurium.

    PubMed Central

    Farr, S B; Kogoma, T

    1991-01-01

    Oxidative stress is strongly implicated in a number of diseases, such as rheumatoid arthritis, inflammatory bowel disorders, and atherosclerosis, and its emerging as one of the most important causative agents of mutagenesis, tumorigenesis, and aging. Recent progress on the genetics and molecular biology of the cellular responses to oxidative stress, primarily in Escherichia coli and Salmonella typhimurium, is summarized. Bacteria respond to oxidative stress by invoking two distinct stress responses, the peroxide stimulon and the superoxide stimulon, depending on whether the stress is mediated by peroxides or the superoxide anion. The two stimulons each contain a set of more than 30 genes. The expression of a subset of genes in each stimulon is under the control of a positive regulatory element; these genes constitute the OxyR and SoxRS regulons. The schemes of regulation of the two regulons by their respective regulators are reviewed in detail, and the overlaps of these regulons with other stress responses such as the heat shock and SOS responses are discussed. The products of Oxy-R- and SoxRS-regulated genes, such as catalases and superoxide dismutases, are involved in the prevention of oxidative damage, whereas others, such as endonuclease IV, play a role in the repair of oxidative damage. The potential roles of these and other gene products in the defense against oxidative damage in DNA, proteins, and membranes are discussed in detail. A brief discussion of the similarities and differences between oxidative stress responses in bacteria and eukaryotic organisms concludes this review. PMID:1779927

  8. Oral treatment with the herbal formula B401 protects against aging-dependent neurodegeneration by attenuating oxidative stress and apoptosis in the brain of R6/2 mice

    PubMed Central

    Wang, Sheue-Er; Lin, Ching-Lung; Hsu, Chih-Hsiang; Sheu, Shuenn-Jyi; Wu, Chung-Hsin

    2015-01-01

    Background Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington’s disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice. Objective To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients. Methods The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques. Results R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue. Conclusion Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration. PMID:26609226

  9. Oxidative Stress and Bronchopulmonary Dysplasia

    PubMed Central

    Perrone, Serafina; Tataranno, Maria Luisa; Buonocore, Giuseppe

    2012-01-01

    Bronchopulmonary dysplasia (BPD) is the major cause of pulmonary disease in infants. The pathophysiology and management of BPD changed with the improvement of neonatal intensive care unit (NICU) management and with the increase of survival rates. Despite the improvements made, BPD is still a public health concern, resulting in frequent hospitalizations with high rates of mortality, impaired weight and height growth, and neurodevelopmental disorders. Lung injury in the neonatal period has multiple etiologic factors – genetic, hemodynamic, metabolic, nutritional, mechanical, and infectious mechanisms – act in a cumulative and synergic way. Free radical (FR) generation is largely recognized as the major cause of lung damage. Oxidative stress (OS) is the final common endpoint for a complex convergence of events, some genetically determined and some triggered by in utero stressors. Inflammatory placental disorders and chorioamnionitis also play an important role due to the coexistence of inflammatory and oxidative lesions. In addition, the contribution of airway inflammation has been extensively studied. The link between inflammation and OS injury involves the direct activation of inflammatory cells, especially granulocytes, which potentiates the inflammatory reaction. Individualized interventions to support ventilation, minimize oxygen exposure, minimize apnea, and encourage growth should decrease both the frequency and severity of BPD. Future perspectives suggest supplementation with enzymatic and/or non-enzymatic antioxidants. The use of antioxidants in preterm newborns particularly exposed to OS and at risk for BPD represents a logical strategy to ameliorate FRs injury, but further studies are needed to support this hypothesis. PMID:24027702

  10. Induction of Oxidative Stress in Kidney

    PubMed Central

    Ozbek, Emin

    2012-01-01

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

  11. Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging

    PubMed Central

    Li, Jing; Cai, Dachuan; Yao, Xin; Zhang, Yanyan; Chen, Linbo; Jing, Pengwei; Wang, Lu; Wang, Yaping

    2016-01-01

    Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1+ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1+ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16Ink4a, Rb, p21Cip1/Waf1 and p53 in senescent Sca-1+ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1+ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16Ink4a-Rb and p53-p21Cip1/Waf1 signaling. PMID:27294914

  12. Oxidative damage and mitochondrial decay in aging.

    PubMed Central

    Shigenaga, M K; Hagen, T M; Ames, B N

    1994-01-01

    We argue for the critical role of oxidative damage in causing the mitochondrial dysfunction of aging. Oxidants generated by mitochondria appear to be the major source of the oxidative lesions that accumulate with age. Several mitochondrial functions decline with age. The contributing factors include the intrinsic rate of proton leakage across the inner mitochondrial membrane (a correlate of oxidant formation), decreased membrane fluidity, and decreased levels and function of cardiolipin, which supports the function of many of the proteins of the inner mitochondrial membrane. Acetyl-L-carnitine, a high-energy mitochondrial substrate, appears to reverse many age-associated deficits in cellular function, in part by increasing cellular ATP production. Such evidence supports the suggestion that age-associated accumulation of mitochondrial deficits due to oxidative damage is likely to be a major contributor to cellular, tissue, and organismal aging. PMID:7971961

  13. Sudden infant death syndrome: oxidative stress.

    PubMed

    Reid, G M; Tervit, H

    1999-06-01

    In studies of oxidative stress in sudden infant death syndrome (SIDS) there were two major findings: (1) During normal post-natal development, there was a gradual decline in the number of Cu/Zn superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) immunoreactive neurons in the hippocampus and parahippocampus gyrus in the brain; (2) The total number of immunoreactive neurons was elevated in SIDS victims compared to age-matched controls in infants 6 months of age and under (1). SOD and neuronal aging and degeneration in the hippocampus and neocortex were features of SIDS, Alzheimer's disease and Down's syndrome. In the SIDS study of infants from 3-6 months of age, the elevation of SOD in SIDS victims was significant, whereas no significant elevation of GSHPx was detected. An imbalance between SOD and GSHPx was said to be crucial in the prevention of toxicity of free radicals (1). Zinc-deficient cells cannot up-regulate gene expression of the scavenger enzymes SOD and GSHPx in cells exposed to high levels of superoxide and hydrogen peroxide (2). GSHPx coupled to reduced nicotine adenine diphosphate (NADPH) regenerating systems via glutathione reductase is virtually able to guarantee an effective protection of biological structures against oxidative attack (22). When the capacity of the cell to regenerate GSH is exceeded - primarily due to an insufficient supply of NADPH-oxidised glutathione (GSSG) is released from the cell and protein synthesis turns off (20). We hypothesize that the increased incidence of aging and neuronal death and increased incidence of SOD and GSHPx reactive neurons in early post-natal development indicates an increased up-regulation of gene expression of scavenger enzymes during high exposure to oxidative stress after birth. GSH-dependent peroxide metabolism is linked to the pentose phosphate shunt via NADPH-dependent glutathione reductase (GR). GSHPx is a selenium containing enzyme which together with catalase (CAT) SOD and vitamin E

  14. Clinical Relevance of Biomarkers of Oxidative Stress

    PubMed Central

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

    2015-01-01

    Abstract Significance: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. Critical Issues: The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. Future Directions: Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 23, 1144–1170. PMID:26415143

  15. Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene and their dose-effects on oxidative stress damage in kindergarten-aged children in Guangzhou, China.

    PubMed

    Li, Junnan; Lu, Shaoyou; Liu, Guihua; Zhou, Yuanxiu; Lv, Yanshan; She, Jianwen; Fan, Ruifang

    2015-08-15

    Polycyclic aromatic hydrocarbons (PAHs), benzene and toluene (BT) are ubiquitous toxic pollutants in the environment. Children are sensitive and susceptible to exposure to these contaminants. To investigate the potential oxidative DNA damage from the co-exposure of PAHs and BT in children, 87 children (aged 3-6) from a kindergarten in Guangzhou, China, were recruited. Ten urinary PAHs and four BT metabolites, as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage)in urine, were determined using a liquid chromatography tandem mass spectrometer. The results demonstrated that the levels of PAHs and BT in children from Guangzhou were 2-30 times higher than those in children from the other countries based on a comparison with recent data from the literature. In particular, the difference is more substantial for pyrene and volatile BT. Co-exposure to PAHs and BT could lead to additive oxidative DNA damage. Significant dose-effects were observed between the sum concentration of urinary monohydroxylated metabolites of PAHs (∑OH-PAHs), the sum concentration of the metabolites of BT (∑BT) and 8-OHdG levels. Every one percent increase in urinary PAHs and BT generated 0.33% and 0.02% increases in urinary 8-OHdG, respectively. We also determined that the urinary levels of PAHs and BT were negatively associated with the age of the children. Moreover, significant differences in the levels of ∑OH-PAHs and ∑BT were determined between 3- and 6-year-old children (p<0.05), which may be caused by different metabolism capabilities or inhalation frequencies. In conclusion, exposure to PAHs or BT could lead to oxidative DNA damage, and 8-OHdG is a good biomarker for indicating the presence of DNA damage. There exists a significant dose-effect relationship between PAH exposure, BT exposure and the concentration of 8-OHdG in urine. Toddlers (3-4 years old) face a higher burden of PAH and BT exposure compared with older children.

  16. Nicotine enantiomers and oxidative stress.

    PubMed

    Yildiz, D; Ercal, N; Armstrong, D W

    1998-09-15

    Nicotine affects a variety of cellular processes ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of this study was to characterize the toxicity of nicotine enantiomers as well as their ability to induce oxidative stress in an in vitro model using Chinese hamster ovary (CHO) cells. Colony formation assay has demonstrated that (-)-nicotine is the more toxic of the enantiomers. At 6 mM concentrations, (-)-nicotine was found to be approximately 28- and 19-fold more potent than (+)-, and (+/-)-nicotine (racemic), respectively. Results also indicated that the toxicity of (+/-)-nicotine is higher than that of (+)-nicotine. (-)-Nicotine at a 10 mM concentration substantially decreased glutathione (GSH) levels (46% decrease). In addition, a 3-fold increase in malondialdehyde (MDA) level was evident in cells after exposure to 10 mM (-)-nicotine. Increased lactate dehydrogenase (LDH) activities in the media demonstrated that cellular membrane integrity was disturbed in nicotine treated cells. In the presence of superoxide dismutase (SOD) and catalase (CAT), the LDH activities returned to control value in 24 h with all concentrations of (-)-, (+)-, and (+/-)-nicotine. The decreases in LDH activities in the presence of the radical scavenging enzymes SOD and CAT suggest that membrane damage may be due to free radical generation. PMID:9865482

  17. Oxidative Stress Related Diseases in Newborns

    PubMed Central

    Aykac, Kubra

    2016-01-01

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

  18. Oxidative Stress Related Diseases in Newborns.

    PubMed

    Ozsurekci, Yasemin; Aykac, Kubra

    2016-01-01

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

  19. Reproductive Benefit of Oxidative Damage: An Oxidative Stress “Malevolence”?

    PubMed Central

    Poljsak, B.; 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. Oxidative stress may be considered a biological imperfection; therefore, the Dawkins' theory of imperfect adaptation of beings to environment was applied to the role of oxidative stress in processes like famine and infectious diseases and their consequences at the molecular level such as mutations and cell signaling. Arguments are presented that oxidative damage is not necessarily an evolutionary mistake but may be beneficial for reproduction; this may prevail over its harmfulness to health and longevity in evolution. Thus, Dawkins' principle of biological “malevolence” may be an additional biological paradigm for explaining the consequences of oxidative stress. PMID:21969876

  20. Oxidative modification of proteins: age-related changes.

    PubMed

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  1. Oxidative Stress to the Cornea, Changes in Corneal Optical Properties, and Advances in Treatment of Corneal Oxidative Injuries

    PubMed Central

    Cejka, Cestmir; Cejkova, Jitka

    2015-01-01

    Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown. PMID:25861412

  2. Oxidative stress to the cornea, changes in corneal optical properties, and advances in treatment of corneal oxidative injuries.

    PubMed

    Cejka, Cestmir; Cejkova, Jitka

    2015-01-01

    Oxidative stress is involved in many ocular diseases and injuries. The imbalance between oxidants and antioxidants in favour of oxidants (oxidative stress) leads to the damage and may be highly involved in ocular aging processes. The anterior eye segment and mainly the cornea are directly exposed to noxae of external environment, such as air pollution, radiation, cigarette smoke, vapors or gases from household cleaning products, chemical burns from splashes of industrial chemicals, and danger from potential oxidative damage evoked by them. Oxidative stress may initiate or develop ocular injury resulting in decreased visual acuity or even vision loss. The role of oxidative stress in the pathogenesis of ocular diseases with particular attention to oxidative stress in the cornea and changes in corneal optical properties are discussed. Advances in the treatment of corneal oxidative injuries or diseases are shown. PMID:25861412

  3. Photoaging and chronological aging profile: Understanding oxidation of the skin.

    PubMed

    Peres, P S; Terra, V A; Guarnier, F A; Cecchini, R; Cecchini, A L

    2011-05-01

    The impact of chronological aging and photoaging on the skin is particularly concerning, especially when oxidative stress is involved. This article provides evidence of quantitative and qualitative differences in the oxidative stress generated by chronological aging and photoaging of the skin in HRS/J hairless mice. Analysis of the results revealed an increase in lipid peroxides as the skin gets older and in photoaged skin (10.086 ± 0.70 η MDA/mg and 14.303 ± 1.81 η MDA/mg protein, respectively), although protein oxidation was only verified in chronological aged skin (15.449 ± 0.99 η protein/mg protein). The difference between both skin types is the decay in the capacity of lipid membrane turnover revealed by the dislocation of older skin to the left in the chemiluminescence curve. Imbalance between antioxidant and oxidation processes was verified by the decrease in total antioxidant capacity of chronological and photoaged skins. Although superoxide dismutase remained unchanged, catalase increased in the 18 and 48-week-old skin groups and decreased in irradiated mice, demonstrating that neither enzyme is a good parameter to determine oxidative stress. The differences observed between chronological and photoaging skin represent a potential new approach to understanding the phenomenon of skin aging and a new target for therapeutic intervention. PMID:21356598

  4. Photoaging and chronological aging profile: Understanding oxidation of the skin.

    PubMed

    Peres, P S; Terra, V A; Guarnier, F A; Cecchini, R; Cecchini, A L

    2011-05-01

    The impact of chronological aging and photoaging on the skin is particularly concerning, especially when oxidative stress is involved. This article provides evidence of quantitative and qualitative differences in the oxidative stress generated by chronological aging and photoaging of the skin in HRS/J hairless mice. Analysis of the results revealed an increase in lipid peroxides as the skin gets older and in photoaged skin (10.086 ± 0.70 η MDA/mg and 14.303 ± 1.81 η MDA/mg protein, respectively), although protein oxidation was only verified in chronological aged skin (15.449 ± 0.99 η protein/mg protein). The difference between both skin types is the decay in the capacity of lipid membrane turnover revealed by the dislocation of older skin to the left in the chemiluminescence curve. Imbalance between antioxidant and oxidation processes was verified by the decrease in total antioxidant capacity of chronological and photoaged skins. Although superoxide dismutase remained unchanged, catalase increased in the 18 and 48-week-old skin groups and decreased in irradiated mice, demonstrating that neither enzyme is a good parameter to determine oxidative stress. The differences observed between chronological and photoaging skin represent a potential new approach to understanding the phenomenon of skin aging and a new target for therapeutic intervention.

  5. Oxidative stress and oxidative damage in chemical carcinogenesis

    SciTech Connect

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

    2011-07-15

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

  6. [Oxidative stress in bipolar affective disorder].

    PubMed

    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

  7. Chronic Stress Increases Vulnerability to Diet-Related Abdominal Fat, Oxidative Stress, and Metabolic Risk

    PubMed Central

    Aschbacher, Kirstin; Kornfeld, Sarah; Picard, Martin; Puterman, Eli; Havel, Peter; Stanhope, Kimber; Lustig, Robert H.; Epel, Elissa

    2014-01-01

    Summary Background In preclinical studies, the combination of chronic stress and a high sugar/fat diet is a more potent driver of visceral adiposity than diet alone, a process mediated by peripheral Neuropeptide Y (NPY). Methods In a human model of chronic stress, we investigated whether the synergistic combination of highly palatable foods (HPF; high sugar/fat) and stress was associated with elevated metabolic risk. Using a case-control design, we compared 33 post-menopausal caregivers (the chronic stress group) to 28 age-matched low-stress control women on reported HPF consumption (modified Block Food Frequency Questionnaire), waistline circumference, truncal fat ultrasound, and insulin sensitivity using a three-hour oral glucose tolerance test. A fasting blood draw was assayed for plasma NPY and oxidative stress markers (8-hydroxyguanosine and F2-Isoprostanes). Results Among chronically stressed women only, greater HPF consumption was associated with greater abdominal adiposity, oxidative stress, and insulin resistance at baseline (all p’s ≤.01). Furthermore, plasma NPY was significantly elevated in chronically stressed women (p<.01), and the association of HPF with abdominal adiposity was stronger among women with high versus low NPY. There were no significant predictions of change over one-year, likely due to high stability (little change) in the primary outcomes over this period. Discussion Chronic stress is associated with enhanced vulnerability to diet-related metabolic risk (abdominal adiposity, insulin resistance, and oxidative stress). Stress-induced peripheral NPY may play a mechanistic role. PMID:24882154

  8. Oxidative stress and the unfulfilled promises of antioxidant agents

    PubMed Central

    Giorgio, Marco

    2015-01-01

    It is well known that aging and its associated diseases, including cancer, are triggered by oxidative damage to biological macromolecules. However, antioxidant compounds are still disappointingly distant from any clinical application, so that Jim Watson has declared that antioxidant supplementation may have caused more cancers than it has prevented Watson J ((2013) Oxidants, antioxidants and the current incurability of metastatic cancers Open Biol 3 DOI: 10.1098/rsob.120144). To clarify this paradox, here, we describe the mechanisms of oxidative stress focusing in particular on redox balance and physiological oxidative signals. PMID:26284120

  9. Bacterial responses to photo-oxidative stress

    PubMed Central

    Ziegelhoffer, Eva C.; Donohue, Timothy J.

    2009-01-01

    Singlet oxygen is one of several reactive oxygen species that can destroy biomolecules, microorganisms and other cells. Traditionally, the response to singlet oxygen has been termed photo-oxidative stress, as light-dependent processes in photosynthetic cells are major biological sources of singlet oxygen. Recent work identifying a core set of singlet oxygen stress response genes across various bacterial species highlights the importance of this response for survival by both photosynthetic and non-photosynthetic cells. Here, we review how bacterial cells mount a transcriptional response to photo-oxidative stress in the context of what is known about bacterial stress responses to other reactive oxygen species. PMID:19881522

  10. Age-related carbonyl stress and erythrocyte membrane protein carbonylation.

    PubMed

    Li, Guolin; Liu, Li; Hu, Hui; Zhao, Qiong; Xie, Fuxia; Chen, Keke; Liu, Shenglin; Chen, Yaqin; Shi, Wang; Yin, Dazhong

    2010-01-01

    Reactive carbonyl species (RCS) have been widely used as indicators of oxidative stress. However, the associations of carbonyl stress with aging process and biochemical alteration of erythrocyte are still poorly understood. Fresh blood samples in vacutainer tubes containing sodium heparinate were obtained from 874 volunteers who were divided into young, adult and old groups based on their age. Plasma RCS and thiols concentrations between different age groups and erythrocyte membrane protein carbonylation in the adult group were detected within 24h of the blood sampling. Results showed that the plasma thiols concentration decreased gradually during aging process, and the p-values between all three groups are less than 0.05. The plasma RCS concentration in different age groups showed a nonlinear association with age. The levels in the young group were slightly higher than the adult group (not significant) and lower than the old group (p < 0.01). The protein carbonylation of erythrocyte membrane was positively correlated with plasma RCS concentration (p < 0.01), but not plasma thiols concentration. We conclude that higher levels of RCS, not lower levels of thiols, in plasma are a direct risk factor for the protein carbonylation of erythrocyte membrane. Owing to the decrease of thiols levels and increase of RCS levels during aging process, a shift from RCS-related redox allostasis to carbonyl stress would contribute to age-related biological dysfunction and even aging process.

  11. REST and stress resistance in ageing and Alzheimer's disease.

    PubMed

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X Shirley; Bennett, David A; Colaiácovo, Monica P; Yankner, Bruce A

    2014-03-27

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain. PMID:24670762

  12. REST and stress resistance in ageing and Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A.

    2014-03-01

    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.

  13. Association between oxidative stress and nutritional status in the elderly.

    PubMed

    Moreira, Priscila Lucelia; Villas Boas, Paulo Jose Fortes; Ferreira, Ana Lucia Anjos

    2014-01-01

    Ageing is a dynamic and progressive process that is characterized by the occurrence of morphological, biochemical, functional and psychological changes in the organism. The aim of the present article is to provide updated concepts on oxidative stress, covering its importance in aging, as well as nutritional status and supplementation with antioxidants (substances that prevent or attenuate oxidation of oxidizable substrates, such as lipids, proteins, carbohydrates and deoxyribonucleic acid) in the geriatric population. Evidence suggests that there is an inverse relationship between oxidative stress and nutritional status in elderly individuals. Although an increase in oxidative stress in chronic diseases associated with aging has been proven, such as Parkinson's disease and Alzheimer's disease, up to now there has been no consistent clinical evidence proving the efficiency of supplementation with antioxidants against oxidative stress. In this context, supplementation is not recommended. On the other hand, the elderly should be encouraged to eat antioxidant foods, such as fruits and vegetables. Maintaining a normal weight (body mass index between 23 and 28 Kg/m(2)) should also be stimulated.

  14. (+)-Catechin protects dermal fibroblasts against oxidative stress-induced apoptosis

    PubMed Central

    2014-01-01

    Background Oxidative stress has been suggested as a mechanism underlying skin aging, as it triggers apoptosis in various cell types, including fibroblasts, which play important roles in the preservation of healthy, youthful skin. Catechins, which are antioxidants contained in green tea, exert various actions such as anti-inflammatory, anti-bacterial, and anti-cancer actions. In this study, we investigated the effect of (+)-catechin on apoptosis induced by oxidative stress in fibroblasts. Methods Fibroblasts (NIH3T3) under oxidative stress induced by hydrogen peroxide (0.1 mM) were treated with either vehicle or (+)-catechin (0–100 μM). The effect of (+)-catechin on cell viability, apoptosis, phosphorylation of c-Jun terminal kinases (JNK) and p38, and activation of caspase-3 in fibroblasts under oxidative stress were evaluated. Results Hydrogen peroxide induced apoptotic cell death in fibroblasts, accompanied by induction of phosphorylation of JNK and p38 and activation of caspase-3. Pretreatment of the fibroblasts with (+)-catechin inhibited hydrogen peroxide-induced apoptosis and reduced phosphorylation of JNK and p38 and activation of caspase-3. Conclusion (+)-Catechin protects against oxidative stress-induced cell death in fibroblasts, possibly by inhibiting phosphorylation of p38 and JNK. These results suggest that (+)-catechin has potential as a therapeutic agent for the prevention of skin aging. PMID:24712558

  15. Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs

    PubMed Central

    2014-01-01

    Background The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Results Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging. Conclusions Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory. PMID:25056725

  16. Proteomics, oxidative stress and male infertility.

    PubMed

    Agarwal, Ashok; Durairajanayagam, Damayanthi; Halabi, Jacques; Peng, Jason; Vazquez-Levin, Monica

    2014-07-01

    Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility. Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free

  17. Oxidative stress in severe acute illness.

    PubMed

    Bar-Or, David; Bar-Or, Raphael; Rael, Leonard T; Brody, Edward N

    2015-01-01

    The overall redox potential of a cell is primarily determined by oxidizable/reducible chemical pairs, including glutathione-glutathione disulfide, reduced thioredoxin-oxidized thioredoxin, and NAD(+)-NADH (and NADP-NADPH). Current methods for evaluating oxidative stress rely on detecting levels of individual byproducts of oxidative damage or by determining the total levels or activity of individual antioxidant enzymes. Oxidation-reduction potential (ORP), on the other hand, is an integrated, comprehensive measure of the balance between total (known and unknown) pro-oxidant and antioxidant components in a biological system. Much emphasis has been placed on the role of oxidative stress in chronic diseases, such as Alzheimer's disease and atherosclerosis. The role of oxidative stress in acute diseases often seen in the emergency room and intensive care unit is considerable. New tools for the rapid, inexpensive measurement of both redox potential and total redox capacity should aid in introducing a new body of literature on the role of oxidative stress in acute illness and how to screen and monitor for potentially beneficial pharmacologic agents.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

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

  20. Protective Effect of Ginsenoside Rg1 on Hematopoietic Stem/Progenitor Cells through Attenuating Oxidative Stress and the Wnt/β-Catenin Signaling Pathway in a Mouse Model of d-Galactose-induced Aging.

    PubMed

    Li, Jing; Cai, Dachuan; Yao, Xin; Zhang, Yanyan; Chen, Linbo; Jing, Pengwei; Wang, Lu; Wang, Yaping

    2016-01-01

    Stem cell senescence is an important and current hypothesis accounting for organismal aging, especially the hematopoietic stem cell (HSC). Ginsenoside Rg1 is the main active pharmaceutical ingredient of ginseng, which is a traditional Chinese medicine. This study explored the protective effect of ginsenoside Rg1 on Sca-1⁺ hematopoietic stem/progenitor cells (HSC/HPCs) in a mouse model of d-galactose-induced aging. The mimetic aging mouse model was induced by continuous injection of d-gal for 42 days, and the C57BL/6 mice were respectively treated with ginsenoside Rg1, Vitamin E or normal saline after 7 days of d-gal injection. Compared with those in the d-gal administration alone group, ginsenoside Rg1 protected Sca-1⁺ HSC/HPCs by decreasing SA-β-Gal and enhancing the colony forming unit-mixture (CFU-Mix), and adjusting oxidative stress indices like reactive oxygen species (ROS), total anti-oxidant (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and malondialdehyde (MDA). In addition, ginsenoside Rg1 decreased β-catenin and c-Myc mRNA expression and enhanced the phosphorylation of GSK-3β. Moreover, ginsenoside Rg1 down-regulated advanced glycation end products (AGEs), 4-hydroxynonenal (4-HNE), phospho-histone H2A.X (r-H2A.X), 8-OHdG, p16(Ink4a), Rb, p21(Cip1/Waf1) and p53 in senescent Sca-1⁺ HSC/HPCs. Our findings indicated that ginsenoside Rg1 can improve the resistance of Sca-1⁺ HSC/HPCs in a mouse model of d-galactose-induced aging through the suppression of oxidative stress and excessive activation of the Wnt/β-catenin signaling pathway, and reduction of DNA damage response, p16(Ink4a)-Rb and p53-p21(Cip1/Waf1) signaling. PMID:27294914

  1. Oxidative Stress in Placenta: Health and Diseases

    PubMed Central

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

    2015-01-01

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

  2. Mammalian Metallothionein-2A and Oxidative Stress

    PubMed Central

    Ling, Xue-Bin; Wei, Hong-Wei; Wang, Jun; Kong, Yue-Qiong; Wu, Yu-You; Guo, Jun-Li; Li, Tian-Fa; Li, Ji-Ke

    2016-01-01

    Mammalian metallothionein-2A (MT2A) has received considerable attention in recent years due to its crucial pathophysiological role in anti-oxidant, anti-apoptosis, detoxification and anti-inflammation. For many years, most studies evaluating the effects of MT2A have focused on reactive oxygen species (ROS), as second messengers that lead to oxidative stress injury of cells and tissues. Recent studies have highlighted that oxidative stress could activate mitogen-activated protein kinases (MAPKs), and MT2A, as a mediator of MAPKs, to regulate the pathogenesis of various diseases. However, the molecule mechanism of MT2A remains elusive. A deeper understanding of the functional, biochemical and molecular characteristics of MT2A would be identified, in order to bring new opportunities for oxidative stress therapy. PMID:27608012

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

    PubMed Central

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

    2014-01-01

    Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER) is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded-protein response (UPR) through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS). Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways have been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease, and others. In this review, we have discussed the UPR signaling pathways, and networking between ER stress-induced inflammatory pathways, oxidative stress, and mitochondrial signaling events, which further induce or exacerbate ER stress. PMID:25120434

  4. Contaminant-induced oxidative stress in fish: a mechanistic approach.

    PubMed

    Lushchak, Volodymyr I

    2016-04-01

    The presence of reactive oxygen species (ROS) in living organisms was described more than 60 years ago and virtually immediately it was suggested that ROS were involved in various pathological processes and aging. The state when ROS generation exceeds elimination leading to an increased steady-state ROS level has been called "oxidative stress." Although ROS association with many pathological states in animals is well established, the question of ROS responsibility for the development of these states is still open. Fish represent the largest group of vertebrates and they inhabit a broad range of ecosystems where they are subjected to many different aquatic contaminants. In many cases, the deleterious effects of contaminants have been connected to induction of oxidative stress. Therefore, deciphering of molecular mechanisms leading to such contaminant effects and organisms' response may let prevent or minimize deleterious impacts of oxidative stress. This review describes general aspects of ROS homeostasis, in particular highlighting its basic aspects, modification of cellular constituents, operation of defense systems and ROS-based signaling with an emphasis on fish systems. A brief introduction to oxidative stress theory is accompanied by the description of a recently developed classification system for oxidative stress based on its intensity and time course. Specific information on contaminant-induced oxidative stress in fish is covered in sections devoted to such pollutants as metal ions (particularly iron, copper, chromium, mercury, arsenic, nickel, etc.), pesticides (insecticides, herbicides, and fungicides) and oil with accompanying pollutants. In the last section, certain problems and perspectives in studies of oxidative stress in fish are described.

  5. Contaminant-induced oxidative stress in fish: a mechanistic approach.

    PubMed

    Lushchak, Volodymyr I

    2016-04-01

    The presence of reactive oxygen species (ROS) in living organisms was described more than 60 years ago and virtually immediately it was suggested that ROS were involved in various pathological processes and aging. The state when ROS generation exceeds elimination leading to an increased steady-state ROS level has been called "oxidative stress." Although ROS association with many pathological states in animals is well established, the question of ROS responsibility for the development of these states is still open. Fish represent the largest group of vertebrates and they inhabit a broad range of ecosystems where they are subjected to many different aquatic contaminants. In many cases, the deleterious effects of contaminants have been connected to induction of oxidative stress. Therefore, deciphering of molecular mechanisms leading to such contaminant effects and organisms' response may let prevent or minimize deleterious impacts of oxidative stress. This review describes general aspects of ROS homeostasis, in particular highlighting its basic aspects, modification of cellular constituents, operation of defense systems and ROS-based signaling with an emphasis on fish systems. A brief introduction to oxidative stress theory is accompanied by the description of a recently developed classification system for oxidative stress based on its intensity and time course. Specific information on contaminant-induced oxidative stress in fish is covered in sections devoted to such pollutants as metal ions (particularly iron, copper, chromium, mercury, arsenic, nickel, etc.), pesticides (insecticides, herbicides, and fungicides) and oil with accompanying pollutants. In the last section, certain problems and perspectives in studies of oxidative stress in fish are described. PMID:26607273

  6. Correlation between in vivo stresses and oxidation of UHMWPE in total hip arthroplasty.

    PubMed

    Regis, M; Bracco, P; Giorgini, L; Fusi, S; Dalla Pria, P; Costa, L; Schmid, C

    2014-09-01

    The possibility of in vivo, stress-induced oxidation in orthopaedic UHMWPE has been investigated. EtO sterilised, uncrosslinked UHMWPE liners, explanted or shelf-aged, have been collected. Linear wear and wear rate were assessed and FTIR spectroscopy was employed to detect oxidation and to build up oxidation products spatial maps across the liners section. Oxidation profiles have been compared to stress distribution profiles, resulting from a FE analysis conducted on the same liners geometries and couplings. It was found that oxidised and stressed areas followed the same asymmetrical, localized distribution profile. It was therefore possible to establish a correlation between stressed areas and observed oxidation.

  7. Phloroglucinol Attenuates Free Radical-induced Oxidative Stress

    PubMed Central

    So, Mi Jung; Cho, Eun Ju

    2014-01-01

    The protective role of phloroglucinol against oxidative stress and stress-induced premature senescence (SIPS) was investigated in vitro and in cell culture. Phloroglucinol had strong and concentration-dependent radical scavenging effects against nitric oxide (NO), superoxide anions (O2−), and hydroxyl radicals. In this study, free radical generators were used to induce oxidative stress in LLC-PK1 renal epithelial cells. Treatment with phloroglucinol attenuated the oxidative stress induced by peroxyl radicals, NO, O2−, and peroxynitrite. Phloroglucinol also increased cell viability and decreased lipid peroxidation in a concentration-dependent manner. WI-38 human diploid fibroblast cells were used to investigate the protective effect of phloroglucinol against hydrogen peroxide (H2O2)-induced SIPS. Phloroglucinol treatment attenuated H2O2-induced SIPS by increasing cell viability and inhibited lipid peroxidation, suggesting that treatment with phloroglucinol should delay the aging process. The present study supports the promising role of phloroglucinol as an antioxidative agent against free radical-induced oxidative stress and SIPS. PMID:25320709

  8. Maillard reaction, mitochondria and oxidative stress: potential role of antioxidants.

    PubMed

    Edeas, M; Attaf, D; Mailfert, A-S; Nasu, M; Joubet, R

    2010-06-01

    Glycation and oxidative stress are two important processes known to play a key role in complications of many disease processes. Oxidative stress, either via increasing reactive oxygen species (ROS), or by depleting the antioxidants may modulate the genesis of early glycated proteins in vivo. Maillard Reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes, aging and age-related diseases. Hyperglycaemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes facilitate the generation of reactive oxygen species and decrease the activity of antioxidant enzymes such as Cu,Zn-superoxide dismutase, resulting in a remarkable increase of oxidative stress. A large body of evidence indicates that mitochondria alteration is involved and plays a central role in various oxidative stress-related diseases. The damaged mitochondria produce more ROS (increase oxidative stress) and less ATP (cellular energy) than normal mitochondria. As they are damaged, they cannot burn or use glucose or lipid and cannot provide cell with ATP. Further, glucose, amino acids and lipid will not be correctly used and will accumulate outside the mitochondria; they will undergo more glycation (as observed in diabetes, obesity, HIV infection and lipodystrophia). The objective of this paper is to discuss how to stop the vicious circle established between oxidative stress, Maillard Reaction and mitochondria. The potential application of some antioxidants to reduce glycation phenomenon and to increase the antioxidant defence system by targeting mitochondria will be discussed. Food and pharmaceutical companies share the same challenge, they must act now, urgently and energetically. PMID:20031340

  9. Age differences in stress and coping processes.

    PubMed

    Folkman, S; Lazarus, R S; Pimley, S; Novacek, J

    1987-06-01

    The dramatic increase in the numbers of people who are living into old age has been accompanied by a growing interest among psychologists and health care professionals in their sources of stress and how they cope with them. Despite this interest, little is known about normative stress and coping patterns and the ways in which these patterns differ in older and younger people. This study, which draws on stress and coping theory, compares younger and older community-dwelling adults in daily hassles and eight kinds of coping. Two interpretations of age differences are evaluated: a developmental interpretation, which says that there are inherent, stage-related changes in the ways people cope as they age, and a contextual interpretation, which says that age differences in coping result from changes in what people must cope with. The findings indicate that there are clear age differences in hassles and coping. Overall, the findings tend to support the developmental interpretation, although the contextual interpretation also applies.

  10. Diabetic Cardiovascular Disease Induced by Oxidative Stress.

    PubMed

    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.

  11. Repression of gene expression by oxidative stress.

    PubMed Central

    Morel, Y; Barouki, R

    1999-01-01

    Gene expression is modulated by both physiological signals (hormones, cytokines, etc.) and environmental stimuli (physical parameters, xenobiotics, etc.). Oxidative stress appears to be a key pleiotropic modulator which may be involved in either pathway. Indeed, reactive oxygen species (ROS) have been described as second messengers for several growth factors and cytokines, but have also been shown to rise following cellular insults such as xenobiotic metabolism or enzymic deficiency. Extensive studies on the induction of stress-response genes by oxidative stress have been reported. In contrast, owing to the historical focus on gene induction, less attention has been paid to gene repression by ROS. However, a growing number of studies have shown that moderate (i.e. non-cytotoxic) oxidative stress specifically down-regulates the expression of various genes. In this review, we describe the alteration of several physiological functions resulting from oxidative-stress-mediated inhibition of gene transcription. We will then focus on the repressive oxidative modulation of various transcription factors elicited by ROS. PMID:10477257

  12. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    PubMed Central

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

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

  13. Plasma levels of oxidative stress-responsive apoptosis inducing protein (ORAIP) in rats subjected to physicochemical oxidative stresses

    PubMed Central

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

    2016-01-01

    Oxidative stress is known to play a pivotal role in the pathogenesis of various disorders including atherosclerosis, aging and especially ischaemia/reperfusion injury. It causes cell damage that leads to apoptosis. However, the precise mechanism has been uncertain. Recently, we identified an apoptosis-inducing humoral factor in a hypoxia/reoxygenated medium of cardiac myocytes. We named this novel post-translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) as oxidative stress-responsive apoptosis inducing protein (ORAIP). We developed a sandwich ELISA and confirmed that myocardial ischaemia/reperfusion markedly increased plasma levels of ORAIP. To investigate whether the role of ORAIP is common to various types of oxidative stress, we measured plasma ORAIP levels in rats subjected to three physicochemical models of oxidative stress including N2/O2 inhalation, cold/warm-stress (heat shock) and blood acidification. In all three models, plasma ORAIP levels significantly increased and reached a peak level at 10–30 min after stimulation, then decreased within 60 min. The (mean±S.E.M.) plasma ORAIP levels before and after (peak) stimulation were (16.4±9.6) and (55.2±34.2) ng/ml in N2/O2 inhalation, (14.1±12.4) and (34.3±14.6) ng/ml in cold/warm-stress, and (18.9±14.3) and (134.0±67.2) ng/ml in blood acidification study. These data strongly suggest that secretion of ORAIP in response to oxidative stress is universal mechanism and plays an essential role. ORAIP will be an important novel biomarker as well as a specific therapeutic target of these oxidative stress-induced cell injuries. PMID:26934977

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

    PubMed

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

    2016-10-01

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

  15. Reliability Impact of Stockpile Aging: Stress Voiding

    SciTech Connect

    ROBINSON,DAVID G.

    1999-10-01

    The objective of this research is to statistically characterize the aging of integrated circuit interconnects. This report supersedes the stress void aging characterization presented in SAND99-0975, ''Reliability Degradation Due to Stockpile Aging,'' by the same author. The physics of the stress voiding, before and after wafer processing have been recently characterized by F. G. Yost in SAND99-0601, ''Stress Voiding during Wafer Processing''. The current effort extends this research to account for uncertainties in grain size, storage temperature, void spacing and initial residual stress and their impact on interconnect failure after wafer processing. The sensitivity of the life estimates to these uncertainties is also investigated. Various methods for characterizing the probability of failure of a conductor line were investigated including: Latin hypercube sampling (LHS), quasi-Monte Carlo sampling (qMC), as well as various analytical methods such as the advanced mean value (Ah/IV) method. The comparison was aided by the use of the Cassandra uncertainty analysis library. It was found that the only viable uncertainty analysis methods were those based on either LHS or quasi-Monte Carlo sampling. Analytical methods such as AMV could not be applied due to the nature of the stress voiding problem. The qMC method was chosen since it provided smaller estimation error for a given number of samples. The preliminary results indicate that the reliability of integrated circuits due to stress voiding is very sensitive to the underlying uncertainties associated with grain size and void spacing. In particular, accurate characterization of IC reliability depends heavily on not only the frost and second moments of the uncertainty distribution, but more specifically the unique form of the underlying distribution.

  16. Oxidative stress in pregnancy and reproduction.

    PubMed

    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

  17. Mild oxidative stress is beneficial for sperm telomere length maintenance

    PubMed Central

    Mishra, Swetasmita; Kumar, Rajeev; Malhotra, Neena; Singh, Neeta; Dada, Rima

    2016-01-01

    AIM: To evaluate telomere length in sperm DNA and its correlation with oxidative stress (normal, mild, severe). METHODS: The study included infertile men (n = 112) and age matched fertile controls (n = 102). The average telomere length from the sperm DNA was measured using a quantitative real time PCR based assay. Seminal reactive oxygen species (ROS) and 8-Isoprostane (8-IP) levels were measured by chemiluminescence assay and ELISA respectively. RESULTS: Average sperm telomere length in infertile men and controls was 0.609 ± 0.15 and 0.789 ± 0.060, respectively (P < 0.0001). Seminal ROS levels in infertile was higher [66.61 ± 28.32 relative light units (RLU)/s/million sperm] than in controls (14.04 ± 10.67 RLU/s/million sperm) (P < 0.0001). The 8-IP level in infertile men was significantly higher (421.55 ± 131.29 pg/mL) than in controls (275.94 ± 48.13 pg/mL) (P < 0.001). When correlated to oxidative stress, in normal range of oxidative stress (ROS, 0-21.3 RLU/s/million sperm) the average telomere length in cases was 0.663 ± 0.14, in mild oxidative stress (ROS, 21.3-35 RLU/s/million sperm) it was elevated (0.684 ± 0.12) and in severe oxidative stress (ROS > 35 RLU/s/million sperm) average telomere length was decreased to 0.595 ± 0.15. CONCLUSION: Mild oxidative stress results in lengthening of telomere length, but severe oxidative stress results in shorter telomeres. Although telomere maintenance is a complex trait, the study shows that mild oxidative stress is beneficial in telomere length maintenance and thus a delicate balance needs to be established to maximize the beneficial effects of free radicals and prevent harmful effects of supra physiological levels. Detailed molecular evaluation of telomere structure, its correlation with oxidative stress would aid in elucidating the cause of accelerated telomere length attrition. PMID:27376021

  18. Oxidative stress markers in patients with hymenoptera venom allergy.

    PubMed

    Patella, Vincenzo; Incorvaia, Cristoforo; Minciullo, Paola Lucia; Oricchio, Carmine; Saitta, Salvatore; Florio, Giovanni; Saija, Antonella; Gangemi, Sebastiano

    2015-01-01

    Oxidative stress occurs in many allergic and immunologic disorders as a result of the imbalance between the endogenous production of free reactive oxygen species (ROS) and/or the reduction of antioxidant defense mechanisms. Advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), and nitrosylated proteins (NPs) can be used as markers of oxidative stress and inflammation. Our objective was to examine the serum levels of AGEs, AOPPs, and NPs in patients with allergic reactions to hymenoptera venom before and after ultrarush venom immunotherapy (VIT). The study included two groups of patients: 30 patients allergic to yellow jacket or honey bee venom and treated by aqueous preparation of Vespula spp (26 patients) or Apis mellifera (four patients) VIT, and 30 healthy donors as controls. Blood samples were collected to measure serum levels of AGEs, AOPPs, and NPs at baseline (T1), at the end of the incremental phase of the VIT protocol (T2), and after 15 days (T3). Serum AOPP levels at T1 were significantly higher in comparison with controls (p = 0.001), whereas serum levels of NPs at T1 were significantly lower than those in controls (p < 0.0001). No significant difference in circulating levels of AOPPs, AGEs, and NPs was found during immunotherapy. These findings suggest that, although hymenoptera venom allergy (HVA) is characterized by isolated episodes of reactions to stinging insect venom and is not included among chronic inflammatory diseases, an oxidative stress status occurs in patients suffering from this kind of allergy. Furthermore, VIT does not modify serum levels of these oxidative stress biomarkers.

  19. Markers of Oxidative Stress during Diabetes Mellitus

    PubMed Central

    Tiwari, Brahm Kumar; Pandey, Kanti Bhooshan; Abidi, A. B.; Rizvi, Syed Ibrahim

    2013-01-01

    The prevalence of diabetes mellitus is rising all over the world. Uncontrolled state of hyperglycemia due to defects in insulin secretion/action leads to a variety of complications including peripheral vascular diseases, nephropathy, neuropathy, retinopathy, morbidity, and/or mortality. Large body of evidence suggests major role of reactive oxygen species/oxidative stress in development and progression of diabetic complications. In the present paper, we have discussed the recent researches on the biomarkers of oxidative stress during type 2 diabetes mellitus. PMID:26317014

  20. Oxidative Stress in Schizophrenia: An Integrated Approach

    PubMed Central

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

    2010-01-01

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

  1. Oxidative stress and seasonal coral bleaching.

    PubMed

    Downs, C A; Fauth, John E; Halas, John C; Dustan, Phillip; Bemiss, John; Woodley, Cheryl M

    2002-08-15

    During the past two decades, coral reefs have experienced extensive degradation worldwide. One etiology for this global degradation is a syndrome known as coral bleaching. Mass coral bleaching events are correlated with increased sea-surface temperatures, however, the cellular mechanism underlying this phenomenon is uncertain. To determine if oxidative stress plays a mechanistic role in the process of sea-surface temperature-related coral bleaching, we examined corals along a depth transect in the Florida Keys over a single season that was characterized by unusually high sea-surface temperatures. We observed strong positive correlations between accumulation of oxidative damage products and bleaching in corals over a year of sampling. High levels of antioxidant enzymes and small heat-shock proteins were negatively correlated with levels of oxidative damage products. Corals that experienced oxidative stress had higher chaperonin levels and protein turnover activity. Our results indicate that coral bleaching is tightly coupled to the antioxidant and cellular stress capacity of the symbiotic coral, supporting the mechanistic model that coral bleaching (zooxanthellae loss) may be a final strategy to defend corals from oxidative stress.

  2. Epigenetic Regulation of Oxidative Stress in Ischemic Stroke

    PubMed Central

    Zhao, Haiping; Han, Ziping; Ji, Xunming; Luo, Yumin

    2016-01-01

    The prevalence and incidence of stroke rises with life expectancy. However, except for the use of recombinant tissue-type plasminogen activator, the translation of new therapies for acute stroke from animal models into humans has been relatively unsuccessful. Oxidative DNA and protein damage following stroke is typically associated with cell death. Cause-effect relationships between reactive oxygen species and epigenetic modifications have been established in aging, cancer, acute pancreatitis, and fatty liver disease. In addition, epigenetic regulatory mechanisms during stroke recovery have been reviewed, with focuses mainly on neural apoptosis, necrosis, and neuroplasticity. However, oxidative stress-induced epigenetic regulation in vascular neural networks following stroke has not been sufficiently explored. Improved understanding of the epigenetic regulatory network upon oxidative stress may provide effective antioxidant approaches for treating stroke. In this review, we summarize the epigenetic events, including DNA methylation, histone modification, and microRNAs, that result from oxidative stress following experimental stroke in animal and cell models, and the ways in which epigenetic changes and their crosstalk influence the redox state in neurons, glia, and vascular endothelial cells, helping us to understand the foregone and vicious epigenetic regulation of oxidative stress in the vascular neural network following stroke. PMID:27330844

  3. Potential Modulation of Sirtuins by Oxidative Stress.

    PubMed

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

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

  4. Potential Modulation of Sirtuins by Oxidative Stress

    PubMed Central

    Santos, Leonardo; Escande, Carlos; Denicola, Ana

    2016-01-01

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

  5. What is the evidence for stress resistance and slowed aging?

    PubMed

    Hamilton, Karyn L; Miller, Benjamin F

    2016-09-01

    Stress resistance is thought to contribute to slowed-aging, although cause and effect between the two is controversial. On October 30, 2015 researchers gathered at the Front Range Consortium on Stress Resistance and Slowed Aging in Fort Collins, CO, to discuss what the current evidence is that stress resistance imparts slowed aging. Included in that discussion was defining stress resistance, distinguishing if there are key stresses to which resistance imparts slowed aging, what models aid in our understanding of stress resistance and aging, and how to translate that knowledge into slowed aging treatment. The following article is a brief summary of that discussion and recommendations for moving forward. PMID:27268049

  6. l-Arginine Enhances Resistance against Oxidative Stress and Heat Stress in Caenorhabditis elegans

    PubMed Central

    Ma, Heran; Ma, Yudan; Zhang, Zhixian; Zhao, Ziyuan; Lin, Ran; Zhu, Jinming; Guo, Yi; Xu, Li

    2016-01-01

    The antioxidant properties of l-arginine (l-Arg) in vivo, and its effect on enhancing resistance to oxidative stress and heat stress in Caenorhabditis elegans were investigated. C. elegans, a worm model popularly used in molecular and developmental biology, was used in the present study. Here, we report that l-Arg, at a concentration of 1 mM, prolonged C. elegans life by 26.98% and 37.02% under oxidative and heat stress, respectively. Further experiments indicated that the longevity-extending effects of l-Arg may be exerted by its free radical scavenging capacity and the upregulation of aging-associated gene expression in worms. This work is important in the context of numerous recent studies that concluded that environment stresses are associated with an increased population death rate. PMID:27690079

  7. The effects of anesthetic agents on oxidative stress

    NASA Astrophysics Data System (ADS)

    Yakan, Selvinaz; Düzgüner, Vesile

    2016-04-01

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

  8. Oxidative stress and tardive dyskinesia: pharmacogenetic evidence.

    PubMed

    Cho, Chul-Hyun; Lee, Heon-Jeong

    2013-10-01

    Tardive dyskinesia (TD) is a serious adverse effect of long-term antipsychotic use. Because of genetic susceptibility for developing TD and because it is difficult to predict and prevent its development prior to or during the early stages of medication, pharmacogenetic research of TD is important. Additionally, these studies enhance our knowledge of the genetic mechanisms underlying abnormal dyskinetic movements, such as Parkinson's disease. However, the pathophysiology of TD remains unclear. The oxidative stress hypothesis of TD is one of the possible pathophysiologic models for TD. Preclinical and clinical studies of the oxidative stress hypothesis of TD indicate that neurotoxic free radical production is likely a consequence of antipsychotic medication and is related to the occurrence of TD. Several studies on TD have focused on examining the genes involved in oxidative stress. Among them, manganese superoxide dismutase gene Ala-9Val polymorphisms show a relatively consistent association with TD susceptibility, although not all studies support this. Numerous pharmacogenetic studies have found a positive relationship between TD and oxidative stress based on genes involved in the antioxidant defense mechanism, dopamine turnover and metabolism, and other antioxidants such as estrogen and melatonin. However, many of the positive findings have not been replicated. We expect that more research will be needed to address these issues. PMID:23123399

  9. Oxidative Stress Control by Apicomplexan Parasites

    PubMed Central

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

    2015-01-01

    Apicomplexan parasites cause infectious diseases that are either a severe public health problem or an economic burden. In this paper we will shed light on how oxidative stress can influence the host-pathogen relationship by focusing on three major diseases: babesiosis, coccidiosis, and toxoplasmosis. PMID:25722976

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

    PubMed

    Busch, Andrea W U; Montgomery, Beronda L

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. IGF-1, oxidative stress, and atheroprotection

    PubMed Central

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

    2009-01-01

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

  13. Oxidative stress and the pathogenesis of muscular dystrophies.

    PubMed

    Rando, Thomas A

    2002-11-01

    The muscular dystrophies represent a diverse group of diseases differing in underlying genetic basis, age of onset, mode of inheritance, and severity of progression, but they share certain common pathologic features. Most prominent among these features is the necrotic degeneration of muscle fibers. Although the genetic basis of many of the dystrophies has been known for over a decade and new disease genes continue to be discovered, the pathogenetic mechanisms leading to muscle cell death in the dystrophies remain a mystery. This review focuses on the oxidative stress theory, which states that the final common pathway of muscle cell death in these diseases involves oxidative damage.

  14. Cocoa phenolic extract protects pancreatic beta cells against oxidative stress.

    PubMed

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

    2013-08-01

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

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

    PubMed Central

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

    2013-01-01

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

  16. Increase of oxidation and inflammation in nervous and immune systems with aging and anxiety.

    PubMed

    Vida, Carmen; González, Eva M; De la Fuente, Mónica

    2014-01-01

    According to the oxidation-inflammation theory of aging, chronic oxidative stress and inflammatory stress situations (with higher levels of oxidant and inflammatory compounds and lower antioxidant and anti-inflammatory defenses) are the basis of the agerelated impairment of organism functions, including those of the nervous and immune systems, as well as of the neuroimmune communication, which explains the altered homeostasis and the resulting increase of morbidity and mortality. Overproduction of oxidant compounds can induce an inflammatory response, since oxidants are inflammation effectors. Thus, oxidation and inflammation are interlinked processes and have many feedback loops. However, the nature of their potential interactions, mainly in the brain and immune cells, and their key involvement in aging remain unclear. Moreover, in the context of the neuroimmune communication, it has been described that an oxidative-inflammatory situation occurs in subjects with anxiety, and this situation contributes to an immunosenescence, alteration of survival responses and shorter life span. As an example of this, a model of premature aging in mice, in which animals show a poor response to stress and high levels of anxiety, an oxidative stress in their immune cells and tissues, as well as a premature immunosenescence and a shorter life expectancy, will be commented in the present review. This model supports the hypothesis that anxiety can be a situation of chronic oxidative stress and inflammation, especially in brain and immune cells, and this accelerates the rate of aging.

  17. Oxidative stress and mitochondrial dysfunction in fibromyalgia.

    PubMed

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

    2010-01-01

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

  18. Stress in biology and medicine, role in aging.

    PubMed

    Robert, L; Labat-Robert, J

    2015-09-01

    In this review, we present a short description of the history of stress in the medical literature followed by a recapitulation of its mechanisms, from the cellular to the organismal level and its role in aging. The medical importance of stress was first taken up as a subject of experimental medicine by physiologists, starting from Claude Bernard's concept of the stability of the "milieu intérieur", altered by stress, followed by others, culminating recently by the elucidation of its mechanisms at the cellular and molecular level. These studies showed that oxidative stress is one of the most important and most frequent form of biological aggression. Its accumulation over time is important for the burnout syndrome and for neuronal aging. There is however a positive side to it also, redox signaling plays an important role in the functional coordination of cellular activities. These mechanisms, still to be more completely evaluated, have to be taken in account for planning efficient protective therapeutic interventions. PMID:26321500

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

    PubMed

    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.

  20. Oxidative Stress and Air Pollution Exposure

    PubMed Central

    Lodovici, Maura; Bigagli, Elisabetta

    2011-01-01

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

  1. Age Attenuates Leucine Oxidation after Eccentric Exercise

    PubMed Central

    Kullman, E. L.; Campbell, W. W.; Krishnan, R. K.; Yarasheski, K. E.; Evans, W. J.; Kirwan, J. P.

    2013-01-01

    Aging may alter protein metabolism during periods of metabolic and physiologic challenge. The purpose of this study was to assess the effects of age on whole-body amino acid turnover in response to eccentric exercise and hyperglycemia-induced hyperinsulinemia. 16 healthy men were divided into young (N = 8) and older (N = 8) groups. Protein metabolism was assessed using a [1-13C]-leucine isotopic tracer approach. Measures were obtained under fasted basal conditions and during 3-h hyperglycemic clamps that were performed without (control) and 48 h after eccentric exercise. Exercise reduced leucine oxidation in the younger men (P < 0.05), but not in older men. Insulin sensitivity was inversely correlated with leucine oxidation (P < 0.05), and was lower in older men (P < 0.05). Healthy aging is associated with an impaired capacity to adjust protein oxidation in response to eccentric exercise. The decreased efficiency of protein utilization in older men may contribute to impaired maintenance, growth, and repair of body tissues with advancing age. PMID:23325713

  2. Senescence-Induced Oxidative Stress Causes Endothelial Dysfunction.

    PubMed

    Bhayadia, Raj; Schmidt, Bernhard M W; Melk, Anette; Hömme, Meike

    2016-02-01

    Age is a risk factor for cardiovascular disease, suggesting a causal relationship between age-related changes and vascular damage. Endothelial dysfunction is an early pathophysiological hallmark in the development of cardiovascular disease. Senescence, the cellular equivalent of aging, was proposed to be involved in endothelial dysfunction, but functional data showing a causal relationship are missing.Endothelium-dependent vasodilation was measured in aortic rings ex vivo. We investigated aortas from aged C57Bl/6 mice (24-28 months), in which p16 (INK4a) and p19 (ARF) expression, markers of stress-induced senescence, were significantly induced compared to young controls (4-6 months). To reflect telomere shortening in human aging, we investigated aortas from telomerase deficient (Terc(-/-)) mice of generation 3 (G3). Endothelium-dependent vasodilation in aged wildtype and in Terc(-/-) G3 mice was impaired. A combination of the superoxide dismutase mimetic 1-Oxyl-2,2,6, 6-tetramethyl-4-hydroxypiperidine (TEMPOL) and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin significantly improved endothelium-dependent vasodilation in aged wildtype and Terc(-/-) G3 mice compared to untreated controls. We show that both, aging and senescence induced by telomere shortening, cause endothelial dysfunction that can be restored by antioxidants, indicating a role for oxidative stress. The observation that cellular senescence is a direct signalling event leading to endothelial dysfunction holds the potential to develop new targets for the prevention of cardiovascular disease.

  3. Tualang Honey Attenuates Noise Stress-Induced Memory Deficits in Aged Rats

    PubMed Central

    Azman, Khairunnuur Fairuz; Abdul Aziz, Che Badariah; Othman, Zahiruddin

    2016-01-01

    Ageing and stress exposure may lead to memory impairment while oxidative stress is thought to be one of the underlying mechanisms involved. This study aimed to investigate the potential protective effects of Tualang honey supplementation on memory performance in aged rats exposed to noise stress. Tualang honey supplementation was given orally, 200 mg/kg body weight for 28 days. Rats in the stress group were subjected to loud noise, 100 dB(A), 4 hours daily for 14 days. All rats were subjected to novel object recognition test for evaluation of memory performance. It was observed that the rats subjected to noise stress exhibited significantly lower memory performance and higher oxidative stress as evident by elevated malondialdehyde and protein carbonyl levels and reduction of antioxidant enzymes activities compared to the nonstressed rats. Tualang honey supplementation was able to improve memory performance, decrease oxidative stress levels, increase brain-derived neurotrophic factor (BDNF) concentration, decrease acetylcholinesterase activity, and enhance neuronal proliferation in the medial prefrontal cortex (mPFC) and hippocampus. In conclusion, Tualang honey protects against memory decline due to stress exposure and/or ageing via enhancement of mPFC and hippocampal morphology possibly secondary to reduction in brain oxidative stress and/or upregulation of BDNF concentration and cholinergic system. PMID:27119005

  4. Vesicular antioxidants: role in age-related cerebral oxidative injury.

    PubMed

    Sarkar, Sibani; Mandal, Ardhendu Kumar; Das, Nirmalendu

    2013-01-01

    Oxidative stress, due to the generation of reactive oxygen species, is a major factor in cerebral ischemic damage and changes the activities of antioxidant enzymes and substantially influences the aging process. Free chemical antioxidant is almost ineffective to treat brain ischemia as blood-brain barrier exists in between blood and brain interstitial fluid, limiting component to pass from the circulation into cerebral region. Different compounds have been tested in vivo in different vesiculated forms to prevent cerebral ischemia. Nanoparticle-encapsulated drug treatment resulted in a significant protection of the antioxidant enzymes in both young and old rats. Nanocapsulated drug treatment causes a substantial protection against cerebral ischemia-reperfusion-induced oxidative damage to all parts of brain specifically hippocampal regions of all age groups of rat brain. PMID:23740123

  5. Comparison of Biomarkers of Oxidative Stress and Cardiovascular Disease in Humans and Chimpanzees (Pan troglodytes)

    PubMed Central

    Videan, Elaine N; Heward, Christopher B; Chowdhury, Kajal; Plummer, John; Su, Yali; Cutler, Richard G

    2009-01-01

    In the oxidative stress hypothesis of aging, the aging process is the result of cumulative damage by reactive oxygen species. Humans and chimpanzees are remarkably similar; but humans live twice as long as chimpanzees and therefore are believed to age at a slower rate. The purpose of this study was to compare biomarkers for cardiovascular disease, oxidative stress, and aging between male chimpanzees and humans. Compared with men, male chimpanzees were at increased risk for cardiovascular disease because of their significantly higher levels of fibrinogen, IGF1, insulin, lipoprotein a, and large high-density lipoproteins. Chimpanzees showed increased oxidative stress, measured as significantly higher levels of 5-hydroxymethyl-2-deoxyuridine and 8-iso-prostaglandin F2α, a higher peroxidizability index, and higher levels of the prooxidants ceruloplasmin and copper. In addition, chimpanzees had decreased levels of antioxidants, including α- and β-carotene, β-cryptoxanthin, lycopene, and tocopherols, as well as decreased levels of the cardiovascular protection factors albumin and bilirubin. As predicted by the oxidative stress hypothesis of aging, male chimpanzees exhibit higher levels of oxidative stress and a much higher risk for cardiovascular disease, particularly cardiomyopathy, compared with men of equivalent age. Given these results, we hypothesize that the longer lifespan of humans is at least in part the result of greater antioxidant capacity and lower risk of cardiovascular disease associated with lower oxidative stress. PMID:19619420

  6. Comparison of biomarkers of oxidative stress and cardiovascular disease in humans and chimpanzees (Pan troglodytes).

    PubMed

    Videan, Elaine N; Heward, Christopher B; Chowdhury, Kajal; Plummer, John; Su, Yali; Cutler, Richard G

    2009-06-01

    In the oxidative stress hypothesis of aging, the aging process is the result of cumulative damage by reactive oxygen species. Humans and chimpanzees are remarkably similar; but humans live twice as long as chimpanzees and therefore are believed to age at a slower rate. The purpose of this study was to compare biomarkers for cardiovascular disease, oxidative stress, and aging between male chimpanzees and humans. Compared with men, male chimpanzees were at increased risk for cardiovascular disease because of their significantly higher levels of fibrinogen, IGF1, insulin, lipoprotein a, and large high-density lipoproteins. Chimpanzees showed increased oxidative stress, measured as significantly higher levels of 5-hydroxymethyl-2-deoxyuridine and 8-iso-prostaglandin F(2alpha), a higher peroxidizability index, and higher levels of the prooxidants ceruloplasmin and copper. In addition, chimpanzees had decreased levels of antioxidants, including alpha- and beta-carotene, beta-cryptoxanthin, lycopene, and tocopherols, as well as decreased levels of the cardiovascular protection factors albumin and bilirubin. As predicted by the oxidative stress hypothesis of aging, male chimpanzees exhibit higher levels of oxidative stress and a much higher risk for cardiovascular disease, particularly cardiomyopathy, compared with men of equivalent age. Given these results, we hypothesize that the longer lifespan of humans is at least in part the result of greater antioxidant capacity and lower risk of cardiovascular disease associated with lower oxidative stress. PMID:19619420

  7. Oxidative stress and Parkinson’s disease

    PubMed Central

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

    2015-01-01

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

  8. Exercise and oxidative stress methodology: a critique.

    PubMed

    Jenkins, R R

    2000-08-01

    Historically, exercise physiologists' interest in oxygen has primarily centered on the problem of oxygen consumption. However, the interest of the general scientific community in oxygen-centered radicals has raised awareness of the oxygen paradox and has motivated investigators to question whether exercise-stimulated "overconsumption" of oxygen might induce an oxidative stress and pose some risk to biological systems. In recent years, a considerable amount of research has demonstrated that radicals are capable of damaging a vast array of biological targets. Unfortunately, the work related to oxidative stress and antioxidants subsequent to exercise has been narrow in scope. This paper provides a brief review of the shortcomings of the present state of knowledge in this discipline and outlines topics requiring attention. PMID:10919973

  9. Roles of TRPM2 in oxidative stress.

    PubMed

    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.

  10. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis.

    PubMed

    Wang, Feng; Yin, Peipei; Lu, Ye; Zhou, Zubin; Jiang, Chaolai; Liu, Yingjie; Yu, Xiaowei

    2015-11-01

    Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2)-induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway. PMID:26462178

  11. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis

    PubMed Central

    Wang, Feng; Yin, Peipei; Lu, Ye; Zhou, Zubin; Jiang, Chaolai; Liu, Yingjie; Yu, Xiaowei

    2015-01-01

    Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2) induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway. PMID:26462178

  12. Oxidative stress in coronary artery bypass surgery

    PubMed Central

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

    2015-01-01

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

  13. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.

    PubMed

    Mitter, Sayak K; Song, Chunjuan; Qi, Xiaoping; Mao, Haoyu; Rao, Haripriya; Akin, Debra; Lewin, Alfred; Grant, Maria; Dunn, William; Ding, Jindong; Bowes Rickman, Catherine; Boulton, Michael

    2014-01-01

    Autophagic dysregulation has been suggested in a broad range of neurodegenerative diseases including age-related macular degeneration (AMD). To test whether the autophagy pathway plays a critical role to protect retinal pigmented epithelial (RPE) cells against oxidative stress, we exposed ARPE-19 and primary cultured human RPE cells to both acute (3 and 24 h) and chronic (14 d) oxidative stress and monitored autophagy by western blot, PCR, and autophagosome counts in the presence or absence of autophagy modulators. Acute oxidative stress led to a marked increase in autophagy in the RPE, whereas autophagy was reduced under chronic oxidative stress. Upregulation of autophagy by rapamycin decreased oxidative stress-induced generation of reactive oxygen species (ROS), whereas inhibition of autophagy by 3-methyladenine (3-MA) or by knockdown of ATG7 or BECN1 increased ROS generation, exacerbated oxidative stress-induced reduction of mitochondrial activity, reduced cell viability, and increased lipofuscin. Examination of control human donor specimens and mice demonstrated an age-related increase in autophagosome numbers and expression of autophagy proteins. However, autophagy proteins, autophagosomes, and autophagy flux were significantly reduced in tissue from human donor AMD eyes and 2 animal models of AMD. In conclusion, our data confirm that autophagy plays an important role in protection of the RPE against oxidative stress and lipofuscin accumulation and that impairment of autophagy is likely to exacerbate oxidative stress and contribute to the pathogenesis of AMD. PMID:25484094

  14. Symbiosis-induced adaptation to oxidative stress.

    PubMed

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

    2005-01-01

    Cnidarians in symbiosis with photosynthetic protists must withstand daily hyperoxic/anoxic transitions within their host cells. Comparative studies between symbiotic (Anemonia viridis) and non-symbiotic (Actinia schmidti) sea anemones show striking differences in their response to oxidative stress. First, the basal expression of SOD is very different. Symbiotic animal cells have a higher isoform diversity (number and classes) and a higher activity than the non-symbiotic cells. Second, the symbiotic animal cells of A. viridis also maintain unaltered basal values for cellular damage when exposed to experimental hyperoxia (100% O(2)) or to experimental thermal stress (elevated temperature +7 degrees C above ambient). Under such conditions, A. schmidti modifies its SOD activity significantly. Electrophoretic patterns diversify, global activities diminish and cell damage biomarkers increase. These data suggest symbiotic cells adapt to stress while non-symbiotic cells remain acutely sensitive. In addition to being toxic, high O(2) partial pressure (P(O(2))) may also constitute a preconditioning step for symbiotic animal cells, leading to an adaptation to the hyperoxic condition and, thus, to oxidative stress. Furthermore, in aposymbiotic animal cells of A. viridis, repression of some animal SOD isoforms is observed. Meanwhile, in cultured symbionts, new activity bands are induced, suggesting that the host might protect its zooxanthellae in hospite. Similar results have been observed in other symbiotic organisms, such as the sea anemone Aiptasia pulchella and the scleractinian coral Stylophora pistillata. Molecular or physical interactions between the two symbiotic partners may explain such variations in SOD activity and might confer oxidative stress tolerance to the animal host. PMID:15634847

  15. Symbiosis-induced adaptation to oxidative stress.

    PubMed

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

    2005-01-01

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

  16. Lamins as mediators of oxidative stress

    SciTech Connect

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

    2012-05-18

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

  17. Oxidative Stress in Patients With Acne Vulgaris

    PubMed Central

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

    2005-01-01

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

  18. Oxidant generation and toxicity enhancement of aged-diesel exhaust

    NASA Astrophysics Data System (ADS)

    Li, Qianfeng; Wyatt, Anna; Kamens, Richard M.

    Diesel exhaust related airborne Particulate Matter (PM) has been linked to a myriad of adverse health outcomes, ranging from cancer to cardiopulmonary disease. The underlying toxicological mechanisms are of great scientific interest. A hypothesis under investigation is that many of the adverse health effects may derive from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within affected cells. In this study, the main objective was to determine whether aged-diesel exhaust PM has a higher oxidant generation and toxicity than fresh diesel exhaust PM. The diesel exhaust PM was generated from a 1980 Mercedes-Benz model 300SD, and a dual 270 m 3 Teflon film chamber was utilized to generate two test atmospheres. One side of the chamber is used to produce ozone-diesel exhaust PM system, and another side of the chamber was used to produce diesel exhaust PM only system. A newly optimized dithiothreitol (DTT) method was used to assess their oxidant generation and toxicity. The results of this study showed: (1) both fresh and aged-diesel exhaust PM had high oxidant generation and toxicity; (2) ozone-diesel exhaust PM had a higher toxicity response than diesel exhaust PM only; (3) the diesel exhaust PM toxicity increased with time; (4) the optimized DTT method could be used as a good quantitative chemical assay for oxidant generation and toxicity measurement.

  19. Measurement of Isoprostanes as Markers of Oxidative Stress

    PubMed Central

    Milatovic, Dejan; Montine, Thomas J.; Aschner, Michael

    2012-01-01

    Oxidative stress results from an imbalance between production of reactive oxygen and nitrogen species (ROS and RNS, respectively) and endogenous antioxidant defense mechanisms. Increased generation of ROS/RNS is implicated in the pathogenesis of a variety of human diseases, including neurodegenerative disease, atherosclerosis, cancer and aging. However, measuring oxidative stress in biological systems is complex and requires accurate quantification of either free radicals or damaged biomolecules. One method to quantify oxidative injury is to measure lipid peroxidation. Lipids are readily attacked by free radicals, resulting in the formation of a number of peroxidation products. F2-isoprostanes (F2-IsoPs) are one group of these compounds and they are derived by the free radical peroxidation of arachidonic acid (AA). The F2-IsoPs, prostaglandine F2-like compounds, provide an accurate measure of oxidative stress both in vitro and in vivo. This protocol details current methodology used to quantify these molecules using gas chromatography-mass spectrometry (GC-MS). PMID:21815067

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

    SciTech Connect

    Saeidnia, Soodabeh; Abdollahi, Mohammad

    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.

  1. Relationship between Oxidative Stress, Circadian Rhythms, and AMD

    PubMed Central

    Fanjul-Moles, María Luisa; López-Riquelme, Germán Octavio

    2016-01-01

    This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed. PMID:26885250

  2. Oxidative Stress and Programmed Cell Death in Yeast

    PubMed Central

    Farrugia, Gianluca; Balzan, Rena

    2012-01-01

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

  3. Oxidative stress and species of genus Ganoderma (higher Basidiomycetes).

    PubMed

    Cilerdzic, Jasmina; Stajic, Mirjana; Vukojevic, Jelena; Duletic-Lausevic, Sonja

    2013-01-01

    Oxidative stress, which is a factor in the aging process and in a series of serious disorders, arises when the reactive oxygen or nitrogen species are produced in excess and the capacity of cellular antioxidant defense is insufficient to detoxify and remove them. An internal antioxidant system is not always active enough to protect the human body from oxidative stress and, therefore, it needs the help of either synthetic or natural antioxidants. Nowadays, there is a growing interest in the substitution of synthetic antioxidants, which could have toxic and mutagen effects, with natural antioxidants. Recent studies revealed that besides their high nutritional value, mushrooms have great potential as antioxidant agents. Species of the genus Ganoderma, especially G. lucidum, are well-known medicinal mushrooms that traditionally are used in the prevention and treatment of many diseases and possess appreciable antioxidant potential. PMID:23510281

  4. Melanocytes as instigators and victims of oxidative stress.

    PubMed

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

    2014-06-01

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

  5. Melanocytes as Instigators and Victims of Oxidative Stress

    PubMed Central

    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 counteract oxidative stress, the role of oxidative stress in melanoma initiation and progression and in melanocyte death in vitiligo, and how this knowledge can be harnessed for melanoma and vitiligo treatment. PMID:24573173

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

    PubMed

    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.

  7. Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress.

    PubMed

    Liu, Shaobin; Zeng, Tingying Helen; Hofmann, Mario; Burcombe, Ehdi; Wei, Jun; Jiang, Rongrong; Kong, Jing; Chen, Yuan

    2011-09-27

    Health and environmental impacts of graphene-based materials need to be thoroughly evaluated before their potential applications. Graphene has strong cytotoxicity toward bacteria. To better understand its antimicrobial mechanism, we compared the antibacterial activity of four types of graphene-based materials (graphite (Gt), graphite oxide (GtO), graphene oxide (GO), and reduced graphene oxide (rGO)) toward a bacterial model-Escherichia coli. Under similar concentration and incubation conditions, GO dispersion shows the highest antibacterial activity, sequentially followed by rGO, Gt, and GtO. Scanning electron microscope (SEM) and dynamic light scattering analyses show that GO aggregates have the smallest average size among the four types of materials. SEM images display that the direct contacts with graphene nanosheets disrupt cell membrane. No superoxide anion (O(2)(•-)) induced reactive oxygen species (ROS) production is detected. However, the four types of materials can oxidize glutathione, which serves as redox state mediator in bacteria. Conductive rGO and Gt have higher oxidation capacities than insulating GO and GtO. Results suggest that antimicrobial actions are contributed by both membrane and oxidation stress. We propose that a three-step antimicrobial mechanism, previously used for carbon nanotubes, is applicable to graphene-based materials. It includes initial cell deposition on graphene-based materials, membrane stress caused by direct contact with sharp nanosheets, and the ensuing superoxide anion-independent oxidation. We envision that physicochemical properties of graphene-based materials, such as density of functional groups, size, and conductivity, can be precisely tailored to either reducing their health and environmental risks or increasing their application potentials.

  8. Oxidative Stress and Nutritional Status in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Dhakal, Niraj; Baral, Nirmal; Shrestha, Shrijana; Dhakal, Subodh Sagar; Bhatta, Narendra; Dubey, Raju Kumar

    2015-01-01

    Background: Oxidative stress and malnutrition are shown to have pathogenic effect in Chronic Obstructive Pulmonary Disease (COPD). Aim: This study was done to assess the burden of oxidative stress in COPD and to determine its relation to their nutritional status. Materials and Methods: In this cross-sectional study, 100 COPD cases from emergency and medical ward and meeting inclusion criteria, along with age, sex and occupation (mainly farmers, housewives and drivers) matched 100 controls without COPD and meeting inclusion criteria were enrolled. Oxidative stress was assessed by measuring lipid peroxidation product, Malondialdehyde (MDA) and antioxidants, like Vitamin C, E and Red Blood Cell Catalase (RBCC). Mini Nutritional Assessment (MNA) tool and Body Mass Index (BMI) were used to assess nutritional status. Statistical Analysis: Chi-square test was applied for categorical variable. Student t-test was applied for comparison of means. Analysis of Variance (ANOVA) was applied for comparison between groups followed by Bonferroni post hoc analysis. Pearson correlation method was used for quantitative variables. Statistical significance was defined as p< 0.05 (two tailed). Results: COPD cases had significantly high MDA level with low level of Vitamin E and catalase as compared to controls (p < 0.001). Most of the COPD cases were underweight (BMI ≤ 18.5 Kg/m2) and malnourished (MNA score less than 7). Bonferroni post-hoc analysis, showed significantly high burden of oxidative stress in underweight and malnourished cases as compared to normal weight (p < 0.05) among COPD cases. Highly significant correlation was seen between BMI and plasma MDA level (r = −0.27, p = 0.008) in COPD cases. Conclusion: This study shows impaired oxidant/antioxidant balance along with malnutrition and underweight in COPD, which signals for considering antioxidant therapy along with nutritional management. PMID:25859442

  9. Cellular mechanisms underlying oxidative stress in human exercise.

    PubMed

    Jackson, Malcolm J; Vasilaki, Aphrodite; McArdle, Anne

    2016-09-01

    A relative increase in oxidation of lipids, proteins and DNA has been recognised to occur in the circulation and tissues of exercising humans and animals since the late 1970s and throughout the ensuing 40 years a great deal of work has been undertaken to elucidate the potential source(s) of this exercise-induced "oxidative stress". Specific aspects of physical exercise (e.g. contractile activity, relative hypoxia, hyperaemia) may theoretically induce increased generation of reactive oxygen species in a number of potential tissues, but data strongly indicate that contractile activity of skeletal muscle predominates as the source of oxidants and contributes to local oxidation and that of extracellular biomaterials. Taken together with the relatively large mass of muscle compared with other tissues and cells it appears that muscle fibres are the major contributor to the relative increase in whole body "oxidative stress" during some forms of exercise. The sub-cellular sources of this increased oxidation have also been the subject of considerable research with early studies predominantly indicating that muscle mitochondria were the likely increased source of oxidants, such as hydrogen peroxide, but assessments of the relative concentrations of hydrogen peroxide in skeletal muscle fibres at rest and during contractile activity do not support this possibility. In contrast, several recent studies have identified NADPH oxidase enzymes in skeletal muscle that appear to play a signalling role in physiological responses exercise and together with xanthine oxidase enzymes may contribute to the relative increase in whole body oxidation. A fuller understanding of the relative roles of these sources and the function(s) of the species generated appears increasingly important in attempts to harness the beneficial effects of exercise for maintenance of health in aging and a variety of chronic conditions.

  10. Hutchinson-Gilford progeria syndrome, cardiovascular disease and oxidative stress.

    PubMed

    Trigueros-Motos, Laia; Gonzalez, Jose M; Rivera, Jose; Andres, Vicente

    2011-06-01

    Hutchinson-Gilford Progeria Syndrome (HGPS), a rare human disease characterized by premature aging, is mainly caused by the abnormal accumulation of progerin, a mutant form of the mammalian nuclear envelope component lamin A. HGPS patients exhibit vascular alterations and die at an average age of 13 years, predominantly from myocardial infarction or stroke. Animal models of HGPS have been a valuable tool in the study of the pathological processes implicated in the origin of this disease and its associated cardiovascular alterations. Some of the molecular mechanisms of HGPS might be relevant to the process of normal aging, since progerin is detected in cells from normal elderly humans. Conversely, processes linked to normal aging, such as the increase in oxidative stress, might be relevant to the pathogenic mechanisms of HGPS. In this review, we discuss recent advances in the understanding of the molecular mechanisms underlying the cardiovascular alterations associated with HGPS, the potential role of oxidative stress, and therapeutic approaches for the treatment of this devastating disease.

  11. Epigenetics, oxidative stress and Alzheimer’s Disease

    PubMed Central

    Zawia, Nasser H.; Lahiri, Debomoy K.; Cardozo–Pelaez, Fernando

    2009-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disorder whose clinical manifestations appear in old age. The sporadic nature of 90% of AD cases, the differential susceptibility and course of illness, as well as the late age onset of the disease suggest that epigenetic and environmental components play a role in the etiology of late onset AD (LOAD). Animal exposure studies demonstrated that AD may begin early in life and may involve the interplay between the environment, epigenetics and oxidative stress. Early life exposure of rodents and primates to the xenobiotic metal lead (Pb) enhanced the expression of genes associated with AD, repressed the expression of others, and increased the burden of oxidative DNA damage in the aged brain. Epigenetic mechanisms that control gene expression and promote the accumulation of oxidative DNA damage are mediated through alterations in the methylation or oxidation of CpG dinucleotides. We found that environmental influences occurring during brain development inhibit DNA methyltransferases, thus hypomethylating promoters of genes associated with AD such as the beta- amyloid precursor protein (APP). This early life imprint was sustained and triggered later in life to increase the levels of APP and amyloid-beta (Aβ). Increased Aβ levels promoted the production of reactive oxygen species (ROS) which damage DNA and accelerate neurodegenerative events. While AD-associated genes were over-expressed late in life, others were repressed, suggesting that these early life perturbations result in hypomethylation as well as hypermethylation of genes. The hypermethylated genes are rendered susceptible to Aβ-enhanced oxidative DNA damage because methylcytosines restrict repair of adjacent hydroxyguanosines. While the conditions leading to early life hypo or hyper methylation of specific genes are not known, these changes can impact gene expression and imprint susceptibility to oxidative DNA damage in the aged brain. PMID

  12. MECHANISMS FOR COUNTERING OXIDATIVE STRESS AND DAMAGE IN RETINAL PIGMENT EPITHELIUM

    PubMed Central

    Plafker, Scott M.; O’Mealey, Gary B.; Szweda, Luke I.

    2013-01-01

    Clinical and experimental evidence supports that chronic oxidative stress is a primary contributing factor to numerous retinal degenerative diseases, such as age-related macular degeneration (AMD). Eyes obtained postmortem from AMD patients have extensive free radical damage to the proteins, lipids, DNA, and mitochondria of their retinal pigment epithelial (RPE) cells. In addition, several mouse models of chronic oxidative stress develop many of the pathological hallmarks of AMD. However, the extent to which oxidative stress is an etiologic component versus its involvement in disease progression remains a major unanswered question. Further, whether the primary target of oxidative stress and damage is photoreceptors or RPE cells, or both, is still unclear. In this review, we discuss the major functions of RPE cells with an emphasis on the oxidative challenges these cells encounter and the endogenous antioxidant mechanisms employed to neutralize the deleterious effects that such stresses can elicit if left unchecked. PMID:22878106

  13. Oxidative Stress and Autophagy in Cardiovascular Homeostasis

    PubMed Central

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

    2014-01-01

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

  14. Air Pollution Stress and the Aging Phenotype: The Telomere Connection.

    PubMed

    Martens, Dries S; Nawrot, Tim S

    2016-09-01

    Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies. PMID:27357566

  15. Air Pollution Stress and the Aging Phenotype: The Telomere Connection.

    PubMed

    Martens, Dries S; Nawrot, Tim S

    2016-09-01

    Aging is a complex physiological phenomenon. The question why some subjects grow old while remaining free from disease whereas others prematurely die remains largely unanswered. We focus here on the role of air pollution in biological aging. Hallmarks of aging can be grouped into three main categories: genomic instability, telomere attrition, and epigenetic alterations leading to altered mitochondrial function and cellular senescence. At birth, the initial telomere length of a person is largely determined by environmental factors. Telomere length shortens with each cell division and exposure to air pollution as well as low residential greens space exposure is associated with shorter telomere length. Recent studies show that the estimated effects of particulate air pollution exposure on the telomere mitochondrial axis of aging may play an important role in chronic health effects of air pollution. The exposome encompasses all exposures over an entire life. As telomeres can be considered as the cellular memories of exposure to oxidative stress and inflammation, telomere maintenance may be a proxy for assessing the "exposome". If telomeres are causally related to the aging phenotype and environmental air pollution is an important determinant of telomere length, this might provide new avenues for future preventive strategies.

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

    PubMed

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

    2016-10-01

    Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. PMID:27422326

  17. Induction of oxidative stress in paraquat formulating workers.

    PubMed

    Ranjbar, Akram; Pasalar, Parvin; Sedighi, Alireza; Abdollahi, Mohammad

    2002-05-28

    Paraquat as a bipyridyl compound is widely used as an effective herbicide worldwide. In this study, oxidative stress was investigated in blood samples of workers in a pesticide factory, formulating paraquat products for use in agriculture. Controls were age-matched workers with no history of pesticide exposure. They were measured for lipid peroxidation (LPO), antioxidant power and total thiol (SH) groups in blood. The results expressed as mean+/-SD show induction of oxidative stress in workers as revealed by increased plasma LPO (11.46+/-0.99 vs 10.11+/-0.69, P<0.001), decreased plasma antioxidant capacity (1.35+/-0.03 vs 1.54+/-0.05, P<0.001) and plasma SH groups (0.16+/-0.01 vs 0.21+/-0.01, P<0.001) in comparison to those of controls. It is concluded that paraquat-formulating factory workers have elevated LPO and decreased antioxidant power, which may put them in further consequences of oxidative stress. PMID:11992738

  18. Induction of oxidative stress in paraquat formulating workers.

    PubMed

    Ranjbar, Akram; Pasalar, Parvin; Sedighi, Alireza; Abdollahi, Mohammad

    2002-05-28

    Paraquat as a bipyridyl compound is widely used as an effective herbicide worldwide. In this study, oxidative stress was investigated in blood samples of workers in a pesticide factory, formulating paraquat products for use in agriculture. Controls were age-matched workers with no history of pesticide exposure. They were measured for lipid peroxidation (LPO), antioxidant power and total thiol (SH) groups in blood. The results expressed as mean+/-SD show induction of oxidative stress in workers as revealed by increased plasma LPO (11.46+/-0.99 vs 10.11+/-0.69, P<0.001), decreased plasma antioxidant capacity (1.35+/-0.03 vs 1.54+/-0.05, P<0.001) and plasma SH groups (0.16+/-0.01 vs 0.21+/-0.01, P<0.001) in comparison to those of controls. It is concluded that paraquat-formulating factory workers have elevated LPO and decreased antioxidant power, which may put them in further consequences of oxidative stress.

  19. Oxidative stress in prostate hyperplasia and carcinogenesis.

    PubMed

    Udensi, Udensi K; Tchounwou, Paul B

    2016-01-01

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

  20. Oxidative stress inhibition and oxidant activity by fibrous clays.

    PubMed

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Gómez-Vidales, Virginia

    2015-09-01

    Fibrous clays (sepiolite, palygorskite) are produced at 1.2m tonnes per year and have a wide range of industrial applications needing to replace long-fibre length asbestos. However, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the effect of sepiolite (Vallecas, Spain) and palygorskite (Torrejón El Rubio, Spain) on cell damage via oxidative stress (determined as the progress of lipid peroxidation, LP). The extent of LP was assessed using the Thiobarbituric Acid Reactive Substances assay. The oxidant activity by fibrous clays was quantified using Electron-Paramagnetic Resonance. Sepiolite and palygorskite inhibited LP, whereby corresponding IC50 values were 6557±1024 and 4250±289μgmL(-1). As evidenced by dose-response experiments LP inhibition by palygorskite was surface-controlled. Fibrous clay surfaces did not stabilize HO species, except for suspensions containing 5000μgmL(-1). A strong oxidant (or weak anti-oxidant) activity favours the inhibition of LP by fibrous clays.

  1. Oxidative stress inhibition and oxidant activity by fibrous clays.

    PubMed

    Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Gómez-Vidales, Virginia

    2015-09-01

    Fibrous clays (sepiolite, palygorskite) are produced at 1.2m tonnes per year and have a wide range of industrial applications needing to replace long-fibre length asbestos. However, information on the beneficial effects of fibrous clays on health remains scarce. This paper reports on the effect of sepiolite (Vallecas, Spain) and palygorskite (Torrejón El Rubio, Spain) on cell damage via oxidative stress (determined as the progress of lipid peroxidation, LP). The extent of LP was assessed using the Thiobarbituric Acid Reactive Substances assay. The oxidant activity by fibrous clays was quantified using Electron-Paramagnetic Resonance. Sepiolite and palygorskite inhibited LP, whereby corresponding IC50 values were 6557±1024 and 4250±289μgmL(-1). As evidenced by dose-response experiments LP inhibition by palygorskite was surface-controlled. Fibrous clay surfaces did not stabilize HO species, except for suspensions containing 5000μgmL(-1). A strong oxidant (or weak anti-oxidant) activity favours the inhibition of LP by fibrous clays. PMID:26071933

  2. Oxidative stress and antioxidants: Distress or eustress?

    PubMed

    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.

  3. Molecular consequences of psychological stress in human aging.

    PubMed

    Moreno-Villanueva, M; Bürkle, A

    2015-08-01

    Psychological stress has often been described as a feeling of being overwhelmed by the necessity of constant adjustment to an individual's changing environment. Stress affects people of all ages, but the lives of the elderly may particularly be affected. Major changes can cause anxiety leading to feelings of insecurity and/or loss of self-esteem and depression. The cellular mechanisms underlying psychological stress are poorly understood. This review focuses on the physical and molecular consequences of psychological stress linked to aging processes and, in particular, how molecular changes induced by psychological stress can compromise healthy aging.

  4. Molecular consequences of psychological stress in human aging.

    PubMed

    Moreno-Villanueva, M; Bürkle, A

    2015-08-01

    Psychological stress has often been described as a feeling of being overwhelmed by the necessity of constant adjustment to an individual's changing environment. Stress affects people of all ages, but the lives of the elderly may particularly be affected. Major changes can cause anxiety leading to feelings of insecurity and/or loss of self-esteem and depression. The cellular mechanisms underlying psychological stress are poorly understood. This review focuses on the physical and molecular consequences of psychological stress linked to aging processes and, in particular, how molecular changes induced by psychological stress can compromise healthy aging. PMID:25481270

  5. Tart cherry extracts reduce inflammatory and oxidative stress signaling in microglial cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tart cherries contain an array of polyphenols that can decrease inflammation and oxidative stress (OS), which contribute to cognitive declines seen in aging populations. Previous studies have shown that polyphenols from dark-colored fruits can reduce stress-mediated signaling in BV-2 mouse microglia...

  6. Comparison of Total Antioxidant Capacity Oxidative Stress and Blood Lipoprotein Parameters in Volleyball Players and Sedentary

    ERIC Educational Resources Information Center

    Gokhan, Ismail

    2013-01-01

    This study aims to measure, then compare sedentary blood lipoproteins, oxidant- antioxidant state and oxidative stress index in volleyball players. The experimental group of the research consists of regularly practising 20 boys between the ages of 12 and 17, and the control group comprises 32 children practising no particular sports branch, 12 of…

  7. Laboratory simulation of oxidative aging of asphalt

    SciTech Connect

    Memon, G.M.; Chollar, B.H.

    1997-12-31

    The objective of this study was to determine the aging characteristics of asphalt mixes, which were mixed and conditioned at times corresponding to times experienced during field mixing. This objective was accomplished by measuring functional group changes of carbonyl and sulfoxide peak areas through infrared spectroscopy techniques of asphalts extracted from mixes subjected to various laboratory and climatic conditioning procedures. Correlations were attempted between these infrared functional group changes of asphalt samples from laboratory aged mixes and that from a pavement mix obtained through drum dryer plant production. Ratios were taken of these unknown peak areas by dividing them by the area of a peak unchanged by oxidation, i.e., the methyl peak. These ratios were evaluated for asphalt mix samples that had undergone a wide range of treatments (oven heating for 0, 1, 2, 3, and 4 hours). It was observed through the carbonyl group changes of the asphalts that an oven aged period of 2 hours for asphalt mixes was needed to simulate the degree of aging occurring during plant mix production.

  8. Melamine Induces Oxidative Stress in Mouse Ovary

    PubMed Central

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

    2015-01-01

    Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS) levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and glutathi-one peroxidase (GPX) were analyzed, and the concentration of malondialdehyde (MDA) were compared between control and melamine-treated ovaries. The result revealed that melamine changed the expression and activities of SOD and GPX in the melamine-treated mice. Therefore, we demonstrate that melamine causes damage to the ovaries via oxidative stress pathway. PMID:26545251

  9. Melamine Induces Oxidative Stress in Mouse Ovary.

    PubMed

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

    2015-01-01

    Melamine is a nitrogen heterocyclic triazine compound which is widely used as an industrial chemical. Although melamine is not considered to be acutely toxic with a high LD50 in animals, food contaminated with melamine expose risks to the human health. Melamine has been reported to be responsible for the renal impairment in mammals, its toxicity on the reproductive system, however, has not been adequately assessed. In the present study, we examined the effect of melamine on the follicle development and ovary formation. The data showed that melamine increased reactive oxygen species (ROS) levels, and induced granulosa cell apoptosis as well as follicle atresia. To further analyze the mechanism by which melamine induces oxidative stress, the expression and activities of two key antioxidant enzymes superoxide dismutase (SOD) and 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.

  10. Vascular oxidant stress and inflammation in hyperhomocysteinemia.

    PubMed

    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.

  11. Nutritionally Mediated Oxidative Stress and Inflammation

    PubMed Central

    Muñoz, Alexandra; Costa, Max

    2013-01-01

    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. PMID:23844276

  12. Advanced oxidation protein products (AOPP) for monitoring oxidative stress in critically ill patients: a simple, fast and inexpensive automated technique.

    PubMed

    Selmeci, László; Seres, Leila; Antal, Magda; Lukács, Júlia; Regöly-Mérei, Andrea; Acsády, György

    2005-01-01

    Oxidative stress is known to be involved in many human pathological processes. Although there are numerous methods available for the assessment of oxidative stress, most of them are still not easily applicable in a routine clinical laboratory due to the complex methodology and/or lack of automation. In research into human oxidative stress, the simplification and automation of techniques represent a key issue from a laboratory point of view at present. In 1996 a novel oxidative stress biomarker, referred to as advanced oxidation protein products (AOPP), was detected in the plasma of chronic uremic patients. Here we describe in detail an automated version of the originally published microplate-based technique that we adapted for a Cobas Mira Plus clinical chemistry analyzer. AOPP reference values were measured in plasma samples from 266 apparently healthy volunteers (university students; 81 male and 185 female subjects) with a mean age of 21.3 years (range 18-33). Over a period of 18 months we determined AOPP concentrations in more than 300 patients in our department. Our experiences appear to demonstrate that this technique is especially suitable for monitoring oxidative stress in critically ill patients (sepsis, reperfusion injury, heart failure) even at daily intervals, since AOPP exhibited rapid responses in both directions. We believe that the well-established relationship between AOPP response and induced damage makes this simple, fast and inexpensive automated technique applicable in daily routine laboratory practice for assessing and monitoring oxidative stress in critically ill or other patients.

  13. A Nucleocytoplasmic Shuttling Protein in Oxidative Stress Tolerance

    SciTech Connect

    Ow, David W.; Song, Wen

    2003-03-26

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

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

    PubMed

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

    2016-09-01

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

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

    PubMed

    Lin, Xiran; Huang, Tian

    2016-06-01

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

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

    PubMed Central

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

    2013-01-01

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

  17. Interfacial stress transfer in graphene oxide nanocomposites.

    PubMed

    Li, Zheling; Young, Robert J; Kinloch, Ian A

    2013-01-23

    Raman spectroscopy has been used for the first time to monitor interfacial stress transfer in poly(vinyl alcohol) nanocomposites reinforced with graphene oxide (GO). The graphene oxide nanocomposites were prepared by a simple mixing method and casting from aqueous solution. They were characterized using scanning electron microscopy, X-ray diffraction, and polarized Raman spectroscopy and their mechanical properties determined by tensile testing and dynamic mechanical thermal analysis. It was found that GO was fully exfoliated during the nanocomposite preparation process and that the GO nanoplatelets tended align in the plane of the films. The stiffness and yield stress of the nanocomposites were found to increase with GO loading but the extension to failure decreased. It was shown that the Raman D band at ~1335 cm(-1) downshifted as the nanocomposites were strained as a result of the interfacial stress transfer between the polymer matrix and GO reinforcement. From knowledge of the Grüneisen parameter for graphene, it was possible to estimate the effective Young's modulus of the GO from the Raman D band shift rate per unit strain to be of the order of 120 GPa. A similar value of effective modulus was found from the tensile mechanical data using the "rule of mixtures" that decreased with GO loading. The accepted value of Young's modulus for GO is in excess of 200 GPa and it is suggested that the lower effective Young's modulus values determined may be due to a combination of finite flake dimensions, waviness and wrinkles, aggregation, and misalignment of the GO flakes.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  1. Oxidative stress modulates theophylline effects on steroid responsiveness.

    PubMed

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

    2008-12-19

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

  2. Mechanisms of Oxidative Stress Resistance in The Brain: Lessons Learned From Hypoxia Tolerant Extremophilic Vertebrates

    PubMed Central

    Garbarino, Valentina R.; Orr, Miranda E.; Rodriguez, Karl A.; Buffenstein, Rochelle

    2016-01-01

    The Oxidative Stress Theory of Aging has had tremendous impact in research involving aging and age-associated diseases including those that affect the nervous system. With over half a century of accrued data showing both strong support for and against this theory, there is a need to critically evaluate the data acquired from common biomedical research models, and to also diversify the species used in studies involving this proximate theory. One approach is to follow Orgel’s second axiom that “evolution is smarter than we are” and judiciously choose species that may have evolved to live with chronic or seasonal oxidative stressors. Vertebrates that have naturally evolved to live under extreme conditions (e.g., anoxia or hypoxia), as well as those that undergo daily or seasonal torpor encounter both decreased oxygen availability and subsequent reoxygenation, with concomitant increased oxidative stress. Due to its high metabolic activity, the brain may be particularly vulnerable to oxidative stress. Here, we focus on oxidative stress responses in the brains of certain mouse models as well as extremophilic vertebrates. Exploring the naturally evolved biological tools utilized to cope with seasonal or environmentally variable oxygen availability may yield key information pertinent for how to deal with oxidative stress and thereby mitigate its propagation of age-associated diseases. PMID:25841340

  3. Mechanisms of oxidative stress resistance in the brain: Lessons learned from hypoxia tolerant extremophilic vertebrates.

    PubMed

    Garbarino, Valentina R; Orr, Miranda E; Rodriguez, Karl A; Buffenstein, Rochelle

    2015-06-15

    The Oxidative Stress Theory of Aging has had tremendous impact in research involving aging and age-associated diseases including those that affect the nervous system. With over half a century of accrued data showing both strong support for and against this theory, there is a need to critically evaluate the data acquired from common biomedical research models, and to also diversify the species used in studies involving this proximate theory. One approach is to follow Orgel's second axiom that "evolution is smarter than we are" and judiciously choose species that may have evolved to live with chronic or seasonal oxidative stressors. Vertebrates that have naturally evolved to live under extreme conditions (e.g., anoxia or hypoxia), as well as those that undergo daily or seasonal torpor encounter both decreased oxygen availability and subsequent reoxygenation, with concomitant increased oxidative stress. Due to its high metabolic activity, the brain may be particularly vulnerable to oxidative stress. Here, we focus on oxidative stress responses in the brains of certain mouse models as well as extremophilic vertebrates. Exploring the naturally evolved biological tools utilized to cope with seasonal or environmentally variable oxygen availability may yield key information pertinent for how to deal with oxidative stress and thereby mitigate its propagation of age-associated diseases.

  4. Thiamin confers enhanced tolerance to oxidative stress in Arabidopsis.

    PubMed

    Tunc-Ozdemir, Meral; Miller, Gad; Song, Luhua; Kim, James; Sodek, Ahmet; Koussevitzky, Shai; Misra, Amarendra Narayan; Mittler, Ron; Shintani, David

    2009-09-01

    Thiamin and thiamin pyrophosphate (TPP) are well known for their important roles in human nutrition and enzyme catalysis. In this work, we present new evidence for an additional role of these compounds in the protection of cells against oxidative damage. Arabidopsis (Arabidopsis thaliana) plants subjected to abiotic stress conditions, such as high light, cold, osmotic, salinity, and oxidative treatments, accumulated thiamin and TPP. Moreover, the accumulation of these compounds in plants subjected to oxidative stress was accompanied by enhanced expression of transcripts encoding thiamin biosynthetic enzymes. When supplemented with exogenous thiamin, wild-type plants displayed enhanced tolerance to oxidative stress induced by paraquat. Thiamin application was also found to protect the reactive oxygen species-sensitive ascorbate peroxidase1 mutant from oxidative stress. Thiamin-induced tolerance to oxidative stress was accompanied by decreased production of reactive oxygen species in plants, as evidenced from decreased protein carbonylation and hydrogen peroxide accumulation. Because thiamin could protect the salicylic acid induction-deficient1 mutant against oxidative stress, thiamin-induced oxidative protection is likely independent of salicylic acid signaling or accumulation. Taken together, our studies suggest that thiamin and TPP function as important stress-response molecules that alleviate oxidative stress during different abiotic stress conditions.

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

    PubMed

    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

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

    PubMed Central

    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

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

    PubMed

    Ipson, Brett R; Fisher, Alfred L

    2016-05-01

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

  8. Effects of oxidative stress on erythrocyte deformability

    NASA Astrophysics Data System (ADS)

    Bayer, Rainer; Wasser, Gerd

    1996-05-01

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

  9. CARBARYL EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF ADOLESCENT AND SENESCENT BROWN NORWAY RATS

    EPA Science Inventory

    Oxidative stress (OS) plays an important role in susceptibility and disease in old age. Understanding age-related susceptibility is crucial in assessing the human health risks of chemicals. Growing evidence implicates as in carbamate toxicity in addition to cholinesterase-inhibit...

  10. Arsenic: toxicity, oxidative stress and human disease.

    PubMed

    Jomova, K; Jenisova, Z; Feszterova, M; Baros, S; Liska, J; Hudecova, D; Rhodes, C J; Valko, M

    2011-03-01

    Arsenic (As) is a toxic metalloid element that is present in air, water and soil. Inorganic arsenic tends to be more toxic than organic arsenic. Examples of methylated organic arsenicals include monomethylarsonic acid [MMA(V)] and dimethylarsinic acid [DMA(V)]. Reactive oxygen species (ROS)-mediated oxidative damage is a common denominator in arsenic pathogenesis. In addition, arsenic induces morphological changes in the integrity of mitochondria. Cascade mechanisms of free radical formation derived from the superoxide radical, combined with glutathione-depleting agents, increase the sensitivity of cells to arsenic toxicity. When both humans and animals are exposed to arsenic, they experience an increased formation of ROS/RNS, including peroxyl radicals (ROO•), the superoxide radical, singlet oxygen, hydroxyl radical (OH•) via the Fenton reaction, hydrogen peroxide, the dimethylarsenic radical, the dimethylarsenic peroxyl radical and/or oxidant-induced DNA damage. Arsenic induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. This review discusses aspects of chronic and acute exposures of arsenic in the etiology of cancer, cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease and renal disease, reproductive health effects, dermal changes and other health disorders. The role of antioxidant defence systems against arsenic toxicity is also discussed. Consideration is given to the role of vitamin C (ascorbic acid), vitamin E (α-tocopherol), curcumin, glutathione and antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase in their protective roles against arsenic-induced oxidative stress.

  11. Fatigue and Oxidative Stress in Children Undergoing Leukemia Treatment.

    PubMed

    Rodgers, Cheryl; Sanborn, Chelse; Taylor, Olga; Gundy, Patricia; Pasvogel, Alice; Moore, Ida M Ki; Hockenberry, Marilyn J

    2016-10-01

    Fatigue is a frequent and distressing symptom in children undergoing leukemia treatment; however, little is known about factors influencing this symptom. Antioxidants such as glutathione can decrease symptom severity in adult oncology patients, but no study has evaluated antioxidants' effects on symptoms in pediatric oncology patients. This study describes fatigue patterns and associations of fatigue with antioxidants represented by reduced glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio among children receiving leukemia treatment. A repeated measures design assessed fatigue and antioxidants among 38 children from two large U.S. cancer centers. Fatigue was assessed among school-age children and by parent proxy among young children. Antioxidants (GSH and GSH/GSSG ratio) were assessed from cerebrospinal fluid at four phases during leukemia treatment. Young children had a steady decline of fatigue from the end of induction treatment through the continuation phase of treatment, but no significant changes were noted among the school-age children. Mean antioxidant scores varied slightly over time; however, the GSH/GSSG ratios in these children were significantly lower than the normal ratio. Mean GSH/GSSG ratios significantly correlated to fatigue scores of the school-age children during early phases of treatment. Children with low mean GSH/GSSG ratios demonstrated oxidative stress. The low ratios noted early in therapy were significantly correlated with higher fatigue scores during induction and postinduction treatment phases. This finding suggests that increased oxidative stress during the more intensive phases of therapy may explain the experience of fatigue children report.

  12. Oxidative Stress and DNA Methylation in Prostate Cancer

    PubMed Central

    Donkena, Krishna Vanaja; 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 alterations. Epigenetics affects genetic regulation, cellular differentiation, embryology, aging, cancer, and other diseases. DNA methylation is perhaps the most extensively studied epigenetic modification, which plays an important role in the regulation of gene expression and chromatin architecture, in association with histone modification and other chromatin-associated proteins. This review will provide a broad overview of the interplay of oxidative stress and DNA methylation, DNA methylation changes in regulation of gene expression, lifestyle changes for prostate cancer prevention, DNA methylation as biomarkers for prostate cancer, methods for detection of methylation, and clinical application of DNA methylation inhibitors for epigenetic therapy. PMID:20671914

  13. Indium and indium tin oxide induce endoplasmic reticulum stress and oxidative stress in zebrafish (Danio rerio).

    PubMed

    Brun, Nadja Rebecca; Christen, Verena; Furrer, Gerhard; Fent, Karl

    2014-10-01

    Indium and indium tin oxide (ITO) are extensively used in electronic technologies. They may be introduced into the environment during production, use, and leaching from electronic devices at the end of their life. At present, surprisingly little is known about potential ecotoxicological implications of indium contamination. Here, molecular effects of indium nitrate (In(NO3)3) and ITO nanoparticles were investigated in vitro in zebrafish liver cells (ZFL) cells and in zebrafish embryos and novel insights into their molecular effects are provided. In(NO3)3 led to induction of endoplasmic reticulum (ER) stress response, induction of reactive oxygen species (ROS) and induction of transcripts of pro-apoptotic genes and TNF-α in vitro at a concentration of 247 μg/L. In(NO3)3 induced the ER stress key gene BiP at mRNA and protein level, as well as atf6, which ultimately led to induction of the important pro-apoptotic marker gene chop. The activity of In(NO3)3 on ER stress induction was much stronger than that of ITO, which is explained by differences in soluble free indium ion concentrations. The effect was also stronger in ZFL cells than in zebrafish embryos. Our study provides first evidence of ER stress and oxidative stress induction by In(NO3)3 and ITO indicating a critical toxicological profile that needs further investigation.

  14. Oxidative stress, free radicals and protein peroxides.

    PubMed

    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.

  15. Oxidative stress in normal and diabetic rats.

    PubMed

    Torres, M D; Canal, J R; Pérez, C

    1999-01-01

    Parameters related to oxidative stress were studied in a group of 10 Wistar diabetic rats and 10 control rats. The levels of total erythrocyte catalase activity in the diabetic animals were significantly (p<0.001) greater than the control levels. The diabetic animals presented an amount of vitamin E far greater (p<0.0001) than the controls, as was also the case for the vitaminE/polyunsaturated fatty acid (PUFA) and vitaminE/linoleic acid (C18:2) ratios. Greater vitaminE/triglyceride (TG) ratio, however, appeared in the control group. The corresponding vitamin A ratios (vitaminA/TG, vitaminA/PUFA, vitaminA/C 18:2) were higher in the control group. Our work corroborates the findings that fatty acid metabolism presents alterations in the diabetes syndrome and that the antioxidant status is affected. PMID:10523056

  16. Amyloids, melanins and oxidative stress in melanomagenesis.

    PubMed

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

    2015-03-01

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

  17. Thyroid Hormones, Oxidative Stress, and Inflammation.

    PubMed

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

    2016-01-01

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

  18. Acrolein induces oxidative stress in brain mitochondria.

    PubMed

    Luo, Jian; Shi, Riyi

    2005-02-01

    Acrolein, a byproduct of lipid peroxidation, has been shown to inflict significant structural and functional damage to isolated guinea pig spinal cord. Reactive oxygen species (ROS) are thought to mediate such detrimental effects. The current study demonstrates that acrolein can directly stimulate mitochondrial oxidative stress. Specifically, exposure of purified brain mitochondria to acrolein resulted in a dose-dependent increase of ROS and decreases in glutathione content and aconitase activity. This effect was not accompanied by significant intramitochondrial calcium influx or mitochondrial permeability transition, but rather by impaired function of the mitochondrial electron transport system. As well, we detected a significant inhibition of mitochondrial adenine nucleotide translocase (ANT) in the presence of acrolein. This inhibition of ANT likely contributes to acrolein-induced ROS elevation since application of atractyloside, a specific ANT inhibitor, induced significant increase of ROS. We hypothesize that inhibition of ANT may mediate, in part, the acrolein-induced ROS increase in mitochondria.

  19. Thyroid Hormones, Oxidative Stress, and Inflammation.

    PubMed

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

    2016-01-01

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

  20. Thyroid Hormones, Oxidative Stress, and Inflammation

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-11-02

    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.

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

    PubMed Central

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

    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 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. PMID:26540040

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

    PubMed Central

    Poljsak, B.

    2011-01-01

    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. PMID:22191011

  4. Oxidative stress decreases with elevation in the lizard Psammodromus algirus.

    PubMed

    Reguera, Senda; Zamora-Camacho, Francisco J; Trenzado, Cristina E; Sanz, Ana; Moreno-Rueda, Gregorio

    2014-06-01

    Oxidative stress is considered one of the main ecological and evolutionary forces. Several environmental stressors vary geographically and thus organisms inhabiting different sites face different oxidant environments. Nevertheless, there is scarce information about how oxidative damage and antioxidant defences vary geographically in animals. Here we study how oxidative stress varies from lowlands (300-700 m asl) to highlands (2200-2500 m asl) in the lizard Psammodromus algirus. To accomplish this, antioxidant enzymatic activity (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione transferase, DT-diaphorase) and lipid peroxidation were assayed in tissue samples from the lizards' tail. Lipid peroxidation was higher in individuals from lowlands than from highlands, indicating higher oxidative stress in lowland lizards. These results suggest that environmental conditions are less oxidant at high elevations with respect to low ones. Therefore, our study shows that oxidative stress varies geographically, which should have important consequences for our understanding of geographic variation in physiology and life-history of organisms.

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

    PubMed

    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

  6. Sport and oxidative stress in oncological patients.

    PubMed

    Knop, K; Schwan, R; Bongartz, M; Bloch, W; Brixius, K; Baumann, F

    2011-12-01

    Oxidative stress is thought to be an important factor in the onset, progression and recurrence of cancer. In order to investigate how it is influenced by physical activity, we measured oxidative stress and antioxidative capacity (aoC) in 12 women with breast cancer and 6 men with prostate cancer, before and after long hiking trips. Before the hike, the men had a ROS-concentration of 1.8±0.6 mM H2O2 and an aoC of 0.7±0.6 mM Trolox-equivalent (Tro), while the women had a ROS-concentration of 3.1±0.7 mM H2O2 and an aoC of 1.2±0.2 mM Tro. After the hike, women showed no significant change in ROS and a significant increase in aoC (1.3±0.2 mM Tro), while the ROS concentration in men increased significantly (2.1±0.3 mM H2O2) and their aoC decreased (0.25±0.1 mM Tro). After a regenerative phase, the ROS concentration of the men decreased to 1.7±0.4 mM H2O2 and their aoC recovered significantly (1.2±0.4 mM Tro), while the women presented no significant change in the concentration of H2O2 but showed an ulterior increase in antioxidant capacity (2.05±0.43 mM Tro). From this data we conclude that physical training programs as for example long distance hiking trips can improve the aoC in the blood of oncological patients.

  7. Protein-bound acrolein: Potential markers for oxidative stress

    PubMed Central

    Uchida, Koji; Kanematsu, Masamichi; Sakai, Kensuke; Matsuda, Tsukasa; Hattori, Nobutaka; Mizuno, Yoshikuni; Suzuki, Daisuke; Miyata, Toshio; Noguchi, Noriko; Niki, Etsuo; Osawa, Toshihiko

    1998-01-01

    Acrolein (CH2=CH—CHO) is known as a ubiquitous pollutant in the environment. Here we show that this notorious aldehyde is not just a pollutant, but also a lipid peroxidation product that could be ubiquitously generated in biological systems. Upon incubation with BSA, acrolein was rapidly incorporated into the protein and generated the protein-linked carbonyl derivative, a putative marker of oxidatively modified proteins under oxidative stress. To verify the presence of protein-bound acrolein in vivo, the mAb (mAb5F6) against the acrolein-modified keyhole limpet hemocyanin was raised. It was found that the acrolein-lysine adduct, Nɛ-(3-formyl-3,4-dehydropiperidino)lysine, constitutes an epitope of the antibody. Immunohistochemical analysis of atherosclerotic lesions from a human aorta demonstrated that antigenic materials recognized by mAb5F6 indeed constituted the lesions, in which intense positivity was associated primarily with macrophage-derived foam cells and the thickening neointima of arterial walls. The observations that (i) oxidative modification of low-density lipoprotein with Cu2+ generated the acrolein-low-density lipoprotein adducts and (ii) the iron-catalyzed oxidation of arachidonate in the presence of protein resulted in the formation of antigenic materials suggested that polyunsaturated fatty acids are sources of acrolein that cause the production of protein-bound acrolein. These data suggest that the protein-bound acrolein represents potential markers of oxidative stress and long-term damage to protein in aging, atherosclerosis, and diabetes. PMID:9560197

  8. Oxidative and nitrative stress in neurodegeneration.

    PubMed

    Cobb, Catherine A; Cole, Marsha P

    2015-12-01

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

  9. Chronic obstructive pulmonary disease and oxidative stress.

    PubMed

    Domej, W; Földes-Papp, Z; Flögel, E; Haditsch, B

    2006-04-01

    The respiratory tract as the main entrance for various inhalative substances has great potential to generate reactive species directly or indirectly in excess. Thus, heavy smokers are at high risk for development, impairment and failed response to treatment of chronic obstructive pulmonary disease (COPD). The article is an update regarding the influence of reactive oxygen (ROS) and nitrogen (RNS) species on COPD; however, we do not intend to describe ROS and RNS actions on the entire lung tissue. Here, we focus on the airways, because in human most of the described effects of ROS and RNS species are measured on respiratory epithelial cells obtained by bronchoscopy. ROS and RNS species are physiological compounds in cells and risk factors for several respiratory diseases. In general, both kinds of species are thermodynamically stabile, but their reaction behaviors in cellular environments are very different. For example, the life times of the superoxide anion radical range from micro/milliseconds up to minutes and even hours in in-vitro model systems. Oxidative stress by cigarette smoke was investigated in detail by the authors of this article. In addition, original studies by the authors on the amount of fine particulate matter and trace elements in lung biopsies after defined inhalation indicate a distortion of the equilibrium between oxidants and antioxidants. We also try to present some modern views with respect to genomic medicine for future therapeutic perspectives, although this is an upcoming sector of COPD therapy. PMID:16724946

  10. Oxidative Stress is Increased in Serum from Mexican Patients with Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Ortiz, Genaro Gabriel; Macías-Islas, Miguel Ángel; Pacheco-Moisés, Fermín P.; Cruz-Ramos, José A.; Sustersik, Silvia; Barba, Elías Alejandro; Aguayo, Adriana

    2009-01-01

    Objective: To determine the oxidative stress markers in serum from patients with relapsing-remitting multiple sclerosis. Methods: Blood samples from healthy controls and 22 patients 15 women (7 aged from 20 to 30 and 8 were > 40 years old) and 7 men (5 aged from 20 to 30 and 2 were > 40 years old) fulfilling the McDonald Criteria and classified as having Relapsing-Remitting Multiple Sclerosis accordingly with Lublin were collected for oxidative stress markers quantification. Results: Nitric oxide metabolites (nitrates/nitrites), lipid peroxidation products (malondialdehyde plus 4-hidroxialkenals), and glutathione peroxidase activity were significantly increased in serum of subjects with relapsing-remitting multiple sclerosis in comparison with that of healthy controls. These data support the hypothesis that multiple sclerosis is a component closely linked to oxidative stress. PMID:19242067

  11. Acacetin promotes healthy aging by altering stress response in Caenorhabditis elegans.

    PubMed

    Asthana, Jyotsna; Mishra, B N; Pandey, Rakesh

    2016-08-01

    The progression in lifespan has been associated with elevated intracellular reactive oxygen species (ROS) and oxidative stress level which contributes to development of age related disorders. The discovery of lifespan modulating phytomolecules may promote development of natural therapies against age related afflictions. Acacetin (5,7-dihydroxy-4-methoxyflavone), is a naturally occurring flavonoid known to possess therapeutic properties. To this end, the present study evaluates effect of acacetin (AC) on lifespan, stress and neurotoxicity for the first time by using well-established free living, multicellular Caenorhabditis elegans model system. The 25 μM dose of AC significantly prolonged the mean lifespan of worms by 27.31% in comparison to untreated control and other tested doses of AC. Additionally, AC enhanced stress resistance against oxidative and thermal stress in worms. Furthermore, AC attenuated age related intracellular ROS level, aggregation of age pigment lipofuscin and increased the mean survival in stress hypersensitive mev-1 mutant by 40.5%. AC supplementation also reduced the alpha synuclein aggregation in transgenic worm model of Parkinson's disease. The enhanced stress resistance, lifespan and alleviation of age related pathology can be attributed to increment in stress modulatory enzymes like superoxide dismutase (SOD) and catalase (CAT) level. Altogether the results suggest AC exposure maintains stress level, health span and extends mean lifespan of C. elegans. The longevity promoting and neuromodulatory effects of AC are mediated by up regulation of the stress response genes sod-3 and gst-4. The present finding gives new insights of natural remedies and their future prospects in developing therapeutic interventions for managing age related diseases. PMID:27150237

  12. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    NASA Technical Reports Server (NTRS)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

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

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

    PubMed

    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.

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

    EPA Science Inventory

    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...

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

    PubMed

    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. PMID:27025055

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

    PubMed

    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.

  17. Ablation of ALCAT1 Mitigates Hypertrophic Cardiomyopathy through Effects on Oxidative Stress and Mitophagy

    PubMed Central

    Liu, Xiaolei; Ye, Benlan; Miller, Shane; Yuan, Huijuan; Zhang, Hongxiu; Tian, Liang; Nie, Jia; Imae, Rieko; Arai, Hiroyuki; Li, Yuanjian; Cheng, Zeneng

    2012-01-01

    Oxidative stress causes mitochondrial dysfunction and heart failure through unknown mechanisms. Cardiolipin (CL), a mitochondrial membrane phospholipid required for oxidative phosphorylation, plays a pivotal role in cardiac function. The onset of age-related heart diseases is characterized by aberrant CL acyl composition that is highly sensitive to oxidative damage, leading to CL peroxidation and mitochondrial dysfunction. Here we report a key role of ALCAT1, a lysocardiolipin acyltransferase that catalyzes the synthesis of CL with a high peroxidation index, in mitochondrial dysfunction associated with hypertrophic cardiomyopathy. We show that ALCAT1 expression was potently upregulated by the onset of hyperthyroid cardiomyopathy, leading to oxidative stress and mitochondrial dysfunction. Accordingly, overexpression of ALCAT1 in H9c2 cardiac cells caused severe oxidative stress, lipid peroxidation, and mitochondrial DNA (mtDNA) depletion. Conversely, ablation of ALCAT1 prevented the onset of T4-induced cardiomyopathy and cardiac dysfunction. ALCAT1 deficiency also mitigated oxidative stress, insulin resistance, and mitochondrial dysfunction by improving mitochondrial quality control through upregulation of PINK1, a mitochondrial GTPase required for mitochondrial autophagy. Together, these findings implicate a key role of ALCAT1 as the missing link between oxidative stress and mitochondrial dysfunction in the etiology of age-related heart diseases. PMID:22949503

  18. Dietary contaminants and oxidative stress in Inuit of Nunavik.

    PubMed

    Bélanger, Marie-Claire; Dewailly, Eric; Berthiaume, Line; Noël, Micheline; Bergeron, Jean; Mirault, Marc-Edouard; Julien, Pierre

    2006-08-01

    The aim of the present study was to investigate the potential deleterious effects of dietary contaminants such as polychlorinated biphenyls (PCBs) and methylmercury (MeHg) on different molecules sensitive to oxidative stress, namely, plasma oxidized low-density lipoproteins (OxLDLs), plasma homocysteine (Hcy), blood glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). We also planned to assess the potential beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) and selenium (Se) that are also present in the traditional Inuit diet. A total of 99 participants were studied. Plasma levels of PCBs, blood levels of Se and MeHg, plasma lipids (triacylglycerols, total, LDL-, and high-density lipoprotein cholesterol [LDL-C and HDL-C, respectively], apolipoprotein B-LDL), erythrocyte n-3 PUFAs, OxLDL, Hcy, blood GPx, GSH, and GR have been determined. Mean concentrations of MeHg, Se, and PCBs were respectively 10- to 14-fold, 8- to 15-fold, and 16- to 18-fold higher than reported in white population consuming little or no fish. Multivariate analyses show that variance in plasma OxLDL concentrations was predicted by LDL-C (P = .007), HDL-C (P = .005), and PCBs (P = .006). The level of LDL oxidation, represented as the ratio OxLDL/apolipoprotein B-LDL, was predicted by LDL-C (P = .0002), HDL-C (P = .002), and GSH (P = .005). Concentration of plasma Hcy was positively predicted by age (P = .02) but negatively by body mass index (P = .04) and Se (P = .005). Glutathione was predicted by the smoking status (P = .004) and the level of LDL oxidation (P = .005), whereas GR was only predicted by the smoking status (P = .0009). The variance of GPx was not predicted by any contaminant or other physiological parameter. Dietary MeHg showed no association with the examined oxidative biomarkers, whereas PCB level was a predictor of the plasma concentration of OxLDL, although this concentration remained very low. The level of GPx activity

  19. Aging Veterans and Posttraumatic Stress Symptoms

    MedlinePlus

    ... the bottom of the page. Share this page Search PTSD Site Choose Section Enter Term and Search ... Coach Online Tools to help you manage stress. Search Pilots Search PILOTS *, the largest citation database on ...

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

    SciTech Connect

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

    2014-03-01

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

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

    PubMed

    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.

  2. Nanoparticles, Lung Injury, and the Role of Oxidant Stress

    PubMed Central

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

    2015-01-01

    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, which have been shown to induce inflammation and oxidative stress in biologic systems. Oxidative stress reflects the imbalance between the generation of reaction oxygen species (ROS) and the biochemical mechanisms to detoxify and repair resulting damage of reactive intermediates. This review examines current research incidental and engineered nanoparticles in terms of their health effects on the lungs and mechanisms by which oxidative stress via physicochemical characteristics influence toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review will also briefly discuss some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site specific fashion. PMID:24215442

  3. Reference range of blood biomarkers for oxidative stress in Thoroughbred racehorses (2–5 years old)

    PubMed Central

    KUSANO, Kanichi; YAMAZAKI, Masahiko; KIUCHI, Masataka; KANEKO, Kouki; KOYAMA, Katsuhiro

    2016-01-01

    ABSTRACT The oxidant and antioxidant equilibrium is known to play an important role in equine medicine and equine exercise physiology. There are abundant findings in this field; however, not many studies have been conducted for reference ranges of oxidative stress biomarkers in horses. This study was conducted to determine the reference values of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) using blood samples from 372 (191 males, 181 females) Thoroughbred racehorse aged 2 to 5 (3.43 ± 1.10 (mean ± SD)) years old. There were obvious gender differences in oxidative biomarkers, and growth/age-related changes were observed especially in females. Gender and age must be considered when interpreting obtained oxidative stress biomarkers for diagnosis of disease or fitness alterations in Thoroughbred racehorses. PMID:27703408

  4. FOXO transcription factors support oxidative stress resistance in human chondrocytes

    PubMed Central

    Akasaki, Yukio; Alvarez-Garcia, Oscar; Saito, Masahiko; Caramés, Beatriz; Iwamoto, Yukihide; Lotz, Martin K.

    2014-01-01

    Objectives A major signaling pathway that regulates cellular aging is the Insulin/IGF-1/Pl3k/Akt/forkhead-box class O (FOXO) transcription factor axis. Previously, we observed that FOXO factors are dysregulated in aged and OA cartilage. The objective of this study was to investigate the impact of downregulated FOXOs on chondrocytes. Methods Small interference RNAs (siRNAs) for FOXO1 and FOXO3 were transfected into human articular chondrocytes. Cell viability following treatment with the oxidant tert-Butyl hydroperoxide (t-BHP) was measured by MTT assay. Caspase-3/7 activation and apoptotic cell were examined. Gene and protein expression of antioxidant proteins and autophagy related proteins and changes in inflammatory mediators following treatment with IL-1β were analyzed. Cells transfected with FOXO plasmids were also analyzed. Results Cell viability was significantly reduced by siFOXO under treatment with t-BHP. Apoptosis accompanied by caspase activation was significantly induced in FOXO-siRNA transfected chondrocytes. Knock-down of FOXO1 and FOXO1+3 resulted in significant reductions of GPX-1, catalase, LC3, Beclin1, and SIRT1 proteins following treatment with t-BHP. In contrast, constitutive active form of FOXO 3 increased cell viability while inducing GPX1, Beclin1, and LC3 in response to t-BHP. Expression and production of ADAMTS-4 and Chemerin were significantly increased in FOXO-siRNA transfected chondrocytes. Conclusions Reduced expression of FOXO transcription factors in chondrocytes increased susceptibility to cell death induced by oxidative stress. This was associated with reduced antioxidant proteins and autophagy related proteins. Our data provide evidence for a key role of FOXO transcription factors as regulators of chondrocyte oxidative stress resistance and tissue homeostasis. PMID:25186470

  5. Clinical Perspective of Oxidative Stress in Sporadic ALS

    PubMed Central

    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

  6. Effects of diet and age on oxidative damage products in healthy subjects.

    PubMed

    Krajcovicová-Kudlácková, M; Valachovicová, M; Pauková, V; Dusinská, M

    2008-01-01

    Damage of molecules as a consequence of oxidative stress has been implicated in the pathogenesis of chronic diseases related to aging. Diet is a key environmental factor affecting the incidence of many chronic diseases. Antioxidant substances in diet enhance the DNA, lipid and protein protection by increasing the scavenging of free radicals. Products of oxidative damage of DNA (DNA strand breaks with oxidized purines or oxidized pyrimidines), lipids (conjugated dienes of fatty acids) and proteins (carbonyls) in relation to nutrition (vegetarian diet vs. non-vegetarian, traditional mixed diet) were measured in young women aged 20-30 years (46 vegetarians, 48 non-vegetarians) vs. older women aged 60-70 years (33 vegetarians, 34 non-vegetarians). In young subjects, no differences in values of oxidative damage as well as plasma values of antioxidative vitamins (C,beta-carotene) were observed between vegetarian and non-vegetarian groups. In older vegetarian group significantly reduced values of DNA breaks with oxidized purines, DNA breaks with oxidized