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Sample records for age-related oxidative stress

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  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. 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

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  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. 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

  18. 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

  19. 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

  20. 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

    Background We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human macular antigens and characterized their identity. Methods Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.2±3.9 years old) included subjects with early to advanced AMD (n = 131) and controls (n = 231). Sera were tested by Western blots for immunoreactive bands against human donor macular tissue homogenates. Immunoreactive bands were identified and graded, and odds ratios (OR) calculated. Based on these findings, sera were immunoprecipitated, and subjected to 2D gel electrophoresis (GE). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the targets recognized by circulating AAbs seen on 2D-GE, followed by ELISAs with recombinant proteins to confirm LC-MS/MS results, and quantify autoreactivities. Results In AMD, 11 immunoreactive bands were significantly more frequent and 13 were significantly stronger than in controls. Nine of the more frequent bands also showed stronger reactivity. OR estimates ranged between 4.06 and 1.93, and all clearly excluded the null value. Following immunoprecipitation, 2D-GE and LC-MS/MS, five of the possible autoreactivity targets were conclusively identified: two members of the heat shock protein 70 (HSP70) family, HSPA8 and HSPA9; another member of the HSP family, HSPB4, also known as alpha-crystallin A chain (CRYAA); Annexin A5 (ANXA5); and Protein S100-A9, also known as calgranulin B that, when complexed with S100A8, forms calprotectin. ELISA testing with recombinant proteins confirmed, on average, significantly higher reactivities against all targets in AMD samples compared to controls. Conclusions Consistent with other evidence supporting the

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  6. 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

  7. 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

  8. 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.

  9. Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress.

    PubMed

    Pitozzi, Vanessa; Jacomelli, Michela; Catelan, Dolores; Servili, Maurizio; Taticchi, Agnese; Biggeri, Annibale; Dolara, Piero; Giovannelli, Lisa

    2012-12-01

    The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment. Parameters of oxidative status and inflammation were measured in different brain areas at the same times and evaluated for correlation with behavioral changes. The treatment with olive oil phenols improved contextual memory in the step-down test to levels similar to young animals and prevented the age-related impairment in motor coordination in the rotarod test. This motor effect was correlated with reduced lipid peroxidation in the cerebellum (p<0.05), whereas the memory effect did not correlate with oxidation or inflammation parameters. In conclusion, this work points out that natural polyphenols contained in extra-virgin olive oil can improve some age-related dysfunctions by differentially affecting different brain areas. Such a modulation can be obtained with an olive oil intake that is normal in the Mediterranean area, provided that the oil has a sufficiently high content of polyphenols.

  10. Stress Constellations and Coping Styles of Older Adults with Age-Related Visual Impairment

    ERIC Educational Resources Information Center

    Lee, Kyoung Othelia; Brennan, Mark

    2006-01-01

    Narrative data from two earlier studies of adaptation to age-related visual impairment were examined for constellations of stressors and coping styles. In the course of previous qualitative analyses, the researchers identified stress and coping codes according to behavioral, psychological, and social domains using a grounded theory approach. In…

  11. The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults

    PubMed Central

    Nita, Małgorzata; Grzybowski, Andrzej

    2016-01-01

    The reactive oxygen species (ROS) form under normal physiological conditions and may have both beneficial and harmful role. We search the literature and current knowledge in the aspect of ROS participation in the pathogenesis of anterior and posterior eye segment diseases in adults. ROS take part in the pathogenesis of keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, stimulating apoptosis of corneal cells. ROS play a role in the pathogenesis of glaucoma stimulating apoptotic and inflammatory pathways on the level of the trabecular meshwork and promoting retinal ganglion cells apoptosis and glial dysfunction in the posterior eye segment. ROS play a role in the pathogenesis of Leber's hereditary optic neuropathy and traumatic optic neuropathy. ROS induce apoptosis of human lens epithelial cells. ROS promote apoptosis of vascular and neuronal cells and stimulate inflammation and pathological angiogenesis in the course of diabetic retinopathy. ROS are associated with the pathophysiological parainflammation and autophagy process in the course of the age-related macular degeneration. PMID:26881021

  12. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  13. Cytochrome P450-2E1 promotes aging-related hepatic steatosis, apoptosis and fibrosis through increased nitroxidative stress.

    PubMed

    Abdelmegeed, Mohamed A; Choi, Youngshim; Ha, Seung-Kwon; Song, Byoung-Joon

    2016-02-01

    The role of ethanol-inducible cytochrome P450-2E1 (CYP2E1) in promoting aging-dependent hepatic disease is unknown and thus was investigated in this study. Young (7 weeks) and aged female (16 months old) wild-type (WT) and Cyp2e1-null mice were used in this study to evaluate age-dependent changes in liver histology, steatosis, apoptosis, fibrosis and many nitroxidative stress parameters. Liver histology showed that aged WT mice exhibited markedly elevated hepatocyte vacuolation, ballooning degeneration, and inflammatory cell infiltration compared to all other groups. These changes were accompanied with significantly higher hepatic triglyceride and serum cholesterol in aged WT mice although serum ALT and insulin resistance were not significantly altered. Aged WT mice showed the highest rates of hepatocyte apoptosis and hepatic fibrosis. Further, the highest levels of hepatic hydrogen peroxide, lipid peroxidation, protein carbonylation, nitration, and oxidative DNA damage were observed in aged WT mice. These increases in the aged WT mice were accompanied by increased levels of mitochondrial nitroxidative stress and alteration of mitochondrial complex III and IV proteins in aged WT mice, although hepatic ATP levels seems to be unchanged. In contrast, the aging-related nitroxidative changes were very low in aged Cyp2e1-null mice. These results suggest that CYP2E1 is important in causing aging-dependent hepatic steatosis, apoptosis and fibrosis possibly through increasing nitroxidative stress and that CYP2E1 could be a potential target for translational research in preventing aging-related liver disease. PMID:26703967

  14. Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration

    PubMed Central

    Ebrahem, Quteba; Renganathan, Kutralanathan; Sears, Jonathan; Vasanji, Amit; Gu, Xiaorong; Lu, Liang; Salomon, Robert G.; Crabb, John W.; Anand-Apte, Bela

    2006-01-01

    Choroidal neovascularization (CNV), the advanced stage of age-related macular degeneration (AMD), accounts for >80% of vision loss in AMD. Carboxyethylpyrrole (CEP) protein modifications, uniquely generated from oxidation of docosahexaenoate-containing lipids, are more abundant in Bruch’s membrane from AMD eyes. We tested the hypothesis that CEP protein adducts stimulate angiogenesis and possibly contribute to CNV in AMD. Human serum albumin (HSA) or acetyl-Gly-Lys-O-methyl ester (dipeptide) were chemically modified to yield CEP-modified HSA (CEP-HSA) or CEP-dipeptide. The in vivo angiogenic properties of CEP-HSA and CEP-dipeptide were demonstrated by using the chick chorioallantoic membrane and rat corneal micropocket assays. Low picomole amounts of CEP-HSA and CEP-dipeptide stimulated neovascularization. Monoclonal anti-CEP antibody neutralized limbal vessel growth stimulated by CEP-HSA, whereas anti-VEGF antibody was found to only partially neutralize vessel growth. Subretinal injections of CEP-modified mouse serum albumin exacerbated laser-induced CNV in mice. In vitro treatments of human retinal pigment epithelial cells with CEP-dipeptide or CEP-HSA did not induce increased VEGF secretion. Overall, these results suggest that CEP-induced angiogenesis utilizes VEGF-independent pathways and that anti-CEP therapeutic modalities might be of value in limiting CNV in AMD. PMID:16938854

  15. Neurotoxicity induced by zinc oxide nanoparticles: age-related differences and interaction

    PubMed Central

    Tian, Lei; Lin, Bencheng; Wu, Lei; Li, Kang; Liu, Huanliang; Yan, Jun; Liu, Xiaohua; Xi, Zhuge

    2015-01-01

    This study mainly investigated the neurotoxicity induced by zinc oxide nanoparticle (ZnO NP) in different-aged mice and the interaction between age and ZnO NP exposure. Sixty adult and old male C57BL/6J mice were assigned to four groups based on a two-factor (age and ZnO NP exposure) design. Results showed that ZnO NPs (5.6 mg/kg, intraperitoneal) induced increased production of pro-inflammatory cytokines in the serum and the brain of mice. A synergistic reaction between aging and ZnO NP exposure occurred regarding serum interleukin 1 (IL-1) and interleukin 6 (IL-6). In the brain, increased oxidative stress level, impaired learning and memory abilities, and hippocampal pathological changes were identified, especially in old mice, following ZnO NP exposure. Then, a potential mechanism of cognitive impairment was examined. The contents of hippocampal cAMP response element binding protein (CREB), phosphorylated CREB, synapsin I, and cAMP were decreased in an age-dependent manner, and the most substantial decrease occurred in old mice treated with ZnO NPs. These findings demonstrated for the first time that aging and ZnO NP exposure synergistically influenced systemic inflammation, and indicated old individuals were more susceptible to ZnO NP-induced neurotoxicity. One of the mechanisms might due to the supression of cAMP/CREB signaling. PMID:26527454

  16. Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus.

    PubMed

    Vasconcelos, Andrea Rodrigues; Kinoshita, Paula Fernanda; Yshii, Lidia Mitiko; Marques Orellana, Ana Maria; Böhmer, Ana Elisa; de Sá Lima, Larissa; Alves, Rosana; Andreotti, Diana Zukas; Marcourakis, Tania; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

    2015-05-01

    Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to changes in α2,3-Na,K-ATPase activity, 3-nitrotyrosine proteins, and inducible nitric oxide synthase gene expression. IF induced adaptative cellular stress-response signaling pathways reverting LPS effects in rat hippocampus of young and older rats. The results suggest that IF in both ages would reduce the risk for deficits on brain function and neurodegenerative disorders linked to inflammatory response in the CNS. PMID:25818175

  17. PMK-S005 Alleviates Age-Related Gastric Acid Secretion, Inflammation, and Oxidative Status in the Rat Stomach

    PubMed Central

    Choi, Yoon Jeong; Kim, Nayoung; Lee, Ju Yup; Nam, Ryoung Hee; Suh, Ji Hyung; Lee, Sun Min; Ham, Min Hee; Jo, Hyun Jin; Shim, Young Kwang; Park, Yo Han; Lee, Jong-Chan; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background/Aims The aim of this study was to evaluate the effect of the synthetic S-allyl-l-cysteine (SAC) PMK-S005 on gastric acid secretion, inflammation, and antioxidant enzymes in aging rats. Methods The rats were divided into four groups at 31 weeks of age and were continuously fed a diet containing a vehicle control, PMK-S005 (5 or 10 mg/kg), or lansoprazole (5 mg/kg). Gastric acid secretion and connective tissue thickness of the lamina propria were evaluated at 74 weeks and 2 years of age. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and COX-2 levels were measured by using enzyme-linked immunosorbent assays (ELISAs) or Western blot assays. Levels of antioxidant enzymes, including heme oxyganase 1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO-1), were also measured. Results As the rats aged, gastric acid secretion significantly decreased, and the connective tissue of the lamina propria increased. However, 74-week-old rats in the PMK-S005 group exhibited greater levels of gastric acid secretion than those of the control and lansoprazole groups. The increase of TNF-α, IL-1β, and COX-2 expression in 74-week and 2-year-old control rats were inhibited by PMK-S005. In addition, the decrease in HO-1 and NQO-1 protein expression that occurred with aging was inhibited by PMK-S005 in the 74-week-old rats. Conclusions These results suggest that PMK-S005 has therapeutic potential as an antiaging agent to ameliorate age-related gastric acid secretion, inflammation, and oxidative stress in the stomach. PMID:27172930

  18. Age-related parenting stress differences in mothers of children with spina bifida.

    PubMed

    Macias, Michelle M; Saylor, Conway F; Rowe, Brandy P; Bell, Nancy L

    2003-12-01

    This study examined whether ages of child and parent were risk factors for general parenting stress and disability-specific stress in families of children with spina bifida. Parents of 64 children with spina bifida completed the Parenting Stress Index-Short Form, Parents of Children with Disabilities Inventory, and measures of family support and resources. Scores of families with children under 6 years (preschool) versus 6- to 12-yr.-old children (school age) were compared, as were scores of mothers above or below Age 35. Parents of school-aged children reported significantly higher stress on the Concerns for the Child domain of the Parents of Children with Disabilities Inventory. Mothers over 35 tended to report higher stress in the Concerns for the Child and Medical/Legal Concerns domains of the Parents of Children with Disabilities Inventory. No associations with medical severity, socioeconomic status, family resources, or family support were detected. As the children age and disability-related differences become more apparent, the same level of functioning and severity of disability may be associated with additional parenting stress. Older mothers and those with school-age children may need more resources than current social support systems typically provide.

  19. Aging related ER stress is not responsible for anabolic resistance in mouse skeletal muscle.

    PubMed

    Chalil, Sreeda; Pierre, Nicolas; Bakker, Astrid D; Manders, Ralph J; Pletsers, Annelies; Francaux, Marc; Klein-Nulend, Jenneke; Jaspers, Richard T; Deldicque, Louise

    2015-12-25

    Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers in each muscle were quantified, and the anabolic response to leucine was assessed by measuring the phosphorylation state of S6K1 in soleus and EDL using an ex vivo muscle model. Aging reduced the muscle-to-body weight ratio in soleus, gastrocnemius, and plantaris, but not in EDL and tibialis anterior. Compared to adult mice, the expression of ER stress markers BiP and IRE1α was higher in EDL, and phospho-eIF2α was higher in soleus and EDL of old mice. S6K1 response to leucine was impaired in soleus, but not in EDL, suggesting that anabolic resistance contributes to soleus weight loss in old mice. Pre-incubation with ER stress inducer tunicamycin before leucine stimulation increased S6K1 phosphorylation beyond the level reached by leucine alone. Since tunicamycin did not impair leucine-induced S6K1 response, and based on the different ER stress marker regulation patterns, ER stress is probably not involved in anabolic resistance in skeletal muscle with aging.

  20. An Anthocyanin-Rich Extract of Acai (Euterpe precatoria Mart.) Increases Stress Resistance and Retards Aging-Related Markers in Caenorhabditis elegans.

    PubMed

    Peixoto, Herbenya; Roxo, Mariana; Krstin, Sonja; Röhrig, Teresa; Richling, Elke; Wink, Michael

    2016-02-17

    Acai fruits (Euterpe precatoria) are rich in antioxidant anthocyanins. Acai consumption is believed to have many health benefits; however, relevant detailed scientific investigations are limited. The current study aimed to investigate an anthocyanin-rich extract from E. precatoria fruits (AE) with regard to its antioxidant and antiaging properties using the model organism Caenorhabditis elegans. AE can protect the worms against oxidative stress and can ameliorate accumulation of reactive oxygen species in vivo. The expression of stress-response genes, such as sod-3::GFP, was upregulated while hsp-16::GFP was down-regulated after AE treatment. Studies with DAF-16/FOXO mutants indicated that some of the antioxidant effects are mediated by this transcription factor. AE can modulate the development of age-related markers, such as pharyngeal pumping. Despite the apparent antioxidant activity, no lifespan-prolonging effect was observed. PMID:26809379

  1. An Anthocyanin-Rich Extract of Acai (Euterpe precatoria Mart.) Increases Stress Resistance and Retards Aging-Related Markers in Caenorhabditis elegans.

    PubMed

    Peixoto, Herbenya; Roxo, Mariana; Krstin, Sonja; Röhrig, Teresa; Richling, Elke; Wink, Michael

    2016-02-17

    Acai fruits (Euterpe precatoria) are rich in antioxidant anthocyanins. Acai consumption is believed to have many health benefits; however, relevant detailed scientific investigations are limited. The current study aimed to investigate an anthocyanin-rich extract from E. precatoria fruits (AE) with regard to its antioxidant and antiaging properties using the model organism Caenorhabditis elegans. AE can protect the worms against oxidative stress and can ameliorate accumulation of reactive oxygen species in vivo. The expression of stress-response genes, such as sod-3::GFP, was upregulated while hsp-16::GFP was down-regulated after AE treatment. Studies with DAF-16/FOXO mutants indicated that some of the antioxidant effects are mediated by this transcription factor. AE can modulate the development of age-related markers, such as pharyngeal pumping. Despite the apparent antioxidant activity, no lifespan-prolonging effect was observed.

  2. 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...

  3. 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.

  4. 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

  5. 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.

  6. Age-related changes in glucose utilization and fatty acid oxidation in a muscle-specific manner during rabbit growth.

    PubMed

    Gondret, Florence; Damon, Marie; Jadhao, Sanjay B; Houdebine, Louis-Marie; Herpin, Patrick; Hocquette, Jean-François

    2004-01-01

    The optimal utilization of energy substrates in muscle fibers is of primary importance for muscle contraction and whole body physiology. This study aimed to investigate the age-related changes in some indicators of glucose catabolism and fatty acid oxidation in muscles of growing rabbits. Longissimus lumborum (fast-twitch, LL) and semimembranosus proprius (slow-twitch, SMP) muscles were collected at 10 or 20 weeks of age ( n=6 per age). Glucose transporter GLUT4 content was investigated by immunoblot assay. Activity levels of five enzymes were measured: lactate dehydrogenase (LDH) and phosphofructokinase (PFK) for glycolysis; citrate synthase (CS), isocitrate dehydrogenase (ICDH) and -3-hydroxyacyl-coenzyme A dehydrogenase (HAD) for oxidation. Mitochondrial and peroxisomal oxidation rates were assessed on fresh homogenates using [1-14C]-oleate as substrate. At both ages, mitochondrial and peroxisomal oxidations rates, as well as activities of oxidative enzymes were higher in SMP than in LL. In both muscles, the apparent rate of fatty acid oxidation by the mitochondria did not differ between the two ages. However, a decrease in the activities of the three oxidative enzymes was observed in LL, whereas activities of CS and HAD and peroxisomal oxidation rate of oleate increased between the two ages in SMP muscle. In both muscles, LDH activity increased between 10 and 20 weeks, without variations in glucose uptake (GLUT4 transporter content) and in the first step of glucose utilization (PFK activity). In conclusion, mitochondrial oxidation rate of fatty acids and activities of selected mitochondrial enzymes were largely unrelated. Moreover, regulation of energy metabolism with advancing age differed between muscle types.

  7. Oxidative damage impact on aging and age-related diseases: drug targeting of telomere attrition and dynamic telomerase activity flirting with imidazole-containing dipeptides.

    PubMed

    Babizhayev, Mark A; Vishnyakova, Khava S; Yegorov, Yegor E

    2014-01-01

    carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur with the demonstrated evidence of telomere shortening appeared to be a hallmark of oxidative stress and disease. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival and an advanced oral nutritional support with non-hydrolyzed carnosine (or carcinine and patented compositions thereof) and patented N-acetylcarnosine lubricant eye drops are useful therapeutic tools of a critical telomere length maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolong life expectancy, increase survival and chronological age of an organism in health control, smoking behavior and disease. PMID:24894799

  8. 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

  9. 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.

  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. Longitudinal changes of telomere length and epigenetic age related to traumatic stress and post-traumatic stress disorder.

    PubMed

    Boks, Marco P; van Mierlo, Hans C; Rutten, Bart P F; Radstake, Timothy R D J; De Witte, Lot; Geuze, Elbert; Horvath, Steve; Schalkwyk, Leonard C; Vinkers, Christiaan H; Broen, Jasper C A; Vermetten, Eric

    2015-01-01

    Several studies have reported an association between traumatic stress and telomere length suggesting that traumatic stress has an impact on ageing at the cellular level. A newly derived tool provides an additional means to investigate cellular ageing by estimating epigenetic age based on DNA methylation profiles. We therefore hypothesise that in a longitudinal study of traumatic stress both indicators of cellular ageing will show increased ageing. We expect that particularly in individuals that developed symptoms of post-traumatic stress disorder (PTSD) increases in these ageing parameters would stand out. From an existing longitudinal cohort study, ninety-six male soldiers were selected based on trauma exposure and the presence of symptoms of PTSD. All military personnel were deployed in a combat zone in Afghanistan and assessed before and 6 months after deployment. The Self-Rating Inventory for PTSD was used to measure the presence of PTSD symptoms, while exposure to combat trauma during deployment was measured with a 19-item deployment experiences checklist. These groups did not differ for age, gender, alcohol consumption, cigarette smoking, military rank, length, weight, or medication use. In DNA from whole blood telomere length was measured and DNA methylation levels were assessed using the Illumina 450K DNA methylation arrays. Epigenetic ageing was estimated using the DNAm age estimator procedure. The association of trauma with telomere length was in the expected direction but not significant (B=-10.2, p=0.52). However, contrary to our expectations, development of PTSD symptoms was associated with the reverse process, telomere lengthening (B=1.91, p=0.018). In concordance, trauma significantly accelerated epigenetic ageing (B=1.97, p=0.032) and similar to the findings in telomeres, development of PTSD symptoms was inversely associated with epigenetic ageing (B=-0.10, p=0.044). Blood cell count, medication and premorbid early life trauma exposure did not

  13. 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

  14. Age-related differences in heat loss capacity occur under both dry and humid heat stress conditions

    PubMed Central

    Larose, Joanie; Boulay, Pierre; Wright-Beatty, Heather E.; Sigal, Ronald J.; Hardcastle, Stephen

    2014-01-01

    This study examined the progression of impairments in heat dissipation as a function of age and environmental conditions. Sixty men (n = 12 per group; 20–30, 40–44, 45–49, 50–54, and 55–70 yr) performed four intermittent exercise/recovery cycles for a duration of 2 h in dry (35°C, 20% relative humidity) and humid (35°C, 60% relative humidity) conditions. Evaporative heat loss and metabolic heat production were measured by direct and indirect calorimetry, respectively. Body heat storage was measured as the temporal summation of heat production and heat loss during the sessions. Evaporative heat loss was reduced during exercise in the humid vs. dry condition in age groups 20–30 (−17%), 40–44 (−18%), 45–49 (−21%), 50–54 (−25%), and 55–70 yr (−20%). HE fell short of being significantly different between groups in the dry condition, but was greater in age group 20–30 yr (279 ± 10 W) compared with age groups 45–49 (248 ± 8 W), 50–54 (242 ± 6 W), and 55–70 yr (240 ± 7 W) in the humid condition. As a result of a reduced rate of heat dissipation predominantly during exercise, age groups 40–70 yr stored between 60–85 and 13–38% more heat than age group 20–30 yr in the dry and humid conditions, respectively. These age-related differences in heat dissipation and heat storage were not paralleled by significant differences in local sweating and skin blood flow, or by differences in core temperature between groups. From a whole body perspective, combined heat and humidity impeded heat dissipation to a similar extent across age groups, but, more importantly, intermittent exercise in dry and humid heat stress conditions created a greater thermoregulatory challenge for middle-aged and older adults. PMID:24812643

  15. Age-related differences in heat loss capacity occur under both dry and humid heat stress conditions.

    PubMed

    Larose, Joanie; Boulay, Pierre; Wright-Beatty, Heather E; Sigal, Ronald J; Hardcastle, Stephen; Kenny, Glen P

    2014-07-01

    This study examined the progression of impairments in heat dissipation as a function of age and environmental conditions. Sixty men (n = 12 per group; 20-30, 40-44, 45-49, 50-54, and 55-70 yr) performed four intermittent exercise/recovery cycles for a duration of 2 h in dry (35°C, 20% relative humidity) and humid (35°C, 60% relative humidity) conditions. Evaporative heat loss and metabolic heat production were measured by direct and indirect calorimetry, respectively. Body heat storage was measured as the temporal summation of heat production and heat loss during the sessions. Evaporative heat loss was reduced during exercise in the humid vs. dry condition in age groups 20-30 (-17%), 40-44 (-18%), 45-49 (-21%), 50-54 (-25%), and 55-70 yr (-20%). HE fell short of being significantly different between groups in the dry condition, but was greater in age group 20-30 yr (279 ± 10 W) compared with age groups 45-49 (248 ± 8 W), 50-54 (242 ± 6 W), and 55-70 yr (240 ± 7 W) in the humid condition. As a result of a reduced rate of heat dissipation predominantly during exercise, age groups 40-70 yr stored between 60-85 and 13-38% more heat than age group 20-30 yr in the dry and humid conditions, respectively. These age-related differences in heat dissipation and heat storage were not paralleled by significant differences in local sweating and skin blood flow, or by differences in core temperature between groups. From a whole body perspective, combined heat and humidity impeded heat dissipation to a similar extent across age groups, but, more importantly, intermittent exercise in dry and humid heat stress conditions created a greater thermoregulatory challenge for middle-aged and older adults.

  16. Age-related alterations of plasma glutathione and oxidation of redox potentials in chimpanzee (Pan troglodytes) and rhesus monkey (Macaca mulatta).

    PubMed

    Paredes, Jamespaul; Jones, Dean P; Wilson, Mark E; Herndon, James G

    2014-04-01

    Chimpanzee (Pan troglodytes) and rhesus macaque (Macaca mulatta) and humans (Homo sapiens) share physiological and genetic characteristics, but have remarkably different life spans, with chimpanzees living 50-60 % and the rhesus living 35-40 % of maximum human survival. Since oxidative processes are associated with aging and longevity, we might expect to see species differences in age-related oxidative processes. Blood and extracellular fluid contain two major thiol redox nodes, glutathione (GSH)/glutathione-disulfide (GSSG) and cysteine (Cys)/cystine (CySS), which are subject to reversible oxidation-reduction reactions and are maintained in a dynamic non-equilibrium state. Disruption of these thiol redox nodes leads to oxidation of their redox potentials (EhGSSG and EhCySS) which affects cellular physiology and is associated with aging and the development of chronic diseases in humans. The purpose of this study was to measure age-related changes in these redox thiols and their corresponding redox potentials (Eh) in chimpanzees and rhesus monkeys. Our results show similar age-related decreases in the concentration of plasma GSH and Total GSH as well as oxidation of the EhGSSG in male and female chimpanzees. Female chimpanzees and female rhesus monkeys also were similar in several outcome measures. For example, similar age-related decreases in the concentration of plasma GSH and Total GSH, as well as age-related oxidation of the EhGSSG were observed. The data collected from chimpanzees and rhesus monkeys corroborates previous reports on oxidative changes in humans and confirms their value as a comparative reference for primate aging.

  17. 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.

  18. 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

  19. Age-related decline in mitochondrial bioenergetics: Does supercomplex destabilization determine lower oxidative capacity and higher superoxide production?

    PubMed Central

    Gόmez, Luis A.; Hagen, Tory M.

    2014-01-01

    Mitochondrial decay plays a central role in the aging process. Although certainly multifactorial in nature, defective operation of the electron transport chain (ETC) constitutes a key mechanism involved in the age-associated loss of mitochondrial energy metabolism. Primarily, mitochondrial dysfunction affects the aging animal by limiting bioenergetic reserve capacity and/or increasing oxidative stress via enhanced electron leakage from the ETC. Even though the important aging characteristics of mitochondrial decay are known, the molecular events underlying inefficient electron flux that ultimately leads to higher superoxide appearance and impaired respiration are not completely understood. This review focuses on the potential role(s) that age-associated destabilization of the macromolecular organization of the ETC (i.e. supercomplexes) may be important for development of the mitochondrial aging phenotype, particularly in post-mitotic tissues. PMID:22521482

  20. 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

  1. 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

  2. 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

  3. Biological, psychological and clinical markers of caregiver's stress in impaired elderly with dementia and age-related disease.

    PubMed

    Neri, M; Bonati, P A; Pinelli, M; Borella, P; Tolve, I; Nigro, N

    2007-01-01

    Stress refers to the experience, produced through a person-environment transaction, that results in psychological or physiological distress. Everyday stress or hassles have a larger impact on health, in this frame caring for elderly disabled and/or demented persons have been shown to be a chronic role strain. The concept of stress and strain encompasses different levels of individual functioning (physiological, cognitive, affective, social). We studied whether 3 different distressing conditions show (i) different profiles in biological, psychological and clinical indices of stress, and (ii) different response to temporary environmental manipulation. A sample of 29 caregivers of elderly subjects temporarily institutionalized for (i) respite program, (ii) behavioral psychological symptoms of dementia (BPSD) in dementia-control and, (iii) a rehabilitation program after hip fracture, was assessed with clinical, psychological and biological measures. The BPSD appear to be the most powerful distressing factor, both at the beginning and at the end of the study. On the whole, to an improvement of patient's clinical picture, it corresponds only a partial improvement in stress indices of the caregiver. The slope of biological indices don not parallel those of psychological ones. Among psychometric indices, the pattern of recovery differentiate affective and cognitive domains. The "respite" care condition seems to be the less effective in reducing stress in the caregivers. The stress process should be considered in its different domains to allow a tailored intervention.

  4. 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.

  5. 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

  6. Stress Responsiveness of the Hypothalamic–Pituitary–Adrenal Axis: Age-Related Features of the Vasopressinergic Regulation

    PubMed Central

    Goncharova, Nadezhda D.

    2013-01-01

    The hypothalamic–pituitary–adrenal (HPA) axis plays a key role in adaptation to environmental stresses. Parvicellular neurons of the hypothalamic paraventricular nucleus secrete corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) into pituitary portal system; CRH and AVP stimulate adrenocorticotropic hormone (ACTH) release through specific G-protein-coupled membrane receptors on pituitary corticotrophs, CRHR1 for CRH and V1b for AVP; the adrenal gland cortex secretes glucocorticoids in response to ACTH. The glucocorticoids activate specific receptors in brain and peripheral tissues thereby triggering the necessary metabolic, immune, neuromodulatory, and behavioral changes to resist stress. While importance of CRH, as a key hypothalamic factor of HPA axis regulation in basal and stress conditions in most species, is generally recognized, role of AVP remains to be clarified. This review focuses on the role of AVP in the regulation of stress responsiveness of the HPA axis with emphasis on the effects of aging on vasopressinergic regulation of HPA axis stress responsiveness. Under most of the known stressors, AVP is necessary for acute ACTH secretion but in a context-specific manner. The current data on the AVP role in regulation of HPA responsiveness to chronic stress in adulthood are rather contradictory. The importance of the vasopressinergic regulation of the HPA stress responsiveness is greatest during fetal development, in neonatal period, and in the lactating adult. Aging associated with increased variability in several parameters of HPA function including basal state, responsiveness to stressors, and special testing. Reports on the possible role of the AVP/V1b receptor system in the increase of HPA axis hyperactivity with aging are contradictory and requires further research. Many contradictory results may be due to age and species differences in the HPA function of rodents and primates. PMID:23486926

  7. Evidence of Highly Conserved β-Crystallin Disulfidome that Can be Mimicked by In Vitro Oxidation in Age-related Human Cataract and Glutathione Depleted Mouse Lens.

    PubMed

    Fan, Xingjun; Zhou, Sheng; Wang, Benlian; Hom, Grant; Guo, Minfei; Li, Binbin; Yang, Jing; Vaysburg, Dennis; Monnier, Vincent M

    2015-12-01

    Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract. To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathione-depleted LEGSKO mouse lenses for intra- versus intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was ∼4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H(2)O(2), whereas γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33, and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130, and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose Cys42, Cys79/80, Cys154 in γC; Cys42, Cys33 in γD, and Cys83, Cys115, and Cys130 in γS. In conclusion, the β-crystallin disulfidome is highly conserved in age-related nuclear cataract and LEGSKO mouse, and reproducible by in vitro oxidation, whereas some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of age-related nuclear cataract.

  8. Tocopherol-mediated modulation of age-related changes in microglial cells: turnover of extracellular oxidized protein material.

    PubMed

    Stolzing, Alexandra; Widmer, Rebecca; Jung, Tobias; Voss, Peter; Grune, Tilman

    2006-06-15

    Proteins accumulate during aging and form insoluble protein aggregates. Microglia are responsible for their removal from the brain. During aging, changes within the microglia might play a crucial role in the malfunctioning of these cells. Therefore, we isolated primary microglial cells from adult rats and compared their activation status and their ability to degrade proteins to that of microglial cells isolated from newborn animals. The ability of adult microglial cells to degrade proteins is substantially decreased. However, the preincubation of microglial cells with vitamin E improves significantly the degradation of such modified proteins. The degradation of proteins from apoptotic vesicles is decreased in microglia isolated from adult rats. This might be the result of a suppression of the CD36 receptor due to vitamin E treatment. We concluded that microglial cells isolated from adult organisms have different metabolic properties and seem to be a more valuable model to study age-related diseases.

  9. [Age-related aspects of the extent of lipid metabolism and post-traumatic stress disorders among veterans of modern warfare].

    PubMed

    Torgashov, M N; Miakotnykh, V S; Pal'tsev, A I

    2013-01-01

    The peculiarities of violations of lipid metabolism and symptoms of post-traumatic stress disorder (PTSD) in 161 patients of 25-69 years, veterans of the military actions on the territory of Afghanistan and the Northern Caucasus were investigated. The dependence of the formation of dyslipidemia and related changes of atherosclerosis in the young age on neuroendocrine effects, accompanying the effects of combat stress and promoting accelerated aging was determined. On the other hand, with the time, after 15-25 years after participating in hostilities, the intensity of PTSD and its influence on the development of violations of lipid spectrum may decline. The leading role in the pathogenesis of dyslipidemia goes to age-related changes, accompanying a process of accelerated aging of veterans of combat operations, and to pathological disorders of metabolism in liver associated with alcohol abuse and the consequences of infectious diseases.

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

    PubMed Central

    Miller, Mark W.; Sadeh, Naomi

    2014-01-01

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

  11. 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

  12. 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

  13. 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.

  14. Age-related changes in the effects of stress in pregnancy on infant motor development by maternal report: The Queensland Flood Study.

    PubMed

    Simcock, Gabrielle; Kildea, Sue; Elgbeili, Guillaume; Laplante, David P; Stapleton, Helen; Cobham, Vanessa; King, Suzanne

    2016-07-01

    The current study examined the effects of a natural disaster (a sudden onset flood) as a stressor in pregnancy on infant fine and gross motor development at 2, 6, and 16 months of age. Whether the timing of the stressor in pregnancy or sex of the infant moderated the impact of the prenatal maternal stress on motor development was also explored. Mothers' objective experiences of the flood, emotional reactions and distress, and their cognitive appraisal of the event were assessed retrospectively. Infants' fine and gross motor skills were assessed with the Ages and Stages Questionnaire, and results showed age-related changes in the effects of prenatal maternal stress on these domains. At 2 months, higher levels of prenatal maternal stress was positively related to infant motor development, yet at 6 and 16 months of age there was a negative association, particularly if flood exposure occurred later in pregnancy and if mothers had negative cognitive appraisals of the event. Results also showed differential effects of the maternal stress responses to the floods on infants' fine and gross motor development at each age and that infant sex did not buffer these effects. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 640-659, 2016. PMID:27004939

  15. 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

  16. Mouse models of age-related mitochondrial neurosensory hearing loss.

    PubMed

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  17. Aging-related expression of inducible nitric oxide synthase and markers of tissue damage in the rat penis.

    PubMed

    Ferrini, M; Magee, T R; Vernet, D; Rajfer, J; González-Cadavid, N F

    2001-03-01

    Erectile dysfunction in the aging male results in part from the loss of compliance of the corpora cavernosal smooth muscle due to the progressive replacement of smooth muscle cells by collagen fibers. We have examined the hypothesis that a spontaneous local induction of inducible nitric oxide synthase (iNOS) expression and the subsequent peroxynitrite formation occurs in the penis during aging and that this process is accompanied by a stimulation of smooth muscle apoptosis and collagen deposition. The penile shaft and crura were excised from young (3-5 mo old) and old (24-30 mo old) rats, with or without perfusion with 4% formalin. Fresh tissue was used for iNOS and proteasome 2C mRNA determinations by reverse transcription polymerase chain reaction assay, ubiquitin mRNA by Northern blot, and iNOS protein by Western blot. Penile sections from perfused animals were embedded in paraffin and immunostained with antibodies against iNOS and nitrotyrosine, submitted to the TUNEL assay for apoptosis, or stained for collagen, followed by image analysis quantitation. A 4.1-fold increase in iNOS mRNA was observed in the old versus young tissues, paralleled by a 4.9-fold increase in iNOS protein. The proteolysis marker, ubiquitin, was increased 1.9-fold, whereas a related gene, proteasome 2c, was not significantly affected. iNOS immunostaining was increased 3.6-fold in the penile smooth muscle of the old rats as compared with the young rats. The peroxynitrite indicator nitrotyrosine was increased by 1.6-fold, accompanied by a 3.6-fold increase in apoptotic cells and a 2.0-fold increase in collagen fibers in the old penis. In conclusion, aging in the penis is accompanied by an induction of iNOS and peroxynitrite formation that may lead to the observed increase in apoptosis and proteolysis and may counteract a higher rate of collagen deposition in the old penis.

  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 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.

  1. 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

  2. [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.

  3. [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.

  4. 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

  5. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

    PubMed Central

    Baehr, Leslie M.; West, Daniel W.D.; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID:26826670

  6. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.

    PubMed

    Baehr, Leslie M; West, Daniel W D; Marcotte, George; Marshall, Andrea G; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength.

  7. 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.

  8. 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

  9. 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.

  10. Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus.

    PubMed

    Shi, Yun; Pulliam, Daniel A; Liu, Yuhong; Hamilton, Ryan T; Jernigan, Amanda L; Bhattacharya, Arunabh; Sloane, Lauren B; Qi, Wenbo; Chaudhuri, Asish; Buffenstein, Rochelle; Ungvari, Zoltan; Austad, Steven N; Van Remmen, Holly

    2013-03-01

    Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus.

  11. 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

  12. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    PubMed

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

  13. Age-related hair pigment loss.

    PubMed

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. PMID:26370651

  14. [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

  15. [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

  16. 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

  17. Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus.

    PubMed

    Shi, Yun; Pulliam, Daniel A; Liu, Yuhong; Hamilton, Ryan T; Jernigan, Amanda L; Bhattacharya, Arunabh; Sloane, Lauren B; Qi, Wenbo; Chaudhuri, Asish; Buffenstein, Rochelle; Ungvari, Zoltan; Austad, Steven N; Van Remmen, Holly

    2013-03-01

    Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus. PMID:23325454

  18. Reduced mitochondrial ROS, enhanced antioxidant defense, and distinct age-related changes in oxidative damage in muscles of long-lived Peromyscus leucopus

    PubMed Central

    Shi, Yun; Pulliam, Daniel A.; Liu, Yuhong; Hamilton, Ryan T.; Jernigan, Amanda L.; Bhattacharya, Arunabh; Sloane, Lauren B.; Qi, Wenbo; Chaudhuri, Asish; Buffenstein, Rochelle; Ungvari, Zoltan; Austad, Steven N.

    2013-01-01

    Comparing biological processes in closely related species with divergent life spans is a powerful approach to study mechanisms of aging. The oxidative stress hypothesis of aging predicts that longer-lived species would have lower reactive oxygen species (ROS) generation and/or an increased antioxidant capacity, resulting in reduced oxidative damage with age than in shorter-lived species. In this study, we measured ROS generation in the young adult animals of the long-lived white-footed mouse, Peromyscus leucopus (maximal life span potential, MLSP = 8 yr) and the common laboratory mouse, Mus musculus (C57BL/6J strain; MLSP = 3.5 yr). Consistent with the hypothesis, our results show that skeletal muscle mitochondria from adult P. leucopus produce less ROS (superoxide and hydrogen peroxide) compared with M. musculus. Additionally, P. leucopus has an increase in the activity of antioxidant enzymes superoxide dismutase 1, catalase, and glutathione peroxidase 1 at young age. P. leucopus compared with M. musculus display low levels of lipid peroxidation (isoprostanes) throughout life; however, P. leucopus although having elevated protein carbonyls at a young age, the accrual of protein oxidation with age is minimal in contrast to the linear increase in M. musculus. Altogether, the results from young animals are in agreement with the predictions of the oxidative stress hypothesis of aging with the exception of protein carbonyls. Nonetheless, the age-dependent increase in protein carbonyls is more pronounced in short-lived M. musculus, which supports enhanced protein homeostasis in long-lived P. leucopus. PMID:23325454

  19. 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

  20. 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

  1. [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

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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...

  11. 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...

  12. Age-Related Renal Disease in Dahl Salt Sensitive Rats is Attenuated with 17β-Estradiol Supplementation by Modulating Nitric Oxide Synthase Expression

    PubMed Central

    Maric, Christine; Xu, Qin; Sandberg, Kathryn; Hinojosa-Laborde, Carmen

    2011-01-01

    Background The incidence of chronic renal disease in women increases with aging especially after menopause suggesting that the loss of sex hormones contributes to the development and progression of renal disease. However, the mechanisms by which sex hormones, estrogens in particular, contribute to the disease process are unclear. Objective The present study examined the effects of ovariectomy (OVX) with or without 17β-estadiol (E2) supplementation (OVX+E2) on the expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase in the kidney. Methods The study was performed in young (4 months, 4M) and aged (12 months, 12M) Dahl salt sensitive (DSS) rats fed a low salt (0.1% NaCl) diet. Results OVX in the aged rats was associated with 35% and 25% decreases, respectively, in medullary iNOS (4M OVX, 1.81±0.14 vs. 12M OVX, 1.17±0.16, P<0.05) and eNOS (4M OVX, 1.91±0.09 vs. 12M OVX, 1.43±0.15, P<0.05) protein expression and a 25-fold increase in the abundance of CD68-positive cells indicating macrophage infiltration (4M OVX, 1.18±0.09 vs. 12M OVX, 30.0±0.74, P<0.001). E2 supplementation either partially or completely attenuated these changes in iNOS (4M OVX+E2, 2.26±0.08 vs. 12M OVX+E2, 1.70±0.09, P<0.05), eNOS (4M OVX+E2, 2.03±0.07 vs 12M OVX+E2, 1.77±0.11) and CD68 (4M OVX+E2, 1.46±0.07 vs. 12M OVX+E2, 6.87±1.6, P<0.01) associated with OVX in the aging kidney. Conclusions These data suggest that ovarian E2 loss with aging may contribute to the development of age-related renal disease through downregulation of iNOS and eNOS protein abundance and increased renal inflammation. Furthermore, E2 supplementation may be protective in the aging kidney by attenuating these changes. PMID:18573482

  13. Climatic Stress during Stand Development Alters the Sign and Magnitude of Age-Related Growth Responses in a Subtropical Mountain Pine

    PubMed Central

    Ruiz-Benito, Paloma; Madrigal-González, Jaime; Young, Sarah; Mercatoris, Pierre; Cavin, Liam; Huang, Tsurng-Juhn; Chen, Jan-Chang; Jump, Alistair S.

    2015-01-01

    The modification of typical age-related growth by environmental changes is poorly understood, In part because there is a lack of consensus at individual tree level regarding age-dependent growth responses to climate warming as stands develop. To increase our current understanding about how multiple drivers of environmental change can modify growth responses as trees age we used tree ring data of a mountain subtropical pine species along an altitudinal gradient covering more than 2,200 m of altitude. We applied mixed-linear models to determine how absolute and relative age-dependent growth varies depending on stand development; and to quantify the relative importance of tree age and climate on individual tree growth responses. Tree age was the most important factor for tree growth in models parameterised using data from all forest developmental stages. Contrastingly, the relationship found between tree age and growth became non-significant in models parameterised using data corresponding to mature stages. These results suggest that although absolute tree growth can continuously increase along tree size when trees reach maturity age had no effect on growth. Tree growth was strongly reduced under increased annual temperature, leading to more constant age-related growth responses. Furthermore, young trees were the most sensitive to reductions in relative growth rates, but absolute growth was strongly reduced under increased temperature in old trees. Our results help to reconcile previous contrasting findings of age-related growth responses at the individual tree level, suggesting that the sign and magnitude of age-related growth responses vary with stand development. The different responses found to climate for absolute and relative growth rates suggest that young trees are particularly vulnerable under warming climate, but reduced absolute growth in old trees could alter the species’ potential as a carbon sink in the future. PMID:25973854

  14. Climatic Stress during Stand Development Alters the Sign and Magnitude of Age-Related Growth Responses in a Subtropical Mountain Pine.

    PubMed

    Ruiz-Benito, Paloma; Madrigal-González, Jaime; Young, Sarah; Mercatoris, Pierre; Cavin, Liam; Huang, Tsurng-Juhn; Chen, Jan-Chang; Jump, Alistair S

    2015-01-01

    The modification of typical age-related growth by environmental changes is poorly understood, In part because there is a lack of consensus at individual tree level regarding age-dependent growth responses to climate warming as stands develop. To increase our current understanding about how multiple drivers of environmental change can modify growth responses as trees age we used tree ring data of a mountain subtropical pine species along an altitudinal gradient covering more than 2,200 m of altitude. We applied mixed-linear models to determine how absolute and relative age-dependent growth varies depending on stand development; and to quantify the relative importance of tree age and climate on individual tree growth responses. Tree age was the most important factor for tree growth in models parameterised using data from all forest developmental stages. Contrastingly, the relationship found between tree age and growth became non-significant in models parameterised using data corresponding to mature stages. These results suggest that although absolute tree growth can continuously increase along tree size when trees reach maturity age had no effect on growth. Tree growth was strongly reduced under increased annual temperature, leading to more constant age-related growth responses. Furthermore, young trees were the most sensitive to reductions in relative growth rates, but absolute growth was strongly reduced under increased temperature in old trees. Our results help to reconcile previous contrasting findings of age-related growth responses at the individual tree level, suggesting that the sign and magnitude of age-related growth responses vary with stand development. The different responses found to climate for absolute and relative growth rates suggest that young trees are particularly vulnerable under warming climate, but reduced absolute growth in old trees could alter the species' potential as a carbon sink in the future.

  15. 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

  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. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-01

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip. PMID:27444019

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Intake of zinc and antioxidant micronutrients and early age-related maculopathy lesions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Macular degeneration, the end stage of age-related maculopathy (ARM), is the leading cause of legal blindness worldwide, and few modifiable risk factors are known. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to ARM, and carotenoids to antioxidation, ge...

  8. 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

  9. 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

  10. Self-serving appraisal as a cognitive coping strategy to deal with age-related limitations: an empirical study with elderly adults in a real-life stressful situation.

    PubMed

    De Raedt, Rudi; Ponjaert-Kristoffersen, I

    2006-03-01

    Elderly people are often confronted with stressful events that threaten psychological homeostasis. Nevertheless, the lack of a general age-related drop in life satisfaction remains intriguing. The objective of this study was to analyze the basic mechanisms of perceived control and self-protective processes. Eighty-four elderly adults who underwent a fitness-to-drive evaluation were asked how they appraised their performance in a driving simulation task and were classified as over-estimators versus people who estimated their performance correctly and people who didn't overestimate their performance. Decreased physical resources were related to self-serving appraisal and less depressive feelings. The results are in line with theories on self-immunizing processes and provide support for the use of cognitive therapies in dealing with age-related limitations.

  11. Targeting MAPK Signaling in Age-Related Macular Degeneration

    PubMed Central

    Kyosseva, Svetlana V.

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease. PMID:27385915

  12. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    PubMed Central

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  13. The potential of chitosan and its derivatives in prevention and treatment of age-related diseases.

    PubMed

    Kerch, Garry

    2015-04-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed.

  14. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    PubMed

    Tanigawa, Tohru; Shibata, Rei; Kondo, Kazuhisa; Katahira, Nobuyuki; Kambara, Takahiro; Inoue, Yoko; Nonoyama, Hiroshi; Horibe, Yuichiro; Ueda, Hiromi; Murohara, Toyoaki

    2015-01-01

    Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  15. 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

  16. 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

  17. 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

  18. [Early experience, stressful dysregulation of the hormonal axis and age-related vulnerability to neurodegenerative processus: a longitudinal study in the rat].

    PubMed

    Mayo, W; Vallée, V; Le Moal, M

    2001-04-01

    The deleterious effects of particular environmental situations have been suspected to augment the repercussions of cerebral injuries leading to increased vulnerability during ageing. The relationship between the hormones of the hypothalamo-pituitary-adrenal axis, mainly glucocorticosteroids, and cerebral structures like the hippocampus has been the subject of intense investigation in the recent years. Data suggest that long-term elevated blood levels of these hormones can induce neuronal alterations leading to cognitive dysfunction. This hypothesis has been tested with relevant animal models of normal/abnormal ageing. The models are based on the existence of considerable inter-individual differences in the degree of age-related cognitive impairments observed in rodents. Results show that long-term glucocorticosteroid exposure induces cerebral changes related to the action of these hormones on their central receptors. Experimental data are in accordance with clinical investigations suggesting that hormonal changes, and chronic life events, could be considered as a predictive factor of future cognitive dysfunction. PMID:11398011

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. [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

  6. 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

  7. eNOS-uncoupling in age-related erectile dysfunction.

    PubMed

    Johnson, J M; Bivalacqua, T J; Lagoda, G A; Burnett, A L; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH(4)) on erectile function in the aged rats. Male Fischer 344 'young' (4-month-old) and 'aged' (19-month-old) rats were treated with a BH(4) precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  8. eNOS-uncoupling in age-related erectile dysfunction

    PubMed Central

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  9. Telomere length variations in aging and age-related diseases.

    PubMed

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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...

  18. 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

  19. Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Griffiths, Richard D.; McArdle, Anne; Jackson, Malcolm J.

    2016-01-01

    Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging.—Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Griffiths, R. D., McArdle, A., Jackson, M. J. Long-term administration of the

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  6. Protein Phosphatase 2A Mediates Oxidative Stress Induced Apoptosis in Osteoblasts.

    PubMed

    Huang, Chong-xin; Lv, Bo; Wang, Yue

    2015-01-01

    Osteoporosis is one of the most common bone diseases, which is characterized by a systemic impairment of bone mass and fragility fractures. Age-related oxidative stress is highly associated with impaired osteoblastic dysfunctions and subsequent osteoporosis. In osteoblasts (bone formation cells), reactive oxygen species (ROS) are continuously generated and further cause lipid peroxidation, protein damage, and DNA lesions, leading to osteoblastic dysfunctions, dysdifferentiations, and apoptosis. Although much progress has been made, the mechanism responsible for oxidative stress induced cellular alternations and osteoblastic toxicity is still not fully elucidated. Here, we demonstrate that protein phosphatase 2A (PP2A), a major protein phosphatase in mammalian cells, mediates oxidative stress induced apoptosis in osteoblasts. Our results showed that lipid peroxidation products (4-HNE) may induce dramatic oxidative stress, inflammatory reactions, and apoptosis in osteoblasts. These oxidative stress responses may ectopically activate PP2A phosphatase activity, which may be mediated by inactivation of AKT/mTOR pathway. Moreover, inhibition of PP2A activity by okadaic acid might partly prevent osteoblastic apoptosis under oxidative conditions. These findings may reveal a novel mechanism to clarify the role of oxidative stress for osteoblastic apoptosis and provide new possibilities for the treatment of related bone diseases, such as osteoporosis. PMID:26538836

  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. 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.

  9. 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

  10. 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

  11. 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

  12. Oxidative Stress Induces Mitochondrial Dysfunction and a Protective Unfolded Protein Response in RPE cells

    PubMed Central

    Cano, Marisol; Wang, Lei; Wan, Jun; Barnett, Bradley P.; Ebrahimi, Katayoon; Qian, Jiang; Handa, James T.

    2014-01-01

    How cells degenerate from oxidative stress in aging-related disease is incompletely understood. The study’s intent was to identify key cytoprotective pathways activated by oxidative stress, and determine the extent of their protection. Using an unbiased strategy with microarray analysis, retinal pigmented epithelial (RPE) cells treated with cigarette smoke extract (CSE) had over-represented genes involved in the antioxidant and unfolded protein response (UPR). Differentially expressed antioxidant genes were predominantly located in the cytoplasm, with no induction of genes that neutralize superoxide and H2O2 in the mitochondria, resulting in accumulation of superoxide and decreased ATP production. Simultaneously, CSE induced the UPR sensors IRE1α, p-PERK, and ATP6, including CHOP, which was cytoprotective because CHOP knockdown decreased cell viability. In mice given intravitreal CSE, the RPE had increased IRE1α and decreased ATP, and developed epithelial-mesenchymal transition, as suggested by decreased LRAT abundance, altered ZO1 immunolabeling, and dysmorphic cell shape. Mildly degenerated RPE from early AMD samples had prominent IRE1α, but minimal mitochondrial TOM20 immunolabeling. While oxidative stress is thought to induce an antioxidant response with cooperation between the mitochondria and ER, herein, we show that mitochondria become impaired sufficiently to induce epithelial-mesenchymal transition despite a protective UPR. With similar responses in early AMD samples, these results suggest that mitochondria are vulnerable to oxidative stress despite a protective UPR during early phases of aging-related disease. PMID:24434119

  13. 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

  14. 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

  15. 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.

  16. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    PubMed

    Machalińska, Anna

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

  17. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Superoxide Dismutase 1 Loss Disturbs Intracellular Redox Signaling, Resulting in Global Age-Related Pathological Changes

    PubMed Central

    2014-01-01

    Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD) serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/−) mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation in Sod1−/− mice. This review will focus on various age-related pathologies caused by the loss of Sod1 and will discuss the molecular mechanisms underlying the pathogenesis in Sod1−/− mice. PMID:25276767

  8. Molecular pathology of age-related macular degeneration

    PubMed Central

    Ding, Xiaoyan; Patel, Mrinali; Chan, Chi-Chao

    2009-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy. This review summarizes, in detail, the molecular pathological findings in both humans and animal models, including genetic variations in CFH, CX3CR1, and ARMS2/HtrA1, as well as the role of numerous molecules implicated in inflammation, apoptosis, cholesterol trafficking, angiogenesis, and oxidative stress. PMID:19026761

  9. Age-related macular degeneration and the complement system.

    PubMed

    Khandhadia, S; Cipriani, V; Yates, J R W; Lotery, A J

    2012-02-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a complex multifactorial disease, and despite new advances in treatment, many patients still succumb to visual impairment. The complement pathway has been implicated in the pathogenesis of many diseases, and recently variants in several genes encoding complement pathway proteins have been associated with AMD. Complement proteins have been found in histological specimens of eyes with AMD. Altered levels of both intrinsic complement proteins and activated products have been found in the circulation of patients with AMD. Complement activation may be triggered by oxidative stress, resulting from retinal exposure to incoming light; indeed an inter-play between these two pathological processes seems to exist. Finally, complement inhibitors are currently being evaluated in clinical trials. This article reviews the role of the complement system in AMD, and the potential of complement inhibition in preventing the devastating blindness resulting from this disease.

  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. 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

  14. 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

  15. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients.

  16. [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".

  17. [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

  18. 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.

  19. Current therapeutic developments in atrophic age-related macular degeneration.

    PubMed

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age-Related Eye Disease Study (AREDS) formulation, which has been demonstrated to slow down the progression of dry AMD. This review summarises recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem cell-based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  20. Current Therapeutic Development for Atrophic Age-related Macular Degeneration

    PubMed Central

    Hanus, Jakub; Zhao, Fangkun; Wang, Shusheng

    2016-01-01

    Age-related macular degeneration (AMD), a degenerative disorder of the central retina, is the leading cause of irreversible blindness in the elderly. The underlying mechanism of the advanced form of dry AMD, also named geographic atrophy (GA) or atrophic AMD, remains unclear. Consequently, no cure is available for dry AMD or GA. The only prevention option currently available is the Age Related Eye Disease Study (AREDS) formulation which has been demonstrated to slow down the progression of dry AMD. This review summarizes recent advances in therapy for dry AMD and GA. Building on the new understanding of the disease and recent technological breakthroughs, numerous ongoing clinical trials have the goal of meeting the need to cure AMD. Therapeutic agents are being developed to target the key features of the disease, including inhibiting the complement pathway and other inflammatory pathways, reducing oxidative stress and protecting retinal pigment epithelial (RPE) cells, inhibiting lipofuscin and visual cycle, regenerating RPE cells from stem cells and restoring choroidal blood flow. Some of these therapeutic options, especially the stem-cell based therapy, hold great promise, which brings great hope for this devastating blinding disease. PMID:26553922

  1. 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

  2. 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.

  3. Systemic treatment with a 5HT1a agonist induces anti-oxidant protection and preserves the retina from mitochondrial oxidative stress.

    PubMed

    Biswal, Manas R; Ahmed, Chulbul M; Ildefonso, Cristhian J; Han, Pingyang; Li, Hong; Jivanji, Hiral; Mao, Haoyu; Lewin, Alfred S

    2015-11-01

    Chronic oxidative stress contributes to age related diseases including age related macular degeneration (AMD). Earlier work showed that the 5-hydroxy-tryptamine 1a (5HT1a) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) protects retinal pigment epithelium (RPE) cells from hydrogen peroxide treatment and mouse retinas from oxidative insults including light injury. In our current experiments, RPE derived cells subjected to mitochondrial oxidative stress were protected from cell death by the up-regulation of anti-oxidant enzymes and of the metal ion chaperone metallothionein. Differentiated RPE cells were resistant to oxidative stress, and the expression of genes for protective proteins was highly increased by oxidative stress plus drug treatment. In mice treated with 8-OH-DPAT, the same genes (MT1, HO1, NqO1, Cat, Sod1) were induced in the neural retina, but the drug did not affect the expression of Sod2, the gene for manganese superoxide dismutase. We used a mouse strain deleted for Sod2 in the RPE to accelerate age-related oxidative stress in the retina and to test the impact of 8-OH-DPAT on the photoreceptor and RPE degeneration developed in these mice. Treatment of mice with daily injections of the drug led to increased electroretinogram (ERG) amplitudes in dark-adapted mice and to a slight improvement in visual acuity. Most strikingly, in mice treated with a high dose of the drug (5 mg/kg) the structure of the RPE and Bruch's membrane and the normal architecture of photoreceptor outer segments were preserved. These results suggest that systemic treatment with this class of drugs may be useful in preventing geographic atrophy, the advanced form of dry AMD, which is characterized by RPE degeneration.

  4. 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.

  5. 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

  6. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

    PubMed Central

    LI, YALI; LIU, JIAN; GAO, DENGFENG; WEI, JIN; YUAN, HAIFENG; NIU, XIAOLIN; ZHANG, QIAOJUN

    2016-01-01

    The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs. PMID:26846626

  7. 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

  8. 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

  9. The Oxidative Stress Product Carboxyethylpyrrole Potentiates TLR2/TLR1 Inflammatory Signaling in Macrophages

    PubMed Central

    Saeed, Ali M.; Duffort, Stephanie; Ivanov, Dmitry; Wang, Hua; Laird, James M.; Salomon, Robert G.; Cruz-Guilloty, Fernando; Perez, Victor L.

    2014-01-01

    Oxidative stress is key in the pathogenesis of several diseases including age-related macular degeneration (AMD), atherosclerosis, diabetes, and Alzheimer's disease. It has previously been established that a lipid peroxidation product, carboxyethylpyrrole (CEP), accumulates in the retinas of AMD patients. Retinal infiltrating macrophages also accumulate in the retinas of both AMD patients and in a murine model of AMD. We therefore investigated the ability of CEP-adducts to activate innate immune signaling in murine bone-marrow derived macrophages (BMDMs). We found that CEP specifically synergizes with low-dose TLR2-agonists (but not agonists for other TLRs) to induce production of inflammatory cytokines. Moreover, CEP selectively augments TLR2/TLR1-signaling instead of TLR2/TLR6-signaling. These studies uncover a novel synergistic inflammatory relationship between an endogenously produced oxidation molecule and a pathogen-derived product, which may have implications in the AMD disease process and other oxidative stress-driven pathologies. PMID:25184331

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. Oxidative stress as an indicator of the costs of reproduction among free-ranging rhesus macaques

    PubMed Central

    Georgiev, Alexander V.; Thompson, Melissa Emery; Mandalaywala, Tara M.; Maestripieri, Dario

    2015-01-01

    ABSTRACT Sex differences in longevity may reflect sex-specific costs of intra-sexual competition and reproductive effort. As male rhesus macaques experience greater intrasexual competition and die younger, we predicted that males would experience greater oxidative stress than females and that oxidative stress would reflect sex-specific measures of reproductive effort. Males, relative to females, had higher concentrations of 8-OHdG and malondialdehyde, which are markers of DNA oxidative damage and lipid peroxidation, respectively. Older macaques had lower 8-OHdG levels than younger ones, suggesting that oxidative stress decreases in parallel with known age-related declines in reproductive investment. Among males, a recent period of social instability affected oxidative status: males who attacked others at higher rates had higher 8-OHdG levels. Multiparous lactating females with daughters had higher 8-OHdG levels than those with sons. No differences in antioxidant capacity were found. These results lend initial support for the use of oxidative stress markers to assess trade-offs between reproductive effort and somatic maintenance in primates. PMID:25908058

  16. 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

  17. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    PubMed

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. The impact of base excision DNA repair in age-related neurodegenerative diseases.

    PubMed

    Leandro, Giovana S; Sykora, Peter; Bohr, Vilhelm A

    2015-06-01

    The aging process and several age-related neurodegenerative disorders have been linked to elevated levels of DNA damage induced by ROS and deficiency in DNA repair mechanisms. DNA damage induced by ROS is a byproduct of cellular respiration and accumulation of damage over time, is a fundamental aspect of a main theory of aging. Mitochondria have a pivotal role in generating cellular oxidative stress, and mitochondrial dysfunction has been associated with several diseases. DNA base excision repair is considered the major pathway for repair of oxidized bases in DNA both in the nuclei and in mitochondria, and in neurons this mechanism is particularly important because non-diving cells have limited back-up DNA repair mechanisms. An association between elevated oxidative stress and a decrease in BER is strongly related to the aging process and has special relevance in age-related neurodegenerative diseases. Here, we review the role of DNA repair in aging, focusing on the implications of the DNA base excision repair pathways and how alterations in expression of these DNA repair proteins are related to the aging process and to age-related neurodegenerative diseases.

  4. 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

  5. Oxidative stress in prostate cancer: changing research concepts towards a novel paradigm for prevention and therapeutics.

    PubMed

    Paschos, A; Pandya, R; Duivenvoorden, W C M; Pinthus, J H

    2013-09-01

    A mounting body of evidence suggests that increased production of reactive oxygen species (ROS) is linked to aging processes and to the etiopathogenesis of aging-related diseases, such as cancer, diabetes, atherosclerosis and degenerative diseases like Parkinson's and Alzheimer's. Excess ROS are deleterious to normal cells, while in cancer cells, they can lead to accelerated tumorigenesis. In prostate cancer (PC), oxidative stress, an innate key event characterized by supraphysiological ROS concentrations, has been identified as one of the hallmarks of the aggressive disease phenotype. Specifically, oxidative stress is associated with PC development, progression and the response to therapy. Nevertheless, a thorough understanding of the relationships between oxidative stress, redox homeostasis and the activation of proliferation and survival pathways in healthy and malignant prostate remains elusive. Moreover, the failure of chemoprevention strategies targeting oxidative stress reduced the level of interest in the field after the recent negative results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) trial. Therefore, a revisit of the concept is warranted and several key issues need to be addressed: The consequences of changes in ROS levels with respect to altered redox homeostasis and redox-regulated processes in PC need to be established. Similarly, the key molecular events that cause changes in the generation of ROS in PC and the role for therapeutic strategies aimed at ameliorating oxidative stress need to be identified. Moreover, the issues whether genetic/epigenetic susceptibility for oxidative stress-induced prostatic carcinogenesis is an individual phenomenon and what measurements adequately quantify prostatic oxidative stress are also crucial. Addressing these matters will provide a more rational basis to improve the design of redox-related clinical trials in PC. This review summarizes accepted concepts and principles in redox research, and

  6. 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

  7. 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

  8. 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.

  9. Pentosidine Accumulation in Human Oocytes and Their Correlation to Age-Related Apoptosis

    PubMed Central

    Matsumine, Miki; Shibata, Noriyuki; Ishitani, Ken; Kobayashi, Makio; Ohta, Hiroaki

    2008-01-01

    Age-related atresia of ovarian follicles is characterized by apoptosis of the constituent cells. Recent studies have indicated that dysfunction of the proteasome and endoplasmic reticulum and subsequent apoptosis in the presence of oxidative stress have relevance to aging. The aim of this study was to assess the involvement of these processes in age-related follicular atresia. Formalin-fixed, paraffin-embedded sections of ovaries obtained at surgery from 74 women (age: 21–54 y) were examined with the terminal deoxynucleotidyl transferase-mediated, dUTP-biotin nick-end labeling (TUNEL) method and an immunohistochemical technique. Primary antibodies used in immunohistochemistry were against pentosidine, ubiquitin and caspase 12. Histological localization of these substances in oocytes was observed by light microscopy, and labeling indices of these cells were evaluated by regression analysis. Positive signals for pentosidine, ubiquitin, caspase 12, and TUNEL were detectable in oocytes of the primordial, primary and their atretic follicles. Regression analysis revealed an age-related increase in the labeling indices for pentosidine, ubiquitin, caspase 12, and TUNEL. These results suggest that pentosidine accumulation in human oocytes is related to apoptosis and increases with age. Further studies will be necessary to clarify the involvement of pentosidine accumulation, proteasome inhibition, and endoplasmic reticulum stress in age-related apoptosis of oocytes in human ovaries. PMID:18787640

  10. Age-related atrial fibrosis.

    PubMed

    Gramley, Felix; Lorenzen, Johann; Knackstedt, Christian; Rana, Obaida R; Saygili, Erol; Frechen, Dirk; Stanzel, Sven; Pezzella, Francesco; Koellensperger, Eva; Weiss, Christian; Münzel, Thomas; Schauerte, Patrick

    2009-03-01

    Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients' age (<50 years, 51-60 years, 61-70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-beta was determined by quantitative RT-PCR and hypoxia-related factors [HIF1 alpha, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% +/- 4.4% vs 16.6% +/- 8.3%) than older individuals (>70 years). While HIF1 alpha, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-beta and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis. PMID:19234766

  11. Melissa Officinalis L. Extracts Protect Human Retinal Pigment Epithelial Cells against Oxidative Stress-Induced Apoptosis

    PubMed Central

    Jeung, In Cheul; Jee, Donghyun; Rho, Chang-Rae; Kang, Seungbum

    2016-01-01

    Background: We evaluated the protective effect of ALS-L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) against oxidative stress-induced apoptosis in human retinal pigment epithelial cells (ARPE-19 cells). Methods: ARPE-19 cells were incubated with ALS-L1023 for 24 h and then treated with hydrogen peroxide (H2O2). Oxidative stress-induced apoptosis and intracellular generation of reactive oxygen species (ROS) were assessed by flow cytometry. Caspase-3/7 activation and cleaved poly ADP-ribose polymerase (PARP) were measured to investigate the protective role of ALS-L1023 against apoptosis. The protective effect of ALS-L1023 against oxidative stress through activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) was evaluated by Western blot analysis. Results: ALS-L1023 clearly reduced H2O2-induced cell apoptosis and intracellular production of ROS. H2O2-induced oxidative stress increased caspase-3/7 activity and apoptotic PARP cleavage, which were significantly inhibited by ALS-L1023. Activation of the PI3K/Akt pathway was associated with the protective effect of ALS-L1023 on ARPE-19 cells. Conclusions: ALS-L1023 protected human RPE cells against oxidative damage. This suggests that ALS-L1023 has therapeutic potential for the prevention of dry age-related macular degeneration. PMID:26941573

  12. Siglec receptors impact mammalian lifespan by modulating oxidative stress.

    PubMed

    Schwarz, Flavio; Pearce, Oliver M T; Wang, Xiaoxia; Samraj, Annie N; Läubli, Heinz; Garcia, Javier O; Lin, Hongqiao; Fu, Xiaoming; Garcia-Bingman, Andrea; Secrest, Patrick; Romanoski, Casey E; Heyser, Charles; Glass, Christopher K; Hazen, Stanley L; Varki, Nissi; Varki, Ajit; Gagneux, Pascal

    2015-01-01

    Aging is a multifactorial process that includes the lifelong accumulation of molecular damage, leading to age-related frailty, disability and disease, and eventually death. In this study, we report evidence of a significant correlation between the number of genes encoding the immunomodulatory CD33-related sialic acid-binding immunoglobulin-like receptors (CD33rSiglecs) and maximum lifespan in mammals. In keeping with this, we show that mice lacking Siglec-E, the main member of the CD33rSiglec family, exhibit reduced survival. Removal of Siglec-E causes the development of exaggerated signs of aging at the molecular, structural, and cognitive level. We found that accelerated aging was related both to an unbalanced ROS metabolism, and to a secondary impairment in detoxification of reactive molecules, ultimately leading to increased damage to cellular DNA, proteins, and lipids. Taken together, our data suggest that CD33rSiglecs co-evolved in mammals to achieve a better management of oxidative stress during inflammation, which in turn reduces molecular damage and extends lifespan. PMID:25846707

  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. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. Oxidative stress-induced telomeric erosion as a mechanism underlying airborne particulate matter-related cardiovascular disease

    PubMed Central

    2012-01-01

    Particulate matter (PM) pollution is responsible for hundreds of thousands of deaths worldwide, the majority due to cardiovascular disease (CVD). While many potential pathophysiological mechanisms have been proposed, there is not yet a consensus as to which are most important in causing pollution-related morbidity/mortality. Nor is there consensus regarding which specific types of PM are most likely to affect public health in this regard. One toxicological mechanism linking exposure to airborne PM with CVD outcomes is oxidative stress, a contributor to the development of CVD risk factors including atherosclerosis. Recent work suggests that accelerated shortening of telomeres and, thus, early senescence of cells may be an important pathway by which oxidative stress may accelerate biological aging and the resultant development of age-related morbidity. This pathway may explain a significant proportion of PM-related adverse health outcomes, since shortened telomeres accelerate the progression of many diseases. There is limited but consistent evidence that vehicular emissions produce oxidative stress in humans. Given that oxidative stress is associated with accelerated erosion of telomeres, and that shortened telomeres are linked with acceleration of biological ageing and greater incidence of various age-related pathology, including CVD, it is hypothesized that associations noted between certain pollution types and sources and oxidative stress may reflect a mechanism by which these pollutants result in CVD-related morbidity and mortality, namely accelerated aging via enhanced erosion of telomeres. This paper reviews the literature providing links among oxidative stress, accelerated erosion of telomeres, CVD, and specific sources and types of air pollutants. If certain PM species/sources might be responsible for adverse health outcomes via the proposed mechanism, perhaps the pathway to reducing mortality/morbidity from PM would become clearer. Not only would pollution

  3. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease.

    PubMed

    Yan, Michael H; Wang, Xinglong; Zhu, Xiongwei

    2013-09-01

    Alzheimer disease (AD) and Parkinson disease (PD) are the two most common age-related neurodegenerative diseases characterized by prominent neurodegeneration in selective neural systems. Although a small fraction of AD and PD cases exhibit evidence of heritability, among which many genes have been identified, the majority are sporadic without known causes. Molecular mechanisms underlying neurodegeneration and pathogenesis of these diseases remain elusive. Convincing evidence demonstrates oxidative stress as a prominent feature in AD and PD and links oxidative stress to the development of neuronal death and neural dysfunction, which suggests a key pathogenic role for oxidative stress in both AD and PD. Notably, mitochondrial dysfunction is also a prominent feature in these diseases, which is likely to be of critical importance in the genesis and amplification of reactive oxygen species and the pathophysiology of these diseases. In this review, we focus on changes in mitochondrial DNA and mitochondrial dynamics, two aspects critical to the maintenance of mitochondrial homeostasis and function, in relationship with oxidative stress in the pathogenesis of AD and PD.

  4. Protective effect of alpha-mangostin against oxidative stress induced-retinal cell death

    PubMed Central

    Fang, Yuan; Su, Tu; Qiu, Xiaorong; Mao, Pingan; Xu, Yidan; Hu, Zizhong; Zhang, Yi; Zheng, Xinhua; Xie, Ping; Liu, Qinghuai

    2016-01-01

    It is known that oxidative stress plays a pivotal role in age-related macular degeneration (AMD) pathogenesis. Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties. The aim of the study was to test the protective effect of alpha-mangostin against oxidative stress both in retina of light-damaged mice model and in hydrogen peroxide (H2O2)-stressed RPE cells. We observed that alpha-mangostin significantly inhibited light-induced degeneration of photoreceptors and 200 μM H2O2-induced apoptosis of RPE cells. 200 μM H2O2-induced generation of reactive oxygen species (ROS) and light-induced generation of malondialdehyde (MDA) were suppressed by alpha-mangostin. Alpha-mangostin stimulation resulted in an increase of superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity and glutathione (GSH) content both in vivo and vitro. Furthermore, the mechanism of retinal protection against oxidative stress by alpha-mangostin involves accumulation and the nuclear translocation of the NF-E2-related factor (Nrf2) along with up-regulation the expression of heme oxygenas-1 (HO-1). Meanwhile, alpha-mangostin can activate the expression of PKC-δ and down-regulate the expression of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, P38. The results suggest that alpha-mangostin could be a new approach to suspend the onset and development of AMD. PMID:26888416

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System.

    PubMed

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-02-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere's disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  15. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    PubMed Central

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  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 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.

  18. 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

  19. Age related degradation in operating nuclear plants

    SciTech Connect

    Hermann, R.A.; Davis, J.A.; Banic, M.J.

    1995-12-01

    The aging issues being addressed for today`s operating commercial nuclear power plants encompass a wide spectrum of components, complexities, and reasons for concern. Issues include such things as the intergranular stress corrosion cracking (IGSCC) of boiling water reactor (BWR) internals, the degradation of pressurized water reactor (PWR) Alloy 600 components by primary water stress corrosion cracking (PWSCC) to those associated with significant portions of piping systems, such as service water systems. a discussion of the regulatory activity and action associated with the above issues is provided. Proactive NRC/Industry programs for inspection and repair or replacement of affected components are essential for continued operation of these nuclear reactors. These programs are also essential as licensees consider license extensions for their facilities. These plants are licensed for 40 years and can be granted an extension for an additional 20 years of operation if all of the NRC rules and regulations are met. Proper handling of potential age related problems will be a key consideration in the granting of a license extension.

  20. 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.

  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. 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.

  3. 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

  4. 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

  5. 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.

  6. A Peroxiredoxin Promotes H2O2 Signaling and Oxidative Stress Resistance by Oxidizing a Thioredoxin Family Protein

    PubMed Central

    Brown, Jonathon D.; Day, Alison M.; Taylor, Sarah R.; Tomalin, Lewis E.; Morgan, Brian A.; Veal, Elizabeth A.

    2013-01-01

    Summary H2O2 can cause oxidative damage associated with age-related diseases such as diabetes and cancer but is also used to initiate diverse responses, including increased antioxidant gene expression. Despite significant interest, H2O2-signaling mechanisms remain poorly understood. Here, we present a mechanism for the propagation of an H2O2 signal that is vital for the adaptation of the model yeast, Schizosaccharomyces pombe, to oxidative stress. Peroxiredoxins are abundant peroxidases with conserved antiaging and anticancer activities. Remarkably, we find that the only essential function for the thioredoxin peroxidase activity of the Prx Tpx1(hPrx1/2) in resistance to H2O2 is to inhibit a conserved thioredoxin family protein Txl1(hTxnl1/TRP32). Thioredoxins regulate many enzymes and signaling proteins. Thus, our discovery that a Prx amplifies an H2O2 signal by driving the oxidation of a thioredoxin-like protein has important implications, both for Prx function in oxidative stress resistance and for responses to H2O2. PMID:24268782

  7. 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.

  8. Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain.

    PubMed

    Ullah, Faheem; Ali, Tahir; Ullah, Najeeb; Kim, Myeong Ok

    2015-11-01

    d-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against d-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against d-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK. Additionally, caffeine treatment significantly reduced the d-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNFα and IL-1β. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our results showed that caffeine prevents the d-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders.

  9. Blueberry treatment decreased D-galactose-induced oxidative stress and brain damage in rats.

    PubMed

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

    2015-06-01

    D-galactose (GAL) causes aging-related changes and oxidative stress in the organism. We investigated the effect of whole fresh blueberry (BB) (Vaccinium corymbosum L.) treatment on oxidative stress in age-related brain damage model. Rats received GAL (300 mg/kg; s.c.; 5 days per week) alone or together with 5 % (BB1) and 10 % (BB2) BB containing chow for two months. Malondialdehyde (MDA),protein carbonyl (PC) and glutathione (GSH) levels, and Cu Zn-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities as well as acetylcholinesterase (AChE) activities were determined. Expressions of B cell lymphoma-2 (Bcl-2), Bax and caspase-3 were also evaluated in the brain by immunohistochemistry. MDA and PC levels and AChE activity increased, but GSH levels, SOD and GSH-Px activities decreased together with histopathological structural damage in the brain of GAL-treated rats. BB treatments, especially BB2 reduced MDA and PC levels and AChE activity and elevated GSH levels and GSH-Px activity. BB1 and BB2 treatments diminished apoptosis and ameliorated histopathological findings in the brain of GAL-treated rats. These results indicate that BB partially prevented the shift towards an imbalanced prooxidative status and apoptosis together with histopathological amelioration by acting as an antioxidant (radical scavenger) itself in GAL-treated rats.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. [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

  3. 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.

  4. Age-related changes in the transcriptome of antibody-secreting cells

    PubMed Central

    Kurupati, Raj; Showe, Louise C.; Ertl, Hildegund C.J.

    2016-01-01

    We analyzed age-related defects in B cell populations from young and aged mice. Microarray analysis of bone marrow resident antibody secreting cells (ASCs) showed significant changes upon aging, affecting multiple genes, pathways and functions including those that play a role in immune regulation, humoral immune responses, chromatin structure and assembly, cell metabolism and the endoplasmic reticulum (ER) stress response. Further analysis showed upon aging defects in energy production through glucose catabolism with reduced oxidative phosphorylation. In addition aged B cells had increased levels of reactive oxygen-species (ROS), which was linked to enhanced expression of the co-inhibitor programmed cell death (PD)-1. PMID:26967249

  5. 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

  6. 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

  7. 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

  8. 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

  9. Mechanism of Inflammation in Age-Related Macular Degeneration

    PubMed Central

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  10. Age-related macular degeneration: experimental and emerging treatments

    PubMed Central

    Hubschman, Jean Pierre; Reddy, Shantan; Schwartz, Steven D

    2009-01-01

    Purpose: This essay reviews the experimental treatments and new imaging modalities that are currently being explored by investigators to help treat patients with age-related macular degeneration (AMD). Design: Interpretative essay. Methods: Literature review and interpretation. Results: Experimental treatments to preserve vision in patients with exudative AMD include blocking vascular endothelial growth factor (VEGF), binding VEGF, and modulating the VEGF receptors. Investigators are also attempting to block signal transduction with receptor tyrosine kinase inhibitors. Experimental treatments for non-exudative AMD include agents that target inflammation, oxidative stress, and implement immune-modulation. The effectiveness of these newer pharmacologic agents has the potential to grow exponentially when used in combination with new and improved imaging modalities that can help identify disease earlier and follow treatment response more precisely. Conclusion: With a better understanding, at the genetic and molecular level, of AMD and the development of superior imaging modalities, investigators are able to offer treatment options that may offer unprecedented visual gains while reducing the need for repetitive treatments. PMID:19668561

  11. 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.

  12. 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.

  13. 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...

  14. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  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. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  18. Methionine restriction affects oxidative stress and glutathione-related redox pathways in the rat.

    PubMed

    Maddineni, Sreenivasa; Nichenametla, Sailendra; Sinha, Raghu; Wilson, Ronald P; Richie, John P

    2013-04-01

    Lifelong dietary methionine restriction (MR) is associated with increased longevity and decreased incidence of age-related disorders and diseases in rats and mice. A reduction in the levels of oxidative stress may be a contributing mechanistic factor for the beneficial effects of MR. To examine this, we determined the effects of an 80% dietary restriction of Met on different biomarkers of oxidative stress and antioxidant pathways in blood, liver, kidney and brain in the rat. Male F-344 rats were fed control (0.86% methionine) or MR (0.17% methionine) diets for up to six months. Blood and tissues were analyzed for glutathione (GSH) concentrations, related enzyme activities and biomarkers of oxidative stress. MR was associated with reductions in oxidative stress biomarkers including plasma 8-hydoxydeoxyguanosine (8-OHdG) and 8-isoprostane and erythrocyte protein-bound glutathione after one month with levels remaining low for at least six months (P < 0.05). Levels of free GSH in blood were increased after 1-6 months of MR feeding whereas liver GSH levels were reduced over this time (P < 0.05). In MR rats, GSH peroxidase activity was decreased in liver and increased in kidney compared with controls. No changes in the activities of GSH reductase in liver and kidney and superoxide dismutase in liver were observed as a result of MR feeding. Altogether, these findings indicate that oxidative stress is reduced by MR feeding in rats, but this effect cannot be explained by changes in the activity of antioxidant enzymes.

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

    PubMed

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

    2013-12-01

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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Oxidative stress: the achilles' heel of neurodegenerative diseases of the retina.

    PubMed

    Cai, Xue; McGinnis, James F

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness among adults in the developed countries. It is characterized by the progressive loss of central vision. AMD is classified into two forms: dry and wet. Dry AMD involves the accumulation of deposits in the RPE and Bruch's membrane; Wet AMD is characterized by neovascularization in the choroid. Whether the two forms of AMD share the same mechanism for the disease development is presently not clear. Oxidative stress, inflammation, and ER-stress are the common modes for the pathogenesis of AMD. In addition, other risk factors and several signaling pathways have been implicated as causative factors of AMD. In this paper, the mechanisms underlying AMD, risk factors involved in the pathology, representative animal models, and therapeutic treatment strategies are reviewed.

  6. 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

  7. Hypertension and physical exercise: The role of oxidative stress.

    PubMed

    Korsager Larsen, Monica; Matchkov, Vladimir V

    2016-01-01

    Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress and endothelial function. The aim of this review is to investigate the effect of oxidative stress in relation to hypertension and physical exercise, including the role of NO in the pathogenesis of hypertension. Endothelial dysfunction and decreased NO levels have been found to have the adverse effects in the correlation between oxidative stress and hypertension. Most of the previous studies found that aerobic exercise significantly decreased blood pressure and oxidative stress in hypertensive subjects, but the intense aerobic exercise can also injure endothelial cells. Isometric exercise decreases normally only systolic blood pressure. An alternative exercise, Tai chi significantly decreases blood pressure and oxidative stress in normotensive elderly, but the effect in hypertensive subjects has not yet been studied. Physical exercise and especially aerobic training can be suggested as an effective intervention in the prevention and treatment of hypertension and cardiovascular disease via reduction in oxidative stress. PMID:26987496

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  11. Aldehyde Dehydrogenases in Cellular Responses to Oxidative/electrophilic Stress

    PubMed Central

    Singh, Surendra; Brocker, Chad; Koppaka, Vindhya; Ying, Chen; Jackson, Brian; Matsumoto, Akiko; Thompson, David C.; Vasiliou, Vasilis

    2013-01-01

    Reactive oxygen species (ROS) are continuously generated within living systems and the inability to manage ROS load leads to elevated oxidative stress and cell damage. Oxidative stress is coupled to the oxidative degradation of lipid membranes, also known as lipid peroxidation. This process generates over 200 types of aldehydes, many of which are highly reactive and toxic. Aldehyde dehydrogenases (ALDHs) metabolize endogenous and exogenous aldehydes and thereby mitigate oxidative/electrophilic stress in prokaryotic and eukaryotic organisms. ALDHs are found throughout the evolutionary gamut, from single celled organisms to complex multicellular species. Not surprisingly, many ALDHs in evolutionarily distant, and seemingly unrelated, species perform similar functions, including protection against a variety of environmental stressors like dehydration and ultraviolet radiation. The ability to act as an ‘aldehyde scavenger’ during lipid peroxidation is another ostensibly universal ALDH function found across species. Up-regulation of ALDHs is a stress response in bacteria (environmental and chemical stress), plants (dehydration, salinity and oxidative stress), yeast (ethanol exposure and oxidative stress), Caenorhabditis elegans (lipid peroxidation) and mammals (oxidative stress and lipid peroxidation). Recent studies have also identified ALDH activity as an important feature of cancer stem cells. In these cells, ALDH expression helps abrogate oxidative stress and imparts resistance against chemotherapeutic agents such as oxazaphosphorine, taxane and platinum drugs. The ALDH superfamily represents a fundamentally important class of enzymes that significantly contributes to the management of electrophilic/oxidative stress within living systems. Mutations in various ALDHs are associated with a variety of pathological conditions in humans, underscoring the fundamental importance of these enzymes in physiological and pathological processes. PMID:23195683

  12. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress.

    PubMed

    Singh, Surendra; Brocker, Chad; Koppaka, Vindhya; Chen, Ying; Jackson, Brian C; Matsumoto, Akiko; Thompson, David C; Vasiliou, Vasilis

    2013-03-01

    Reactive oxygen species (ROS) are continuously generated within living systems and the inability to manage ROS load leads to elevated oxidative stress and cell damage. Oxidative stress is coupled to the oxidative degradation of lipid membranes, also known as lipid peroxidation. This process generates over 200 types of aldehydes, many of which are highly reactive and toxic. Aldehyde dehydrogenases (ALDHs) metabolize endogenous and exogenous aldehydes and thereby mitigate oxidative/electrophilic stress in prokaryotic and eukaryotic organisms. ALDHs are found throughout the evolutionary gamut, from single-celled organisms to complex multicellular species. Not surprisingly, many ALDHs in evolutionarily distant, and seemingly unrelated, species perform similar functions, including protection against a variety of environmental stressors such as dehydration and ultraviolet radiation. The ability to act as an "aldehyde scavenger" during lipid peroxidation is another ostensibly universal ALDH function found across species. Upregulation of ALDHs is a stress response in bacteria (environmental and chemical stress), plants (dehydration, salinity, and oxidative stress), yeast (ethanol exposure and oxidative stress), Caenorhabditis elegans (lipid peroxidation), and mammals (oxidative stress and lipid peroxidation). Recent studies have also identified ALDH activity as an important feature of cancer stem cells. In these cells, ALDH expression helps abrogate oxidative stress and imparts resistance against chemotherapeutic agents such as oxazaphosphorine, taxane, and platinum drugs. The ALDH superfamily represents a fundamentally important class of enzymes that contributes significantly to the management of electrophilic/oxidative stress within living systems. Mutations in various ALDHs are associated with a variety of pathological conditions in humans, highlighting the fundamental importance of these enzymes in physiological and pathological processes. PMID:23195683

  13. Aldehyde dehydrogenases in cellular responses to oxidative/electrophilic stress.

    PubMed

    Singh, Surendra; Brocker, Chad; Koppaka, Vindhya; Chen, Ying; Jackson, Brian C; Matsumoto, Akiko; Thompson, David C; Vasiliou, Vasilis

    2013-03-01

    Reactive oxygen species (ROS) are continuously generated within living systems and the inability to manage ROS load leads to elevated oxidative stress and cell damage. Oxidative stress is coupled to the oxidative degradation of lipid membranes, also known as lipid peroxidation. This process generates over 200 types of aldehydes, many of which are highly reactive and toxic. Aldehyde dehydrogenases (ALDHs) metabolize endogenous and exogenous aldehydes and thereby mitigate oxidative/electrophilic stress in prokaryotic and eukaryotic organisms. ALDHs are found throughout the evolutionary gamut, from single-celled organisms to complex multicellular species. Not surprisingly, many ALDHs in evolutionarily distant, and seemingly unrelated, species perform similar functions, including protection against a variety of environmental stressors such as dehydration and ultraviolet radiation. The ability to act as an "aldehyde scavenger" during lipid peroxidation is another ostensibly universal ALDH function found across species. Upregulation of ALDHs is a stress response in bacteria (environmental and chemical stress), plants (dehydration, salinity, and oxidative stress), yeast (ethanol exposure and oxidative stress), Caenorhabditis elegans (lipid peroxidation), and mammals (oxidative stress and lipid peroxidation). Recent studies have also identified ALDH activity as an important feature of cancer stem cells. In these cells, ALDH expression helps abrogate oxidative stress and imparts resistance against chemotherapeutic agents such as oxazaphosphorine, taxane, and platinum drugs. The ALDH superfamily represents a fundamentally important class of enzymes that contributes significantly to the management of electrophilic/oxidative stress within living systems. Mutations in various ALDHs are associated with a variety of pathological conditions in humans, highlighting the fundamental importance of these enzymes in physiological and pathological processes.

  14. Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis.

    PubMed

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

    2013-12-01

    Sporadic amyotrophic lateral sclerosis (ALS) 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/antioxidative 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 that 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 supports 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

  15. 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.

  16. Parainflammation, chronic inflammation, and age-related macular degeneration.

    PubMed

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration.

  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 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

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

    PubMed

    Jordan, Katherine W; Craver, Kyle L; Magwire, Michael M; Cubilla, Carmen E; Mackay, Trudy F C; Anholt, Robert R H

    2012-01-01

    Reactive oxygen species (ROS) are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host defense mechanisms. However, an imbalance of ROS induces oxidative stress and cellular death and is associated with human disease, including age-related locomotor impairment. To identify genes affecting sensitivity and resistance to ROS-induced locomotor decline, we assessed locomotion of aged flies of the sequenced, wild-derived lines from the Drosophila melanogaster Genetics Reference Panel on standard medium and following chronic exposure to medium supplemented with 3 mM menadione sodium bisulfite (MSB). We found substantial genetic variation in sensitivity to oxidative stress with respect to locomotor phenotypes. We performed genome-wide association analyses to identify candidate genes associated with variation in sensitivity to ROS-induced decline in locomotor performance, and confirmed the effects for 13 of 16 mutations tested in these candidate genes. Candidate genes associated with variation in sensitivity to MSB-induced oxidative stress form networks of genes involved in neural development, immunity, and signal transduction. Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease. PMID:22715409

  20. 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

  1. Aldose Reductase, Oxidative Stress, and Diabetic Mellitus

    PubMed Central

    Tang, Wai Ho; Martin, Kathleen A.; Hwa, John

    2012-01-01

    Diabetes mellitus (DM) is a complex metabolic disorder arising from lack of insulin production or insulin resistance (Diagnosis and classification of diabetes mellitus, 2007). DM is a leading cause of morbidity and mortality in the developed world, particularly from vascular complications such as atherothrombosis in the coronary vessels. Aldose reductase (AR; ALR2; EC 1.1.1.21), a key enzyme in the polyol pathway, catalyzes nicotinamide adenosine dinucleotide phosphate-dependent reduction of glucose to sorbitol, leading to excessive accumulation of intracellular reactive oxygen species (ROS) in various tissues of DM including the heart, vasculature, neurons, eyes, and kidneys. As an example, hyperglycemia through such polyol pathway induced oxidative stress, may have dual heart actions, on coronary blood vessel (atherothrombosis) and myocardium (heart failure) leading to severe morbidity and mortality (reviewed in Heather and Clarke, 2011). In cells cultured under high glucose conditions, many studies have demonstrated similar AR-dependent increases in ROS production, confirming AR as an important factor for the pathogenesis of many diabetic complications. Moreover, recent studies have shown that AR inhibitors may be able to prevent or delay the onset of cardiovascular complications such as ischemia/reperfusion injury, atherosclerosis, and atherothrombosis. In this review, we will focus on describing pivotal roles of AR in the pathogenesis of cardiovascular diseases as well as other diabetic complications, and the potential use of AR inhibitors as an emerging therapeutic strategy in preventing DM complications. PMID:22582044

  2. Aldose reductase, oxidative stress, and diabetic mellitus.

    PubMed

    Tang, Wai Ho; Martin, Kathleen A; Hwa, John

    2012-01-01

    Diabetes mellitus (DM) is a complex metabolic disorder arising from lack of insulin production or insulin resistance (Diagnosis and classification of diabetes mellitus, 2007). DM is a leading cause of morbidity and mortality in the developed world, particularly from vascular complications such as atherothrombosis in the coronary vessels. Aldose reductase (AR; ALR2; EC 1.1.1.21), a key enzyme in the polyol pathway, catalyzes nicotinamide adenosine dinucleotide phosphate-dependent reduction of glucose to sorbitol, leading to excessive accumulation of intracellular reactive oxygen species (ROS) in various tissues of DM including the heart, vasculature, neurons, eyes, and kidneys. As an example, hyperglycemia through such polyol pathway induced oxidative stress, may have dual heart actions, on coronary blood vessel (atherothrombosis) and myocardium (heart failure) leading to severe morbidity and mortality (reviewed in Heather and Clarke, 2011). In cells cultured under high glucose conditions, many studies have demonstrated similar AR-dependent increases in ROS production, confirming AR as an important factor for the pathogenesis of many diabetic complications. Moreover, recent studies have shown that AR inhibitors may be able to prevent or delay the onset of cardiovascular complications such as ischemia/reperfusion injury, atherosclerosis, and atherothrombosis. In this review, we will focus on describing pivotal roles of AR in the pathogenesis of cardiovascular diseases as well as other diabetic complications, and the potential use of AR inhibitors as an emerging therapeutic strategy in preventing DM complications. PMID:22582044

  3. Effect of Oxidative Stress on Male Reproduction

    PubMed Central

    Virk, Gurpriya; Ong, Chloe; du Plessis, Stefan S

    2014-01-01

    Infertility affects approximately 15% of couples trying to conceive, and a male factor contributes to roughly half of these cases. Oxidative stress (OS) has been identified as one of the many mediators of male infertility by causing sperm dysfunction. OS is a state related to increased cellular damage triggered by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). During this process, augmented production of ROS overwhelms the body's antioxidant defenses. While small amounts of ROS are required for normal sperm functioning, disproportionate levels can negatively impact the quality of spermatozoa and impair their overall fertilizing capacity. OS has been identified as an area of great attention because ROS and their metabolites can attack DNA, lipids, and proteins; alter enzymatic systems; produce irreparable alterations; cause cell death; and ultimately, lead to a decline in the semen parameters associated with male infertility. This review highlights the mechanisms of ROS production, the physiological and pathophysiological roles of ROS in relation to the male reproductive system, and recent advances in diagnostic methods; it also explores the benefits of using antioxidants in a clinical setting. PMID:24872947

  4. Peroxiredoxins, oxidative stress, and cell proliferation.

    PubMed

    Immenschuh, Stephan; Baumgart-Vogt, Eveline

    2005-01-01

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

  5. Tyrosine phosphorylation of clathrin heavy chain under oxidative stress.

    PubMed

    Ihara, Yoshito; Yasuoka, Chie; Kageyama, Kan; Wada, Yoshinao; Kondo, Takahito

    2002-09-20

    In mouse pancreatic insulin-producing betaTC cells, oxidative stress due to H(2)O(2) causes tyrosine phosphorylation in various proteins. To identify proteins bearing phosphotyrosine under stress, the proteins were affinity purified using an anti-phosphotyrosine antibody-conjugated agarose column. A protein of 180kDa was identified as clathrin heavy chain (CHC) by electrophoresis and mass spectrometry. Immunoprecipitated CHC showed tyrosine phosphorylation upon H(2)O(2) treatment and the phosphorylation was suppressed by the Src kinase inhibitor, PP2. The phosphorylation status of CHC affected the intracellular localization of CHC and the clathrin-dependent endocytosis of transferrin under oxidative stress. In conclusion, CHC is a protein that is phosphorylated at tyrosine by H(2)O(2) and this phosphorylation status is implicated in the intracellular localization and functions of CHC under oxidative stress. The present study demonstrates that oxidative stress affects intracellular vesicular trafficking via the alteration of clathrin-dependent vesicular trafficking.

  6. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?

    PubMed Central

    Hussain, Tarique; Yin, Yulong; Blachier, Francois; Tossou, Myrlene C. B.; Rahu, Najma

    2016-01-01

    Oxidative stress is viewed as an imbalance between the production of reactive oxygen species (ROS) and their elimination by protective mechanisms, which can lead to chronic inflammation. Oxidative stress can activate a variety of transcription factors, which lead to the differential expression of some genes involved in inflammatory pathways. The inflammation triggered by oxidative stress is the cause of many chronic diseases. Polyphenols have been proposed to be useful as adjuvant therapy for their potential anti-inflammatory effect, associated with antioxidant activity, and inhibition of enzymes involved in the production of eicosanoids. This review aims at exploring the properties of polyphenols in anti-inflammation and oxidation and the mechanisms of polyphenols inhibiting molecular signaling pathways which are activated by oxidative stress, as well as the possible roles of polyphenols in inflammation-mediated chronic disorders. Such data can be helpful for the development of future antioxidant therapeutics and new anti-inflammatory drugs. PMID:27738491

  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. Ameliorative effect of aspalathin from rooibos (Aspalathus linearis) on acute oxidative stress in Caenorhabditis elegans.

    PubMed

    Chen, Wei; Sudji, Ikhwan Resmala; Wang, Erjia; Joubert, Elizabeth; van Wyk, Ben-Erik; Wink, Michael

    2013-02-15

    Rooibos leaves and fine stems (Aspalathus linearis; Fabaceae) are increasingly enjoyed as herbal tea, largely in fermented (oxidised) red-brown form, but also in unfermented (unoxidised) green form. Rooibos is rich in antioxidant polyphenols, with the dihydrochalcone, aspalathin, as a major active ingredient. We used Caenorhabditis elegans as model organism to investigate the effect of rooibos extracts against oxidative stress in vivo. In a high glucose environment, C. elegans treated with rooibos extract exhibited an extended lifespan. Furthermore, green rooibos was a more potent antioxidant than red rooibos, probably due to its substantially higher aspalathin content. In addition, rooibos decreased acute oxidative damage caused by the superoxide anion radical generator, juglone, with aspalathin playing a major role in improving the survival rate of C. elegans. Quantitative real-time PCR results demonstrated that aspalathin targets stress and ageing related genes, reducing the endogenous intracellular level of ROS. These findings suggest that rooibos increases stress resistance and promotes longevity under stress, probably mediated via a regulation of the DAF-16/FOXO insulin-like signalling pathway, supporting some of the health claims put forward for rooibos tea. PMID:23218401

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

    PubMed Central

    Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

    2016-01-01

    Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

  10. Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies.

    PubMed

    Rani, Vibha; Deep, Gagan; Singh, Rakesh K; Palle, Komaraiah; Yadav, Umesh C S

    2016-03-01

    Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy.

  11. GENETICS OF HUMAN AGE RELATED DISORDERS.

    PubMed

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

  12. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  13. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

    PubMed

    Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

    2015-12-01

    Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

  14. Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation

    PubMed Central

    Hytti, Maria; Piippo, Niina; Korhonen, Eveliina; Honkakoski, Paavo; Kaarniranta, Kai; Kauppinen, Anu

    2015-01-01

    Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD. PMID:26619957

  15. Markers of oxidative stress and erythrocyte antioxidant enzyme activity in older men and women with differing physical activity.

    PubMed

    Rowiński, Rafał; Kozakiewicz, Mariusz; Kędziora-Kornatowska, Kornelia; Hübner-Woźniak, Elżbieta; Kędziora, Józef

    2013-11-01

    The aim of the present study was to examine the relationship between markers of oxidative stress and erythrocyte antioxidant enzyme activity and physical activity in older men and women. The present study included 481 participants (233 men and 248 women) in the age group 65-69 years (127 men and 125 women) and in the age group 90 years and over (106 men and 123 women). The classification of respondents by physical activity was based on answers to the question if, in the past 12 months, they engaged in any pastimes which require physical activity. The systemic oxidative stress status was assessed by measuring plasma iso-PGF2α and protein carbonyl concentration as well as erythrocyte antioxidant enzymes activity, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The concentration of plasma iso-PGF2α and protein carbonyls (CP) was lower in groups of younger men and women compared to the respective older groups. In all examined groups, physical activity resulted in decrease of these oxidative stress markers and simultaneously caused adaptive increase in the erythrocyte SOD activity. Additionally, in active younger men CAT, GPx, and GR activities were higher than in sedentary ones. In conclusion, oxidative stress increase is age-related, but physical activity can reduce oxidative stress markers and induce adaptive increase in the erythrocyte antioxidant enzyme activity, especially SOD, even in old and very old men and women.

  16. The Role of Flavonoids on Oxidative Stress in Epilepsy

    PubMed Central

    Diniz, Tâmara Coimbra; Silva, Juliane Cabral; de Lima-Saraiva, Sarah Raquel Gomes; Ribeiro, Fernanda Pires Rodrigues de Almeida; Pacheco, Alessandra Gomes Marques; de Freitas, Rivelilson Mendes; Quintans-Júnior, Lucindo José; Quintans, Jullyana de Souza Siqueira; Mendes, Rosemairy Luciane; Almeida, Jackson Roberto Guedes da Silva

    2015-01-01

    Backgrounds. Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. Objective. This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed. Results/Conclusions. There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy. PMID:25653736

  17. Increased Age-Related Cardiac Dysfunction in Bradykinin B2 Receptor-Deficient Mice.

    PubMed

    Feng, Wenjing; Xu, Xizhen; Zhao, Gang; Zhao, Junjie; Dong, Ruolan; Ma, Ben; Zhang, Yanjun; Long, Guangwen; Wang, Dao Wen; Tu, Ling

    2016-02-01

    Experimental evidence indicates that the kinin peptide binds to bradykinin B2 receptor (B2R) to trigger various beneficial effects on the cardiovascular system. However, the effects and underlying mechanisms of B2R in cardiac aging remain unknown. A significant age-dependent decrease in B2R expression in the myocardium was observed in C57BL/6J mice. Echocardiographic measurements showed that aging caused a significant cardiac dysfunction in C57BL/6J mice, and importantly B2R deficiency augmented this dysfunction in aging mice. The deficiency of B2R expression in the aging heart repressed p53-pGC-1α-induced mitochondria renewal, increased reactive oxygen species production, and destroyed mitochondrial ultrastructure. Age-related decrease or lack of B2R increased oxidative stress, macrophage infiltration, and inflammatory cytokine expression and compromised antioxidant enzyme expression. Moreover, the inflammatory signals were mainly mediated by the activation of p38 MAPK, JNK, and subsequent translocation of nuclear factor-kappa B to the nucleus. In summary, our data provide evidence that B2R deficiency contributes to the aging-induced cardiac dysfunction, which is likely mediated by increased mitochondrial dysfunction, oxidative stress, and inflammation. This study indicates that preventing the loss of cardioprotective B2R expression may be a novel approach for the prevention and treatment of age-related cardiac dysfunction.

  18. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    PubMed Central

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988

  19. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

    PubMed

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988

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

    PubMed

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

    2015-05-01

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

  1. Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology

    PubMed Central

    Jaquet, Vincent; Trabace, Luigia; Krause, Karl-Heinz

    2013-01-01

    Abstract Significance: Severe life stress (SLS), as opposed to trivial everyday stress, is defined as a serious psychosocial event with the potential of causing an impacting psychological traumatism. Recent Advances: Numerous studies have attempted to understand how the central nervous system (CNS) responds to SLS. This response includes a variety of morphological and neurochemical modifications; among them, oxidative stress is almost invariably observed. Oxidative stress is defined as disequilibrium between oxidant generation and the antioxidant response. Critical Issues: In this review, we discuss how SLS leads to oxidative stress in the CNS, and how the latter impacts pathophysiological outcomes. We also critically discuss experimental methods that measure oxidative stress in the CNS. The review covers animal models and human observations. Animal models of SLS include sleep deprivation, maternal separation, and social isolation in rodents, and the establishment of hierarchy in non-human primates. In humans, SLS, which is caused by traumatic events such as child abuse, war, and divorce, is also accompanied by oxidative stress in the CNS. Future Directions: The outcome of SLS in humans ranges from resilience, over post-traumatic stress disorder, to development of chronic mental disorders. Defining the sources of oxidative stress in SLS might in the long run provide new therapeutic avenues. Antioxid. Redox Signal. 18, 1475–1490. PMID:22746161

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

    PubMed

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

    2016-07-15

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

  3. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver

    PubMed Central

    Satapati, Santhosh; Kucejova, Blanka; Duarte, Joao A.G.; Fletcher, Justin A.; Reynolds, Lacy; Sunny, Nishanth E.; He, Tianteng; Nair, L. Arya; Livingston, Kenneth; Fu, Xiaorong; Merritt, Matthew E.; Sherry, A. Dean; Malloy, Craig R.; Shelton, John M.; Lambert, Jennifer; Parks, Elizabeth J.; Corbin, Ian; Magnuson, Mark A.; Browning, Jeffrey D.; Burgess, Shawn C.

    2015-01-01

    Mitochondria are critical for respiration in all tissues; however, in liver, these organelles also accommodate high-capacity anaplerotic/cataplerotic pathways that are essential to gluconeogenesis and other biosynthetic activities. During nonalcoholic fatty liver disease (NAFLD), mitochondria also produce ROS that damage hepatocytes, trigger inflammation, and contribute to insulin resistance. Here, we provide several lines of evidence indicating that induction of biosynthesis through hepatic anaplerotic/cataplerotic pathways is energetically backed by elevated oxidative metabolism and hence contributes to oxidative stress and inflammation during NAFLD. First, in murine livers, elevation of fatty acid delivery not only induced oxidative metabolism, but also amplified anaplerosis/cataplerosis and caused a proportional rise in oxidative stress and inflammation. Second, loss of anaplerosis/cataplerosis via genetic knockdown of phosphoenolpyruvate carboxykinase 1 (Pck1) prevented fatty acid–induced rise in oxidative flux, oxidative stress, and inflammation. Flux appeared to be regulated by redox state, energy charge, and metabolite concentration, which may also amplify antioxidant pathways. Third, preventing elevated oxidative metabolism with metformin also normalized hepatic anaplerosis/cataplerosis and reduced markers of inflammation. Finally, independent histological grades in human NAFLD biopsies were proportional to oxidative flux. Thus, hepatic oxidative stress and inflammation are associated with elevated oxidative metabolism during an obesogenic diet, and this link may be provoked by increased work through anabolic pathways. PMID:26571396

  4. Protective mechanisms of Cucumis sativus in diabetes-related modelsof oxidative stress and carbonyl stress

    PubMed Central

    Heidari, Himan; Kamalinejad, Mohammad; Noubarani, Maryam; Rahmati, Mokhtar; Jafarian, Iman; Adiban, Hasan; Eskandari, Mohammad Reza

    2016-01-01

    Introduction: Oxidative stress and carbonyl stress have essential mediatory roles in the development of diabetes and its related complications through increasing free radicals production and impairing antioxidant defense systems. Different chemical and natural compounds have been suggested for decreasing such disorders associated with diabetes. The objectives of the present study were to investigate the protective effects of Cucumis sativus (C. sativus) fruit (cucumber) in oxidative and carbonyl stress models. These diabetes-related models with overproduction of reactive oxygen species (ROS) and reactive carbonyl species (RCS) simulate conditions observed in chronic hyperglycemia. Methods: Cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonyl stress model) were measured and the protective effects of C. sativus were evaluated using freshly isolated rat hepatocytes. Results: Aqueous extract of C. sativus fruit (40 μg/mL) prevented all cytotoxicity markers in both the oxidative and carbonyl stress models including cell lysis, ROS formation, membrane lipid peroxidation, depletion of glutathione, mitochondrial membrane potential decline, lysosomal labialization, and proteolysis. The extract also protected hepatocytes from protein carbonylation induced by glyoxal. Our results indicated that C. sativus is able to prevent oxidative stress and carbonyl stress in the isolated hepatocytes. Conclusion: It can be concluded that C. sativus has protective effects in diabetes complications and can be considered a safe and suitable candidate for decreasing the oxidative stress and carbonyl stress that is typically observed in diabetes mellitus. PMID:27340622

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

    PubMed

    Zimmer, Cédric; Spencer, Karen A

    2015-05-01

    Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context.

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

    PubMed

    Zimmer, Cédric; Spencer, Karen A

    2015-05-01

    Stress exposure during early-life development can have long-term consequences for a variety of biological functions including oxidative stress. The link between early-life stress and oxidative balance is beginning to be explored and previous studies have focused on this link in adult non-breeding or immature individuals. However, as oxidative stress is considered as the main physiological mechanism underlying the trade-off between self-maintenance and investment in reproduction, it is necessary to look at the consequences of early-life stress on oxidative status during reproduction. Here, we investigated the effects of exposure to pre- and/or post-natal stress on oxidative balance during reproduction under benign or stressful environmental conditions in an avian model species, the Japanese quail. We determined total antioxidant status (TAS), total oxidant status (TOS) and resistance to a free-radical attack in individual exposed to pre-natal stress, post-natal stress or both and in control individuals exposed to none of the stressors. TAS levels decreased over time in all females that reproduced under stressful conditions. TOS decreased between the beginning and the end of reproductive period in pre-natal control females. In all females, resistance to a free-radical attack decreased over the reproductive event but this decrease was more pronounced in females from a pre-natal stress development. Our results suggest that pre-natal stress may be associated with a higher cost of reproduction in terms of oxidative stress. These results also confirm that early-life stress can be associated with both benefits and costs depending of the life-history stage or environmental context. PMID:25542633

  7. 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.

  8. Oxidized Extracellular DNA as a Stress Signal in Human Cells

    PubMed Central

    Ermakov, Aleksei V.; Konkova, Marina S.; Kostyuk, Svetlana V.; Izevskaya, Vera L.; Veiko, Natalya N.

    2013-01-01

    The term “cell-free DNA” (cfDNA) was recently coined for DNA fragments from plasma/serum, while DNA present in in vitro cell culture media is known as extracellular DNA (ecDNA). Under oxidative stress conditions, the levels of oxidative modification of cellular DNA and the rate of cell death increase. Dying cells release their damaged DNA, thus, contributing oxidized DNA fragments to the pool of cfDNA/ecDNA. Oxidized cell-free DNA could serve as a stress signal that promotes irradiation-induced bystander effect. Evidence points to TLR9 as a possible candidate for oxidized DNA sensor. An exposure to oxidized ecDNA stimulates a synthesis of reactive oxygen species (ROS) that evokes an adaptive response that includes transposition of the homologous loci within the nucleus, polymerization and the formation of the stress fibers of the actin, as well as activation of the ribosomal gene expression, and nuclear translocation of NF-E2 related factor-2 (NRF2) that, in turn, mediates induction of phase II detoxifying and antioxidant enzymes. In conclusion, the oxidized DNA is a stress signal released in response to oxidative stress in the cultured cells and, possibly, in the human body; in particular, it might contribute to systemic abscopal effects of localized irradiation treatments. PMID:23533696

  9. Antioxidant-enriched diet does not delay the progression of age-related hearing loss.

    PubMed

    Sha, Su-Hua; Kanicki, Ariane; Halsey, Karin; Wearne, Kimberly Anne; Schacht, Jochen

    2012-05-01

    Oxidative stress has been linked to noise- and drug-induced as well as age-related hearing loss. Antioxidants can attenuate the decline of cochlear structure and function after exposure to noise or drugs, but it is debated as to whether they can protect from age-related hearing loss. In a long-term longitudinal study, 10-month-old female CBA/J mice were placed on either a control or antioxidant-enriched diet and monitored through 24 months of age. Supplementation with vitamins A, C, and E, L-carnitine, and α-lipoic acid significantly increased the antioxidant capacity of inner ear tissues. However, by 24 months of age, the magnitude of hearing loss was equal between the two groups. Likewise, there were no significant differences in hair cell loss or degeneration of spiral ganglion cells. We conclude that dietary manipulations can alter cochlear antioxidant capacity but do not ameliorate age-related sensorineural hearing loss in the CBA/J mouse. PMID:22154190

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

    PubMed Central

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

    2016-01-01

    Objective To investigate if salivary nitrate correlates to the daily psychological stress and anxiety in a group of human subjects. Methods The convenient sample recruitment method was employed; data from seventy three subjects were analyzed. The Perceived Stress Scale (PSS) and Hamilton Anxiety Rating Scale (HAM-A) inventories were used to determine stress and anxiety scores respectively. Salivary nitric oxide was measured through nitrate (NOx) levels using the Griess reaction method. Results Although stress and anxiety were correlated. No significant correlation exists between salivary nitrate and daily psychological stress and anxiety in the study's participants. Conclusion While all previous studies focused NOx levels in acute stress models. This is the first study to investigate the correlation between salivary nitrates and daily psychological stress and anxiety. Although stress and anxiety were correlated, there is no correlation between salivary nitrates and daily psychological stress and anxiety. Further studies are required to investigate this correlation using other biological samples such as plasma. PMID:27247597

  11. Oxidative stress in juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum)

    USGS Publications Warehouse

    Welker, T.L.; Congleton, J.L.

    2004-01-01

    Juvenile chinook salmon, Oncorhynchus tshawytscha (Walbaum), were held in 8-11??C freshwater, starved for 3 days and subjected to a low-water stressor to determine the relationship between the general stress response and oxidative stress. Lipid peroxidation (LPO) levels (lipid hydroperoxides) were measured in kidney, liver and brain samples taken at the beginning of the experiment (0-h unstressed controls) and at 6, 24 and 48 h after application of a continuous low-water stressor. Tissue samples were also taken at 48 h from fish that had not been exposed to the stressor (48-h unstressed controls). Exposure to the low-water stressor affected LPO in kidney and brain tissues. In kidney, LPO decreased 6 h after imposition of the stressor; similar but less pronounced decreases also occurred in the liver and brain. At 48 h, LPO increased (in comparison with 6-h stressed tissues) in the kidney and brain. In comparison with 48-h unstressed controls, LPO levels were higher in the kidney and brain of stressed fish. Although preliminary, results suggest that stress can cause oxidative tissue damage in juvenile chinook salmon. Measures of oxidative stress have shown similar responses to stress in mammals; however, further research is needed to determine the extent of the stress-oxidative stress relationship and the underlying physiological mechanisms in fish.

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

    PubMed

    Rebbani, Khadija; Tsukiyama-Kohara, Kyoko

    2016-01-01

    About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis. PMID:27293514

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

    PubMed Central

    Rebbani, Khadija; Tsukiyama-Kohara, Kyoko

    2016-01-01

    About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis. PMID:27293514

  14. The Role of Oxidative Stress in Neurodegenerative Diseases

    PubMed Central

    Kim, Geon Ha; Kim, Jieun E.; Rhie, Sandy Jeong

    2015-01-01

    Oxidative stress is induced by an imbalanced redox states, involving either excessive generation of reactive oxygen species (ROS) or dysfunction of the antioxidant system. The brain is one of organs especially vulnerable to the effects of ROS because of its high oxygen demand and its abundance of peroxidation-susceptible lipid cells. Previous studies have demonstrated that oxidative stress plays a central role in a common pathophysiology of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases, although the results with regard to their efficacy of treating neurodegenerative disease have been inconsistent. In this review, we will discuss the role of oxidative stress in the pathophysiology of neurodegenerative diseases and in vivo measurement of an index of damage by oxidative stress. Moreover, the present knowledge on antioxidant in the treatment of neurodegenerative diseases and future directions will be outlined. PMID:26713080

  15. OXIDATIVE STRESS STATUS IN HUMANS WITH METABOLIC SYNDROME

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Each component of the constellation of Metabolic Syndrome signs - dyslipidemia, hyperglycemia, hypertension, and obesity - has been associated, though not unequivocally, with an elevation of oxidative stress. Moreover, reductions in these conditions appear generally associated with attenuation of b...

  16. Futile cycling increases sensitivity toward oxidative stress in Escherichia coli

    PubMed Central

    Adolfsen, Kristin J.; Brynildsen, Mark P.

    2015-01-01

    Reactive oxygen species (ROS) are toxic molecules utilized by the immune system to combat invading pathogens. Recent evidence suggests that inefficiencies in ATP production or usage can lead to increased endogenous ROS production and sensitivity to oxidative stress in bacteria. With this as inspiration, and knowledge that ATP is required for a number of DNA repair mechanisms, we hypothesized that futile cycling would be an effective way to increase sensitivity to oxidative stress. We developed a mixed integer linear optimization framework to identify experimentally-tractable futile cycles, and confirmed metabolic modeling predictions that futile cycling depresses growth rate, and increases both O2 consumption and ROS production per biomass generated. Further, intracellular ATP was decreased and sensitivity to oxidative stress increased in all actively cycling strains compared to their catalytically inactive controls. This research establishes a fundamental connection between ATP metabolism, endogenous ROS production, and tolerance toward oxidative stress in bacteria. PMID:25732623

  17. Inhibition of phagocytic activity of ARPE-19 cells by free radical mediated oxidative stress.

    PubMed

    Olchawa, Magdalena M; Pilat, Anna K; Szewczyk, Grzegorz M; Sarna, Tadeusz Jan

    2016-08-01

    Oxidative stress is a main factor responsible for key changes leading to the onset of age-related macular degeneration (ARMD) that occur in the retinal pigment epithelium (RPE), which is involved in phagocytosis of photoreceptor outer segments (POS). In this study, hydrogen peroxide (H2O2), H2O2 and iron ions (Fe) or rose Bengal (RB) in the presence of NADH and Fe were used to model free radical mediated oxidative stress to test if free radicals and singlet oxygen have different efficiency to inhibit phagocytosis of ARPE-19 cells. Free radical mediated oxidative stress was confirmed by HPLC-EC(Hg) measurements of cholesterol hydroperoxides in treated cells. Electron paramagnetic resonance (EPR) spin trapping was employed to detect superoxide anion. Cell survival was analyzed by the MTT assay. Specific phagocytosis of fluorescein-5-isothiocyanate-labeled POS and non-specific phagocytosis of fluorescent beads were measured by flow cytometry. HPLC analysis of cells photosensitized with RB in the presence of NADH and Fe indicated substantial increase in formation of free radical-dependent 7α/7β-hydroperoxides. EPR spin trapping confirmed the photogeneration of superoxide anion in samples enriched with RB, NADH and Fe. For all three protocols sub-lethal oxidative stress induced significant inhibition of the specific phagocytosis of POS. In contrast, non-specific phagocytosis was inhibited only by H2O2 or H2O2 and Fe treatment. Inhibition of phagocytosis was transient and recoverable by 24 h. These results suggest that free radicals may exert similar to singlet oxygen efficiency in inhibiting phagocytosis of RPE cells, and that the effect depends on the location where initial reactive species are formed. PMID:27225587

  18. Omega-3 Fatty Acids, Oxidative Stress, and Leukocyte Telomere Length: A Randomized Controlled Trial

    PubMed Central

    Kiecolt-Glaser, Janice K.; Epel, Elissa S.; Belury, Martha A.; Andridge, Rebecca; Lin, Jue; Glaser, Ronald; Malarkey, William B.; Hwang, Beom Seuk; Blackburn, Elizabeth

    2012-01-01

    Shorter telomeres have been associated with poor health behaviors, age-related diseases, and early mortality. Telomere length is regulated by the enzyme telomerase, and is linked to exposure to proinflammatory cytokines and oxidative stress. In our recent randomized controlled trial, omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation lowered the concentration of serum proinflammatory cytokines. This study assessed whether n-3 PUFA supplementation also affected leukocyte telomere length, telomerase, and oxidative stress. In addition to testing for group differences, changes in the continuous n-6:n-3 PUFA ratio were assessed to account for individual differences in adherence, absorption, and metabolism. The double-blind 4-month trial included 106 healthy sedentary overweight middle-aged and older adults who received (1) 2.5 g/day n-3 PUFAs, (2) l.25 g/day n-3 PUFAs, or (3) placebo capsules that mirrored the proportions of fatty acids in the typical American diet. Supplementation significantly lowered oxidative stress as measured by F2-isoprostanes (p=0.02). The estimated geometric mean log-F2-isoprostanes values were 15% lower in the two supplemented groups compared to placebo. Although group differences for telomerase and telomere length were nonsignificant, changes in the n-6:n-3 PUFA plasma ratios helped clarify the intervention’s impact: telomere length increased with decreasing n-6:n-3 ratios, p=0.02. The data suggest that lower n-6:n-3 PUFA ratios can impact cell aging. The triad of inflammation, oxidative stress, and immune cell aging represents important pre-disease mechanisms that may be ameliorated through nutritional interventions. This translational research broadens our understanding of the potential impact of the n-6:n-3 PUFA balance. ClinicalTrials.gov identifier: NCT00385723 PMID:23010452

  19. Introduction to Oxidative Stress in Biomedical and Biological Research

    PubMed Central

    Breitenbach, Michael; Eckl, Peter

    2015-01-01

    Oxidative stress is now a well-researched area with thousands of new articles appearing every year. We want to give the reader here an overview of the topics in biomedical and basic oxidative stress research which are covered by the authors of this thematic issue. We also want to give the newcomer a short introduction into some of the basic concepts, definitions and analytical procedures used in this field. PMID:26117854

  20. Mitochondrial oxidant stress in locus coeruleus is regulated by activity and nitric oxide synthase

    PubMed Central

    Sanchez–Padilla, J.; Guzman, J.N.; Ilijic, E.; Kondapalli, J.; Galtieri, D.J.; Yang, B.; Schieber, S.; Oertel, W.; Wokosin, D.; Schumacker, P. T.; Surmeier, D. J.

    2014-01-01

    Summary Loss of noradrenergic locus coeruleus (LC) neurons is a prominent feature of aging–related neurodegenerative diseases, like Parkinson’s disease (PD). The basis of this vulnerability is not understood. To explore possible physiological determinants, LC neurons were studied using electrophysiological and optical approaches in ex vivo mouse brain slices. These studies revealed that autonomous activity in LC neurons was accompanied by oscillations in dendritic Ca2+ concentration attributable to opening of L–type Ca2+ channels. This oscillation elevated mitochondrial oxidant stress and was attenuated by inhibition of nitric oxide synthase. The relationship between activity and stress was malleable, as arousal and carbon dioxide, each increased the spike rate, but differentially affected mitochondrial oxidant stress. Oxidant stress also was increased in an animal model of PD. Thus, our results point to activity–dependent Ca2+ entry and a resulting mitochondrial oxidant stress as factors contributing to the vulnerability of LC neurons. PMID:24816140

  1. Ubiquitin-proteasome pathway and cellular responses to oxidative stress

    PubMed Central

    Taylor, Allen

    2011-01-01

    The ubiquitin-proteasome pathway (UPP) is the primary cytosolic proteolytic machinery for the selective degradation of various forms of damaged proteins. Thus, the UPP is an important protein quality control mechanism. In the canonical UPP, both ubiquitin and the 26S proteasome are involved. Substrate proteins of the canonical UPP are first tagged by multiple ubiquitin molecules and then degraded by the 26S proteasome. However, in non-canonical UPP, proteins can be degraded by the 26S or the 20S proteasome without being ubiquitinated. It is clear that a proteasome is responsible for selective degradation of oxidized proteins, but the extent to which ubiquitination is involved in this process remains a subject of debate. While many publications suggest that the 20S proteasome degrades oxidized proteins independent of ubiquitin, there is also solid evidence indicating that ubiquitin and ubiquitination are involved in degradation of some forms of oxidized proteins. A fully functional UPP is required for cells to cope with oxidative stress and the activity of the UPP is also modulated by cellular redox status. Mild or transient oxidative stress up-regulates the ubiquitination system and proteasome activity in cells and tissues and transiently enhances intracellular proteolysis. Severe or sustained oxidative stress impairs the function of the UPP and decreases intracellular proteolysis. Both the ubiquitin conjugation enzymes and the proteasome can be inactivated by sustained oxidative stress, especially the 26S proteasome. Differential susceptibilities of the ubiquitin conjugation enzymes and the 26S proteasome to oxidative damage lead to an accumulation of ubiquitin conjugates in cells in response to mild oxidative stress. Thus, increased levels of ubiquitin conjugates in cells appear to be an indicator of mild oxidative stress. PMID:21530648

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

    PubMed Central

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

    2013-01-01

    Mycotoxins which mainly consist of Aflatoxin (AF), Zearalenone (ZEN) and Deoxynivalenol (DON) are commonly found in many food commodities. Although each component has been shown to cause liver toxicity and oxidative stress in several species, there is no evidence regarding the effect of naturally contained multiple mycotoxins on tissue toxicity and oxidative stress in vivo. In the present study, mycotoxins-contaminated maize (AF 597 µg/kg, ZEN 729 µg/kg, DON 3.1 mg/kg maize) was incorporated into the diet at three different doses (0, 5 and 20%) to feed the mice, and blood and tissue samples were collected to examine the oxidative stress related indexes. The results showed that the indexes of liver, kidney and spleen were all increased and the liver and kidney morphologies changed in the mycotoxin-treated mice. Also, the treatment resulted in the elevated glutathione peroxidase (GPx) activity and malondialdehyde (MDA) level in the serum and liver, indicating the presence of the oxidative stress. Moreover, the decrease of catalase (CAT) activity in the serum, liver and kidney as well as superoxide dismutase (SOD) activity in the liver and kidney tissue further confirmed the occurrence of oxidative stress. In conclusion, our data indicate that the naturally contained mycotoxins are toxic in vivo and able to induce the oxidant stress in the mouse. PMID:23555961

  3. The role of oxidative stress in nickel and chromate genotoxicity.

    PubMed

    Costa, Max; Salnikow, Konstantin; Sutherland, Jessica E; Broday, Limor; Peng, Wu; Zhang, Qunwei; Kluz, Thomas

    2002-01-01

    Some general principles regarding oxidative stress and molecular responses to toxic metals are presented in this manuscript. The remainder of the manuscript, however, will focus on the role of oxidative stress in particulate nickel-induced genetic damage and mutations. The phagocytosis of particulate nickel compounds and the dissolution of the particles inside the cell and the resulting oxidative stress produced in the nucleus is a key component of the nickel carcinogenic mechanism. The crosslinking of amino acids to DNA by nickel that does not involve direct participation of nickel in a ternary complex but nickel-induced oxidative stress will be discussed as well. The selective ability of particulate nickel compounds to silence the expression of genes located near heterochromatin and the effect of vitamin E on the genotoxicity and mutations induced by particulate and soluble nickel compounds will also be discussed. Particulate nickel compounds have been shown to produce more oxidative stress than water-soluble nickel compounds. In addition to nickel, the role of oxidative stress in chromate-induced genotoxicity will also be discussed with particular attention directed to the effects of vitamin E on mutations and chromosomal aberrations inducedby chromate.

  4. Sensing pulmonary oxidative stress by lung vagal afferents

    PubMed Central

    Taylor-Clark, Thomas E.; Undem, Bradley J.

    2011-01-01

    Oxidative stress in the bronchopulmonary airways can occur through a variety of inflammatory mechanisms and also following the inhalation of environmental pollutants. Oxidative stress causes cellular dysfunction and thus mammals (including humans) have developed mechanisms for detecting oxidative stress, such that defensive behavior and defensive biological mechanisms can be induced to lessen its potential damage. Vagal sensory nerves innervating the airways play a critical role in the detection of the microenvironment in the airways. Oxidative stress and associated compounds activate unmyelinated bronchopulmonary C-fibers, initiating action potentials in these nerves that conduct centrally to evoke unpleasant sensations (e.g. urge to cough, dyspnea, chest-tightness) and to stimulate/modulate reflexes (e.g. cough, bronchoconstriction, respiratory rate, inspiratory drive). This review will summarize the published evidence regarding the mechanisms by which oxidative stress, reactive oxygen species, environmental pollutants and lipid products of peroxidation activate bronchopulmonary C-fibers. Evidence suggests a key role for transient receptor potential ankyrin 1 (TRPA1), although transient receptor potential vanilloid 1 (TRPV1) and purinergic P2X channels may also play a role. Knowledge of these pathways greatly aids our understanding of the role of oxidative stress in health and disease and represents novel therapeutic targets for diseases of the airways. PMID:21600314

  5. [Mitochondria and oxidative stress participation in renal inflammatory process].

    PubMed

    Manucha, Walter

    2014-01-01

    The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.

  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. Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

    PubMed

    Rathor, Laxmi; Akhoon, Bashir Akhlaq; Pandey, Swapnil; Srivastava, Swati; Pandey, Rakesh

    2015-12-01

    Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments. PMID:26546011

  8. Folic acid supplementation at lower doses increases oxidative stress resistance and longevity in Caenorhabditis elegans.

    PubMed

    Rathor, Laxmi; Akhoon, Bashir Akhlaq; Pandey, Swapnil; Srivastava, Swati; Pandey, Rakesh

    2015-12-01

    Folic acid (FA) is an essential nutrient that the human body needs but cannot be synthesized on its own. Fortified foods and plant food sources such as green leafy vegetables, beans, fruits, and juices are good sources of FA to meet the daily requirements of the body. The aim was to evaluate the effect of dietary FA levels on the longevity of well-known experimental aging model Caenorhabditis elegans. Here, we show for first time that FA extends organism life span and causes a delay in aging. We observed that FA inhibits mechanistic target of rapamycin (mTOR) and insulin/insulin growth factor 1 (IGF-1) signaling pathways to control both oxidative stress levels and life span. The expression levels of stress- and life span-relevant gerontogenes, viz. daf-16, skn-1, and sir. 2.1, and oxidative enzymes, such as glutathione S-transferase 4 (GST-4) and superoxide dismutase 3 (SOD-3), were also found to be highly enhanced to attenuate the intracellular reactive oxygen species (ROS) damage and to delay the aging process. Our study promotes the use of FA to mitigate abiotic stresses and other aging-related ailments.

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

    PubMed Central

    Rajendran, Ramkumar; Garva, Richa; Krstic-Demonacos, Marija; Demonacos, Constantinos

    2011-01-01

    Transcription is regulated by acetylation/deacetylation reactions of histone and nonhistone proteins mediated by enzymes called KATs and HDACs, respectively. As a major mechanism of transcriptional regulation, protein acetylation is a key controller of physiological processes such as cell cycle, DNA damage response, metabolism, apoptosis, and autophagy. The deacetylase activity of class III histone deacetylases or sirtuins depends on the presence of NAD+ (nicotinamide adenine dinucleotide), and therefore, their function is closely linked to cellular energy consumption. This activity of sirtuins connects the modulation of chromatin dynamics and transcriptional regulation under oxidative stress to cellular lifespan, glucose homeostasis, inflammation, and multiple aging-related diseases including cancer. Here we provide an overview of the recent developments in relation to the diverse biological activities associated with sirtuin enzymes and stress responsive transcription factors, DNA damage, and oxidative stress and relate the involvement of sirtuins in the regulation of these processes to oncogenesis. Since the majority of the molecular mechanisms implicated in these pathways have been described for Sirt1, this sirtuin family member is more extensively presented in this paper. PMID:21912480

  10. Photo-oxidative stress in the eye: role of retinal pigment epithelial pigments

    NASA Astrophysics Data System (ADS)

    Glickman, Randolph D.; Dontsov, Alexander E.; Ostrovsky, Michail A.; Kumar, Neeru; Vendal, Meena; Gonzales, Mary A.

    1999-09-01

    The pigments of the retinal pigment epithelium, i.e. the intracellular granules of melanin, lipofuscin, and melanolipofuscin, have been shown to catalyze free radical activity, especially when illuminated with visible or ultraviolet light. An important question is whether these reactions are sufficient to produce oxidative damage in the eye. To address this question, the relative photoreactivity of isolated RPE pigment granules towards polyunsaturated fatty acids has been determined, including the dark as well as the light-stimulated reactions. Hydroperoxide derivatives of docosahexaenoic acid were produced by irradiation with short wavelength (< 550 nm) visible light when RPE pigments were present. Although melanosomes exhibited the greatest light-induced activity in these reactions, lipofuscin granules induced peroxidation of fatty acids in the dark. In intact, cultured RPE cells, the existence of pigment-medicated photo-reactions were demonstrated with a fluorescent indicator probe of oxidation, 2',7'- dichlorofluorescein, that was photooxidized in probe-labeled cells in a wavelength dependence fashion with peak activity in the 450 to 500 nm region. This behavior resembled the action spectrum for melanin reactivity. These findings support the hypotheses that the RPE pigments contribute to general photooxidative stress in ocular tissue, and that accumulation of lipofuscin pigment contributes to age-related oxidative stress in the RPE.

  11. In Vivo Imaging of Retinal Oxidative Stress Using a Reactive Oxygen Species–Activated Fluorescent Probe

    PubMed Central

    Prunty, Megan C.; Aung, Moe H.; Hanif, Adam M.; Allen, Rachael S.; Chrenek, Micah A.; Boatright, Jeffrey H.; Thule, Peter M.; Kundu, Kousik; Murthy, Niren; Pardue, Machelle T.

    2015-01-01

    Purpose In vivo methods for detecting oxidative stress in the eye would improve screening and monitoring of the leading causes of blindness: diabetic retinopathy, glaucoma, and age-related macular degeneration. Methods To develop an in vivo biomarker for oxidative stress in the eye, we tested the efficacy of a reactive oxygen species (ROS)–activated, near-infrared hydrocyanine-800CW (H-800CW) fluorescent probe in light-induced retinal degeneration (LIRD) mouse models. After intravitreal delivery in LIRD rats, fluorescent microscopy was used to confirm that the oxidized H-800CW appeared in the same retinal layers as an established ROS marker (dichlorofluorescein). Results Dose–response curves of increasing concentrations of intravenously injected H-800CW demonstrated linear increases in both intensity and total area of fundus hyperfluorescence in LIRD mice, as detected by scanning laser ophthalmoscopy. Fundus hyperfluorescence also correlated with the duration of light damage and functional deficits in vision after LIRD. In LIRD rats with intravitreal injections of H-800CW, fluorescent labeling was localized to photoreceptor inner segments, similar to dichlorofluorescein. Conclusions Hydrocyanine-800CW detects retinal ROS in vivo and shows potential as a novel biomarker for ROS levels in ophthalmic diseases. PMID:26348635

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

    PubMed

    Wang, Jing; Yang, Xin; Zhang, Jingjing

    2016-08-01

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

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

    EPA Science Inventory

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

  14. ELECTROSTATIC CHARGE STIMULATES OXIDATIVE STRESS IN CNS MICROGLIA.

    EPA Science Inventory

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

  15. Infrared Dielectric Properties of Low-Stress Silicon Oxide

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  17. Topical Nutraceutical Optixcare EH Ameliorates Experimental Ocular Oxidative Stress in Rats

    PubMed Central

    Guo, Changmei; Kawada, Hiroyoshi; Randazzo, James; Blessing, Karen

    2014-01-01

    Abstract Purpose: Based on the hypothesis that oral nutraceuticals do not adequately reach all ocular tissues in the anterior segment, we evaluated the ability of a 3% concentration of the ingredients in a topical nutraceutical antioxidant formulation called Optixcare Eye Health (Optixcare EH) to ameliorate oxidative stress in rat models of age-related ocular diseases. Methods: Diabetes was induced by tail-vein injection of streptozotocin, and the development of cataracts was monitored by slit lamp. Young rats were exposed to ultraviolet (UV) light, and the reduction in lens glutathione (GSH) levels and increase in 4-hydroxynonenol (4-HNE) were measured. Oxidative stress in the neural retina was generated by exposure of dark-adapted rats to 1,000 lx of light, and oxidative stress markers were measured. Dry eye was induced in rats by twice daily (b.i.d.) subcutaneous scopolamine injections. Topical Optixcare EH was administered b.i.d. and compared in select experiments to the multifunctional antioxidant JHX-4, the topical aldose reductase inhibitor (ARI) Kinostat™, oral Ocu-GLO™, and the topical ocular comfort agents Optixcare Eye Lube, Optixcare Eye Lube + Hyaluron, and Idrop Vet Plus hyaluronic acid. Results: In diabetic rats, topical ARI treatment prevented cataract formation while the nutraceuticals delayed their development with Optixcare EH>Ocu-GLO. In UV-exposed rats, the reduction of GSH and increase in 4-HNE in the lens were normalized in order JHX-4>Optixcare EH>Ocu-GLO. In the retina, oxidative stress markers were reduced better by oral JHX-4 compared with topical Optixcare EH. In the scopolamine-induced dry-eye rats, tear flow was maintained by Optixcare EH treatment, while none of the comfort agents examined altered tear flow. Conclusions: Topical administration of a 3% concentration of the ingredients in Optixcare EH reduces experimentally induced reactive oxygen species in rats exposed to several sources of ocular oxidative stress. In addition

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

    PubMed

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

    2008-02-01

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

  19. Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in Alzheimer disease: therapeutic implications.

    PubMed

    Candore, Giuseppina; Bulati, Matteo; Caruso, Calogero; Castiglia, Laura; Colonna-Romano, Giuseppina; Di Bona, Danilo; Duro, Giovanni; Lio, Domenico; Matranga, Domenica; Pellicanò, Mariavaleria; Rizzo, Claudia; Scapagnini, Giovanni; Vasto, Sonya

    2010-01-01

    Alzheimer disease (AD) is a heterogeneous and progressive neurodegenerative disease, which in Western society mainly accounts for senile dementia. Today many countries have rising aging populations and are facing an increased prevalence of age-related diseases, such as AD, with increasing health-care costs. Understanding the pathophysiology process of AD plays a prominent role in new strategies for extending the health of the elderly population. Considering the future epidemic of AD, prevention and treatment are important goals of ongoing research. However, a better understanding of AD pathophysiology must be accomplished to make this objective feasible. In this paper, we review some hot topics concerning AD pathophysiology that have an important impact on therapeutic perspectives. Hence, we have focused our attention on inflammation, cytokines, immune response, apolipoprotein E (APOE), cholesterol, oxidative stress, as well as exploring the related therapeutic possibilities, i.e., nonsteroidal antiinflammatory drugs, cytokine blocking antibodies, immunotherapy, diet, and curcumin.

  20. Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia.

    PubMed

    Osawa, Toshihiko; Kato, Yoji

    2005-06-01

    Hyperglycemia causes the autoxidation of glucose, glycation of proteins, and the activation of polyol metabolism. These changes accelerate generation of reactive oxygen species (ROS) and increases in oxidative chemical modification of lipids, DNA, and proteins in various tissues. Oxidative stress may play an important role in the development of complications in diabetes such as lens cataracts, nephropathy, and neuropathy. Glycation reactions, especially Maillard reactions, occur in vivo as well as in vitro and are associated with the chronic complications of diabetes mellitus and aging and age-related diseases by increases in oxidative chemical modification of lipids, DNA, and proteins. In particular, long-lived proteins such as lens crystallines, collagens, and hemoglobin may react with reducing sugars to form advanced glycation end products (AGEs). Recently, we found a novel type of AGE, named MRX, and we found that MRX is a good biomarker for detecting oxidative stress produced during Maillard reaction. We also examined in detail the role of lipid peroxidation reaction in hyperglycemia and found that hexanoyl modification formed by the reaction of oxidized lipids and proteins must be important for oxidative stress. Detailed analyses of the formation mechanism of hexanoyl lysine (HEL) moiety in proteins were conducted, and excretion of HEL into urine was quantified by using LC/MS/MS. Macrophages and neutrophils play an important role in oxidative stress during hyperglycemia, and we determined that oxidatively modified tyrosines are a good biomarker for formation of oxidative stress at an early stage. Immunochemical analyses by application of monoclonal antibodies specific to lipid hydroperoxide-modified proteins produced by polyunsaturated fatty acids including docosahexaenoic acid (DHA) in oxidative stress caused by hyperglycemia were conducted, and the relationship between glycation and lipid peroxidation reactions both by chemical and immunochemical approaches

  1. 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

  2. Trypanosoma cruzi: Oxidative stress induces arginine kinase expression.

    PubMed

    Miranda, Mariana R; Canepa, Gaspar E; Bouvier, Leon A; Pereira, Claudio A

    2006-12-01

    Trypanosoma cruzi arginine kinase is a key enzyme in cell energy management and is also involved in pH and nutritional stress response mechanisms. T. cruzi epimastigotes treated with hydrogen peroxide presented a time-dependent increase in arginine kinase expression, up to 10-fold, when compared with untreated parasites. Among other oxidative stress-generating compounds tested, only nifurtimox produced more than 2-fold increase in arginine kinase expression. Moreover, parasites overexpressing arginine kinase showed significantly increased survival capability during hydrogen peroxide exposure. These findings suggest the participation of arginine kinase in oxidative stress response systems. PMID:16725140

  3. Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway.

    PubMed

    Na, Hyun-Jin; Park, Joung-Sun; Pyo, Jung-Hoon; Jeon, Ho-Jun; Kim, Young-Shin; Arking, Robert; Yoo, Mi-Ae

    2015-07-01

    We delineated the mechanism regulating the inhibition of centrosome amplification by metformin in Drosophila intestinal stem cells (ISCs). Age-related changes in tissue-resident stem cells may be closely associated with tissue aging and age-related diseases, such as cancer. Centrosome amplification is a hallmark of cancers. Our recent work showed that Drosophila ISCs are an excellent model for stem cell studies evaluating age-related increase in centrosome amplification. Here, we showed that metformin, a recognized anti-cancer drug, inhibits age- and oxidative stress-induced centrosome amplification in ISCs. Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway. Additionally, AKT/TOR signaling hyperactivation and metformin treatment indicated a strong correlation between DNA damage accumulation and centrosome amplification in ISCs, suggesting that DNA damage might mediate centrosome amplification. Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation. We identified a new target for the inhibition of age- and oxidative stress-induced centrosome amplification. We propose that the Drosophila ISCs may be an excellent model system for in vivo studies evaluating the effects of anti-cancer drugs on tissue-resident stem cell aging.

  4. Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of γ-glutamylcysteine.

    PubMed

    Ferguson, Gavin; Bridge, Wallace

    2016-03-01

    A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide γ-glutamylcysteine (γ-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous γ-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases. PMID:26845022

  5. Oxidative stress in β-thalassaemia and sickle cell disease

    PubMed Central

    Voskou, S.; Aslan, M.; Fanis, P.; Phylactides, M.; Kleanthous, M.

    2015-01-01

    Sickle cell disease and β-thalassaemia are inherited haemoglobinopathies resulting in structural and quantitative changes in the β-globin chain. These changes lead to instability of the generated haemoglobin or to globin chain imbalance, which in turn impact the oxidative environment both intracellularly and extracellularly. The ensuing oxidative stress and the inability of the body to adequately overcome it are, to a large extent, responsible for the pathophysiology of these diseases. This article provides an overview of the main players and control mechanisms involved in the establishment of oxidative stress in these haemoglobinopathies. PMID:26285072

  6. Role of oxidative stress in infectious diseases. A review.

    PubMed

    Pohanka, Miroslav

    2013-11-01

    Oxidative stress plays a dual role in infections. Free radicals protect against invading microorganisms, and they can also cause tissue damage during the resulting inflammation. In the process of infection, there is generation of reactive species by myeloperoxidase, NADPH oxidase, and nitric oxide synthase. On the other hand, reactive species can be generated among others, by cytochrome P450, some metals, and xanthine oxidase. Some pathologies arising during infection can be attributed to oxidative stress and generation of reactive species in infection can even have fatal consequences. This article reviews the basic pathways in which reactive species can accumulate during infectious diseases and discusses the related health consequences.

  7. 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.

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

    PubMed

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

    2015-07-01

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

  9. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD.

  10. Melatonin in Retinal Physiology and Pathology: The Case of Age-Related Macular Degeneration

    PubMed Central

    Reiter, Russel J.; Kaarniranta, Kai

    2016-01-01

    Melatonin, an indoleamine, is synthesized mainly in the pineal gland in a circadian fashion, but it is produced in many other organs, including the retina, which seems to be especially important as the eye is a primary recipient of circadian signals. Melatonin displays strong antioxidative properties, which predispose it to play a protective role in many human pathologies associated with oxidative stress, including premature aging and degenerative disease. Therefore, melatonin may play a role in age-related macular degeneration (AMD), a disease affecting photoreceptors, and retinal pigment epithelium (RPE) with an established role of oxidative stress in its pathogenesis. Several studies have shown that melatonin could exert the protective effect against damage to RPE cells evoked by reactive oxygen species (ROS), but it has also been reported to increase ROS-induced damage to photoreceptors and RPE. Melatonin behaves like synthetic mitochondria-targeted antioxidants, which concentrate in mitochondria at relatively high levels; thus, melatonin may prevent mitochondrial damage in AMD. The retina contains telomerase, an enzyme implicated in maintaining the length of telomeres, and oxidative stress inhibits telomere synthesis, while melatonin overcomes this effect. These features support considering melatonin as a preventive and therapeutic agent in the treatment of AMD. PMID:27688828

  11. Oxidative stress contributes to autophagy induction in response to endoplasmic reticulum stress in Chlamydomonas reinhardtii.

    PubMed

    Pérez-Martín, Marta; Pérez-Pérez, María Esther; Lemaire, Stéphane D; Crespo, José L

    2014-10-01

    The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) results in the activation of stress responses, such as the unfolded protein response or the catabolic process of autophagy to ultimately recover cellular homeostasis. ER stress also promotes the production of reactive oxygen species, which play an important role in autophagy regulation. However, it remains unknown whether reactive oxygen species are involved in ER stress-induced autophagy. In this study, we provide evidence connecting redox imbalance caused by ER stress and autophagy activation in the model unicellular green alga Chlamydomonas reinhardtii. Treatment of C. reinhardtii cells with the ER stressors tunicamycin or dithiothreitol resulted in up-regulation of the expression of genes encoding ER resident endoplasmic reticulum oxidoreductin1 oxidoreductase and protein disulfide isomerases. ER stress also triggered autophagy in C. reinhardtii based on the protein abundance, lipidation, cellular distribution, and mRNA levels of the autophagy marker ATG8. Moreover, increases in the oxidation of the glutathione pool and the expression of oxidative stress-related genes were detected in tunicamycin-treated cells. Our results revealed that the antioxidant glutathione partially suppressed ER stress-induced autophagy and decreased the toxicity of tunicamycin, suggesting that oxidative stress participates in the control of autophagy in response to ER stress in C. reinhardtii In close agreement, we also found that autophagy activation by tunicamycin was more pronounced in the C. reinhardtii sor1 mutant, which shows increased expression of oxidative stress-related genes.

  12. Oxidative stress contributes to autophagy induction in response to endoplasmic reticulum stress in Chlamydomonas reinhardtii.

    PubMed

    Pérez-Martín, Marta; Pérez-Pérez, María Esther; Lemaire, Stéphane D; Crespo, José L

    2014-10-01

    The accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) results in the activation of stress responses, such as the unfolded protein response or the catabolic process of autophagy to ultimately recover cellular homeostasis. ER stress also promotes the production of reactive oxygen species, which play an important role in autophagy regulation. However, it remains unknown whether reactive oxygen species are involved in ER stress-induced autophagy. In this study, we provide evidence connecting redox imbalance caused by ER stress and autophagy activation in the model unicellular green alga Chlamydomonas reinhardtii. Treatment of C. reinhardtii cells with the ER stressors tunicamycin or dithiothreitol resulted in up-regulation of the expression of genes encoding ER resident endoplasmic reticulum oxidoreductin1 oxidoreductase and protein disulfide isomerases. ER stress also triggered autophagy in C. reinhardtii based on the protein abundance, lipidation, cellular distribution, and mRNA levels of the autophagy marker ATG8. Moreover, increases in the oxidation of the glutathione pool and the expression of oxidative stress-related genes were detected in tunicamycin-treated cells. Our results revealed that the antioxidant glutathione partially suppressed ER stress-induced autophagy and decreased the toxicity of tunicamycin, suggesting that oxidative stress participates in the control of autophagy in response to ER stress in C. reinhardtii In close agreement, we also found that autophagy activation by tunicamycin was more pronounced in the C. reinhardtii sor1 mutant, which shows increased expression of oxidative stress-related genes. PMID:25143584

  13. Salivary markers of oxidative stress in oral diseases

    PubMed Central

    Tóthová, L'ubomíra; Kamodyová, Natália; Červenka, Tomáš; Celec, Peter

    2015-01-01

    Saliva is an interesting alternative diagnostic body fluid with several specific advantages over blood. These include non-invasive and easy collection and related possibility to do repeated sampling. One of the obstacles that hinders the wider use of saliva for diagnosis and monitoring of systemic diseases is its composition, which is affected by local oral status. However, this issue makes saliva very interesting for clinical biochemistry of oral diseases. Periodontitis, caries, oral precancerosis, and other local oral pathologies are associated with oxidative stress. Several markers of lipid peroxidation, protein oxidation and DNA damage induced by reactive oxygen species can be measured in saliva. Clinical studies have shown an association with oral pathologies at least for some of the established salivary markers of oxidative stress. This association is currently limited to the population level and none of the widely used markers can be applied for individual diagnostics. Oxidative stress seems to be of local oral origin, but it is currently unclear whether it is caused by an overproduction of reactive oxygen species due to inflammation or by the lack of antioxidants. Interventional studies, both, in experimental animals as well as humans indicate that antioxidant treatment could prevent or slow-down the progress of periodontitis. This makes the potential clinical use of salivary markers of oxidative stress even more attractive. This review summarizes basic information on the most commonly used salivary markers of oxidative damage, antioxidant status, and carbonyl stress and the studies analyzing these markers in patients with caries or periodontitis. PMID:26539412

  14. Stressed Oxidation of C/SiC Composites

    NASA Technical Reports Server (NTRS)

    Halbig, Michael C.; Brewer, David N.; Eckel, Andrew J.; Cawley, James D.

    1997-01-01

    Constant load, stressed oxidation testing was performed on T-300 C/SiC composites with a SiC seal coat. Test conditions included temperatures ranging from 350 C to 1500 C at stresses of 69 MPa and 172 MPa (10 and 25 ksi). The coupon subjected to stressed oxidation at 550 C/69 MPa for 25 hours had a room temperature residual strength one-half that of the as-received coupons. The coupon tested at the higher stress and all coupons tested at higher temperatures failed in less than 25 hr. Microstructural analysis of the fracture surfaces, using SEM (scanning electron microscopy), revealed the formation of reduced cross-sectional fibers with pointed tips. Analysis of composite cross-sections show pathways for oxygen ingress. The discussion will focus on fiber/matrix interphase oxidation and debonding as well as the formation and implications of the fiber tip morphology.

  15. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  16. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  17. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  18. Oxidative stress treatment for clinical trials in neurodegenerative diseases.

    PubMed

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

    2011-01-01

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

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

    PubMed

    Vaváková, Magdaléna; Ďuračková, Zdeňka; Trebatická, Jana

    2015-01-01

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

  20. Markers of Oxidative Stress and Neuroprogression in Depression Disorder

    PubMed Central

    Vaváková, Magdaléna; Trebatická, Jana

    2015-01-01

    Major depression is multifactorial disorder with high prevalence and alarming prognostic in the nearest 15 years. Several mechanisms of depression are known. Neurotransmitters imbalance and imbalance between neuroprogressive and neuroprotective factors are observed in major depression. Depression is accompanied by inflammatory responses of the organism and consequent elevation of proinflammatory cytokines and increased lipid peroxidation are described in literature. Neuropsychiatric disorders including major depression are also associated with telomerase shortening, oxidative changes in nucleotides, and polymorphisms in several genes connected to metabolism of reactive oxygen species. Mitochondrion dysfunction is directly associated with increasing levels of oxidative stress. Oxidative stress plays significant role in pathophysiology of major depression via actions of free radicals, nonradical molecules, and reactive oxygen and nitrogen species. Products of oxidative stress represent important parameters for measuring and predicting of depression status as well as for determining effectiveness of administrated antidepressants. Positive effect of micronutrients, vitamins, and antioxidants in depression treatment is also reviewed. PMID:26078821

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

    PubMed

    Shiota, Masaki; Yokomizo, Akira; Naito, Seiji

    2014-12-01

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

  2. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus

    PubMed Central

    Tangvarasittichai, Surapon

    2015-01-01

    Oxidative stress is increased in metabolic syndrome and type 2 diabetes mellitus (T2DM) and this appears to underlie the development of cardiovascular disease, T2DM and diabetic complications. Increased oxidative stress appears to be a deleterious factor leading to insulin resistance, dyslipidemia, β-cell dysfunction, impaired glucose tolerance and ultimately leading to T2DM. Chronic oxidative stress, hyperglycemia and dyslipidemia are particularly dangerous for β-cells from lowest levels of antioxidant, have high oxidative energy requirements, decrease the gene expression of key β-cell genes and induce cell death. If β-cell functioning is impaired, it results in an under production of insulin, impairs glucose stimulated insulin secretion, fasting hyperglycemia and eventually the development of T2DM. PMID:25897356

  3. OXIDATIVE STRESS 3 Is a Chromatin-Associated Factor Involved in Tolerance to Heavy Metals and Oxidative Stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A cDNA expression library from Brassica juncea was introduced into the fission yeast Schizosaccharomyces pombe to select for transformants tolerant to cadmium. Transformants expressing OXIDATIVE STRESS 3 (OXS3) or OXS3-Like cDNA exhibited enhanced tolerance to a range of metals and oxidizing chemica...

  4. Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction.

    PubMed

    Neri, Margherita; Fineschi, Vittorio; Di Paolo, Marco; Pomara, Cristoforo; Riezzo, Irene; Turillazzi, Emanuela; Cerretani, Daniela

    2015-01-01

    Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-α (Tumor Necrosis Factor α), IL-1β (Interleukin- 1β) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injury.

  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.

  6. 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

  7. Oxidative stress-induced calcium signalling in Aspergillus nidulans.

    PubMed

    Greene, Vilma; Cao, Hong; Schanne, Francis A X; Bartelt, Diana C

    2002-05-01

    The effects of oxidative stress on levels of calcium ion (Ca(2+)) in Aspergillus nidulans were measured using strains expressing aequorin in the cytoplasm (Aeq(cyt)) and mitochondria (Aeq(mt)). When oxidative stress was induced by exposure to 10-mM H(2)O(2), the mitochondrial calcium response (Ca(mt)(2+)) was greater than the change in cytoplasmic calcium (Ca(c)(2+)). The Ca(mt)(2+) response to H(2)O(2) was dose dependent, while the increase in [Ca(c)(2+)] did not change with increasing H(2)O(2). The increase in both [Ca(c)(2+)] and [Ca(mt)(2+)] in response to oxidative stress was enhanced by exposure of cells to Ca(2+). The presence of chelator in the external medium only partially inhibited the Ca(mt)(2+) and Ca(c)(2+) responses to oxidative stress. Reagents that alter calcium fluxes had varied effects on the Ca(mt)(2+) response to peroxide. Ruthenium red blocked the increase in [Ca(mt)(2+)], while neomycin caused an even greater increase in [Ca(mt)(2+)]. Treatment with ruthenium red and neomycin had no effect on the Ca(c)(2+) response. Bafilomycin A and oligomycin had no effect on either the mitochondrial or cytoplasmic response. Inhibitors of both voltage-regulated calcium channels and intracellular calcium release channels inhibited the Ca(2+)-dependent component of the Ca(mt)(2+) response to oxidative stress. We conclude that the more significant Ca(2+) response to oxidative stress occurs in the mitochondria and that both intracellular and extracellular calcium pools can contribute to the increases in [Ca(c)(2+)] and [Ca(mt)(2+)] induced by oxidative stress.

  8. 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

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

    PubMed

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

    2012-10-01

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

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

    PubMed

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

    2012-10-01

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

  11. Oxidative stress alters global histone modification and DNA methylation.

    PubMed

    Niu, Yingmei; DesMarais, Thomas L; Tong, Zhaohui; Yao, Yixin; Costa, Max

    2015-05-01

    The JmjC domain-containing histone demethylases can remove histone lysine methylation and thereby regulate gene expression. The JmjC domain uses iron Fe(II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl lysine. We hypothesize that reactive oxygen species will oxidize Fe(II) to Fe(III), thereby attenuating the activity of JmjC domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3h) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3h exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; preincubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2',7'-dichlorofluorescein, GSH/GSSG ratio, and protein carbonyl content. A cell-free system indicated that H2O2 inhibited histone demethylase activity where increased Fe(II) rescued this inhibition. TET protein showed a decreased activity under oxidative stress. Cells exposed to a low-dose and long-term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short-term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters the epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones. PMID:25656994

  12. A Meta-Analysis of Oxidative Stress Markers in Depression

    PubMed Central

    Liu, Tao; Zhong, Shuming; Liao, Xiaoxiao; Chen, Jian; He, Tingting; Lai, Shunkai; Jia, Yanbin

    2015-01-01

    Object Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis aims to analyse the clinical data quantitatively by comparing the oxidative stress markers between depressed patients and healthy controls. Methods A search was conducted to collect the studies that measured the oxidative stress markers in depressed patients. Studies were searched in Embase, Medline, PsychINFO, Science direct, CBMDisc, CNKI and VIP from 1990 to May 2015. Data were subjected to meta-analysis by using a random effects model for examining the effect sizes of the results. Bias assessments, heterogeneity assessments and sensitivity analyses were also conducted. Results 115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin, high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy (p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were no differences between the depressed patients and controls for other oxidative stress markers. Conclusion This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication

  13. Red blood cell antioxidant enzymes in age-related macular degeneration.

    PubMed Central

    De La Paz, M A; Zhang, J; Fridovich, I

    1996-01-01

    AIMS/BACKGROUND: Oxidative damage has been proposed to be involved in the pathogenesis of age-related macular degeneration (ARMD). The purpose of this study was to evaluate whether red blood cell antioxidant enzyme activity correlates with severity of aging maculopathy in affected individuals. METHODS: Blood samples were obtained from 54 patients with varying severity of aging maculopathy and 12 similarly aged individuals with normal ophthalmoscopic examination. Macular findings were graded according to a modification of the method described for the Age-Related Eye Disease Study. (AREDS). The activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase were measured in red blood cells. Haemoglobin content of whole blood was measured, and enzyme activity was determined per mg haemoglobin. RESULTS: Multiple regression analysis and ordinal logistic regression analysis were performed to determine whether antioxidant enzyme activity was associated with severity of ARMD. No significant association between disease severity of ARMD and antioxidant enzyme activity was identified for any of the enzymes. CONCLUSION: These results do not provide evidence for a relation between oxidative stress, as measured by antioxidant enzyme activity in red blood cells, and disease severity in ARMD. PMID:8695567

  14. Role of Nrf2 in Oxidative Stress and Toxicity

    PubMed Central

    Ma, Qiang

    2015-01-01

    Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body’s needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol–based redox signaling. The nuclear factor erythroid 2–related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how Nrf2 senses oxidants and regulates antioxidant defense. PMID:23294312

  15. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  16. 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

  17. 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

  18. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone

    SciTech Connect

    Carney, J.M.; Starke-Reed, P.E.; Oliver, C.N.; Landum, R.W.; Cheng, M.S.; Wu, J.F.; Floyd, R.A. )

    1991-05-01

    Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls.

  19. Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling

    PubMed Central

    Baek, Sang-Min; Yu, Seung-Young; Son, Youngsook

    2016-01-01

    Purpose Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress. Methods To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3β activation in RPE cells in vitro. Results H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3β signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells. Conclusions SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3β signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases. PMID:27582624

  20. 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

  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. PMID:27251462

  2. 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

  3. Cellular Mechanisms of Oxidative Stress and Action in Melanoma

    PubMed Central

    Venza, Mario; Visalli, Maria; Beninati, Concetta; De Gaetano, Giuseppe Valerio; Teti, Diana; Venza, Isabella

    2015-01-01

    Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment. PMID:26064422

  4. Oxidative stress in fibromyalgia and its relationship to symptoms.

    PubMed

    Chung, Cecilia P; Titova, Dina; Oeser, Annette; Randels, Margaret; Avalos, Ingrid; Milne, Ginger L; Morrow, Jason D; Stein, C Michael

    2009-04-01

    Oxidative stress is thought to play a role in the pathogenesis of fibromyalgia. We examined the hypothesis that oxidative stress was increased in patients with fibromyalgia and related to the severity of symptoms. Urinary F(2)-isoprostane excretion was measured in 48 patients with fibromyalgia and compared to those of 96 control subjects. In patients, we examined the association between oxidative stress and symptoms. Patients with fibromyalgia were significantly more symptomatic than control subjects, but urinary F(2)-isoprostane excretion did not differ significantly (2.3+/-1.9 vs. 2.8+/-2.2 ng/mg creatinine, p=0.16). In patients with fibromyalgia, F(2)-isoprostane excretion was associated with fatigue visual analog scale (rho=0.30, p=0.04) but not with pain, quality of life, functional capacity, depression, number of tender points, or overall impact of fibromyalgia. Oxidative stress is not increased in patients with fibromyalgia, but as was previously found in patients with systemic lupus erythematosus, oxidative stress was associated with fatigue.

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

    SciTech Connect

    Lefevre, Sophie; Sliwa, Dominika; Rustin, Pierre; Camadro, Jean-Michel; Santos, Renata

    2012-02-10

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

  6. Oxidative stress modulation in hepatitis C virus infected cells

    PubMed Central

    Lozano-Sepulveda, Sonia A; Bryan-Marrugo, Owen L; Cordova-Fletes, Carlos; Gutierrez-Ruiz, Maria C; Rivas-Estilla, Ana M

    2015-01-01

    Hepatitis C virus (HCV) replication is associated with the endoplasmic reticulum, where the virus can induce cellular stress. Oxidative cell damage plays an important role in HCV physiopathology. Oxidative stress is triggered when the concentration of oxygen species in the extracellular or intracellular environment exceeds antioxidant defenses. Cells are protected and modulate oxidative stress through the interplay of intracellular antioxidant agents, mainly glutathione system (GSH) and thioredoxin; and antioxidant enzyme systems such as superoxide dismutase, catalase, GSH peroxidase, and heme oxygenase-1. Also, the use of natural and synthetic antioxidants (vitamin C and E, N-acetylcysteine, glycyrrhizin, polyenylphosphatidyl choline, mitoquinone, quercetin, S-adenosylmethionine and silymarin) has already shown promising results as co-adjuvants in HCV therapy. Despite all the available information, it is not known how different agents with antiviral activity can interfere with the modulation of the cell redox state induced by HCV and decrease viral replication. This review describes an evidence-based consensus on molecular mechanisms involved in HCV replication and their relationship with cell damage induced by oxidative stress generated by the virus itself and cell antiviral machinery. It also describes some molecules that modify the levels of oxidative stress in HCV-infected cells. PMID:26692473

  7. (+)-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

  8. Cellular Mechanisms of Oxidative Stress and Action in Melanoma.

    PubMed

    Venza, Mario; Visalli, Maria; Beninati, Concetta; De Gaetano, Giuseppe Valerio; Teti, Diana; Venza, Isabella

    2015-01-01

    Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment. PMID:26064422

  9. Losartan abolishes oxidative stress induced by intermittent hypoxia in humans.

    PubMed

    Pialoux, Vincent; Foster, Glen E; Ahmed, Sofia B; Beaudin, Andrew E; Hanly, Patrick J; Poulin, Marc J

    2011-11-15

    The aim of this study was to assess the role of the type 1 angiotensin II (AT(1)) receptor in the increase of oxidative stress and NO metabolism during a single 6 h exposure to intermittent hypoxia (IH). Nine healthy young men were exposed, while awake, to sham IH, IH with placebo medication, and IH with the AT(1) receptor antagonist, losartan, using a double-blind, placebo-controlled, randomized, crossover study design. In addition to blood pressure, oxidative stress, peroxynitrite activity, uric acid, global antioxidant status and the end-products of NO (NOx) metabolism were measured in plasma before and after 6 h of IH. Oxidative stress and peroxynitrite activity increased and NOx decreased during IH with placebo. In contrast, neither sham IH nor IH with losartan affected these parameters. With respect to each condition, blood pressure had the same profile as oxidative stress. These results demonstrate that blockade of AT(1) receptors prevented the increase in oxidative stress and peroxynitrite activity and the decrease in NO metabolism induced by IH. Finally, this study suggests that the renin-angiotensin system may participate in the overproduction of reactive oxygen species associated with IH by upregulation of the actions of angiotensin II.

  10. Arterial Stiffness, Oxidative Stress, and Smoke Exposure in Wildland Firefighters

    PubMed Central

    Gaughan, Denise M.; Siegel, Paul D.; Hughes, Michael D.; Chang, Chiung-Yu; Law, Brandon F.; Campbell, Corey R.; Richards, Jennifer C.; Kales, Stefanos F.; Chertok, Marcia; Kobzik, Lester; Nguyen, Phuongson; O’Donnell, Carl R.; Kiefer, Max; Wagner, Gregory R.; Christiani, David C.

    2015-01-01

    Objectives To assess the association between exposure, oxidative stress, symptoms, and cardiorespiratory function in wildland firefighters. Methods We studied two Interagency Hotshot Crews with questionnaires, pulse wave analysis for arterial stiffness, spirometry, urinary 8-iso-prostaglandin F2α (8-isoprostane) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and the smoke exposure marker (urinary levoglucosan). Arterial stiffness was assessed by examining levels of the aortic augmentation index, expressed as a percentage. An oxidative stress score comprising the average of z-scores created for 8-OHdG and 8-isoprostane was calculated. Results Mean augmentation index % was higher for participants with higher oxidative stress scores after adjusting for smoking status. Specifically for every one unit increase in oxidative stress score the augmentation index % increased 10.5% (95% CI: 2.5, 18.5%). Higher mean lower respiratory symptom score was associated with lower percent predicted forced expiratory volume in one second/forced vital capacity. Conclusions Biomarkers of oxidative stress may serve as indicators of arterial stiffness in wildland firefighters. PMID:24909863

  11. Cellular Mechanisms of Oxidative Stress and Action in Melanoma.

    PubMed

    Venza, Mario; Visalli, Maria; Beninati, Concetta; De Gaetano, Giuseppe Valerio; Teti, Diana; Venza, Isabella

    2015-01-01

    Most melanomas occur on the skin, but a small percentage of these life-threatening cancers affect other parts of the body, such as the eye and mucous membranes, including the mouth. Given that most melanomas are caused by ultraviolet radiation (UV) exposure, close attention has been paid to the impact of oxidative stress on these tumors. The possibility that key epigenetic enzymes cannot act on a DNA altered by oxidative stress has opened new perspectives. Therefore, much attention has been paid to the alteration of DNA methylation by oxidative stress. We review the current evidence about (i) the role of oxidative stress in melanoma initiation and progression; (ii) the mechanisms by which ROS influence the DNA methylation pattern of transformed melanocytes; (iii) the transformative potential of oxidative stress-induced changes in global and/or local gene methylation and expression; (iv) the employment of this epimutation as a biomarker for melanoma diagnosis, prognosis, and drug resistance evaluation; (v) the impact of this new knowledge in clinical practice for melanoma treatment.

  12. 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

  13. Aluminum Induces Oxidative Stress Genes in Arabidopsis thaliana1

    PubMed Central

    Richards, Keith D.; Schott, Eric J.; Sharma, Yogesh K.; Davis, Keith R.; Gardner, Richard C.

    1998-01-01

    Changes in gene expression induced by toxic levels of Al were characterized to investigate the nature of Al stress. A cDNA library was constructed from Arabidopsis thaliana seedlings treated with Al for 2 h. We identified five cDNA clones that showed a transient induction of their mRNA levels, four cDNA clones that showed a longer induction period, and two down-regulated genes. Expression of the four long-term-induced genes remained at elevated levels for at least 48 h. The genes encoded peroxidase, glutathione-S-transferase, blue copper-binding protein, and a protein homologous to the reticuline:oxygen oxidoreductase enzyme. Three of these genes are known to be induced by oxidative stresses and the fourth is induced by pathogen treatment. Another oxidative stress gene, superoxide dismutase, and a gene for Bowman-Birk protease inhibitor were also induced by Al in A. thaliana. These results suggested that Al treatment of Arabidopsis induces oxidative stress. In confirmation of this hypothesis, three of four genes induced by Al stress in A. thaliana were also shown to be induced by ozone. Our results demonstrate that oxidative stress is an important component of the plant's reaction to toxic levels of Al. PMID:9449849

  14. Oxidative stress: a concept in redox biology and medicine.

    PubMed

    Sies, Helmut

    2015-01-01

    "Oxidative stress" as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this term. This concept has its merits and its pitfalls. Among the merits is the notion, elicited by the combined two terms of (i) aerobic metabolism as a steady-state redox balance and (ii) the associated potential strains in the balance as denoted by the term, stress, evoking biological stress responses. Current research on molecular redox switches governing oxidative stress responses is in full bloom. The fundamental importance of linking redox shifts to phosphorylation/dephosphorylation signaling is being more fully appreciated, thanks to major advances in methodology. Among the pitfalls is the fact that the underlying molecular details are to be worked out in each particular case, which is bvious for a global concept, but which is sometimes overlooked. This can lead to indiscriminate use of the term, oxidative stress, without clear relation to redox chemistry. The major role in antioxidant defense is fulfilled by antioxidant enzymes, not by small-molecule antioxidant compounds. The field of oxidative stress research embraces chemistry, biochemistry, cell biology, physiology and pathophysiology, all the way to medicine and health and disease research.

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

    PubMed Central

    Aliev, Gjumrakch; Palacios, Hector H.; Gasimov, Eldar; Obrenovich, Mark E.; Morales, Ludis; Leszek, Jerzy; Bragin, Valentin; Herrera, Arturo Solís; Gokhman, Dmitry

    2010-01-01

    Mitochondrial dysfunction may be a principal underlying event in aging, including age-associated brain degeneration. Mitochondria provide energy for basic metabolic processes. Their decay with age impairs cellular metabolism and leads to a decline of cellular function. Alzheimer disease (AD) and cerebrovascular accidents (CVAs) are two leading causes of age-related dementia. Increasing evidence strongly supports the theory that oxidative stress, largely due to reactive oxygen species (ROS), induces mitochondrial damage, which arises from chronic hypoperfusion and is primarily responsible for the pathogenesis that underlies both disease processes. Mitochondrial membrane potential, respiratory control ratios and cellular oxygen consumption decline with age and correlate with increased oxidant production. The sustained hypoperfusion and oxidative stress in brain tissues can stimulate the expression of nitric oxide synthases (NOSs) and brain endothelium probably increase the accumulation of oxidative stress products, which therefore contributes to blood brain barrier (BBB) breakdown and brain parenchymal cell damage. Determining the mechanisms behind these imbalances may provide crucial information in the development of new, more effective therapies for stroke and AD patients in the near future. PMID:27713247

  16. Acute exercise and oxidative stress: a 30 year history

    PubMed Central

    Fisher-Wellman, Kelsey; Bloomer, Richard J

    2009-01-01

    The topic of exercise-induced oxidative stress has received considerable attention in recent years, with close to 300 original investigations published since the early work of Dillard and colleagues in 1978. Single bouts of aerobic and anaerobic exercise can induce an acute state of oxidative stress. This is indicated by an increased presence of oxidized molecules in a variety of tissues. Exercise mode, intensity, and duration, as well as the subject population tested, all can impact the extent of oxidation. Moreover, the use of antioxidant supplements can impact the findings. Although a single bout of exercise often leads to an acute oxidative stress, in accordance with the principle of hormesis, such an increase appears necessary to allow for an up-regulation in endogenous antioxidant defenses. This review presents a comprehensive summary of original investigations focused on exercise-induced oxidative stress. This should provide the reader with a well-documented account of the research done within this area of science over the past 30 years. PMID:19144121

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

    PubMed

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

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention. PMID:26596837

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

    PubMed

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

    2016-05-01

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

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

    PubMed

    Wages, Phillip A; Lavrich, Katelyn S; Zhang, Zhenfa; Cheng, Wan-Yun; Corteselli, Elizabeth; Gold, Avram; Bromberg, Philip; Simmons, Steven O; Samet, James M

    2015-12-21

    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 (H2O2). Cysteinyl thiolate residues on regulatory proteins are subjected to oxidative modification by H2O2 in physiological contexts and are also toxicological targets of oxidant stress induced by environmental contaminants. We investigated whether exposure to environmentally relevant concentrations of 1,2-NQ can induce H2O2-dependent oxidation of cysteinyl thiols in regulatory proteins as a readout of oxidant stress in human airway epithelial cells. BEAS-2B cells were exposed to 0-1000 μM 1,2-NQ for 0-30 min, and levels of H2O2 were measured by ratiometric spectrofluorometry of HyPer. H2O2-dependent protein sulfenylation was measured using immunohistochemistry, immunoblotting, and isotopic mass spectrometry. Catalase overexpression was used to investigate the relationship between H2O2 generation and protein sulfenylation in cells exposed to 1,2-NQ. Multiple experimental approaches showed that exposure to 1,2-NQ at concentrations as low as 3 μM induces H2O2-dependent protein sulfenylation in BEAS-2B cells. Moreover, the time of onset and duration of 1,2-NQ-induced sulfenylation of the regulatory proteins GAPDH and PTP1B showed significant differences. Oxidative modification of regulatory cysteinyl thiols in human lung cells exposed to relevant concentrations of an ambient air contaminant represents a novel marker of oxidative environmental stress.

  20. Cytoprotective Mechanism of Cyanidin and Delphinidin against Oxidative Stress-Induced Tenofibroblast Death

    PubMed Central

    Nam, Dae Cheol; Hah, Young Sool; Nam, Jung Been; Kim, Ra Jeong; Park, Hyung Bin

    2016-01-01

    Age-related rotator cuff tendon degeneration is related to tenofibroblast apoptosis. Anthocyanins reduce oxidative stress-induced apoptotic cell death in tenofibroblasts. The current study investigated the presence of cell protective effects in cyanidin and delphinidin, the most common aglycon forms of anthocyanins. We determined whether these anthocyanidins have antiapoptotic and antinecrotic effects in tenofibroblasts exposed to H2O2, and evaluated their biomolecular mechanisms. Both cyanidin and delphinidin inhibited H2O2-induced apoptosis in a dose-dependent manner. However, at concentrations of 100 μg/ml or greater, delphinidin showed cytotoxicity against tenofibroblasts and a decreased antinecrotic effect. Cyanidin and delphinidin both showed inhibitory effects on the H2O2-induced increase in intracellular ROS formation and the activation of ERK1/2 and JNK. In conclusion, both cyanidin and delphinidin have cytoprotective effects on cultured tenofibroblasts exposed to H2O2. These results suggest that cyanidin and delphinidin are both beneficial for the treatment of oxidative stress-mediated tenofibroblast cell death, but their working concentrations are different. PMID:27098861

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

    PubMed

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

    2013-01-01

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

  2. Novel biomarker pipeline to probe the oxidation sites and oxidation degrees of hemoglobin in bovine erythrocytes exposed to oxidative stress.

    PubMed

    Zong, Wansong; Wang, Xiaoning; Yang, Chuanxi; Du, Yonggang; Sun, Weijun; Xu, Zhenzhen

    2016-06-01

    Research on biomarkers for protein oxidation might give insight into the mechanistic mode of oxidative stress. In the work present here, a novel pipeline was established to probe the oxidation mechanism of bovine hemoglobin (Hb) with its oxidation products serving as the biomarkers. Reactive oxygen species generated by irradiation were used to mimic oxidative stress conditions to oxidize Hb in bovine erythrocytes. After Hb extraction and digestion, oxidized peptides in the tryptic fragments were assigned by comparison with the extracted ion chromatography spectra of native peptide from the control sample. Subsequent tandem mass spectrometry analysis of these peptides proved that oxidation was limited to partially exposed amino acid residues (α-Phe36 , β-Met1 , β-Trp14 , for instance) in Hb. Quantitation analysis on these oxidized peptides showed that oxidation degrees of target sites had positive correlations with the extended oxidation dose and the oxidation processes were also controlled by residues types. Compared with the conventional protein carbonyl assay, the identified oxidized products were feasibility biomarkers for Hb oxidation, indicating that the proposed biomarker pipeline was suitable to provide specific and valid information for protein oxidation. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Regulation of the Arabidopsis Transcriptome by Oxidative Stress

    PubMed Central

    Desikan, Radhika; A.-H.-Mackerness, Soheila; Hancock, John T.; Neill, Steven J.

    2001-01-01

    Oxidative stress, resulting from an imbalance in the accumulation and removal of reactive oxygen species such as hydrogen peroxide (H2O2), is a challenge faced by all aerobic organisms. In plants, exposure to various abiotic and biotic stresses results in accumulation of H2O2 and oxidative stress. Increasing evidence indicates that H2O2 functions as a stress signal in plants, mediating adaptive responses to various stresses. To analyze cellular responses to H2O2, we have undertaken a large-scale analysis of the Arabidopsis transcriptome during oxidative stress. Using cDNA microarray technology, we identified 175 non-redundant expressed sequence tags that are regulated by H2O2. Of these, 113 are induced and 62 are repressed by H2O2. A substantial proportion of these expressed sequence tags have predicted functions in cell rescue and defense processes. RNA-blot analyses of selected genes were used to verify the microarray data and extend them to demonstrate that other stresses such as wilting, UV irradiation, and elicitor challenge also induce the expression of many of these genes, both independently of, and, in some cases, via H2O2. PMID:11553744

  4. The Mismetallation of Enzymes during Oxidative Stress*

    PubMed Central

    Imlay, James A.

    2014-01-01

    Mononuclear iron enzymes can tightly bind non-activating metals. How do cells avoid mismetallation? The model bacterium Escherichia coli may control its metal pools so that thermodynamics favor the correct metallation of each enzyme. This system is disrupted, however, by superoxide and hydrogen peroxide. These species oxidize ferrous iron and thereby displace it from many iron-dependent mononuclear enzymes. Ultimately, zinc binds in its place, confers little activity, and imposes metabolic bottlenecks. Data suggest that E. coli compensates by using thiols to extract the zinc and by importing manganese to replace the catalytic iron atom. Manganese resists oxidants and provides substantial activity. PMID:25160623

  5. Immunology of age-related macular degeneration

    PubMed Central

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  6. [Epidemiology of age related macular degeneration].

    PubMed

    Leveziel, N; Delcourt, C; Zerbib, J; Dollfus, H; Kaplan, J; Benlian, P; Coscas, G; Souied, E H; Soubrane, G

    2009-06-01

    Age-related macular degeneration (ARMD) is a multifactorial and polygenic disease and is the main cause of vision loss in developed countries. The environmental factors of ARMD can modify prevalence and incidence of this disease. This article is a review of the main environmental factors currently recognized as at risk or protective factor for ARMD. Modification of these factors is of crucial importance because it could delay the onset of exudative or atrophic forms of the disease. PMID:19515460

  7. 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

  8. 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

  9. Oxidative Stress, Inflammation, and DNA Damage Responses Elicited by Silver, Titanium Dioxide, and Cerium Oxide Nanomaterials

    EPA Science Inventory

    Previous literature on the biological effects of engineered nanomaterials has focused largely on oxidative stress and inflammation endpoints without further investigating potential pathways. Here we examine time-sensitive biological response pathways affected by engineered nanoma...

  10. Does aspirin-induced oxidative stress cause asthma exacerbation?

    PubMed

    Kacprzak, Dorota; Pawliczak, Rafał

    2015-06-19

    Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.

  11. Transketolase counteracts oxidative stress to drive cancer development

    PubMed Central

    Xu, Iris Ming-Jing; Lai, Robin Kit-Ho; Lin, Shu-Hai; Tse, Aki Pui-Wah; Chiu, David Kung-Chun; Koh, Hui-Yu; Law, Cheuk-Ting; Wong, Chun-Ming; Cai, Zongwei; Wong, Carmen Chak-Lui; Ng, Irene Oi-Lin

    2016-01-01

    Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer cells by genetic knockdown or pharmacologic inhibition of TKT sensitizes cancer cells to existing targeted therapy (Sorafenib). Our study strengthens the notion that antioxidants are beneficial to cancer growth and highlights the therapeutic benefits of targeting pathways that generate antioxidants. PMID:26811478

  12. Engrailed Homeoprotein Protects Mesencephalic Dopaminergic Neurons from Oxidative Stress

    PubMed Central

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

    2016-01-01

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

  13. Alzheimer´s disease and oxidative stress: a review.

    PubMed

    Pohanka, Miroslav

    2014-01-01

    Alzheimer´s disease (AD) is a neurodegenerative disorder with no known cure and rapid rise in incidence. The predominant cognitive impairment is currently treated using cognitive enhancers like cholinesterase inhibitors. The two molecular hallmarks of AD are amyloid plaques created from an amyloid precursor protein and hyperphosphorylated tau protein that is deposited as neurofibrillary tangles inside neurons. A number of pathological mechanisms follow or precede these formations. Alteration in mitochondrial function and deposition of heavy metals are reported. The disease progression is enhanced by oxidative stress. However, the role of oxidative stress is not universally accepted. The current review covers and discusses the basic evidence and role of oxidative stress in AD development.

  14. Transketolase counteracts oxidative stress to drive cancer development.

    PubMed

    Xu, Iris Ming-Jing; Lai, Robin Kit-Ho; Lin, Shu-Hai; Tse, Aki Pui-Wah; Chiu, David Kung-Chun; Koh, Hui-Yu; Law, Cheuk-Ting; Wong, Chun-Ming; Cai, Zongwei; Wong, Carmen Chak-Lui; Ng, Irene Oi-Lin

    2016-02-01

    Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers. Disturbing the redox homeostasis of cancer cells by genetic knockdown or pharmacologic inhibition of TKT sensitizes cancer cells to existing targeted therapy (Sorafenib). Our study strengthens the notion that antioxidants are beneficial to cancer growth and highlights the therapeutic benefits of targeting pathways that generate antioxidants. PMID:26811478

  15. Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity.

    PubMed

    Dutta, Debapriya; Xu, Jinze; Kim, Jae-Sung; Dunn, William A; Leeuwenburgh, Christiaan

    2013-03-01

    Autophagy is a cellular self-digestion process that mediates protein quality control and serves to protect against neurodegenerative disorders, infections, inflammatory diseases and cancer. Current evidence suggests that autophagy can selectively remove damaged organelles such as the mitochondria. Mitochondria-induced oxidative stress has been shown to play a major role in a wide range of pathologies in several organs, including the heart. Few studies have investigated whether enhanced autophagy can offer protection against mitochondrially-generated oxidative stress. We induced mitochondrial stress in cardiomyocytes using antimycin A (AMA), which increased mitochondrial superoxide generation, decreased mitochondrial membrane potential and depressed cellular respiration. In addition, AMA augmented nuclear DNA oxidation and cell death in cardiomyocytes. Interestingly, although oxidative stress has been proposed to induce autophagy, treatment with AMA did not result in stimulation of autophagy or mitophagy in cardiomyocytes. Our results showed that the MTOR inhibitor rapamycin induced autophagy, promoted mitochondrial clearance and protected cardiomyocytes from the cytotoxic effects of AMA, as assessed by apoptotic marker activation and viability assays in both mouse atrial HL-1 cardiomyocytes and human ventricular AC16 cells. Importantly, rapamycin improved mitochondrial function, as determined by cellular respiration, mitochondrial membrane potential and morphology analysis. Furthermore, autophagy induction by rapamycin suppressed the accumulation of ubiquitinylated proteins induced by AMA. Inhibition of rapamycin-induced autophagy by pharmacological or genetic interventions attenuated the cytoprotective effects of rapamycin against AMA. We propose that rapamycin offers cytoprotection against oxidative stress by a combined approach of removing dysfunctional mitochondria as well as by degrading damaged, ubiquitinated proteins. We conclude that autophagy induction by

  16. Upregulated autophagy protects cardiomyocytes from oxidative stress-induced toxicity

    PubMed Central

    Dutta, Debapriya; Xu, Jinze; Kim, Jae-Sung; Dunn, Jr., William A.; Leeuwenburgh, Christiaan

    2013-01-01

    Autophagy is a cellular self-digestion process that mediates protein quality control and serves to protect against neurodegenerative disorders, infections, inflammatory diseases and cancer. Current evidence suggests that autophagy can selectively remove damaged organelles such as the mitochondria. Mitochondria-induced oxidative stress has been shown to play a major role in a wide range of pathologies in several organs, including the heart. Few studies have investigated whether enhanced autophagy can offer protection against mitochondrially-generated oxidative stress. We induced mitochondrial stress in cardiomyocytes using antimycin A (AMA), which increased mitochondrial superoxide generation, decreased mitochondrial membrane potential and depressed cellular respiration. In addition, AMA augmented nuclear DNA oxidation and cell death in cardiomyocytes. Interestingly, although oxidative stress has been proposed to induce autophagy, treatment with AMA did not result in stimulation of autophagy or mitophagy in cardiomyocytes. Our results showed that the MTOR inhibitor rapamycin induced autophagy, promoted mitochondrial clearance and protected cardiomyocytes from the cytotoxic effects of AMA, as assessed by apoptotic marker activation and viability assays in both mouse atrial HL-1 cardiomyocytes and human ventricular AC16 cells. Importantly, rapamycin improved mitochondrial function, as determined by cellular respiration, mitochondrial membrane potential and morphology analysis. Furthermore, autophagy induction by rapamycin suppressed the accumulation of ubiquitinylated proteins induced by AMA. Inhibition of rapamycin-induced autophagy by pharmacological or genetic interventions attenuated the cytoprotective effects of rapamycin against AMA. We propose that rapamycin offers cytoprotection against oxidative stress by a combined approach of removing dysfunctional mitochondria as well as by degrading damaged, ubiquitinated proteins. We conclude that autophagy induction by

  17. Trap generation and occupation in stressed gate oxides under spatially variable oxide electric field

    NASA Astrophysics Data System (ADS)

    Avni, E.; Shappir, J.

    1987-11-01

    The spatial variation of the oxide field in metal-oxide-silicon devices due to charge trapping under electron injection stress is included in a self-consistent trapping model. The model predicts the spatial distribution of the stress-generated trapping sites and their occupation level under different conditions of applied voltages and total injected charge. The calculated results agree quite well with the experimental results of prolonged charge injection, as expressed in shifts of the flatband voltage.

  18. 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 ...

  19. Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

    PubMed Central

    Kurita-Ochiai, Tomoko; Jia, Ru; Cai, Yu; Yamaguchi, Yohei; Yamamoto, Masafumi

    2015-01-01

    Periodontal disease is a highly prevalent disorder affecting up to 80% of the global population. Recent epidemiological studies have shown an association between periodontal disease and cardiovascular disease, as oxidative stress plays an important role in chronic inflammatory diseases such as periodontal disease and cardiovascular disease. In this review, we focus on the mechanisms by which periodontopathic bacteria cause chronic inflammation through the enhancement of oxidative stress and accelerate cardiovascular disease. Furthermore, we comment on the antioxidative activity of catechin in atherosclerosis accelerated by periodontitis. PMID:26783845

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

    PubMed Central

    Spiers, Jereme G.; Chen, Hsiao-Jou Cortina; Sernia, Conrad; Lavidis, Nickolas A.

    2015-01-01

    Glucocorticoids released from the adrenal gland in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis induce activity in the cellular reduction-oxidation (redox) system. The redox system is a ubiquitous chemical mechanism allowing the transfer of electrons between donor/acceptors and target molecules during oxidative phosphorylation while simultaneously maintaining the overall cellular environment in a reduced state. The objective of this review is to present an overview of the current literature discussing the link between HPA axis-derived glucocorticoids and increased oxidative stress, particularly focussing on the redox changes observed in the hippocampus following glucocorticoid exposure. PMID:25646076

  1. Tyrosine phosphorylation of clathrin heavy chain under oxidative stress.

    PubMed

    Ihara, Yoshito; Yasuoka, Chie; Kageyama, Kan; Wada, Yoshinao; Kondo, Takahito

    2002-09-20

    In mouse pancreatic insulin-producing betaTC cells, oxidative stress due to H(2)O(2) causes tyrosine phosphorylation in various proteins. To identify proteins bearing phosphotyrosine under stress, the proteins were affinity purified using an anti-phosphotyrosine antibody-conjugated agarose column. A protein of 180kDa was identified as clathrin heavy chain (CHC) by electrophoresis and mass spectrometry. Immunoprecipitated CHC showed tyrosine phosphorylation upon H(2)O(2) treatment and the phosphorylation was suppressed by the Src kinase inhibitor, PP2. The phosphorylation status of CHC affected the intracellular localization of CHC and the clathrin-dependent endocytosis of transferrin under oxidative stress. In conclusion, CHC is a protein that is phosphorylated at tyrosine by H(2)O(2) and this phosphorylation status is implicated in the intracellular localization and functions of CHC under oxidative stress. The present study demonstrates that oxidative stress affects intracellular vesicular trafficking via the alteration of clathrin-dependent vesicular trafficking. PMID:12237126

  2. Overexpression of calreticulin sensitizes SERCA2a to oxidative stress.

    PubMed

    Ihara, Yoshito; Kageyama, Kan; Kondo, Takahito

    2005-04-22

    Calreticulin (CRT), a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum, plays a vital role in cardiac physiology and pathology. Oxidative stress is a main cause of myocardiac disorder in the ischemic heart, but the function of CRT under oxidative stress is not fully understood. In this study, the effect of overexpression of CRT on sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2a under oxidative stress was examined using myocardiac H9c2 cells transfected with the CRT gene. The in vitro activity of SERCA2a and uptake of (45)Ca(2+) into isolated microsomes were suppressed by H(2)O(2) in CRT-overexpressing cells compared with controls. Moreover, SERCA2a protein was degraded via a proteasome-dependent pathway following the formation of a complex with CRT under the stress with H(2)O(2). Thus, we conclude that overexpression of CRT enhances the inactivation and degradation of SERCA2a in the cells under oxidative stress, suggesting some pathophysiological functions of CRT in Ca(2+) homeostasis of myocardiac disease. PMID:15766574

  3. Oxidative stress: a concept in redox biology and medicine

    PubMed Central

    Sies, Helmut

    2015-01-01

    Oxidative stress” as a concept in redox biology and medicine has been formulated in 1985; at the beginning of 2015, approx. 138,000 PubMed entries show for this term. This concept has its merits and its pitfalls. Among the merits is the notion, elicited by the combined two terms of (i) aerobic metabolism as a steady-state redox balance and (ii) the associated potential strains in the balance as denoted by the term, stress, evoking biological stress responses. Current research on molecular redox switches governing oxidative stress responses is in full bloom. The fundamental importance of linking redox shifts to phosphorylation/dephosphorylation signaling is being more fully appreciated, thanks to major advances in methodology. Among the pitfalls is the fact that the underlying molecular details are to be worked out in each particular case, which is bvious for a global concept, but which is sometimes overlooked. This can lead to indiscriminate use of the term, oxidative stress, without clear relation to redox chemistry. The major role in antioxidant defense is fulfilled by antioxidant enzymes, not by small-molecule antioxidant compounds. The field of oxidative stress research embraces chemistry, biochemistry, cell biology, physiology and pathophysiology, all the way to medicine and health and disease research. PMID:25588755

  4. Overexpression of calreticulin sensitizes SERCA2a to oxidative stress.

    PubMed

    Ihara, Yoshito; Kageyama, Kan; Kondo, Takahito

    2005-04-22

    Calreticulin (CRT), a Ca(2+)-binding molecular chaperone in the endoplasmic reticulum, plays a vital role in cardiac physiology and pathology. Oxidative stress is a main cause of myocardiac disorder in the ischemic heart, but the function of CRT under oxidative stress is not fully understood. In this study, the effect of overexpression of CRT on sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) 2a under oxidative stress was examined using myocardiac H9c2 cells transfected with the CRT gene. The in vitro activity of SERCA2a and uptake of (45)Ca(2+) into isolated microsomes were suppressed by H(2)O(2) in CRT-overexpressing cells compared with controls. Moreover, SERCA2a protein was degraded via a proteasome-dependent pathway