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

Science.gov (United States)

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

2017-02-01

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

Mechanism of H₂O₂-induced oxidative stress regulating viability and biocontrol ability of Rhodotorula glutinis.

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Chen, Jian; Li, Boqiang; Qin, Guozheng; Tian, Shiping

2015-01-16

The use of antagonistic yeasts to control postharvest pathogens is a promising alternative to fungicides. The effectiveness of the antagonists against fungal pathogens is greatly dependent on their viability, which is usually mediated by reactive oxygen species (ROS). Here, we investigated the effects of H₂O₂-induced oxidative stress on the viability and biocontrol efficacy of Rhodotorula glutinis and, using flow cytometric analysis, observed the changes of ROS accumulation and apoptosis in the yeast cells with or without H₂O₂ treatment. We found that the viability of R. glutinis decreased in a time- and dose-dependent manner under H₂O₂-induced oxidative stress. Compared to the control, yeast cells exposed to oxidative stress exhibited more accumulation of ROS and higher levels of protein oxidative damage, but showed lower efficacy for biocontrol of Penicillium expansum causing blue mold rot on peach fruit. The results indicate that apoptosis is a main cause of the cell viability loss in R. glutinis, which is attributed to ROS accumulation under oxidative stress. These findings offer a plausible explanation that oxidative stress affects biocontrol efficacy of R. glutinis via regulating its viability and cell apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlation between oxidation and stress corrosion cracking of U-4.5 wt.% Nb

International Nuclear Information System (INIS)

Magnani, N.J.; Holloway, P.H.

1976-01-01

To investigate the mechanisms causing stress corrosion cracking on uranium alloys, the kinetics of crack propagation and oxide film growth for U-4.5 percent Nb were investigated at temperatures between 0 0 C and 200 0 C in oxygen, water vapor and oxygen-water vapor mixtures. Three regions of crack velocity rate versus stress intensity were observed in laboratory air. At low stress intensities (but above an effective K/sub ISCC/ of 22 MN/m/sup 3 / 2 /) crack velocity varied approximately as K 70 . In an intermediate stress intensity region (region II) the crack velocity was dependent upon K 4 . In the high stress intensity region, mechanical overloading was observed and crack velocities varied approximately as K 12 . Both cracking (region II) and oxidation rates were characterized by an activation energy of 7 kcal/mole. For stress corrosion cracking it was shown that oxygen was the primary stress corrodent, but a synergistic effect upon crack propagation rates was observed for oxygen-water vapor mixtures. Crack velocities were dependent upon the pressure of oxygen (P/sub O 2 //sup 1 / 3 /) and water vapor, while the oxidation rate was essentially independent of the pressure of these species. Stress sorption and oxide film formation stress corrosion cracking mechanisms were considered and reconciled with the stress corrosion and oxidation data

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

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

2013-09-01

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

Low voltage stress-induced leakage current and traps in ultrathin oxide (1.2 2.5 nm) after constant voltage stresses

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Petit, C.; Zander, D.

2007-10-01

It has been shown that the low voltage gate current in ultrathin oxide metal-oxide-semiconductor devices is very sensitive to electrical stresses. Therefore, it can be used as a reliability monitor when the oxide thickness becomes too small for traditional electrical measurements to be used. In this work, we present a study on n-MOSCAP devices at negative gate bias in the direct tunneling (DT) regime. If the low voltage stress-induced leakage current (LVSILC) depends strongly on the low sense voltages, it also depends strongly on the stress voltage magnitude. We show that two LVSILC peaks appear as a function of the sense voltage in the LVSILC region and that their magnitude, one compared to the other, depends strongly on the stress voltage magnitude. One is larger than the other at low stress voltage and smaller at high stress voltage. From our experimental results, different conduction mechanisms are analyzed. To explain LVSILC variations, we propose a model of the conduction through the ultrathin gate oxide based on two distinctly different trap-assisted tunneling mechanisms: inelastic of gate electron (INE) and trap-assisted electron (ETAT).

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

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

2012-06-01

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress

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Saba Naqvi

2010-11-01

Full Text Available Saba Naqvi1, Mohammad Samim2, MZ Abdin3, Farhan Jalees Ahmed4, AN Maitra5, CK Prashant6, Amit K Dinda61Faculty of Engineering and Interdisciplinary Sciences, 2Department of Chemistry, 3Department of Biotechnology, Faculty of Science, 4Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, 5Department of Chemistry, University of Delhi, 6Department of Pathology, All India Institute of Medical Sciences, New Delhi, IndiaAbstract: Iron oxide nanoparticles with unique magnetic properties have a high potential for use in several biomedical, bioengineering and in vivo applications, including tissue repair, magnetic resonance imaging, immunoassay, drug delivery, detoxification of biologic fluids, cell sorting, and hyperthermia. Although various surface modifications are being done for making these nonbiodegradable nanoparticles more biocompatible, their toxic potential is still a major concern. The current in vitro study of the interaction of superparamagnetic iron oxide nanoparticles of mean diameter 30 nm coated with Tween 80 and murine macrophage (J774 cells was undertaken to evaluate the dose- and time-dependent toxic potential, as well as investigate the role of oxidative stress in the toxicity. A 15–30 nm size range of spherical nanoparticles were characterized by transmission electron microscopy and zeta sizer. MTT assay showed >95% viability of cells in lower concentrations (25–200 µg/mL and up to three hours of exposure, whereas at higher concentrations (300–500 µg/mL and prolonged (six hours exposure viability reduced to 55%–65%. Necrosis-apoptosis assay by propidium iodide and Hoechst-33342 staining revealed loss of the majority of the cells by apoptosis. H2DCFDDA assay to quantify generation of intracellular reactive oxygen species (ROS indicated that exposure to a higher concentration of nanoparticles resulted in enhanced ROS generation, leading to cell injury and death. The cell membrane injury

Oxidative Stress in Neurodegeneration

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Varsha Shukla

2011-01-01

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

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

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

2015-01-01

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

BRCA1 and Oxidative Stress

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

2014-04-03

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

Impact of aerobic exercise on cognitive impairment and oxidative stress markers in methamphetamine-dependent patients.

Science.gov (United States)

Zhang, Kai; Zhang, Qiaoyang; Jiang, Haifeng; Du, Jiang; Zhou, Chenglin; Yu, Shunying; Hashimoto, Kenji; Zhao, Min

2018-03-17

This study aimed to investigate whether 12-week moderate-intensity aerobic exercise has beneficial effects on oxidative stress markers in blood and on cognitive functions in patients who have methamphetamine dependence. Serum levels of oxidative stress markers, including total anti-oxidation capability, super oxide dismutase (SOD), catalase (CAT), and methane dicarboxylic aldehyde (MDA), were measured at baseline (all participants) and the 12-week follow-up (methamphetamine-dependent patients). Serum levels of CAT and MDA in methamphetamine-dependent patients (n = 68) were higher than those in healthy controls (n = 35) at baseline. Furthermore, the international shopping list (ISL) task scores of methamphetamine-dependent patients were significantly lower than those of the controls, indicating verbal memory deficits in methamphetamine-dependent patients. Although there were no significant interactions for all cognitive function scores, aerobic exercise improved the processing speed in methamphetamine-dependent patients. Of interest, aerobic exercise significantly attenuated a spontaneous increase in serum MDA levels in methamphetamine-dependent patients after 12-weeks of abstinence. In conclusion, this study showed that methamphetamine-dependent patients with verbal learning and memory deficits have higher serum levels of MDA, and that a 12-week aerobic exercise program may have beneficial effects on the processing speed as well as blood lipid peroxidation in methamphetamine-dependent patients. Copyright © 2018. Published by Elsevier B.V.

Mechanisms Underlying the Delayed Activation of the Cap1 Transcription Factor in Candida albicans following Combinatorial Oxidative and Cationic Stress Important for Phagocytic Potency.

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Kos, Iaroslava; Patterson, Miranda J; Znaidi, Sadri; Kaloriti, Despoina; da Silva Dantas, Alessandra; Herrero-de-Dios, Carmen M; d'Enfert, Christophe; Brown, Alistair J P; Quinn, Janet

2016-03-29

Following phagocytosis, microbes are exposed to an array of antimicrobial weapons that include reactive oxygen species (ROS) and cationic fluxes. This is significant as combinations of oxidative and cationic stresses are much more potent than the corresponding single stresses, triggering the synergistic killing of the fungal pathogenCandida albicansby "stress pathway interference." Previously we demonstrated that combinatorial oxidative plus cationic stress triggers a dramatic increase in intracellular ROS levels compared to oxidative stress alone. Here we show that activation of Cap1, the major regulator of antioxidant gene expression inC. albicans, is significantly delayed in response to combinatorial stress treatments and to high levels of H2O2 Cap1 is normally oxidized in response to H2O2; this masks the nuclear export sequence, resulting in the rapid nuclear accumulation of Cap1 and the induction of Cap1-dependent genes. Here we demonstrate that following exposure of cells to combinatorial stress or to high levels of H2O2, Cap1 becomes trapped in a partially oxidized form, Cap1(OX-1) Notably, Cap1-dependent gene expression is not induced when Cap1 is in this partially oxidized form. However, while Cap1(OX-1)readily accumulates in the nucleus and binds to target genes following high-H2O2stress, the nuclear accumulation of Cap1(OX-1)following combinatorial H2O2and NaCl stress is delayed due to a cationic stress-enhanced interaction with the Crm1 nuclear export factor. These findings define novel mechanisms that delay activation of the Cap1 transcription factor, thus preventing the rapid activation of the stress responses vital for the survival ofC. albicanswithin the host. Combinatorial stress-mediated synergistic killing represents a new unchartered area in the field of stress signaling. This phenomenon contrasts starkly with "stress cross-protection," where exposure to one stress protects against subsequent exposure to a different stress. Previously we

Oxidative stress protection and stomatal patterning as components of salinity tolerance mechanism in quinoa (Chenopodium quinoa).

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Shabala, Lana; Mackay, Alex; Tian, Yu; Jacobsen, Sven-Erik; Zhou, Daowei; Shabala, Sergey

2012-09-01

Two components of salinity stress are a reduction in water availability to plants and the formation of reactive oxygen species. In this work, we have used quinoa (Chenopodium quinoa), a dicotyledonous C3 halophyte species displaying optimal growth at approximately 150 mM NaCl, to study mechanisms by which halophytes cope with the afore-mentioned components of salt stress. The relative contribution of organic and inorganic osmolytes in leaves of different physiological ages (e.g. positions on the stem) was quantified and linked with the osmoprotective function of organic osmolytes. We show that the extent of the oxidative stress (UV-B irradiation) damage to photosynthetic machinery in young leaves is much less when compared with old leaves, and attribute this difference to the difference in the size of the organic osmolyte pool (1.5-fold difference under control conditions; sixfold difference in plants grown at 400 mM NaCl). Consistent with this, salt-grown plants showed higher Fv/Fm values compared with control plants after UV-B exposure. Exogenous application of physiologically relevant concentrations of glycine betaine substantially mitigated oxidative stress damage to PSII, in a dose-dependent manner. We also show that salt-grown plants showed a significant (approximately 30%) reduction in stomatal density observed in all leaves. It is concluded that accumulation of organic osmolytes plays a dual role providing, in addition to osmotic adjustment, protection of photosynthetic machinery against oxidative stress in developing leaves. It is also suggested that salinity-induced reduction in stomatal density represents a fundamental mechanism by which plants optimize water use efficiency under saline conditions. Copyright © Physiologia Plantarum 2012.

DJ-1-dependent regulation of oxidative stress in the retinal pigment epithelium (RPE.

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Karen G Shadrach

Full Text Available DJ-1 is found in many tissues, including the brain, where it has been extensively studied due to its association with Parkinson's disease. DJ-1 functions as a redox-sensitive molecular chaperone and transcription regulator that robustly protects cells from oxidative stress.Retinal pigment epithelial (RPE cultures were treated with H2O2 for various times followed by biochemical and immunohistological analysis. Cells were transfected with adenoviruses carrying the full-length human DJ-1 cDNA and a mutant construct, which has the cysteine residues at amino acid 46, 53 and 106 mutated to serine (C to S prior to stress experiments. DJ-1 localization, levels of expression and reactive oxygen species (ROS generation were also analyzed in cells expressing exogenous DJ-1 under baseline and oxidative stress conditions. The presence of DJ-1 and oxidized DJ-1 was evaluated in human RPE total lysates. The distribution of DJ-1 was assessed in AMD and non-AMD cryosectionss and in isolated human Bruch's membrane (BM/choroid from AMD eyes.DJ-1 in RPE cells under baseline conditions, displays a diffuse cytoplasmic and nuclear staining. After oxidative challenge, more DJ-1 was associated with mitochondria. Increasing concentrations of H2O2 resulted in a dose-dependent increase in DJ-1. Overexpression of DJ-1 but not the C to S mutant prior to exposure to oxidative stress led to significant decrease in the generation of ROS. DJ-1 and oxDJ-1 intensity of immunoreactivity was significantly higher in the RPE lysates from AMD eyes. More DJ-1 was localized to RPE cells from AMD donors with geographic atrophy and DJ-1 was also present in isolated human BM/choroid from AMD eyes.DJ-1 regulates RPE responses to oxidative stress. Most importantly, increased DJ-1 expression prior to oxidative stress leads to decreased generation of ROS, which will be relevant for future studies of AMD since oxidative stress is a known factor affecting this disease.

Oxidative Stress and Antioxidant Defense Mechanisms Linked to Exercise During Cardiopulmonary and Metabolic Disorders

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Kelsey Fisher-Wellman

2009-01-01

Full Text Available Oxidative stress has been implicated in the pathophysiology of multiple human diseases, in addition to the aging process. Although various stimuli exist, acute exercise is known to induce a transient increase in reactive oxygen and nitrogen species (RONS, evident by several reports of increased oxidative damage following acute bouts of aerobic and anaerobic exercise. Although the results are somewhat mixed and appear disease dependent, individuals with chronic disease experience an exacerbation in oxidative stress following acute exercise when compared to healthy individuals. However, this increased oxidant stress may serve as a necessary “signal” for the upregulation in antioxidant defenses, thereby providing protection against subsequent exposure to prooxidant environments within susceptible individuals. Here we present studies related to both acute exercise-induced oxidative stress in those with disease, in addition to studies focused on adaptations resulting from increased RONS exposure associated with chronic exercise training in persons with disease.

Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.

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Petrović, Anja; Bogojević, Desanka; Korać, Aleksandra; Golić, Igor; Jovanović-Stojanov, Sofija; Martinović, Vesna; Ivanović-Matić, Svetlana; Stevanović, Jelena; Poznanović, Goran; Grigorov, Ilijana

2017-11-01

The progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.

Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

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Fereshteh Ahmadinejad

2017-07-01

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

Degradation of ultra-thin gate oxide LDD NMOSFET under GIDL stress

International Nuclear Information System (INIS)

Hu Shigang; Hao Yue; Cao Yanrong; Ma Xiaohua; Wu Xiaofeng; Chen Chi; Zhou Qingjun

2009-01-01

The degradation of device under GIDL (gate-induced drain leakage current) stress has been studied using LDD NMOSFETs with 1.4 nm gate oxides. Experimental result shows that the degradation of device parameters depends more strongly on V d than on V g . The characteristics of the GIDL current are used to analyze the damage generated during the stress. It is clearly found that the change of GIDL current before and after stress can be divided into two stages. The trapping of holes in the oxide is dominant in the first stage, but that of electrons in the oxide is dominant in the second stage. It is due to the common effects of edge direct tunneling and band-to-band tunneling. SILC (stress induced leakage current) in the NMOSFET decreases with increasing stress time under GIDL stress. The degradation characteristic of SILC also shows saturating time dependence. SILC is strongly dependent on the measured gate voltage. The higher the measured gate voltage, the less serious the degradation of the gate current. A likely mechanism is presented to explain the origin of SILC during GIDL stress.

Blockade of Drp1 rescues oxidative stress-induced osteoblast dysfunction

Energy Technology Data Exchange (ETDEWEB)

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

2015-12-25

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

Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic Escherichia coli.

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Molina-Quiroz, Roberto C; Silva-Valenzuela, Cecilia; Brewster, Jennifer; Castro-Nallar, Eduardo; Levy, Stuart B; Camilli, Andrew

2018-01-09

Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli , as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli , the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds. Copyright © 2018 Molina-Quiroz et al.

HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

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Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

2015-01-01

Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells

International Nuclear Information System (INIS)

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L’Azou, Béatrice

2012-01-01

Silica nanoparticles (nano-SiO 2 ) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO 2 can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO 2 of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK 1 ). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO 2 nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24 h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO 2 . The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO 2 .

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

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

2011-06-01

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

Mechanism of glucose electrochemical oxidation on gold surface

KAUST Repository

Pasta, Mauro; La Mantia, Fabio; Cui, Yi

2010-01-01

The complex oxidation of glucose at the surface of gold electrodes was studied in detail in different conditions of pH, buffer and halide concentration. As observed in previous studies, an oxidative current peak occurs during the cathodic sweep showing a highly linear dependence on glucose concentration, when other electrolyte conditions are unchanged. The effect of the different conditions on the intensity of this peak has stressed the limitations of the previously proposed mechanisms. A mechanism able to explain the presence of this oxidative peak was proposed. The mechanism takes into account ion-sorption and electrochemical adsorption of OH-, buffer species (K2HPO4/KH2PO4) and halides. © 2010 Elsevier Ltd. All rights reserved.

Mechanism of glucose electrochemical oxidation on gold surface

KAUST Repository

Pasta, Mauro

2010-08-01

The complex oxidation of glucose at the surface of gold electrodes was studied in detail in different conditions of pH, buffer and halide concentration. As observed in previous studies, an oxidative current peak occurs during the cathodic sweep showing a highly linear dependence on glucose concentration, when other electrolyte conditions are unchanged. The effect of the different conditions on the intensity of this peak has stressed the limitations of the previously proposed mechanisms. A mechanism able to explain the presence of this oxidative peak was proposed. The mechanism takes into account ion-sorption and electrochemical adsorption of OH-, buffer species (K2HPO4/KH2PO4) and halides. © 2010 Elsevier Ltd. All rights reserved.

Impact of Oxidative Stress in Fetal Programming

OpenAIRE

Thompson, Loren P.; Al-Hasan, Yazan

2012-01-01

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

Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

Science.gov (United States)

Woodman, Andrew G; Mah, Richard; Keddie, Danae; Noble, Ronan M N; Panahi, Sareh; Gragasin, Ferrante S; Lemieux, Hélène; Bourque, Stephane L

2018-06-01

Prenatal iron deficiency alters fetal developmental trajectories, which results in persistent changes in organ function. Here, we studied the effects of prenatal iron deficiency on fetal kidney and liver mitochondrial function. Pregnant Sprague-Dawley rats were fed partially or fully iron-restricted diets to induce a state of moderate or severe iron deficiency alongside iron-replete control rats. We assessed mitochondrial function via high-resolution respirometry and reactive oxygen species generation via fluorescence microscopy on gestational d 21. Hemoglobin levels were reduced in dams in the moderate (-31%) and severe groups (-54%) compared with controls, which was accompanied by 55% reductions in fetal hemoglobin levels in both moderate and severe groups versus controls. Male iron-deficient kidneys exhibited globally reduced mitochondrial content and respiration, as well as increased cytosolic superoxide and decreased NO. Female iron-deficient kidneys exhibited complex II down-regulation and increased mitochondrial oxidative stress. Male iron-deficient livers exhibited reduced complex IV respiration and increased cytosolic superoxide, whereas female liver tissues exhibited no alteration in oxidant levels or mitochondrial function. These findings indicate that prenatal iron deficiency causes changes in mitochondrial content and function as well as oxidant status in a sex- and organ-dependent manner, which may be an important mechanism that underlies the programming of cardiovascular disease.-Woodman, A. G., Mah, R., Keddie, D., Noble, R. M. N., Panahi, S., Gragasin, F. S., Lemieux, H., Bourque, S. L. Prenatal iron deficiency causes sex-dependent mitochondrial dysfunction and oxidative stress in fetal rat kidneys and liver.

Impact of Oxidative Stress in Fetal Programming

Directory of Open Access Journals (Sweden)

Loren P. Thompson

2012-01-01

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

Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells.

Science.gov (United States)

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L'azou, Béatrice

2012-09-28

Silica nanoparticles (nano-SiO(2)) are one of the most popular nanomaterials used in industrial manufacturing, synthesis, engineering and medicine. While inhalation of nanoparticles causes pulmonary damage, nano-SiO(2) can be transported into the blood and deposit in target organs where they exert potential toxic effects. Kidney is considered as such a secondary target organ. However, toxicological information of their effect on renal cells and the mechanisms involved remain sparse. In the present study, the cytotoxicity of nano-SiO(2) of different sizes was investigated on two renal proximal tubular cell lines (human HK-2 and porcine LLC-PK(1)). The molecular pathways involved were studied with a focus on the involvement of oxidative stress. Nanoparticle characterization was performed (primary nanoparticle size, surface area, dispersion) in order to investigate a potential relationship between their physical properties and their toxic effects. Firstly, evidence of particle internalization was obtained by transmission electron microscopy and conventional flux cytometry techniques. The use of specific inhibitors of endocytosis pathways showed an internalization process by macropinocytosis and clathrin-mediated endocytosis for 100 nm nano-SiO(2) nanoparticles. These nanoparticles were localized in vesicles. Toxicity was size- and time-dependent (24h, 48 h, 72 h). Indeed, it increased as nanoparticles became smaller. Secondly, analysis of oxidative stress based on the assessment of ROS (reactive oxygen species) production (DHE, dihydroethidium) or lipid peroxidation (MDA, malondialdehyde) clearly demonstrated the involvement of oxidative stress in the toxicity of 20 nm nano-SiO(2). The induction of antioxidant enzymes (catalase, GSTpi, thioredoxin reductase) could explain their lesser toxicity with 100 nm nano-SiO(2). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Involvement of oxidative stress in the mechanism of p,p'-DDT-induced nephrotoxicity in adult rats.

Science.gov (United States)

Marouani, Neila; Hallegue, Dorsaf; Sakly, Mohsen; Benkhalifa, Moncef; Ben Rhouma, Khémais; Tebourbi, Olfa

2017-07-01

The 1,1,1-trichloro-2,2-bis(4-chlorophenyl) ethane (p,p'-DDT) is an organochlorine pesticide that persists in the environment and has a risk to human health. We investigated whether p,p'-DDT-induces nephrotoxicity in rats and whether oxidative stress and apoptosis are involved in the pathogenesis of this process. Male rats received the pesticide at doses of 50 and 100 mg/kg for 10 days. Renal damage was evaluated by histopathological examination and serum markers. The oxidative stress was evaluated by lipid peroxidation (LPO), metallothioneins (MTs) and protein carbonyl levels. Antioxidant enzymes were assessed by determination of superoxide dismutase (SOD) and catalase (CAT) activities. Glutathione-dependent enzymes and reducing power in kidney were evaluated by glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activities. Renal tubular cells apoptosis was assessed through the TUNEL assay. After 10 days of treatment, an increase of serum creatinine and urea levels occurred, LPO and protein carbonyl levels were increased, while MTs level, SOD and CAT activities were decreased. Besides, the GPx, GR, GST, and GSH activities were decreased. Histological alterations in kidney tissue and intense apoptosis in renal tubular cells were observed. These results suggest that DDT sub-acute treatment causes oxidative stress and apoptosis, which may be the chief mechanisms of DDT-induced nephrotoxicity.

Oxidative stress and the ageing endocrine system.

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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.

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

International Nuclear Information System (INIS)

Zana, Marianna; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Szabo, Krisztina; Vetro, Agnes; Szucs, Peter; Varkonyi, Agnes; Pakaski, Magdolna; Boda, Krisztina; Rasko, Istvan; Janka, Zoltan; Kalman, Janos

2006-01-01

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

The role of stress in self-ordered porous anodic oxide formation and corrosion of aluminum

Science.gov (United States)

Capraz, Omer Ozgur

sufficient information to understand the potential stress mechanisms. We developed a new method, which enables us to discriminate the potential stress mechanisms during anodizing and characterize the evolution of the stress profile during film growth. Using stress measurement and characterization techniques, we demonstrated the evolution of the stress profile during the film formation and discussed the role of stress on the PAO film formation. Compressive stress builds up linearly during the anodizing, while barrier oxide film gets thicker until the onset of the pore initiation. Both barrier layer thickness and the integrated oxide stress decreased rapidly to the steady-state period when pore initiation began. The morphology change and stress transients points out the transition from elastic to plastic oxide behavior, similar to those observed in other situations such as lithium intercalation into silicon. The stress profile is consistent with the stress gradient needed to drive plastic flow observed experimentally. We also addressed the dependence of overall stress generation on applied current density. Apparently, stress caused by expansion or contraction of oxide and metal interface depends on the volume change due to overall reactions. In the last chapter, the stress generation during alkaline Al corrosion will be discussed. The enhancement of mechanical degradation by corrosion is the basis for the damage process such as stress-corrosion cracking. Understanding the synergistic effect of stress on stress-corrosion cracking mechanism is necessary to design new materials to improve the safety and viability of existing energy conversion systems. the high-resolution in-situ stress measurements during Al corrosion in alkaline solution was presented, supported by characterization techniques and Fast Fourier Transform analysis. Unprecedented curvature resolution of curvature interferometry permits the monitoring of stress during extended periods of corrosion of thick metal

Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models.

Science.gov (United States)

Ishii, Takamasa; Yasuda, Kayo; Miyazawa, Masaki; Mitsushita, Junji; Johnson, Thomas E; Hartman, Phil S; Ishii, Naoaki

2016-04-01

Oxidative stress is associated with some forms of both male and female infertility. However, there is insufficient knowledge of the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. There are a number of animal models for understanding age-dependent decrease of reproductive ability and diabetic embryopathy, especially abnormal spermatogenesis, oogenesis and embryogenesis with mitochondrial dysfunctions. Several important processes occur in mitochondria, including ATP synthesis, calcium ion storage, induction of apoptosis and production of reactive oxygen species (ROS). These events have different effects on the several aspects of reproductive function. Tet-mev-1 conditional transgenic mice, developed after studies with the mev-1 mutant of the nematode C. elegans, offer the ability to carefully regulate expression of doxycycline-induced mutated SDHC(V69E) levels and hence modulate endogenous oxidative stress. The mev-1 models have served to illuminate the effects of complex II deficiency-dependent mitochondrial ROS production, although interestingly they maintain normal mitochondrial and intracellular ATP levels. In this review, the reproductive dysfunctions are presented focusing on fertility potentials in each gamete, early embryogenesis, maternal conditions with placental function and neonatal development. Copyright © 2016. Published by Elsevier Ireland Ltd.

Oxidative stress and apoptotic events during thermal stress in the symbiotic sea anemone, Anemonia viridis.

Science.gov (United States)

Richier, Sophie; Sabourault, Cécile; Courtiade, Juliette; Zucchini, Nathalie; Allemand, Denis; Furla, Paola

2006-09-01

Symbiosis between cnidarian and photosynthetic protists is widely distributed over temperate and tropical seas. These symbioses can periodically breakdown, a phenomenon known as cnidarian bleaching. This event can be irreversible for some associations subjected to acute and/or prolonged environmental disturbances, and leads to the death of the animal host. During bleaching, oxidative stress has been described previously as acting at molecular level and apoptosis is suggested to be one of the mechanisms involved. We focused our study on the role of apoptosis in bleaching via oxidative stress in the association between the sea anemone Anemonia viridis and the dinoflagellates Symbiodinium species. Characterization of caspase-like enzymes were conducted at the biochemical and molecular level to confirm the presence of a caspase-dependent apoptotic phenomenon in the cnidarian host. We provide evidence of oxidative stress followed by induction of caspase-like activity in animal host cells after an elevated temperature stress, suggesting the concomitant action of these components in bleaching.

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

Directory of Open Access Journals (Sweden)

Mohammed Saeed-Zidane

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

Oxidative stress resistance in Porphyromonas gingivalis

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

2012-01-01

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

Mitochondrial oxidative stress in human hepatoma cells exposed to stavudine

International Nuclear Information System (INIS)

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

2004-01-01

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

Analgesic activity of piracetam: effect on cytokine production and oxidative stress.

Science.gov (United States)

Navarro, Suelen A; Serafim, Karla G G; Mizokami, Sandra S; Hohmann, Miriam S N; Casagrande, Rubia; Verri, Waldiceu A

2013-04-01

Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2011-10-01

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

Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress

DEFF Research Database (Denmark)

Brouwers, O; Niessen, P M; Haenen, G

2010-01-01

-hydro-5-methylimidazolone (MG-H1) was detected with an antibody against MG-H1 and quantified with ultra-performance liquid chromatography (tandem) mass spectrometry. Reactive oxygen species formation was measured with a 5-(and-6)-chloromethyl-2'7'-dichlorodihydrofluorescein diacetate acetyl ester probe...... for AGE ligand S100b did (p cells and adventitia by fivefold accompanied by an eightfold increase in the oxidative stress marker nitrotyrosine. Antioxidant pre-incubation prevented methylglyoxal......-induced impairment of vasoreactivity. CONCLUSIONS/INTERPRETATION: These data show that hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation is mediated by increased intracellular methylglyoxal levels in a pathway dependent on oxidative stress....

Nitric oxide signalling and neuronal nitric oxide synthase in the heart under stress.

Science.gov (United States)

Zhang, Yin Hua

2017-01-01

Nitric oxide (NO) is an imperative regulator of the cardiovascular system and is a critical mechanism in preventing the pathogenesis and progression of the diseased heart. The scenario of bioavailable NO in the myocardium is complex: 1) NO is derived from both endogenous NO synthases (endothelial, neuronal, and/or inducible NOSs [eNOS, nNOS, and/or iNOS]) and exogenous sources (entero-salivary NO pathway) and the amount of NO from exogenous sources varies significantly; 2) NOSs are located at discrete compartments of cardiac myocytes and are regulated by distinctive mechanisms under stress; 3) NO regulates diverse target proteins through different modes of post-transcriptional modification (soluble guanylate cyclase [sGC]/cyclic guanosine monophosphate [cGMP]/protein kinase G [PKG]-dependent phosphorylation, S -nitrosylation, and transnitrosylation); 4) the downstream effectors of NO are multidimensional and vary from ion channels in the plasma membrane to signalling proteins and enzymes in the mitochondria, cytosol, nucleus, and myofilament; 5) NOS produces several radicals in addition to NO (e.g. superoxide, hydrogen peroxide, peroxynitrite, and different NO-related derivatives) and triggers redox-dependent responses. However, nNOS inhibits cardiac oxidases to reduce the sources of oxidative stress in diseased hearts. Recent consensus indicates the importance of nNOS protein in cardiac protection under pathological stress. In addition, a dietary regime with high nitrate intake from fruit and vegetables together with unsaturated fatty acids is strongly associated with reduced cardiovascular events. Collectively, NO-dependent mechanisms in healthy and diseased hearts are better understood and shed light on the therapeutic prospects for NO and NOSs in clinical applications for fatal human heart diseases.

Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.

Science.gov (United States)

Tsutsui, Ayumi; Imamaki, Rie; Kitazume, Shinobu; Hanashima, Shinya; Yamaguchi, Yoshiki; Kaneda, Masato; Oishi, Shinya; Fujii, Nobutaka; Kurbangalieva, Almira; Taniguchi, Naoyuki; Tanaka, Katsunori

2014-07-28

Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane formation effectively neutralized acrolein toxicity, the diazacyclooctane hydrogel produced through a sequential diazacyclooctane polymerization reaction was highly cytotoxic. This study suggests that diazacyclooctane formation is involved in the mechanism underlying acrolein-mediated oxidative stress.

Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Therapeutic Perspectives

Directory of Open Access Journals (Sweden)

Ailton Melo

2011-01-01

Full Text Available The incidence and prevalence of neurodegenerative diseases (ND increase with life expectancy. This paper reviews the role of oxidative stress (OS in ND and pharmacological attempts to fight against reactive oxygen species (ROS-induced neurodegeneration. Several mechanisms involved in ROS generation in neurodegeneration have been proposed. Recent articles about molecular pathways involved in ROS generation were reviewed. The progress in the development of neuroprotective therapies has been hampered because it is difficult to define targets for treatment and determine what should be considered as neuroprotective. Therefore, the attention was focused on researches about pharmacological targets that could protect neurons against OS. Since it is necessary to look for genes as the ultimate controllers of all biological processes, this paper also tried to identify gerontogenes involved in OS and neurodegeneration. Since neurons depend on glial cells to survive, recent articles about the functioning of these cells in aging and ND were also reviewed. Finally, clinical trials testing potential neuroprotective agents were critically reviewed. Although several potential drugs have been screened in in vitro and in vivo models of ND, these results were not translated in benefit of patients, and disappointing results were obtained in the majority of clinical trials.

Melatonin membrane receptor (MT1R) expression and nitro-oxidative stress in testis of golden hamster, Mesocricetus auratus: An age-dependent study.

Science.gov (United States)

Mukherjee, Arun; Haldar, Chandana

2015-09-01

Age-dependent decline in melatonin level induces nitro-oxidative stress that compromises physiological homeostasis including reproduction. However, less information exist regarding the age-dependent variation in local melatonin (lMel) concentration and MT1R expression in testis and its interaction with testicular steroidogenesis and nitro-oxidative stress in golden hamster, Mesocricetus auratus. Therefore, we evaluated lMel level along with MT1R expression and its possible interaction with steroidogenesis and nitro-oxidative stress in testes of young (6weeks), adult (15weeks) and old (2years) aged hamsters. Further, we injected the old hamsters with melatonin to address whether age-related decline in lMel and MT1R is responsible for the reduction in testicular steroidogenesis and antioxidant status. Increased expression of steroidogenic markers suggests increased testicular steroidogenesis in adult hamsters that declined in old hamsters. An age-dependent elevation in the level of NOX, TBARS, corticosterone and the expression of iNOS and GR with a concomitant decrease in enzyme activities for SOD, CAT, GSH-PX indicate increased nitro-oxidative stress in testes. Data suggest that reproductive senescence in male hamsters might be a consequence of declined lMel concentration with MT1R expression inducing nitro-oxidative stress resulting in diminished testicular steroidogenesis. However, administration of Mel in old-aged hamsters significantly increased steroidogenesis and antioxidant status without a significant variation in lMel concentration and MT1R expression in testes. Therefore, decreased lMel and MT1R might not be the causative factor underlying the age-associated decrease in antioxidant defence and steroidogenesis in testes. In conclusion, Mel induced amelioration of testicular oxidative insult and elevation of steroidogenic activity suggests a potential role of increased nitro-oxidative stress underlying the age-dependent decrease in steroidogenesis. Copyright

Curcumin attenuates oxidative stress induced NFκB mediated inflammation and endoplasmic reticulum dependent apoptosis of splenocytes in diabetes.

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Rashid, Kahkashan; Chowdhury, Sayantani; Ghosh, Sumit; Sil, Parames C

2017-11-01

The present study was aimed to determine the curative role of curcumin against diabetes induced oxidative stress and its associated splenic complications. Diabetes was induced in the experimental rats via the intraperitoneal administration of a single dose of STZ (65mgkg -1 body weight). Increased blood glucose and intracellular ROS levels along with decreased body weight, the activity of cellular antioxidant enzymes and GSH/GSSG ratio were observed in the diabetic animals. Histological assessment showed white pulp depletion and damaged spleen anatomy in these animals. Oral administration of curcumin at a dose of 100mgkg -1 body weight daily for 8weeks, however, restored these alterations. Investigation of the mechanism of hyperglycemia induced oxidative stress mediated inflammation showed upregulation of inflammatory cytokines, chemokines, adhesion molecules and increased translocation of NFκB into the nucleus. Moreover, ER stress dependent cell death showed induction of eIF2α and CHOP mediated signalling pathways as well as increment in the expression of GRP78, Caspase-12, Calpain-1, phospho JNK, phospho p38 and phospho p53 in the diabetic group. Alteration of Bax/Bcl-2 ratio; disruption of mitochondrial membrane potential, release of cytochrome-C from mitochondria and upregulation of caspase 3 along with the formation of characteristic DNA ladder in the diabetic animals suggest the involvement of mitochondria dependent apoptotic pathway in the splenic cells. Treatment with curcumin could, however, protect cells from inflammatory damage and ER as well as mitochondrial apoptotic death by restoring the alterations of these parameters. Our results suggest that curcumin has the potential to act as an anti-diabetic, anti-oxidant, anti-inflammatory and anti-apoptotic therapeutic against diabetes mediated splenic damage. Copyright © 2017 Elsevier Inc. All rights reserved.

ERβ-dependent neuroglobin up-regulation impairs 17β-estradiol-induced apoptosis in DLD-1 colon cancer cells upon oxidative stress injury.

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Fiocchetti, Marco; Camilli, Giulia; Acconcia, Filippo; Leone, Stefano; Ascenzi, Paolo; Marino, Maria

2015-05-01

Besides other mechanism(s) 17β-estradiol (E2) facilitates neuronal survival by increasing, via estrogen receptor β (ERβ), the levels of neuroglobin (NGB) an anti-apoptotic protein. In contrast, E2 could exert protective effects in cancer cells by activating apoptosis when the ERβ level prevails on that of ERα as in colon cancer cell lines. These apparently contrasting results raise the possibility that E2-induced NGB up-regulation could regulate the ERβ activities shunning this receptor subtype to trigger an apoptotic cascade in neurons but not in non-neuronal cells. Here, human colorectal adenocarcinoma cell line (DLD-1) that only expresses ERβ and HeLa cells transiently transfected with ERβ encoding vector has been used to verify this hypothesis. In addition, neuroblastoma SK-N-BE cells were used as positive control. Surprisingly, E2 also induced NGB up-regulation, in a dose- and time-dependent manner, in DLD-1 cells. The ERβ-mediated activation of p38/MAPK was necessary for this E2 effect. E2 induced NGB re-allocation in mitochondria where, subsequently to an oxidative stress injury (i.e., 100μM H2O2), NGB interacted with cytochrome c preventing its release into the cytosol and the activation of an apoptotic cascade. As a whole, these results demonstrate that E2-induced NGB up-regulation could act as an oxidative stress sensor, which does not oppose to the pro-apoptotic E2 effect in ERβ-containing colon cancer cells unless a rise of oxidative stress occurs. These results support the concept that oxidative stress plays a critical role in E2-induced carcinogenesis and further open an important scenario to develop novel therapeutic strategies that target NGB against E2-related cancers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of pH on uranium uptake and oxidative stress responses induced in Arabidopsis thaliana

OpenAIRE

Saenen, Eline; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Biermans, Geert; Van Hees, May; Wannijn, Jean; Vangronsveld, Jaco; Cuypers, Ann

2013-01-01

Uranium (U) causes oxidative stress in Arabidopsis thaliana plants grown at pH 5.5. However, U speciation and its toxicity strongly depend on environmental parameters, for example pH. It is unknown how different U species determine U uptake and translocation within plants and how they might affect the oxidative defense mechanisms of these plants. The present study analyzed U uptake and oxidative stress-related responses in A. thaliana (Columbia ecotype) under contrasted U chemical speciation ...

Mini-review: Biofilm responses to oxidative stress.

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Gambino, Michela; Cappitelli, Francesca

2016-01-01

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

Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.

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Kim, Jung; Bilder, David; Neufeld, Thomas P

2018-01-15

Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the Drosophila larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers. We found that insulin signaling in Drosophila fat body cells is abolished in the absence of physical activity and mechanical stress even when excess insulin is present. Physical movement is required for insulin sensitivity in both intact larvae and fat bodies cultured ex vivo. Interestingly, the insulin receptor and other downstream components are recruited to the plasma membrane in response to mechanical stress, and this membrane localization is rapidly lost upon disruption of larval or tissue movement. Sensing of mechanical stimuli is mediated in part by integrins, whose activation is necessary and sufficient for mechanical stress-dependent insulin signaling. Insulin resistance develops naturally during the transition from the active larval stage to the immotile pupal stage, suggesting that regulation of insulin sensitivity by mechanical stress may help coordinate developmental programming with metabolism. © 2018 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

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

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

2017-04-01

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

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Liang-Jun Yan

2014-01-01

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

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

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

2013-02-01

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

Regulatory mechanism of the flavoprotein Tah18-dependent nitric oxide synthesis and cell death in yeast.

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Yoshikawa, Yuki; Nasuno, Ryo; Kawahara, Nobuhiro; Nishimura, Akira; Watanabe, Daisuke; Takagi, Hiroshi

2016-07-01

Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. The regulatory mechanism of NO generation in unicellular eukaryotic yeast cells is poorly understood due to the lack of mammalian and bacterial NO synthase (NOS) orthologues, even though yeast produces NO under oxidative stress conditions. Recently, we reported that the flavoprotein Tah18, which was previously shown to transfer electrons to the iron-sulfur cluster protein Dre2, is involved in NOS-like activity in the yeast Saccharomyces cerevisiae. On the other hand, Tah18 was reported to promote apoptotic cell death after exposure to hydrogen peroxide (H2O2). Here, we showed that NOS-like activity requiring Tah18 induced cell death upon treatment with H2O2. Our experimental results also indicate that Tah18-dependent NO production and cell death are suppressed by enhancement of the interaction between Tah18 and its molecular partner Dre2. Our findings indicate that the Tah18-Dre2 complex regulates cell death as a molecular switch via Tah18-dependent NOS-like activity in response to environmental changes. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

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Xiaochun Duan

2016-01-01

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

Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

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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

Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches.

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Balmus, Ioana Miruna; Ciobica, Alin; Antioch, Iulia; Dobrin, Romeo; Timofte, Daniel

2016-01-01

The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context.

Copper oxide nanoparticles induce the transcriptional modulation of oxidative stress-related genes in Arbacia lixula embryos.

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Giannetto, Alessia; Cappello, Tiziana; Oliva, Sabrina; Parrino, Vincenzo; De Marco, Giuseppe; Fasulo, Salvatore; Mauceri, Angela; Maisano, Maria

2018-06-14

Copper oxide nanoparticles (CuO NPs) are widely used in various industrial applications, i.e. semiconductor devices, batteries, solar energy converter, gas sensor, microelectronics, heat transfer fluids, and have been recently recognized as emerging pollutants of increasing concern for human and marine environmental health. Therefore, the toxicity of CuO NPs needs to be thoroughly understood. In this study, we evaluated the potential role of oxidative stress in CuO NP toxicity by exploring the molecular response of Arbacia lixula embryos to three CuO NP concentrations (0.7, 10, 20 ppb) by investigating the transcriptional patterns of oxidative stress-related genes (catalase and superoxide dismutase) and metallothionein, here cloned and characterized for the first time. Time- and concentration-dependent changes in gene expression were detected in A. lixula embryos exposed to CuO NPs, up to pluteus stage (72 h post-fertilization, hpf), indicating that oxidative stress is one of the toxicity mechanisms for CuO NPs. These findings provide new insights into the comprehension of the molecular mechanisms underlying copper nanoparticle toxicity in A. lixula sea urchin and give new tools for monitoring of aquatic areas, thus corroborating the suitability of this embryotoxicity assay for future evaluation of impacted sites. Copyright © 2018 Elsevier B.V. All rights reserved.

Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

KAUST Repository

Yun, Kil-Young; Park, Myoung Ryoul; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Mauleon, Ramil; Wijaya, Edward; Bajic, Vladimir B.; Bruskiewich, Richard; de los Reyes, Benildo G

2010-01-01

-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress

The Role of Oxidative Stress in Carcinogenesis Induced by Metals and Xenobiotics

International Nuclear Information System (INIS)

Henkler, Frank; Brinkmann, Joep; Luch, Andreas

2010-01-01

In addition to a wide range of adverse effects on human health, toxic metals such as cadmium, arsenic and nickel can also promote carcinogenesis. The toxicological properties of these metals are partly related to generation of reactive oxygen species (ROS) that can induce DNA damage and trigger redox-dependent transcription factors. The precise mechanisms that induce oxidative stress are not fully understood. Further, it is not yet known whether chronic exposures to low doses of arsenic, cadmium or other metals are sufficient to induce mutations in vivo, leading to DNA repair responses and/or tumorigenesis. Oxidative stress can also be induced by environmental xenobiotics, when certain metabolites are generated that lead to the continuous release of superoxide, as long as the capacity to reduce the resulting dions (quinones) into hydroquinones is maintained. However, the specific significance of superoxide-dependent pathways to carcinogenesis is often difficult to address, because formation of DNA adducts by mutagenic metabolites can occur in parallel. Here, we will review both mechanisms and toxicological consequences of oxidative stress triggered by metals and dietary or environmental pollutants in general. Besides causing DNA damage, ROS may further induce multiple intracellular signaling pathways, notably NF-κB, JNK/SAPK/p38, as well as Erk/MAPK. These signaling routes can lead to transcriptional induction of target genes that could promote proliferation or confer apoptosis resistance to exposed cells. The significance of these additional modes depends on tissue, cell-type and is often masked by alternate oncogenic mechanisms being activated in parallel

NRF2 Oxidative Stress Induced by Heavy Metals is Cell Type Dependent

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Exposure to metallic environmental toxicants has been demonstrated to induce a variety of oxidative stress responses in mammalian cells. The transcription factor Nrf2 is activated in response to oxidative stress and coordinates the expression of antioxidant gene products. In this...

Possible involvement of membrane lipids peroxidation and oxidation of catalytically essential thiols of the cerebral transmembrane sodium pump as component mechanisms of iron-mediated oxidative stress-linked dysfunction of the pump's activity

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T.I. Omotayo

2015-04-01

Full Text Available The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enzyme in Fe2+-mediated in vitro oxidative stress model. The results show that Fe2+ inhibited the transmembrane enzyme in a concentration dependent manner and this effect was accompanied by a biphasic generation of aldehydic product of lipid peroxidation. While dithiothreitol prevented both Fe2+ inhibitory effect on the pump and lipid peroxidation, vitamin E prevented only lipid peroxidation but not inhibition of the pump. Besides, malondialdehyde (MDA inhibited the pump by a mechanism not related to oxidation of its critical thiols. Apparently, the low activity of the pump in degenerative diseases mediated by Fe2+ may involve complex multi-component mechanisms which may partly involve an initial oxidation of the critical thiols of the enzyme directly mediated by Fe2+ and during severe progression of such diseases; aldehydic products of lipid peroxidation such as MDA may further exacerbate this inhibitory effect by a mechanism that is likely not related to the oxidation of the catalytically essential thiols of the ouabain-sensitive cerebral electrogenic pump.

Targeting oxidant-dependent mechanisms for the treatment of COPD and its comorbidities.

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Bernardo, Ivan; Bozinovski, Steven; Vlahos, Ross

2015-11-01

Chronic obstructive pulmonary disease (COPD) is an incurable global health burden and is characterised by progressive airflow limitation and loss of lung function. In addition to the pulmonary impact of the disease, COPD patients often develop comorbid diseases such as cardiovascular disease, skeletal muscle wasting, lung cancer and osteoporosis. One key feature of COPD, yet often underappreciated, is the contribution of oxidative stress in the onset and development of the disease. Patients experience an increased burden of oxidative stress due to the combined effects of excess reactive oxygen species (ROS) and nitrogen species (RNS) generation, antioxidant depletion and reduced antioxidant enzyme activity. Currently, there is a lack of effective treatments for COPD, and an even greater lack of research regarding interventions that treat both COPD and its comorbidities. Due to the involvement of oxidative stress in the pathogenesis of COPD and many of its comorbidities, a unique therapeutic opportunity arises where the treatment of a multitude of diseases may be possible with only one therapeutic target. In this review, oxidative stress and the roles of ROS/RNS in the context of COPD and comorbid cardiovascular disease, skeletal muscle wasting, lung cancer, and osteoporosis are discussed and the potential for therapeutic benefit of anti-oxidative treatment in these conditions is outlined. Because of the unique interplay between oxidative stress and these diseases, oxidative stress represents a novel target for the treatment of COPD and its comorbidities. Copyright © 2015. Published by Elsevier Inc.

Taurine inhibits 2,5-hexanedione-induced oxidative stress and mitochondria-dependent apoptosis in PC12 cells.

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Li, Shuangyue; Guan, Huai; Qian, Zhiqiang; Sun, Yijie; Gao, Chenxue; Li, Guixin; Yang, Yi; Piao, Fengyuan; Hu, Shuhai

2017-04-07

2,5-hexanedione (HD) is the ultimate neurotoxic metabolite of hexane, causing the progression of nerve diseases in human. It was reported that HD induced apoptosis and oxidative stress. Taurine has been shown to be a potent antioxidant. In the present study, we investigated the protection of taurine against HD-induced apoptosis in PC12 cells and the underlying mechanism. Our results showed the decreased viability and increased apoptosis in HD-exposed PC12 cells. HD also induced the disturbance of Bax and Bcl-2 expression, the loss of MMP, the release of mitochondrial cytochrome c and caspase-3 activation in PC12 cells. Moreover, HD resulted in an increase in reactive oxygen species (ROS) level and a decline in the activities of superoxidedismutase and catalase in PC12 cells. However, taurine pretreatment ameliorated the increased apoptosis and the alterations in key regulators of mitochondria-dependent pathway in PC12 exposed to HD. The increased ROS level and the decreased activities of the antioxidant enzymes in HD group were attenuated by taurine. These results indicate that pretreatment of taurine may, at least partly, prevent HD-induced apoptosis via inhibiting mitochondria-dependent pathway. It is also suggested that the potential of taurine against HD-induced apoptosis may benefit from its anti-oxidative property.

Pulmonary Oxidative Stress, Inflammation and Cancer: Respirable Particulate Matter, Fibrous Dusts and Ozone as Major Causes of Lung Carcinogenesis through Reactive Oxygen Species Mechanisms

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Spyridon Loridas

2013-08-01

Full Text Available Reactive oxygen or nitrogen species (ROS, RNS and oxidative stress in the respiratory system increase the production of mediators of pulmonary inflammation and initiate or promote mechanisms of carcinogenesis. The lungs are exposed daily to oxidants generated either endogenously or exogenously (air pollutants, cigarette smoke, etc.. Cells in aerobic organisms are protected against oxidative damage by enzymatic and non-enzymatic antioxidant systems. Recent epidemiologic investigations have shown associations between increased incidence of respiratory diseases and lung cancer from exposure to low levels of various forms of respirable fibers and particulate matter (PM, at occupational or urban air polluting environments. Lung cancer increases substantially for tobacco smokers due to the synergistic effects in the generation of ROS, leading to oxidative stress and inflammation with high DNA damage potential. Physical and chemical characteristics of particles (size, transition metal content, speciation, stable free radicals, etc. play an important role in oxidative stress. In turn, oxidative stress initiates the synthesis of mediators of pulmonary inflammation in lung epithelial cells and initiation of carcinogenic mechanisms. Inhalable quartz, metal powders, mineral asbestos fibers, ozone, soot from gasoline and diesel engines, tobacco smoke and PM from ambient air pollution (PM10 and PM2.5 are involved in various oxidative stress mechanisms. Pulmonary cancer initiation and promotion has been linked to a series of biochemical pathways of oxidative stress, DNA oxidative damage, macrophage stimulation, telomere shortening, modulation of gene expression and activation of transcription factors with important role in carcinogenesis. In this review we are presenting the role of ROS and oxidative stress in the production of mediators of pulmonary inflammation and mechanisms of carcinogenesis.

Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

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Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

2015-01-01

This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

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Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

2015-01-01

We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism.

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Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Di Santo, Serena; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Del Ben, Maria; De Marco, Luigi; Pignatelli, Pasquale; Violi, Francesco

2014-11-01

Platelets generate oxidized LDL (ox-LDL) via NOX2-derived oxidative stress. We investigated if once generated by activated platelets ox-LDL can propagate platelet activation. Experiments were performed in platelets from healthy subjects (HS), hyper-cholesterolemic patients and patients with NOX2 hereditary deficiency. Agonist-stimulated platelets from HS added with LDL were associated with a dose-dependent increase of reactive oxidant species and ox-LDL. Agonist-stimulated platelets from HS added with a fixed dose of LDL (57.14 μmol/L) or added with homogenized human atherosclerotic plaque showed enhanced ox-LDL formation (approximately +50% and +30% respectively), which was lowered by a NOX2 inhibitor (approximately -35% and -25% respectively). Compared to HS, ox-LDL production was more pronounced in agonist-stimulated platelet rich plasma (PRP) from hyper-cholesterolemic patients but was almost absent in PRP from NOX2-deficient patients. Platelet aggregation and 8-iso-PGF2α-ΙΙΙ formation increased in LDL-treated washed platelets (+42% and +53% respectively) and PRP (+31% and +53% respectively). Also, LDL enhanced platelet-dependent thrombosis at arterial shear rate (+33%) but did not affect platelet activation in NOX2-deficient patients. Platelet activation by LDL was significantly inhibited by CD36 or LOX1 blocking peptides, two ox-LDL receptor antagonists, or by a NOX2 inhibitor. LDL-added platelets showed increased p38MAPK (+59%) and PKC (+51%) phosphorylation, p47(phox) translocation to platelet membrane (+34%) and NOX2 activation (+30%), which were inhibited by ox-LDL receptor antagonists. Platelets oxidize LDL, which in turn amplify platelet activation via specific ox-LDL receptors; both effects are mediated by NOX2 activation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

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

2017-01-01

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

Oxidative stress

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Stevanović Jelka

2012-01-01

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

[Protective effect and mechanism of compound Ginkgo biloba granules on oxidative stress injury of HUVEC].

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Li, Qi; Chen, Xi; Kan, Xiao-Xi; Li, Yu-Jie; Yang, Qing; Wang, Ya-Jie; Chen, Ying; Weng, Xiao-Gang; Cai, Wei-Yan; Huang, He-Fei; Zhu, Xiao-Xin

2016-02-01

To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC. Copyright© by the Chinese Pharmaceutical Association.

Insulin receptor substrate-1 prevents autophagy-dependent cell death caused by oxidative stress in mouse NIH/3T3 cells

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Chan Shih-Hung

2012-07-01

Full Text Available Abstract Background Insulin receptor substrate (IRS-1 is associated with tumorigenesis; its levels are elevated in several human cancers. IRS-1 protein binds to several oncogene proteins. Oxidative stress and reactive oxygen species (ROS are involved in the initiation and progression of cancers. Cancer cells produce greater levels of ROS than normal cells do because of increased metabolic stresses. However, excessive production of ROS kills cancer cells. Autophagy usually serves as a survival mechanism in response to stress conditions, but excessive induction of autophagy results in cell death. In addition to inducing necrosis and apoptosis, ROS induces autophagic cell death. ROS inactivates IRS-1 mediated signaling and reduces intracellular IRS-1 concentrations. Thus, there is a complex relationship between IRS-1, ROS, autophagy, and cancer. It is not fully understood how cancer cells grow rapidly and survive in the presence of high ROS levels. Methods and results In this study, we established mouse NIH/3T3 cells that overexpressed IRS-1, so mimicking cancers with increased IRS-1 expression levels; we found that the IRS-1 overexpressing cells grow more rapidly than control cells do. Treatment of cells with glucose oxidase (GO provided a continuous source of ROS; low dosages of GO promoted cell growth, while high doses induced cell death. Evidence for GO induced autophagy includes increased levels of isoform B-II microtubule-associated protein 1 light chain 3 (LC3, aggregation of green fluorescence protein-tagged LC3, and increased numbers of autophagic vacuoles in cells. Overexpression of IRS-1 resulted in inhibition of basal autophagy, and reduced oxidative stress-induced autophagy and cell death. ROS decreased the mammalian target of rapamycin (mTOR/p70 ribosomal protein S6 kinase signaling, while overexpression of IRS-1 attenuated this inhibition. Knockdown of autophagy-related gene 5 inhibited basal autophagy and diminished oxidative stress

Nutrients and Oxidative Stress: Friend or Foe?

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Bee Ling Tan

2018-01-01

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

Nutrients and Oxidative Stress: Friend or Foe?

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

2018-01-01

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

Signaling in a polluted world: oxidative stress as an overlooked mechanism linking contaminants to animal communication

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Valeria Marasco

2016-08-01

Full Text Available The capacity to communicate effectively with other individuals plays a critical role in the daily life of an individual and can have important fitness consequences. Animals rely on a number of visual and non-visual signals, whose production brings costs to the individual. The theory of honest signaling states that these costs are higher for low than for high-quality individuals, which prevents cheating and makes signals, such as skin and plumage colouration, indicators of individual’s quality or condition. The condition-dependent nature of signals makes them ideally suited as indicators of environmental quality, implying that signal production might be affected by contaminants. In this mini-review article, we have made the point that oxidative stress (OS is one overlooked mechanism linking exposure to contaminants to signaling because (i many contaminants can influence the individual’s oxidative balance, and (ii generation of both visual and non-visual signals is sensitive to oxidative stress. To this end, we have provided the first comprehensive review on the way both non-organic (heavy metals, especially mercury and organic (persistent organic pollutants contaminants may influence either OS or sexual signaling. We have also paid special attention to emerging classes of pollutants like brominated flame-retardants and perfluoroalkoxy alkanes in order to stimulate research in this area. We have finally provided suggestions and warnings for future work on the links among OS, sexual signaling and contaminant exposure.

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

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

2017-03-14

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

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

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

2017-04-01

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

A STUDY OF OXIDATIVE STRESS IN DIABETES

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Babu Rao

2015-06-01

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

Tiliacora triandra, an Anti-Intoxication Plant, Improves Memory Impairment, Neurodegeneration, Cholinergic Function, and Oxidative Stress in Hippocampus of Ethanol Dependence Rats

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Nattaporn Phunchago

2015-01-01

Full Text Available Oxidative stress plays an important role in brain dysfunctions induced by alcohol. Since less therapeutic agent against cognitive deficit and brain damage induced by chronic alcohol consumption is less available, we aimed to assess the effect of Tiliacora triandra extract, a plant possessing antioxidant activity, on memory impairment, neuron density, cholinergic function, and oxidative stress in hippocampus of alcoholic rats. Male Wistar rats were induced ethanol dependence condition by semivoluntary intake of alcohol for 15 weeks. Alcoholic rats were orally given T. triandra at doses of 100, 200, and 400 mg·kg−1BW for 14 days. Memory assessment was performed every 7 days while neuron density, activities of AChE, SOD, CAT, and GSH-Px and, MDA level in hippocampus were assessed at the end of study. Interestingly, the extract mitigated the increased escape latency, AChE and MDA level. The extract also mitigated the decreased retention time, SOD, CAT, and GSH-Px activities, and neurons density in hippocampus induced by alcohol. These data suggested that the extract improved memory deficit in alcoholic rats partly via the decreased oxidative stress and the suppression of AChE. Therefore, T. triandra is the potential reagent for treating brain dysfunction induced by alcohol. However, further researches are necessary to understand the detail mechanism and possible active ingredient.

Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved?

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Thalia M. T. Avelar

2015-08-01

Full Text Available ABSTRACTMetabolic syndrome (MS is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD, catalase (CAT and gluthatione peroxidase (GPx. The high-density lipoprotein cholesterol (HDL-c is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1 activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse

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Qianying Liu

2018-05-01

Full Text Available Mequindox (MEQ, belonging to quinoxaline-di-N-oxides (QdNOs, is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo.

Oxidative stress

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Osredkar Joško

2012-05-01

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

Oxidative stress mediated toxicity of TiO2 nanoparticles after a concentration and time dependent exposure of the aquatic macrophyte Hydrilla verticillata.

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Spengler, Annette; Wanninger, Lena; Pflugmacher, Stephan

2017-09-01

The present study focused on oxidative stress effects in the aquatic macrophyte Hydrilla verticillata after exposure to titanium dioxide nanoparticles (TiO 2 -NPs). Experiments were conducted with different TiO 2 -NPs and concentrations (0.1 mg/L and 10 mg/L) in a time-dependent manner (0 h, 24 h, 48 h, 96 h, 168 h). To assess various levels of the oxidative stress response in H. verticillata, the level of hydrogen peroxide (H 2 O 2 ), the ratio of reduced to oxidized glutathione (GSH/GSSG), and activities of the antioxidative enzymes catalase (CAT) and glutathione reductase (GR) were evaluated. Study results imply oxidative stress effects after TiO 2 -NP exposure as adaptations in plant metabolism became apparent to counteract increased ROS formation. All TiO 2 -NPs caused elevated activities of the enzymes CAT and GR. Moreover, decreased ratios of GSH/GSSG indicated an activation of GSH-dependent pathways counteracting ROS formation. Plants exposed to a bulk-sized control revealed a size-dependent influence on the antioxidative stress response. As H 2 O 2 level increases were solely detected after exposure to 10 mg/L TiO 2 -NPs and nano-exposed plants showed normalization in its antioxidative stress response after 168h of exposure, it can be suggested that macrophytes are able to cope with currently predicted low-level exposures to TiO 2 -NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

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Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000 (China); Wu, Jincai [College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000 (China); Fang, Jianguo, E-mail: fangjg@lzu.edu.cn [State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000 (China); College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000 (China)

2012-08-01

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. �

Curcumin targeting the thioredoxin system elevates oxidative stress in HeLa cells

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Cai, Wenqing; Zhang, Baoxin; Duan, Dongzhu; Wu, Jincai; Fang, Jianguo

2012-01-01

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH, is ubiquitous in all cells and involved in many redox-dependent signaling pathways. Curcumin, a naturally occurring pigment that gives a specific yellow color in curry food, is consumed in normal diet up to 100 mg per day. This molecule has also been used in traditional medicine for the treatment of a variety of diseases. Curcumin has numerous biological functions, and many of these functions are related to induction of oxidative stress. However, how curcumin elicits oxidative stress in cells is unclear. Our previous work has demonstrated the way by which curcumin interacts with recombinant TrxR1 and alters the antioxidant enzyme into a reactive oxygen species (ROS) generator in vitro. Herein we reported that curcumin can target the cytosolic/nuclear thioredoxin system to eventually elevate oxidative stress in HeLa cells. Curcumin-modified TrxR1 dose-dependently and quantitatively transfers electrons from NADPH to oxygen with the production of ROS. Also, curcumin can drastically down-regulate Trx1 protein level as well as its enzyme activity in HeLa cells, which in turn remarkably decreases intracellular free thiols, shifting the intracellular redox balance to a more oxidative state, and subsequently induces DNA oxidative damage. Furthermore, curcumin-pretreated HeLa cells are more sensitive to oxidative stress. Knockdown of TrxR1 sensitizes HeLa cells to curcumin cytotoxicity, highlighting the physiological significance of targeting TrxR1 by curcumin. Taken together, our data disclose a previously unrecognized prooxidant mechanism of curcumin in cells, and provide a deep insight in understanding how curcumin works in vivo. -- Highlights: ► Curcumin induces oxidative stress by targeting the thioredoxin system. ► Curcumin-modified TrxR quantitatively oxidizes NADPH to generate ROS. ► Knockdown of TrxR1 augments curcumin's cytotoxicity in HeLa cells. ► Curcumin

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

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

2010-07-01

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

The Toxicological Mechanisms of Environmental Soot (Black Carbon and Carbon Black: Focus on Oxidative Stress and Inflammatory Pathways

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Rituraj Niranjan

2017-06-01

Full Text Available The environmental soot and carbon blacks (CBs cause many diseases in humans, but their underlying mechanisms of toxicity are still poorly understood. Both are formed after the incomplete combustion of hydrocarbons but differ in their constituents and percent carbon contents. For the first time, “Sir Percival Pott” described soot as a carcinogen, which was subsequently confirmed by many others. The existing data suggest three main types of diseases due to soot and CB exposures: cancer, respiratory diseases, and cardiovascular dysfunctions. Experimental models revealed the involvement of oxidative stress, DNA methylation, formation of DNA adducts, and Aryl hydrocarbon receptor activation as the key mechanisms of soot- and CB-induced cancers. Metals including Si, Fe, Mn, Ti, and Co in soot also contribute in the reactive oxygen species (ROS-mediated DNA damage. Mechanistically, ROS-induced DNA damage is further enhanced by eosinophils and neutrophils via halide (Cl− and Br− dependent DNA adducts formation. The activation of pulmonary dendritic cells, T helper type 2 cells, and mast cells is crucial mediators in the pathology of soot- or CB-induced respiratory disease. Polyunsaturated fatty acids (PUFAs were also found to modulate T cells functions in respiratory diseases. Particularly, telomerase reverse transcriptase was found to play the critical role in soot- and CB-induced cardiovascular dysfunctions. In this review, we propose integrated mechanisms of soot- and CB-induced toxicity emphasizing the role of inflammatory mediators and oxidative stress. We also suggest use of antioxidants and PUFAs as protective strategies against soot- and CB-induced disorders.

Salinity-dependent nickel accumulation and effects on respiration, ion regulation and oxidative stress in the galaxiid fish, Galaxias maculatus.

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Blewett, Tamzin A; Wood, Chris M; Glover, Chris N

2016-07-01

Inanga (Galaxias maculatus) are a euryhaline and amphidromous Southern hemisphere fish species inhabiting waters highly contaminated in trace elements such as nickel (Ni). Ni is known to exert its toxic effects on aquatic biota via three key mechanisms: inhibition of respiration, impaired ion regulation, and stimulation of oxidative stress. Inanga acclimated to freshwater (FW), 50% seawater (SW) or 100% SW were exposed to 0, 150 or 2000 μg Ni L(-1), and tissue Ni accumulation, metabolic rate, ion regulation (tissue ions, calcium (Ca) ion influx), and oxidative stress (catalase activity, protein carbonylation) were measured after 96 h. Ni accumulation increased with Ni exposure concentration in gill, gut and remaining body, but not in liver. Only in the gill was Ni accumulation affected by exposure salinity, with lower branchial Ni burdens in 100% and 50% SW inanga, relative to FW fish. There were no Ni-dependent effects on respiration, or Ca influx, and the only Ni-dependent effect on tissue ion content was on gill potassium. Catalase activity and protein carbonylation were affected by Ni, primarily in FW, but only at 150 μg Ni L(-1). Salinity therefore offsets the effects of Ni, despite minimal changes in Ni bioavailability. These data suggest only minor effects of Ni in inanga, even at highly elevated environmental Ni concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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Maria Pantelidou

2017-02-01

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

Corrosion mechanisms of zirconium alloys - study of the initial oxidation kinetics and of the mechanical behaviour of the metal/oxide system

International Nuclear Information System (INIS)

Parise, M.

1996-12-01

Nuclear fuel claddings are made of zirconium alloys. The conditions of use lead the cladding oxidize outside. The so-formed layers behaves like a thermal barrier and prevents from using oxidized claddings with an oxide thickness larger than 100 μm. The oxidation kinetic is approximately cubic for oxide thicknesses smaller than about 2μm, linear beyond. A kinetic model has been proposed which estimates the post-transition growth rate from the kinetic parameters of the pre-transition state and morphological features of post-transition layers. This work aims at providing the necessary elements to validate this model and studying the layers around the kinetic transition, in order to determine whether the oxidation mechanisms before and after the transition are similar. Thicknesses of the 50 - 500 nm range of the oxide layers are measured by an optical method; pre-transition kinetics are thus precisely determined. The effect of the composition, the thermal treatment and the presence of oxygen in solid solution is studied. The morphological and crystallographic study of the layers show that they exhibit a lot of similarities before and after the kinetic transition. The results concerning the kinetic aspects and the morphology of the post-transition layers point out that the proposed model leads to realistic post-transition growth rates. Furthermore, the kinetic transition corresponds to the appearance of cracks in the oxide layer. The mechanical behaviour of the metal/oxide system has been modelled at different scales. When the specific behaviours of the metal and the oxide are taken into account together with the interface geometry, radial stresses appear, which are high enough to locally open cracks. The appearance and localization of cracks depend on both the interface geometry and the stress distribution in the metal/oxide system. (author)

Exercise-Induced Oxidative Stress Responses in the Pediatric Population

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Alexandra Avloniti

2017-01-01

Full Text Available Adults demonstrate an upregulation of their pro- and anti-oxidant mechanisms in response to acute exercise while systematic exercise training enhances their antioxidant capacity, thereby leading to a reduced generation of free radicals both at rest and in response to exercise stress. However, less information exists regarding oxidative stress responses and the underlying mechanisms in the pediatric population. Evidence suggests that exercise-induced redox perturbations may be valuable in order to monitor exercise-induced inflammatory responses and as such training overload in children and adolescents as well as monitor optimal growth and development. The purpose of this review was to provide an update on oxidative stress responses to acute and chronic exercise in youth. It has been documented that acute exercise induces age-specific transient alterations in both oxidant and antioxidant markers in children and adolescents. However, these responses seem to be affected by factors such as training phase, training load, fitness level, mode of exercise etc. In relation to chronic adaptation, the role of training on oxidative stress adaptation has not been adequately investigated. The two studies performed so far indicate that children and adolescents exhibit positive adaptations of their antioxidant system, as adults do. More studies are needed in order to shed light on oxidative stress and antioxidant responses, following acute exercise and training adaptations in youth. Available evidence suggests that small amounts of oxidative stress may be necessary for growth whereas the transition to adolescence from childhood may promote maturation of pro- and anti-oxidant mechanisms. Available evidence also suggests that obesity may negatively affect basal and exercise-related antioxidant responses in the peripubertal period during pre- and early-puberty.

Oxidative stress in organophosphate poisoning: role of standard antidotal therapy.

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Vanova, Nela; Pejchal, Jaroslav; Herman, David; Dlabkova, Alzbeta; Jun, Daniel

2018-08-01

Despite the main mechanism of organophosphate (OP) toxicity through inhibition of acetylcholinesterase (AChE) being well known over the years, some chronic adverse health effects indicate the involvement of additional pathways. Oxidative stress is among the most intensively studied. Overstimulation of cholinergic and glutamatergic nervous system is followed by intensified generation of reactive species and oxidative damage in many tissues. In this review, the role of oxidative stress in pathophysiology of OP poisoning and the influence of commonly used medical interventions on its levels are discussed. Current standardized therapy of OP intoxications comprises live-saving administration of the anticholinergic drug atropine accompanied by oxime AChE reactivator and diazepam. The capability of these antidotes to ameliorate OP-induced oxidative stress varies between both therapeutic groups and individual medications within the drug class. Regarding oxidative stress, atropine does not seem to have a significant effect on oxidative stress parameters in OP poisoning. In a case of AChE reactivators, pro-oxidative and antioxidative properties could be found. It is assumed that the ability of oximes to trigger oxidative stress is rather associated with their chemical structure than reactivation efficacy. The data indicating the potency of diazepam in preventing OP-induced oxidative stress are not available. Based on current knowledge on the mechanism of OP-mediated oxidative stress, alternative approaches (including antioxidants or multifunctional drugs) in therapy of OP poisoning are under consideration. Copyright © 2018 John Wiley & Sons, Ltd.

Oxidative stress-induced autophagy: Role in pulmonary toxicity

International Nuclear Information System (INIS)

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

2014-01-01

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

Oxidative stress-induced autophagy: Role in pulmonary toxicity

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

2014-03-01

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

Protein Sulfenylation: A Novel Readout of Environmental Oxidant Stress

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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...

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

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Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

2016-01-01

Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. PMID:26315342

An update on oxidative stress-mediated organ pathophysiology.

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

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

Science.gov (United States)

Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

2016-10-01

Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H 2 O 2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H 2 O 2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidatively generated DNA/RNA damage in psychological stress states

DEFF Research Database (Denmark)

Jørgensen, Anders

2013-01-01

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

Differential roles of tau class glutathione S-transferases in oxidative stress

DEFF Research Database (Denmark)

Kilili, Kimiti G; Atanassova, Neli; Vardanyan, Alla

2004-01-01

The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous...... Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress......-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery...

HCV-Induced Oxidative Stress: Battlefield-Winning Strategy

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Khadija Rebbani

2016-01-01

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

Transcriptome-Based Modeling Reveals that Oxidative Stress Induces Modulation of the AtfA-Dependent Signaling Networks in Aspergillus nidulans

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Erzsébet Orosz

2017-01-01

Full Text Available To better understand the molecular functions of the master stress-response regulator AtfA in Aspergillus nidulans, transcriptomic analyses of the atfA null mutant and the appropriate control strains exposed to menadione sodium bisulfite- (MSB-, t-butylhydroperoxide- and diamide-induced oxidative stresses were performed. Several elements of oxidative stress response were differentially expressed. Many of them, including the downregulation of the mitotic cell cycle, as the MSB stress-specific upregulation of FeS cluster assembly and the MSB stress-specific downregulation of nitrate reduction, tricarboxylic acid cycle, and ER to Golgi vesicle-mediated transport, showed AtfA dependence. To elucidate the potential global regulatory role of AtfA governing expression of a high number of genes with very versatile biological functions, we devised a model based on the comprehensive transcriptomic data. Our model suggests that an important function of AtfA is to modulate the transduction of stress signals. Although it may regulate directly only a limited number of genes, these include elements of the signaling network, for example, members of the two-component signal transduction systems. AtfA acts in a stress-specific manner, which may increase further the number and diversity of AtfA-dependent genes. Our model sheds light on the versatility of the physiological functions of AtfA and its orthologs in fungi.

On the mechanical stress of Zr, Zry, and other materials due to the formation of oxide layers

International Nuclear Information System (INIS)

Hofmann, P.

1977-06-01

Several mechanisms are indicated which during oxidation of sheets, tubes, and cylinders of pure metals and alloys might lead to plastic deformation of the remaining uncorroded cross section. Some experimental methods are described which allow evaluation of stresses occurring in oxide layers. The main reason for the creep deformation of flat and tubular specimens made of Zr and Zr alloys lies in the stresses that arise from volume increase due to the growth of oxide layers. Plastic deformations of the sheet metal specimens can be up to 100% and are anisotropic. In tubular specimens the changes in geometry (axial, radial) are much smaller in the course of oxidation and attain 2% at the maximum for Zr- or Zry-tubes and go up to 10% for Ta-tubes when no differential pressure is applied simultaneously. (orig.) [de

Stathmin Mediates Hepatocyte Resistance to Death from Oxidative Stress by down Regulating JNK

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Zhao, Enpeng; Amir, Muhammad; Lin, Yu; Czaja, Mark J.

2014-01-01

Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK). The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth. PMID:25285524

Stathmin mediates hepatocyte resistance to death from oxidative stress by down regulating JNK.

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Enpeng Zhao

Full Text Available Stathmin 1 performs a critical function in cell proliferation by regulating microtubule polymerization. This proliferative function is thought to explain the frequent overexpression of stathmin in human cancer and its correlation with a bad prognosis. Whether stathmin also functions in cell death pathways is unclear. Stathmin regulates microtubules in part by binding free tubulin, a process inhibited by stathmin phosphorylation from kinases including c-Jun N-terminal kinase (JNK. The involvement of JNK activation both in stathmin phosphorylation, and in hepatocellular resistance to oxidative stress, led to an examination of the role of stathmin/JNK crosstalk in oxidant-induced hepatocyte death. Oxidative stress from menadione-generated superoxide induced JNK-dependent stathmin phosphorylation at Ser-16, Ser-25 and Ser-38 in hepatocytes. A stathmin knockdown sensitized hepatocytes to both apoptotic and necrotic cell death from menadione without altering levels of oxidant generation. The absence of stathmin during oxidative stress led to JNK overactivation that was the mechanism of cell death as a concomitant knockdown of JNK1 or JNK2 blocked death. Hepatocyte death from JNK overactivation was mediated by the effects of JNK on mitochondria. Mitochondrial outer membrane permeabilization occurred in stathmin knockdown cells at low concentrations of menadione that triggered apoptosis, whereas mitochondrial β-oxidation and ATP homeostasis were compromised at higher, necrotic menadione concentrations. Stathmin therefore mediates hepatocyte resistance to death from oxidative stress by down regulating JNK and maintaining mitochondrial integrity. These findings demonstrate a new mechanism by which stathmin promotes cell survival and potentially tumor growth.

Two-stage unified stretched-exponential model for time-dependence of threshold voltage shift under positive-bias-stresses in amorphous indium-gallium-zinc oxide thin-film transistors

Science.gov (United States)

Jeong, Chan-Yong; Kim, Hee-Joong; Hong, Sae-Young; Song, Sang-Hun; Kwon, Hyuck-In

2017-08-01

In this study, we show that the two-stage unified stretched-exponential model can more exactly describe the time-dependence of threshold voltage shift (ΔV TH) under long-term positive-bias-stresses compared to the traditional stretched-exponential model in amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). ΔV TH is mainly dominated by electron trapping at short stress times, and the contribution of trap state generation becomes significant with an increase in the stress time. The two-stage unified stretched-exponential model can provide useful information not only for evaluating the long-term electrical stability and lifetime of the a-IGZO TFT but also for understanding the stress-induced degradation mechanism in a-IGZO TFTs.

Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

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Zhu, Xue [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Wang, Ke, E-mail: wangke@jsinm.org [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Zhang, Kai [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China); Zhou, Fanfan [Faculty of Pharmacy, University of Sydney, New South Wales 2006 (Australia); Zhu, Ling [Save Sight Institute, University of Sydney, New South Wales 2000 (Australia)

2016-10-15

Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

International Nuclear Information System (INIS)

Zhu, Xue; Wang, Ke; Zhang, Kai; Zhou, Fanfan; Zhu, Ling

2016-01-01

Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

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Verónica Pérez-De La Cruz

2012-01-01

Full Text Available Quinolinic acid (QUIN, an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca 2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.

Elevated Atherosclerosis-Related Gene Expression, Monocyte Activation and Microparticle-Release Are Related to Increased Lipoprotein-Associated Oxidative Stress in Familial Hypercholesterolemia

DEFF Research Database (Denmark)

Hjuler Nielsen, Morten; Irvine, Helle; Vedel, Simon

2015-01-01

OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate the hypoth......OBJECTIVE: Animal and in vitro studies have suggested that hypercholesterolemia and increased oxidative stress predisposes to monocyte activation and enhanced accumulation of oxidized LDL cholesterol (oxLDL-C) through a CD36-dependent mechanism. The aim of this study was to investigate...... in subjects with heterozygous familial hypercholesterolemia (FH), in particular in the presence of Achilles tendon xanthomas (ATX). APPROACH AND RESULTS: We studied thirty FH subjects with and without ATX and twenty-three healthy control subjects. Intima-media thickness (IMT) and Achilles tendon (AT......LDL-C-CD36 interaction was increased in FH, especially in ATX+ subjects. Monocyte chemokine receptor CX3CR1 was identified as an independent contributor to IMT. CONCLUSIONS: Our data support that lipoprotein-associated oxidative stress is involved in accelerated atherosclerosis in FH, particularly...

Streptococcus pneumoniae-Induced Oxidative Stress in Lung Epithelial Cells Depends on Pneumococcal Autolysis and Is Reversible by Resveratrol.

Science.gov (United States)

Zahlten, Janine; Kim, Ye-Ji; Doehn, Jan-Moritz; Pribyl, Thomas; Hocke, Andreas C; García, Pedro; Hammerschmidt, Sven; Suttorp, Norbert; Hippenstiel, Stefan; Hübner, Ralf-Harto

2015-06-01

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia worldwide. During pneumococcal pneumonia, the human airway epithelium is exposed to large amounts of H2O2 as a product of host and pathogen oxidative metabolism. Airway cells are known to be highly vulnerable to oxidant damage, but the pathophysiology of oxidative stress induced by S. pneumoniae and the role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant systems of the host are not well characterized. For gluthation/gluthathion disulfide analysis BEAS-2B cells, primary broncho-epithelial cells (pBEC), explanted human lung tissue and mouse lungs were infected with different S. pneumoniae strains (D39, A66, R6x, H2O2/pneumolysin/LytA- deficient mutants of R6x). Cell death was proven by LDH assay and cell viability by IL-8 ELISA. The translocation of Nrf2 and the expression of catalase were shown via Western blot. The binding of Nrf2 at the catalase promoter was analyzed by ChIP. We observed a significant induction of oxidative stress induced by S. pneumoniae in vivo, ex vivo, and in vitro. Upon stimulation, the oxidant-responsive transcription factor Nrf2 was activated, and catalase was upregulated via Nrf2. The pneumococci-induced oxidative stress was independent of S. pneumoniae-derived H2O2 and pneumolysin but depended on the pneumococcal autolysin LytA. The Nrf2 inducer resveratrol, as opposed to catalase, reversed oxidative stress in lung epithelial cells. These observations indicate a H2O2-independent induction of oxidative stress in lung epithelial cells via the release of bacterial factors of S. pneumoniae. Resveratrol might be an option for prevention of acute lung injury and inflammatory responses observed in pneumococcal pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

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Allison L Weber

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

Coordination of frontline defense mechanisms under severe oxidative stress.

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

2010-07-01

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

Wet-cupping removes oxidants and decreases oxidative stress.

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Tagil, Suleyman Murat; Celik, Huseyin Tugrul; Ciftci, Sefa; Kazanci, Fatmanur Hacievliyagil; Arslan, Muzeyyen; Erdamar, Nazan; Kesik, Yunus; Erdamar, Husamettin; Dane, Senol

2014-12-01

Wet-cupping therapy is one of the oldest known medical techniques. Although it is widely used in various conditions such as acute\\chronic inflammation, infectious diseases, and immune system disorders, its mechanism of action is not fully known. In this study, we investigated the oxidative status as the first step to elucidate possible mechanisms of action of wet cupping. Wet cupping therapy is implemented to 31 healthy volunteers. Venous blood samples and Wet cupping blood samples were taken concurrently. Serum nitricoxide, malondialdehyde levels and activity of superoxide dismutase and myeloperoxidase were measured spectrophotometrically. Wet cupping blood had higher activity of myeloperoxidase, lower activity of superoxide dismutase, higher levels of malondialdehyde and nitricoxide compared to the venous blood. Wet cupping removes oxidants and decreases oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

The TDDB Characteristics of Ultra-Thin Gate Oxide MOS Capacitors under Constant Voltage Stress and Substrate Hot-Carrier Injection

Directory of Open Access Journals (Sweden)

Jingyu Shen

2018-01-01

Full Text Available The breakdown characteristics of ultra-thin gate oxide MOS capacitors fabricated in 65 nm CMOS technology under constant voltage stress and substrate hot-carrier injection are investigated. Compared to normal thick gate oxide, the degradation mechanism of time-dependent dielectric breakdown (TDDB of ultra-thin gate oxide is found to be different. It is found that the gate current (Ig of ultra-thin gate oxide MOS capacitor is more likely to be induced not only by Fowler-Nordheim (F-N tunneling electrons, but also by electrons surmounting barrier and penetrating electrons in the condition of constant voltage stress. Moreover it is shown that the time to breakdown (tbd under substrate hot-carrier injection is far less than that under constant voltage stress when the failure criterion is defined as a hard breakdown according to the experimental results. The TDDB mechanism of ultra-thin gate oxide will be detailed. The differences in TDDB characteristics of MOS capacitors induced by constant voltage stress and substrate hot-carrier injection will be also discussed.

Andrographis paniculata ameliorates carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity: diminution of oxidative stress.

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Koh, Pei Hoon; Mokhtar, Ruzaidi Azli Mohd; Iqbal, Mohammad

2011-01-01

Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P paniculata (P paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.

Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice.

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Zhang, Limin; Krishnan, Prasad; Ehresman, David J; Smith, Philip B; Dutta, Mainak; Bagley, Bradford D; Chang, Shu-Ching; Butenhoff, John L; Patterson, Andrew D; Peters, Jeffrey M

2016-09-01

The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD diet supplemented with 0.012% PFOS compared with those fed the control diet supplemented with 0.012% PFOS. Surprisingly, serum PFOS concentrations were higher while liver PFOS concentrations were lower in mMCD-fed mice compared with corresponding control-fed mice. To determine if supplemental dietary choline could prevent PFOS-induced hepatic effects, C57BL/6 mice were fed a control diet, or a choline supplemental diet (1.2%) with or without 0.003% PFOS. Lipidomic analysis demonstrated that PFOS caused alterations in hepatic lipid metabolism in the PFOS-fed mice compared with controls, and supplemental dietary choline prevented these PFOS-induced changes. Interestingly, dietary choline supplementation also prevented PFOS-induced oxidative damage. These studies are the first to suggest that PFOS may cause hepatic steatosis and oxidative stress by effectively reducing the choline required for hepatic VLDL production and export by forming an ion pair with choline, and suggest that choline supplementation may prevent and/or treat PFOS-induced hepatic steatosis and oxidative stress. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Effects of naringin on apoptosis and oxidative stress in type 2 diabetic rats

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Adelani, Isaacson; Bankole, Esther; Rotimi, Oluwakemi; Rotimi, Solomon

2018-04-01

Oxidative stress and apoptosis have been reported to play major roles in the pathogenesis of Type 2 Diabetes Mellitus (T2DM) through insulin resistance and β-cell dysfunction. Naringin is a citrus derived flavonoid that has been reported for its antioxidant properties. Even though effects of naringin in T2DM related oxidative stress has been reported, varying dose concentration in oxidative stress and mechanism of action involving T2DM related apoptosis is far-fetched. This research studied the effects of naringin at varying dose concentration on apoptosis, biomarkers of organ function and oxidative stress in high fat diet/low-streptozotocin-induced T2DM in albino Wistar rats. Diabetic rats were treated with naringin at 50mg/kg, 100mg/kg and 200mg/kg body weight for 21 days. Some biomarkers of organ function and oxidative stress in the animals were assayed using spectrophotometric techniques. The levels of expression of caspases and apoptotic regulators were quantified using semi-quantitative reverse transcriptase polymerase chain reaction (RT PCR). Enzyme - linked immunosorbent assay was used to determine inducible nitric oxide synthase (iNOS) level. Naringin treatment shows a dose dependent significant (plipid peroxidation, glutathione- s-transferase, glutathione peroxidase and glutathione reductase activities in the liver. Naringin treatment also showed a significant (p<0.05) increase in the expression of caspase 3 and reduction in BCL-2 as against the diabetic control. In addition, there was dose dependent decrease in plasma CO2 concentration and increase in the plasma iNOS concentration as compared to the diabetic control. This result highlights positive effect of naringin as an antioxidant, its role in apoptosis and also reverting the effects of organ damage in type 2 diabetes.

Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

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Wijaya Edward

2010-01-01

Full Text Available Abstract Background The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10°C, an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach. Results Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10°C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters. Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2 spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters. Conclusion Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries.

Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

KAUST Repository

Yun, Kil-Young

2010-01-25

Background: The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.Results: Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.Conclusion: Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries. 2010 Yun et al; licensee BioMed Central Ltd.

Role of Oxidative Stress in Epigenetic Modification in Endometriosis.

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Ito, Fuminori; Yamada, Yuki; Shigemitsu, Aiko; Akinishi, Mika; Kaniwa, Hiroko; Miyake, Ryuta; Yamanaka, Shoichiro; Kobayashi, Hiroshi

2017-11-01

Aberrant DNA methylation and histone modification are associated with an increased risk of reproductive disorders such as endometriosis. However, a cause-effect relationship between epigenetic mechanisms and endometriosis development has not been fully determined. This review provides current information based on oxidative stress in epigenetic modification in endometriosis. This article reviews the English-language literature on epigenetics, DNA methylation, histone modification, and oxidative stress associated with endometriosis in an effort to identify epigenetic modification that causes a predisposition to endometriosis. Oxidative stress, secondary to the influx of hemoglobin, heme, and iron during retrograde menstruation, is involved in the expression of CpG demethylases, ten-eleven translocation, and jumonji (JMJ). Ten-eleven translocation and JMJ recognize a wide range of endogenous DNA methyltransferases (DNMTs). The increased expression levels of DNMTs may be involved in the subsequent downregulation of the decidualization-related genes. This review supports the hypothesis that there are at least 2 distinct phases of epigenetic modification in endometriosis: the initial wave of iron-induced oxidative stress would be followed by the second big wave of epigenetic modulation of endometriosis susceptibility genes. We summarize the recent advances in our understanding of the underlying epigenetic mechanisms focusing on oxidative stress in endometriosis.

Oxidative stress in MeHg-induced neurotoxicity

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Farina, Marcelo, E-mail: farina@ccb.ufsc.br [Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Florianopolis, SC (Brazil); Aschner, Michael [Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN (United States); Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN (United States); Rocha, Joao B.T., E-mail: jbtrocha@yahoo.com.br [Departamento de Quimica, Centro de Ciencias Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, RS (Brazil)

2011-11-15

Methylmercury (MeHg) is an environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. Although the molecular mechanisms mediating MeHg-induced neurotoxicity are not completely understood, several lines of evidence indicate that oxidative stress represents a critical event related to the neurotoxic effects elicited by this toxicant. The objective of this review is to summarize and discuss data from experimental and epidemiological studies that have been important in clarifying the molecular events which mediate MeHg-induced oxidative damage and, consequently, toxicity. Although unanswered questions remain, the electrophilic properties of MeHg and its ability to oxidize thiols have been reported to play decisive roles to the oxidative consequences observed after MeHg exposure. However, a close examination of the relationship between low levels of MeHg necessary to induce oxidative stress and the high amounts of sulfhydryl-containing antioxidants in mammalian cells (e.g., glutathione) have led to the hypothesis that nucleophilic groups with extremely high affinities for MeHg (e.g., selenols) might represent primary targets in MeHg-induced oxidative stress. Indeed, the inhibition of antioxidant selenoproteins during MeHg poisoning in experimental animals has corroborated this hypothesis. The levels of different reactive species (superoxide anion, hydrogen peroxide and nitric oxide) have been reported to be increased in MeHg-exposed systems, and the mechanisms concerning these increments seem to involve a complex sequence of cascading molecular events, such as mitochondrial dysfunction, excitotoxicity, intracellular calcium dyshomeostasis and decreased antioxidant capacity. This review also discusses potential therapeutic strategies to counteract MeHg-induced toxicity and oxidative stress, emphasizing the use of organic selenocompounds, which generally present higher affinity for MeHg when compared to the classically

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

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Lushchak, Volodymyr I

2014-12-05

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

Neonatal oxidative stress depends on oxygen blood pressure in umbilical artery.

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Proietti, F; De Bernardo, G; Longini, M; Sordino, D; Scaramuzzini, G; Tataranno, M L; Belvisi, E; Bazzini, F; Perrone, S; Buonocore, G

2016-01-01

With advancing gestation, partial pressure of oxygen (pO2) and pH fall significantly. Hypoxia is a main factor inducing free radical generation and thereby oxidative stress (OS). Placental and fetal tissue response when oxygen becomes restricted is complex and partially known. We tested the hypothesis that changes in umbilical artery and vein blood gas concentrations modulate OS occurrence in the newborn. Seventy umbilical artery and vein plasma samples were collected from healthy term newborns immediately after delivery. F2 Isoprostanes (F2-Isop) were measured in all samples as reliable markers of lipid peroxidation. Significantly lower pCO2 and higher pO2 and pH were found in umbilical vein than in artery, as expected. A positive correlation was detected between pH and pO2 only in umbilical artery (p=0.019). F2-Isop levels were no different between artery and vein in cord blood. Significant correlations were found between F2-Isop and pCO2 (p=0.025) as well as between F2-Isop and pH in umbilical vein (p=0.027). F2-Isop correlated with pCO2 (p=0.007) as well as with pO2 values (p=0.005) in umbilical artery blood. Oxidative stress (OS) in newborns depends on oxygen concentrations in umbilical artery. OS biomarkers significantly correlate with pO2 and in umbilical artery but not in umbilical vein. In normoxic conditions fetal-maternal gas exchanges occurring in placenta re-establish normal higher oxygen levels in umbilical vein than artery, with a normal production of free radicals without any deleterious effects.

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

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Dmytro I Lytvyn

2016-04-01

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

Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

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Aparna Areti

2014-01-01

Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

Macroscopic and microscopic determinations of residual stresses in thin oxide dispersion strengthened steel tubes

International Nuclear Information System (INIS)

Bechade, J.L.; Toualbi, L.; Bosonnet, S.; Carlan, Y. de; Castelnau, O.

2014-01-01

To improve the efficiency of components operating at high temperatures, many efforts are deployed to develop new materials. Oxide Dispersion Strengthened (ODS) materials could be used for heat exchangers or cladding tubes for the new GENIV nuclear reactors. This type of materials are composed with a metallic matrix (usually iron base alloy for nuclear applications or nickel base alloy for heat exchangers) reinforced by a distribution of nano-oxides. They are obtained by powder metallurgy and mechanical alloying. The creep resistance of these materials is excellent, and they usually exhibit a high tensile strength at room temperature. Depending on the cold working and/or the heat treatments, several types of microstructure can be obtained: recrystallised, stress relieved. One of the key challenges is to transform ODS materials into thin tubes (up to 500 microns thick) within a robust fabrication route while keeping the excellent mechanical properties. To prevent cracking during the process or to obtain a final product with low residual stresses, it is important to quantify the effect of the heat treatments on the release of internal stresses. The aim of this study is to show how residual stresses can be determined on different thin tubes using two complementary approaches: (i) macroscopic stresses determination in the tube using beam theory (small cuts along the longitudinal and circumferential directions and measurements of the deflection), (ii) stress determination from x-ray diffraction analyses (surface analyses, using 'sin"2ψ' method with different hypothesis). Depending on the material and the heat treatment, residual stresses vary dramatically and can reach 800 MPa which is not far from the yield stress; comparisons between both methods are performed and suggestions are given in order to optimize the thermo-mechanical treatment of thin ODS tubes. (authors)

Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells.

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Sordillo, Lorraine M; Weaver, James A; Cao, Yu-Zhang; Corl, Chris; Sylte, Matt J; Mullarky, Isis K

2005-05-01

Oxidant stress plays an important role in the etiology of vascular diseases by increasing rates of endothelial cell apoptosis, but few data exist on the mechanisms involved. Using a unique model of oxidative stress based on selenium deficiency (-Se), the effects of altered eicosanoid production on bovine aortic endothelial cells (BAEC) apoptosis was evaluated. Oxidant stress significantly increased the immediate oxygenation product of arachidonic acid metabolized by the 15-lipoxygenase pathway, 15-hydroxyperoxyeicosatetraenoic acid (15-HPETE). Treatment of -Se BAEC with TNFalpha/cyclohexamide (CHX) exhibited elevated levels of apoptosis, which was significantly reduced by the addition of a specific 15-lipoxygenase inhibitor PD146176. Furthermore, the addition of 15-HPETE to PD146176-treated BAEC, partially restored TNF/CHX-induced apoptosis. Increased exposure to 15-HPETE induced apoptosis, as determined by internucleosomal DNA fragmentation, chromatin condensation, caspase-3 activation, and caspase-9 activation, which suggests mitochondrial dysfunction. The expression of Bcl-2 protein also was decreased in -Se BAEC. Addition of a caspase-9 inhibitor (LEHD-fmk) completely blocked 15-HPETE-induced chromatin condensation in -Se BAEC, suggesting that 15-HPETE-induced apoptosis is caspase-9 dependent. Increased apoptosis of BAEC as a result of oxidant stress and subsequent production of 15-HPETE may play a critical role in a variety of inflammatory based diseases.

Yeast signaling pathways in the oxidative stress response

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Ikner, Aminah [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States); Shiozaki, Kazuhiro [Section of Microbiology, Division of Biological Sciences, University of California, Davis, CA 95616 (United States)]. E-mail: kshiozaki@ucdavis.edu

2005-01-06

Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed.

Yeast signaling pathways in the oxidative stress response

International Nuclear Information System (INIS)

Ikner, Aminah; Shiozaki, Kazuhiro

2005-01-01

Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The 'DNA damage checkpoint' that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed

Reduced coupling of oxidative phosphorylation in vivo precedes electron transport chain defects due to mild oxidative stress in mice.

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Michael P Siegel

Full Text Available Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ treatment of wild type mice and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1(-/- models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain.

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

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Jereme G. Spiers

2015-01-01

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

A novel mechanism of oxidative genotoxicity

Indian Academy of Sciences (India)

The genotoxicity of reactive oxygen species (ROS) is well established. The underlying mechanism involves oxidation of DNA by ROS. However, we have recently shown that hydrogen peroxide (H2O2), the major mediator of oxidative stress, can also cause genomic damage indirectly. Thus, H2O2 at pathologically relevant ...

Sex differences in oxidative stress resistance in relation to longevity in Drosophila melanogaster.

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Niveditha, S; Deepashree, S; Ramesh, S R; Shivanandappa, T

2017-10-01

Gender differences in lifespan and aging are known across species. Sex differences in longevity within a species can be useful to understand sex-specific aging. Drosophila melanogaster is a good model to study the problem of sex differences in longevity since females are longer lived than males. There is evidence that stress resistance influences longevity. The objective of this study was to investigate if there is a relationship between sex differences in longevity and oxidative stress resistance in D. melanogaster. We observed a progressive age-dependent decrease in the activity of SOD and catalase, major antioxidant enzymes involved in defense mechanisms against oxidative stress in parallel to the increased ROS levels over time. Longer-lived females showed lower ROS levels and higher antioxidant enzymes than males as a function of age. Using ethanol as a stressor, we have shown differential susceptibility of the sexes to ethanol wherein females exhibited higher resistance to ethanol-induced mortality and locomotor behavior compared to males. Our results show strong correlation between sex differences in oxidative stress resistance, antioxidant defenses and longevity. The study suggests that higher antioxidant defenses in females may confer resistance to oxidative stress, which could be a factor that influences sex-specific aging in D. melanogaster.

D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway

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Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

2011-12-15

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D-saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20-120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic {beta}-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic {beta}-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. Highlights: Black-Right-Pointing-Pointer Oxidative stress is suggested as a key event in the pathogenesis of diabetes. Black-Right-Pointing-Pointer D-saccharic acid 1,4-lactone (DSL) reduces the alloxan-induced diabetes mellitus. Black-Right-Pointing-Pointer DSL normalizes cellular antioxidant machineries

D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway

International Nuclear Information System (INIS)

Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan; Sil, Parames C.

2011-01-01

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D-saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20–120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic β-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic β-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. Highlights: ► Oxidative stress is suggested as a key event in the pathogenesis of diabetes. ► D-saccharic acid 1,4-lactone (DSL) reduces the alloxan-induced diabetes mellitus. ► DSL normalizes cellular antioxidant machineries disturbed due to alloxan toxicity. ► DSL inhibits pancreatic β-cells apoptosis

Oxidative Stress, Redox Signaling, and Autophagy: Cell Death Versus Survival

Science.gov (United States)

Navarro-Yepes, Juliana; Burns, Michaela; Anandhan, Annadurai; Khalimonchuk, Oleh; del Razo, Luz Maria; Quintanilla-Vega, Betzabet; Pappa, Aglaia; Panayiotidis, Mihalis I.

2014-01-01

Abstract Significance: The molecular machinery regulating autophagy has started becoming elucidated, and a number of studies have undertaken the task to determine the role of autophagy in cell fate determination within the context of human disease progression. Oxidative stress and redox signaling are also largely involved in the etiology of human diseases, where both survival and cell death signaling cascades have been reported to be modulated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). Recent Advances: To date, there is a good understanding of the signaling events regulating autophagy, as well as the signaling processes by which alterations in redox homeostasis are transduced to the activation/regulation of signaling cascades. However, very little is known about the molecular events linking them to the regulation of autophagy. This lack of information has hampered the understanding of the role of oxidative stress and autophagy in human disease progression. Critical Issues: In this review, we will focus on (i) the molecular mechanism by which ROS/RNS generation, redox signaling, and/or oxidative stress/damage alter autophagic flux rates; (ii) the role of autophagy as a cell death process or survival mechanism in response to oxidative stress; and (iii) alternative mechanisms by which autophagy-related signaling regulate mitochondrial function and antioxidant response. Future Directions: Our research efforts should now focus on understanding the molecular basis of events by which autophagy is fine tuned by oxidation/reduction events. This knowledge will enable us to understand the mechanisms by which oxidative stress and autophagy regulate human diseases such as cancer and neurodegenerative disorders. Antioxid. Redox Signal. 21, 66–85. PMID:24483238

ROS-mediated inhibition of S-nitrosoglutathione reductase contributes to the activation of anti-oxidative mechanisms

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Izabella Kovacs

2016-11-01

Full Text Available Nitric oxide (NO has emerged as a signaling molecule in plants being involved in diverse physiological processes like germination, root growth, stomata closing and response to biotic and abiotic stress. S-nitrosoglutathione (GSNO as a biological NO donor has a very important function in NO signaling since it can transfer its NO moiety to other proteins (trans-nitrosylation. Such trans-nitrosylation reactions are equilibrium reactions and depend on GSNO level. The breakdown of GSNO and thus the level of S-nitrosylated proteins are regulated by GSNO-reductase (GSNOR. In this way, this enzyme controls S-nitrosothiol levels and regulates NO signaling. Here we report that Arabidopsis thaliana GSNOR activity is reversibly inhibited by H2O2 in-vitro and by paraquat-induced oxidative stress in-vivo. Light scattering analyses of reduced and oxidized recombinant GSNOR demonstrated that GSNOR proteins form dimers under both reducing and oxidizing conditions. Moreover, mass spectrometric analyses revealed that H2O2-treatment increased the amount of oxidative modifications on Zn2+-coordinating Cys47 and Cys177. Inhibition of GSNOR results in enhanced levels of S-nitrosothiols followed by accumulation of glutathione. Moreover, transcript levels of redox-regulated genes and activities of glutathione-dependent enzymes are increased in gsnor-ko plants, which may contribute to the enhanced resistance against oxidative stress. In sum, our results demonstrate that ROS-dependent inhibition of GSNOR is playing an important role in activation of anti-oxidative mechanisms to damping oxidative damage and imply a direct crosstalk between ROS- and NO-signaling.

Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

International Nuclear Information System (INIS)

Kumagai, Yoshito; Pi Jingbo

2004-01-01

Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

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

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

2004-05-04

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

Diabetic Cardiovascular Disease Induced by Oxidative Stress

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Yosuke Kayama

2015-10-01

Full Text Available Cardiovascular disease (CVD is the leading cause of morbidity and mortality among patients with diabetes mellitus (DM. DM can lead to multiple cardiovascular complications, including coronary artery disease (CAD, cardiac hypertrophy, and heart failure (HF. HF represents one of the most common causes of death in patients with DM and results from DM-induced CAD and diabetic cardiomyopathy. Oxidative stress is closely associated with the pathogenesis of DM and results from overproduction of reactive oxygen species (ROS. ROS overproduction is associated with hyperglycemia and metabolic disorders, such as impaired antioxidant function in conjunction with impaired antioxidant activity. Long-term exposure to oxidative stress in DM induces chronic inflammation and fibrosis in a range of tissues, leading to formation and progression of disease states in these tissues. Indeed, markers for oxidative stress are overexpressed in patients with DM, suggesting that increased ROS may be primarily responsible for the development of diabetic complications. Therefore, an understanding of the pathophysiological mechanisms mediated by oxidative stress is crucial to the prevention and treatment of diabetes-induced CVD. The current review focuses on the relationship between diabetes-induced CVD and oxidative stress, while highlighting the latest insights into this relationship from findings on diabetic heart and vascular disease.

Hydrogen sulfide increases nitric oxide production from endothelial cells by an Akt-dependent mechanism

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Arturo J Cardounel

2011-12-01

Full Text Available Hydrogen sulfide (H2S and nitric oxide (NO are both gasotransmitters that can elicit synergistic vasodilatory responses in the in the cardiovascular system, but the mechanisms behind this synergy are unclear. In the current study we investigated the molecular mechanisms through which H2S regulates endothelial NO production. Initial studies were performed to establish the temporal and dose-dependent effects of H2S on NO generation using EPR spin trapping techniques. H2S stimulated a two-fold increase in NO production from endothelial nitric oxide synthase (eNOS, which was maximal 30 min after exposure to 25-150 µM H2S. Following 30 min H2S exposure, eNOS phosphorylation at Ser 1177 was significantly increased compared to control, consistent with eNOS activation. Pharmacological inhibition of Akt, the kinase responsible for Ser 1177 phosphorylation, attenuated the stimulatory effect of H2S on NO production. Taken together, these data demonstrate that H2S up-regulates NO production from eNOS through an Akt-dependent mechanism. These results implicate H2S in the regulation of NO in endothelial cells, and suggest that deficiencies in H2S signaling can directly impact processes regulated by NO.

Does oxidative stress shorten telomeres?

NARCIS (Netherlands)

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

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

Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

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Pergolizzi, Barbara; Carriero, Vitina; Abbadessa, Giuliana; Penna, Claudia; Berchialla, Paola; De Francia, Silvia; Bracco, Enrico; Racca, Silvia

2017-10-01

Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

Characteristic of the Oxidative Stress in Blood of Patients in Dependence of Community-Acquired Pneumonia Severity.

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Muravlyova, Larissa; Molotov-Luchankiy, Vilen; Bakirova, Ryszhan; Klyuyev, Dmitriy; Demidchik, Ludmila; Lee, Valentina

2016-03-15

At the present time the alternation of the oxidative metabolism is considered as one of the leading pathogenic mechanisms in the development and progression of community-acquired pneumonia (CAP). However the nature and direction of the oxidative protein changes in CAP patient's blood had been almost unexplored. To define oxidative and modified proteins in erythrocytes and blood plasma of CAP patients. Blood plasma and erythrocytes obtained from: 42 patients with moderate severity pneumonia, 12 patients with grave severity pneumonia and 32 healthy volunteers. Content of advanced oxidation protein products, malondialdehyde and reactive carbonyl derivatives were estimated as indicators of the oxidative stress and oxidative damage of proteins. In patients with grave severity the level of oxidative proteins and MDA in erythrocytes exceeded both: control values and similar meanings in CAP patients with moderate severity. The further growth of MDA in this group patients' blood plasma was observed, but the level of oxidative proteins decreased in comparison with those in CAP patients with moderate severity. To sum up, our derived data show, that injury of erythrocytes' redox-status and blood plasma components plays an essential role in development and progression CAP.

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn.

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Ramírez-Vélez, Robinson; Romero, Miryam; Echeverri, Isabella; Ortega, José Guillermo; Mosquera, Mildrey; Salazar, Blanca; Girón, Sandra Lorena; Saldarriaga, Wilmar; Aguilar de Plata, Ana Cecilia; Mateus, Julio Cesar

2011-02-28

Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. usual prenatal care (PC) and placebo (maltodextrine). 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg), selenium (70 μg), vitamin A (400 μg), alphatocopherol (30 mg), vitamin C (200 mg), and niacin (100 mg). 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. NCT00872365.

Hypertension and physical exercise: The role of oxidative stress.

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Korsager Larsen, Monica; Matchkov, Vladimir V

2016-01-01

Oxidative stress is associated with the pathogenesis of hypertension. Decreased bioavailability of nitric oxide (NO) is one of the mechanisms involved in the pathogenesis. It has been suggested that physical exercise could be a potential non-pharmacological strategy in treatment of hypertension because of its beneficial effects on oxidative stress and endothelial function. The aim of this review is to investigate the effect of oxidative stress in relation to hypertension and physical exercise, including the role of NO in the pathogenesis of hypertension. Endothelial dysfunction and decreased NO levels have been found to have the adverse effects in the correlation between oxidative stress and hypertension. Most of the previous studies found that aerobic exercise significantly decreased blood pressure and oxidative stress in hypertensive subjects, but the intense aerobic exercise can also injure endothelial cells. Isometric exercise decreases normally only systolic blood pressure. An alternative exercise, Tai chi significantly decreases blood pressure and oxidative stress in normotensive elderly, but the effect in hypertensive subjects has not yet been studied. Physical exercise and especially aerobic training can be suggested as an effective intervention in the prevention and treatment of hypertension and cardiovascular disease via reduction in oxidative stress. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The Role of Oxidative Stress in Diabetes Mellitus: A 24-year Review ...

African Journals Online (AJOL)

Background: Diabetes mellitus is a widespread and devastating disease. Diabetes is associated with several mechanisms of tissue damage, one of which is oxidative stress. Oxidative stress and oxidative damage to tissues are common end points to chronic diseases such as atherosclerosis, diabetes and cardiovascular ...

Status epilepticus in immature rats is associated with oxidative stress and mitochondrial dysfunction

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Jaroslava eFolbergrová

2016-05-01

Full Text Available Epilepsy is a neurologic disorder, particularly frequent in infants and children where it can lead to serious consequences later in life. Oxidative stress and mitochondrial dysfunction are implicated in the pathogenesis of many neurological disorders including epilepsy in adults. However, their role in immature epileptic brain is unclear since there have been two contrary opinions: oxidative stress is age-dependent and does not occur in immature brain during status epilepticus and, on the other hand, evidence of oxidative stress in immature brain during a specific model of status epilepticus. To solve this dilemma, we have decided to investigate oxidative stress following status epilepticus induced in immature 12-day-old rats by three substances with a different mechanism of action, namely 4-aminopyridine, LiCl-pilocarpine or kainic acid. FluoroJade-B staining revealed mild brain damage especially in hippocampus and thalamus in each of the tested models. Decrease of glucose and glycogen with parallel rises of lactate clearly indicate high rate of glycolysis, which was apparently not sufficient in 4-AP and Li-Pilo status, as evident from the decreases of PCr levels. Hydroethidium method revealed significantly higher levels of superoxide anion (by ~60 % in the hippocampus, cerebral cortex and thalamus of immature rats during status. Status epilepticus lead to mitochondrial dysfunction with a specific pronounced decrease of complex I activity that persisted for a long period of survival. Complex II and IV activities remained in the control range. Antioxidant treatment with SOD mimetic MnTMPYP or peroxynitrite scavenger FeTPPS significantly attenuated oxidative stress and inhibition of complex I activity. These findings bring evidence that oxidative stress and mitochondrial dysfunction are age and model independent, and may thus be considered a general phenomenon. They can have a clinical relevance for a novel approach to the treatment of epilepsy

Brain imaging for oxidative stress and mitochondrial dysfunction in neurodegenerative diseases

International Nuclear Information System (INIS)

Okazawa, H.; Tsujikawa, T.; Kiyono, Y.; Ikawa, M.; Yoneda, M.

2014-01-01

Oxidative stress, one of the most probable molecular mechanisms for neuronal impairment, is reported to occur in the affected brain regions of various neurodegenerative diseases. Recently, many studies showed evidence of a link between oxidative stress or mitochondrial damage and neuronal degeneration. Basic in vitro experiments and postmortem studies demonstrated that biomarkers for oxidative damage can be observed in the pathogenic regions of the brain and the affected neurons. Model animal studies also showed oxidative damage associated with neuronal degeneration. The molecular imaging method with positron emission tomography (PET) is expected to delineate oxidatively stressed microenvironments to elucidate pathophysiological changes of the in vivo brain; however, only a few studies have successfully demonstrated enhanced stress in patients. Radioisotope copper labeled diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) may be the most promising candidate for this oxidative stress imaging. The tracer is usually known as a hypoxic tissue imaging PET probe, but the accumulation mechanism is based on the electron rich environment induced by mitochondrial impairment and/or microsomal over-reduction, and thus it is considered to represent the oxidative stress state correlated with the degree of disease severity. In this review, Cu-ATSM PET is introduced in detail from the basics to practical methods in clinical studies, as well as recent clinical studies on cerebrovascular diseases and neurodegenerative diseases. Several other PET probes are also introduced from the point of view of neuronal oxidative stress imaging. These molecular imaging methods should be promising tools to reveal oxidative injuries in various brain diseases

Oxidative stress by monosodium urate crystals promotes renal cell apoptosis through mitochondrial caspase-dependent pathway in human embryonic kidney 293 cells: mechanism for urate-induced nephropathy.

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Choe, Jung-Yoon; Park, Ki-Yeun; Kim, Seong-Kyu

2015-01-01

The aim of this study is to clarify the effect of oxidative stress on monosodium urate (MSU)-mediated apoptosis of renal cells. Quantitative real-time polymerase chain reaction and immunoblotting for Bcl-2, caspase-9, caspase-3, iNOS, cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), IL-18, TNF receptor-associated factor-6 (TRAF-6), and mitogen-activated protein kinases were performed on human embryonic kidney 293 (HEK293) cells, which were stimulated by MSU crystals. Fluorescence-activated cell sorting was performed using annexin V for assessment of apoptosis. Reactive oxygen species (ROS) were measured. IL-1β siRNA was used for blocking IL-1β expression. MSU crystals promoted ROS, iNOS, and COX-2 expression and also increased TRAF-6 and IL-1β expression in HEK293 cells, which was inhibited by an antioxidant ascorbic acid. Caspase-dependent renal cell apoptosis was induced through attenuation of Bcl-2 and enhanced caspase-3 and caspase-9 expression by MSU crystals, which was significantly reversed by ascorbic acid and transfection of IL-1β siRNA to HEK293 cells. Ascorbic acid inhibited phosphorylation of extracellular signal-regulated kinase and Jun N-terminal protein kinase stimulated by MSU crystals. ROS accumulation and iNOS and COX-2 mRNA expression by MSU crystals was also suppressed by transfection with IL-1β siRNA. Oxidative stress generated by MSU crystals promotes renal apoptosis through the mitochondrial caspase-dependent apoptosis pathway.

Molecular mechanism of catalase activity change under sodium dodecyl sulfate-induced oxidative stress in the mouse primary hepatocytes.

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Wang, Jing; Wang, Jiaxi; Xu, Chi; Liu, Rutao; Chen, Yadong

2016-04-15

Sodium dodecyl sulfate (SDS) contributes to adverse effects of organisms probably because of its ability to induce oxidative stress via changing the activity of antioxidant enzyme catalase (CAT). But the underlying molecular mechanisms still remain unclear. This study characterized the harmful effects of SDS-induced oxidative stress on the mouse primary hepatocytes as well as the structure and function of CAT molecule and investigated the underlying molecular mechanism. After 12h SDS (0.1μM to 0.2mM) exposure, no significant change was observed in CAT activity of the hepatocytes. After 0.5 and 0.8mM SDS exposure, the state of oxidative stress stimulated CAT production in the hepatocytes. The inhibition of CAT activity induced by directly interacting with SDS was unable to catch the synthesis of CAT and therefore resulted in the increased activity and elevated ROS level. Further molecular experiments showed that SDS prefers to bind to the interface with no direct effect on the active site and the structure of heme groups of CAT molecule. When the sites in the interface is saturated, SDS interacts with VAL 73, HIS 74, ASN 147 and PHE 152, the key residues of the enzyme activity, and leads to the decrease of CAT activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress.

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Benoit, Stéphane L; Maier, Robert J

2016-11-04

Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H 2 O 2 ). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains ( katA H56A and katA Y339A ) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalase-deletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H 2 O 2 -dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new non-enzymatic protective mechanism of action for the ubiquitous enzyme. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening.

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Sun, Wen-xiao; Zheng, Hai-ya; Lan, Jun

2015-11-01

Existing evidences have emphasized an important role of oxidative stress in dexamethasone (Dex)-induced osteoblastic cell damages. Here, we investigated the possible anti-Dex activity of edaravone in osteoblastic cells, and studied the underlying mechanisms. We showed that edaravone dose-dependently attenuated Dex-induced death and apoptosis of established human or murine osteoblastic cells. Further, Dex-mediated damages to primary murine osteoblasts were also alleviated by edaravone. In osteoblastic cells/osteoblasts, Dex induced significant oxidative stresses, tested by increased levels of reactive oxygen species and lipid peroxidation, which were remarkably inhibited by edaravone. Meanwhile, edaravone repressed Dex-induced mitochondrial permeability transition pore (mPTP) opening, or mitochondrial membrane potential reduction, in osteoblastic cells/osteoblasts. Significantly, edaravone-induced osteoblast-protective activity against Dex was alleviated with mPTP inhibition through cyclosporin A or cyclophilin-D siRNA. Together, we demonstrate that edaravone protects osteoblasts from Dex-induced damages probably through inhibiting oxidative stresses and following mPTP opening.

Periodontal Disease-Induced Atherosclerosis and Oxidative Stress

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Tomoko Kurita-Ochiai

2015-09-01

Full Text Available 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.

Intrinsic stress evolution during amorphous oxide film growth on Al surfaces

International Nuclear Information System (INIS)

Flötotto, D.; Wang, Z. M.; Jeurgens, L. P. H.; Mittemeijer, E. J.

2014-01-01

The intrinsic stress evolution during formation of ultrathin amorphous oxide films on Al(111) and Al(100) surfaces by thermal oxidation at room temperature was investigated in real-time by in-situ substrate curvature measurements and detailed atomic-scale microstructural analyses. During thickening of the oxide a considerable amount of growth stresses is generated in, remarkably even amorphous, ultrathin Al 2 O 3 films. The surface orientation-dependent stress evolutions during O adsorption on the bare Al surfaces and during subsequent oxide-film growth can be interpreted as a result of (i) adsorption-induced surface stress changes and (ii) competing processes of free volume generation and structural relaxation, respectively

Oxidative Stress in BPH

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Murat Savas

2009-01-01

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

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

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Mohammad, Mohammad K; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

2012-01-01

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. PMID:23026831

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

Science.gov (United States)

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

2010-02-28

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

Relationship between mitochondrial dysfunction, oxidative stress and diabetic retinopathy

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Song Yue

2014-12-01

Full Text Available As one of the serious complications of diabetes, diabetic retinopathy(DRhas become a main eye disease which causes blindness. The occurrence and development of DR is related to many factors. The pathogenesis is complicated, and the mechanism has not been clear. Early data suggest that the occurrence and development of DR has relations with many factors such as blood sugar level, diabetes duration and the environment. Among the factors, mitochondrial dysfunction and oxidative stress is the important mechanisms of DR and has become research focus in recent years. Consequences of mitochondrial dysfunction within cells include elevation of the rate of reactive oxygen species(ROSproduction due to damage of electron transport chain proteins, mitochondrial DNA(mtDNAdamage, and loss of metabolic capacity. Clear understanding on the mechanism of mitochondrial functional change under high sugar level and oxidative stress response in the occurrence and development of DR is of great significance on prevention and cure of DR. In this article, the development of mitochondrial metabolism and oxidative stress of DR is reviewed.

Oxidative Stress in Myopia

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Bosch-Morell Francisco

2015-01-01

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

MAPK pathway activation by chronic lead-exposure increases vascular reactivity through oxidative stress/cyclooxygenase-2-dependent pathways

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Simões, Maylla Ronacher, E-mail: yllars@hotmail.com [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Aguado, Andrea [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Fiorim, Jonaína; Silveira, Edna Aparecida; Azevedo, Bruna Fernandes; Toscano, Cindy Medice [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Zhenyukh, Olha; Briones, Ana María [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain); Alonso, María Jesús [Dept. of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Alcorcón (Spain); Vassallo, Dalton Valentim [Dept. of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES CEP 29040-091 (Brazil); Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402 (Brazil); Salaices, Mercedes, E-mail: mercedes.salaices@uam.es [Department of Pharmacology, Universidad Autonoma de Madrid, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid (Spain)

2015-03-01

Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10 μg/100 g; subsequent doses: 0.125 μg/100 g, intramuscular, 30 days) and cultured aortic vascular smooth muscle cells (VSMCs) from Sprague Dawley rats stimulated with lead (20 μg/dL) were used. Lead blood levels of treated rats attained 21.7 ± 2.38 μg/dL. Lead exposure increased systolic blood pressure and aortic ring contractile response to phenylephrine, reduced acetylcholine-induced relaxation and did not affect sodium nitroprusside relaxation. Endothelium removal and L-NAME left-shifted the response to phenylephrine more in untreated than in lead-treated rats. Apocynin and indomethacin decreased more the response to phenylephrine in treated than in untreated rats. Aortic protein expression of gp91(phox), Cu/Zn-SOD, Mn-SOD and COX-2 increased after lead exposure. In cultured VSMCs lead 1) increased superoxide anion production, NADPH oxidase activity and gene and/or protein levels of NOX-1, NOX-4, Mn-SOD, EC-SOD and COX-2 and 2) activated ERK1/2 and p38 MAPK. Both antioxidants and COX-2 inhibitors normalized superoxide anion production, NADPH oxidase activity and mRNA levels of NOX-1, NOX-4 and COX-2. Blockade of the ERK1/2 and p38 signaling pathways abolished lead-induced NOX-1, NOX-4 and COX-2 expression. Results show that lead activation of the MAPK signaling pathways activates inflammatory proteins such as NADPH oxidase and COX-2, suggesting a reciprocal interplay and contribution to vascular dysfunction as an underlying mechanisms for lead-induced hypertension. - Highlights: • Lead-exposure increases oxidative stress, COX-2 expression and vascular reactivity. • Lead exposure activates MAPK signaling pathway. • ROS and COX-2 activation by

Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

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Su, Cunjin; Shi, Aiming; Cao, Guowen [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Tao, Tao [Department of Urology, Zhongda Hospital, Medical School of Southeast University, Nanjing, 210009 (China); Chen, Ruidong [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Zhanhong; Shen, Zhu; Tao, Hong; Cao, Bin [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Hu, Duanmin, E-mail: hudmsdfey@sina.com [Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China); Bao, Junjie, E-mail: baojjsdfey@sina.com [Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China)

2015-05-15

There are no appropriate drugs for metastatic neuroblastoma (NB), which is the most common extra-cranial solid tumor for childhood. Thioredoxin binding protein (TXNIP), the endogenous inhibitor of ROS elimination, has been identified as a tumor suppressor in various solid tumors. It reported that fenofibrate exerts anti-tumor effects in several human cancer cell lines. However, its detail mechanisms remain unclear. The present study assessed the effects of fenofibrate on NB cells and investigated TXNIP role in its anti-tumor mechanisms. We used MTT assay to detect cells proliferation, starch wound test to investigate cells migration, H{sub 2}DCF-DA to detect intracellular ROS, siRNA to interfere TXNIP and peroxisome proliferator-androgen receptor-alpha (PPAR-α) expression, western blot to determine protein levels, flow cytometry to analyze apoptosis. Fenofibrate suppressed proliferation and migration of NB cells, remarkably increased intracellular ROS, upregulated TXNIP expression, promoted cell apoptosis. Furthermore, inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. Our results indicated the anti-tumor role of fenofibrate on NB cells by exacerbating oxidative stress and inducing apoptosis was dependent on the upregulation of TXNIP. - Highlights: • We found that fenofibrate suppressed proliferation and migration of NB cells. • We found that fenofibrate remarkably increased intracellular ROS, upregulated TXNIP expression, and promoted cell apoptosis. • Inhibition of TXNIP expression attenuated anti-tumor effects of fenofibrate, while inhibition of PPAR-α had no influences. • Our results indicated the anti-tumor role of fenofibrate on NB cells was dependent on the upregulation of TXNIP.

Structural and functional characteristics of cGMP-dependent methionine oxidation in Arabidopsis thaliana proteins

KAUST Repository

Marondedze, Claudius

2013-01-05

Background: Increasing structural and biochemical evidence suggests that post-translational methionine oxidation of proteins is not just a result of cellular damage but may provide the cell with information on the cellular oxidative status. In addition, oxidation of methionine residues in key regulatory proteins, such as calmodulin, does influence cellular homeostasis. Previous findings also indicate that oxidation of methionine residues in signaling molecules may have a role in stress responses since these specific structural modifications can in turn change biological activities of proteins. Findings. Here we use tandem mass spectrometry-based proteomics to show that treatment of Arabidopsis thaliana cells with a non-oxidative signaling molecule, the cell-permeant second messenger analogue, 8-bromo-3,5-cyclic guanosine monophosphate (8-Br-cGMP), results in a time-dependent increase in the content of oxidised methionine residues. Interestingly, the group of proteins affected by cGMP-dependent methionine oxidation is functionally enriched for stress response proteins. Furthermore, we also noted distinct signatures in the frequency of amino acids flanking oxidised and un-oxidised methionine residues on both the C- and N-terminus. Conclusions: Given both a structural and functional bias in methionine oxidation events in response to a signaling molecule, we propose that these are indicative of a specific role of such post-translational modifications in the direct or indirect regulation of cellular responses. The mechanisms that determine the specificity of the modifications remain to be elucidated. 2013 Marondedze et al.; licensee BioMed Central Ltd.

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

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Sibmooh, Nathawut; Fucharoen, Suthat

2017-01-01

Abstract Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The βE-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794–813. PMID:27650096

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

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Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

2017-05-10

Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

Study on the serum oxidative stress status in silicosis patients | He ...

African Journals Online (AJOL)

To determine whether oxidative-stress damage play an important role in the mechanism of silicosis, the oxidative stress parameters were investigated in silicosis patients and controls group. 128 silicosis patients and 130 healthy controls were included. The serum superoxide dismutase (SOD) activity and the levels of ...

Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

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Ding-I Yang

2011-10-01

Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

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

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Ramkumar Rajendran

2011-01-01

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

Oxidative Stress State Is Associated with Left Ventricular Mechanics Changes, Measured by Speckle Tracking in Essential Hypertensive Patients

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Luis Antonio Moreno-Ruíz

2015-01-01

Full Text Available The oxidative stress state is characterized by an increase in oxygen reactive species that overwhelms the antioxidant defense; we do not know if these pathological changes are correlated with alterations in left ventricular mechanics. The aim was correlating the oxidative stress state with the left ventricular global longitudinal strain (GLS and the left ventricular end diastolic pressure (LVEDP. Twenty-five patients with essential hypertension and 25 controls paired by age and gender were studied. All of the participants were subjected to echocardiography and biochemical determination of oxidative stress markers. The hypertensive patients, compared with control subjects, had significantly (p<0.05 higher levels of oxidized proteins (5.03±1.05 versus 4.06±0.63 nmol/mg, lower levels of extracellular superoxide dismutase (EC-SOD activity (0.045±0.02 versus 0.082±0.02 U/mg, higher LVEDP (16.2±4.5 versus 11.3±1.6 mm Hg, and lower GLS (−12% versus −16%. Both groups had preserved ejection fraction and the results showed a positive correlation of oxidized proteins with GLS (r=0.386, p=0.006 and LVEDP (r=0.389, p=0.005; we also found a negative correlation of EC-SOD activity with GLS (r=-0.404, p=0.004 and LVEDP (r=-0.347, p=0.014.

The involvement of oxidative stress in the mechanisms of damaging cadmium action in bone tissue: A study in a rat model of moderate and relatively high human exposure

International Nuclear Information System (INIS)

Brzoska, Malgorzata M.; Rogalska, Joanna; Kupraszewicz, Elzbieta

2011-01-01

It was investigated whether cadmium (Cd) may induce oxidative stress in the bone tissue in vivo and in this way contribute to skeleton damage. Total antioxidative status (TAS), antioxidative enzymes (glutathione peroxidase, superoxide dismutase, catalase), total oxidative status (TOS), hydrogen peroxide (H 2 O 2 ), lipid peroxides (LPO), total thiol groups (TSH) and protein carbonyl groups (PC) as well as Cd in the bone tissue at the distal femoral epiphysis and femoral diaphysis of the male rats that received drinking water containing 0, 5, or 50 mg Cd/l for 6 months were measured. Cd, depending on the level of exposure and bone location, decreased the bone antioxidative capacity and enhanced its oxidative status resulting in oxidative stress and oxidative protein and/or lipid modification. The treatment with 5 and 50 mg Cd/l decreased TAS and activities of antioxidative enzymes as well as increased TOS and concentrations of H 2 O 2 and PC at the distal femur. Moreover, at the higher exposure, the concentration of LPO increased and that of TSH decreased. The Cd-induced changes in the oxidative/antioxidative balance of the femoral diaphysis, abundant in cortical bone, were less advanced than at the distal femur, where trabecular bone predominates. The results provide evidence that, even moderate, exposure to Cd induces oxidative stress and oxidative modifications in the bone tissue. Numerous correlations noted between the indices of oxidative/antioxidative bone status, and Cd accumulation in the bone tissue as well as indices of bone turnover and bone mineral status, recently reported by us (Toxicology 2007, 237, 89-103) in these rats, allow for the hypothesis that oxidative stress is involved in the mechanisms of damaging Cd action in the skeleton. The paper is the first report from an in vivo study indicating that Cd may affect bone tissue through disorders in its oxidative/antioxidative balance resulting in oxidative stress.

Melatonin ameliorates myocardial ischemia reperfusion injury through SIRT3-dependent regulation of oxidative stress and apoptosis.

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Zhai, Mengen; Li, Buying; Duan, Weixun; Jing, Lin; Zhang, Bin; Zhang, Meng; Yu, Liming; Liu, Zhenhua; Yu, Bo; Ren, Kai; Gao, Erhe; Yang, Yang; Liang, Hongliang; Jin, Zhenxiao; Yu, Shiqiang

2017-09-01

Sirtuins are a family of highly evolutionarily conserved nicotinamide adenine nucleotide-dependent histone deacetylases. Sirtuin-3 (SIRT3) is a member of the sirtuin family that is localized primarily to the mitochondria and protects against oxidative stress-related diseases, including myocardial ischemia/reperfusion (MI/R) injury. Melatonin has a favorable effect in ameliorating MI/R injury. We hypothesized that melatonin protects against MI/R injury by activating the SIRT3 signaling pathway. In this study, mice were pretreated with or without a selective SIRT3 inhibitor and then subjected to MI/R operation. Melatonin was administered intraperitoneally (20 mg/kg) 10 minutes before reperfusion. Melatonin treatment improved postischemic cardiac contractile function, decreased infarct size, diminished lactate dehydrogenase release, reduced the apoptotic index, and ameliorated oxidative damage. Notably, MI/R induced a significant decrease in myocardial SIRT3 expression and activity, whereas the melatonin treatment upregulated SIRT3 expression and activity, and thus decreased the acetylation of superoxide dismutase 2 (SOD2). In addition, melatonin increased Bcl-2 expression and decreased Bax, Caspase-3, and cleaved Caspase-3 levels in response to MI/R. However, the cardioprotective effects of melatonin were largely abolished by the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl)pyridine (3-TYP), suggesting that SIRT3 plays an essential role in mediating the cardioprotective effects of melatonin. In vitro studies confirmed that melatonin also protected H9c2 cells against simulated ischemia/reperfusion injury (SIR) by attenuating oxidative stress and apoptosis, while SIRT3-targeted siRNA diminished these effects. Taken together, our results demonstrate for the first time that melatonin treatment ameliorates MI/R injury by reducing oxidative stress and apoptosis via activating the SIRT3 signaling pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons

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

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

2013-09-01

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

Implantation of Neural Probes in the Brain Elicits Oxidative Stress

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Evon S. Ereifej

2018-02-01

Full Text Available Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp, and Stearoyl-Coenzyme A desaturase 1 (Scd1 were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1 relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage

Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Mazière, Cécile, E-mail: maziere.cecile@chu-amiens.fr [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France); Salle, Valéry [Internal Medicine, North Hospital University, Place Victor Pauchet, Amiens 80000 (France); INSERM U1088 (EA 4292), SFR CAP-Santé (FED 4231), University of Picardie – Jules Verne (France); Gomila, Cathy; Mazière, Jean-Claude [Biochemistry Laboratory, South Hospital University, René Laennec Avenue, Amiens 80000 (France)

2013-10-18

Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

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

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Tönnies, Eric; Trushina, Eugenia

2017-01-01

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

COPD and stroke: are systemic inflammation and oxidative stress the missing links?

Science.gov (United States)

Austin, Victoria; Crack, Peter J; Bozinovski, Steven; Miller, Alyson A; Vlahos, Ross

2016-07-01

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress. © 2016 The Author(s).

13 reasons why the brain is susceptible to oxidative stress

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James Nathan Cobley

2018-05-01

Full Text Available The human brain consumes 20% of the total basal oxygen (O2 budget to support ATP intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, such that, even transient ischemia is neurodegenerative. While the essentiality of O2 to brain function is clear, how oxidative stress causes neurodegeneration is ambiguous. Ambiguity exists because many of the reasons why the brain is susceptible to oxidative stress remain obscure. Many are erroneously understood as the deleterious result of adventitious O2 derived free radical and non-radical species generation. To understand how many reasons underpin oxidative stress, one must first re-cast free radical and non-radical species in a positive light because their deliberate generation enables the brain to achieve critical functions (e.g. synaptic plasticity through redox signalling (i.e. positive functionality. Using free radicals and non-radical derivatives to signal sensitises the brain to oxidative stress when redox signalling goes awry (i.e. negative functionality. To advance mechanistic understanding, we rationalise 13 reasons why the brain is susceptible to oxidative stress. Key reasons include inter alia unsaturated lipid enrichment, mitochondria, calcium, glutamate, modest antioxidant defence, redox active transition metals and neurotransmitter auto-oxidation. We review RNA oxidation as an underappreciated cause of oxidative stress. The complex interplay between each reason dictates neuronal susceptibility to oxidative stress in a dynamic context and neural identity dependent manner. Our discourse sets the stage for investigators to interrogate the biochemical basis of oxidative stress in the brain in health and disease.

A factorial randomized controlled trial to evaluate the effect of micronutrients supplementation and regular aerobic exercise on maternal endothelium-dependent vasodilatation and oxidative stress of the newborn

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Girón Sandra

2011-02-01

Full Text Available Abstract Background Many studies have suggested a relationship between metabolic abnormalities and impaired fetal growth with the development of non-transmissible chronic diseases in the adulthood. Moreover, it has been proposed that maternal factors such as endothelial function and oxidative stress are key mechanisms of both fetal metabolic alterations and subsequent development of non-transmissible chronic diseases. The objective of this project is to evaluate the effect of micronutrient supplementation and regular aerobic exercise on endothelium-dependent vasodilation maternal and stress oxidative of the newborn. Methods and design 320 pregnant women attending to usual prenatal care in Cali, Colombia will be included in a factorial randomized controlled trial. Women will be assigned to the following intervention groups: 1. Control group: usual prenatal care (PC and placebo (maltodextrine. 2. Exercise group: PC, placebo and aerobic physical exercise. 3. Micronutrients group: PC and a micronutrients capsule consisting of zinc (30 mg, selenium (70 μg, vitamin A (400 μg, alphatocopherol (30 mg, vitamin C (200 mg, and niacin (100 mg. 4. Combined interventions Group: PC, supplementation of micronutrients, and aerobic physical exercise. Anthropometric measures will be taken at the start and at the end of the interventions. Discussion Since in previous studies has been showed that the maternal endothelial function and oxidative stress are related to oxidative stress of the newborn, this study proposes that complementation with micronutrients during pregnancy and/or regular physical exercise can be an early and innovative alternative to strengthen the prevention of chronic diseases in the population. Trial registration NCT00872365.

Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury

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Ren, Luqing [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Tao, Jianjian; Chen, Huaicheng; Bian, Yang; Yang, Xi [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Chen, Gaozhi; Zhang, Xin; Liang, Guang [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Wencan, E-mail: wuwencan118@163.com [The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Song, Zongming, E-mail: szmeyes@126.com [The Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang (China); Wang, Yi, E-mail: yi.wang1122@wmu.edu.cn [Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2017-02-15

Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury. We confirmed these findings using MD2 knockout mice. Furthermore, we utilized human retinal pigment epithelial cells (ARPE-19 cells) to show that oxidative stress-induced cell death as well as inflammatory response are mediated through MD2. Inhibition of MD2 through a chemical inhibitor or knockdown prevented oxidative stress-induced cell death and expression of inflammatory cytokines. Oxidative stress was found to activate TLR4 in a MD2-dependent manner via increasing the expression of high mobility group box 1. In summary, our study shows that oxidative stress in retinal I/R injury can activate TLR4 signaling via MD2, resulting in induction of inflammatory genes and retinal damage. MD2 may represent an attractive therapeutic target for retinal I/R injury. - Highlights: • MD2 inhibition reduced retinal damage after I/R induction in mice. • TBHP induced TLR4/MD2 binding via increasing HMGB-1 expression. • TLR4/MD2 initiated inflammatory response via activation of MAPKs and NF-κB. • MD2 could be the therapeutic target for the treatment of retinal I/R.

Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury

International Nuclear Information System (INIS)

Ren, Luqing; Tao, Jianjian; Chen, Huaicheng; Bian, Yang; Yang, Xi; Chen, Gaozhi; Zhang, Xin; Liang, Guang; Wu, Wencan; Song, Zongming; Wang, Yi

2017-01-01

Retinal ischemia-reperfusion (I/R) injury is a common pathological process in many eye disorders. Oxidative stress and inflammation play a role in retinal I/R injury. Recent studies show that toll-like receptor 4 (TLR4) is involved in initiating sterile inflammatory response in retinal I/R. However, the molecular mechanism by which TLR4 is activated is not known. In this study, we show that retinal I/R injury involves a co-receptor of TLR4, myeloid differentiation 2 (MD2). Inhibition of MD2 prevented cell death and preserved retinal function following retinal I/R injury. We confirmed these findings using MD2 knockout mice. Furthermore, we utilized human retinal pigment epithelial cells (ARPE-19 cells) to show that oxidative stress-induced cell death as well as inflammatory response are mediated through MD2. Inhibition of MD2 through a chemical inhibitor or knockdown prevented oxidative stress-induced cell death and expression of inflammatory cytokines. Oxidative stress was found to activate TLR4 in a MD2-dependent manner via increasing the expression of high mobility group box 1. In summary, our study shows that oxidative stress in retinal I/R injury can activate TLR4 signaling via MD2, resulting in induction of inflammatory genes and retinal damage. MD2 may represent an attractive therapeutic target for retinal I/R injury. - Highlights: • MD2 inhibition reduced retinal damage after I/R induction in mice. • TBHP induced TLR4/MD2 binding via increasing HMGB-1 expression. • TLR4/MD2 initiated inflammatory response via activation of MAPKs and NF-κB. • MD2 could be the therapeutic target for the treatment of retinal I/R.

Chitosan oligosaccharides attenuates oxidative-stress related retinal degeneration in rats.

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I-Mo Fang

Full Text Available This study investigated the therapeutic potential and mechanisms of chitosan oligosaccharides (COS for oxidative stress-induced retinal diseases. Retinal oxidative damage was induced in Sprague-Dawley rats by intravitreal injection of paraquat (PQ. Low-dose (5 mg/kg or high-dose (10 mg/kg COS or PBS was intragastrically given for 14 days after PQ injection. Electroretinograms were performed to determine the functionality of the retinas. The surviving neurons in the retinal ganglion cell layer and retinal apoptosis were determined by counting Neu N-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS was determined by lucigenin- and luminol-enhanced chemiluminescence. Retinal oxidative damages were assessed by staining with nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG. Immunohistochemical studies were used to demonstrate the expression of nuclear factor-kappa B (NF-κB p65 in retinas. An in vitro study using RGC-5 cells was performed to verify the results. We demonstrated COS significantly enhanced the recovery of retinal function, preserved inner retinal thickness, and decreased retinal neurons loss in a dose-dependent manner. COS administration demonstrated anti-oxidative effects by reducing luminol- and lucigenin-dependent chemiluminenscense levels and activating superoxide dismutase and catalase, leading to decreased retinal apoptosis. COS markedly reduced retinal NF-κB p65. An in vitro study demonstrated COS increased IκB expression, attenuated the increase of p65 and thus decreased NF-κB/DNA binding activity in PQ-stimulated RGC-5 cells. In conclusion, COS attenuates oxidative stress-induced retinal damages, probably by decreasing free radicals, maintaining the activities of anti-oxidative enzymes, and inhibiting the activation of NF-κB.

Tocotrienol rich tocomin attenuates oxidative stress and improves endothelium-dependent relaxation in aortae from rats fed a high-fat western diet

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Saher F Ali

2016-10-01

Full Text Available We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat or control rat chow (SD, 6% fat for 12 weeks. Tocomin (40 mg/kg/day sc or its vehicle (peanut oil was administered for the last 4 weeks of the feeding regime. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the vascular generation of superoxide measured using L-012 chemiluminescence. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin and phosphorylated Akt and an increase in caveolin-Tocotrienol rich tocomin, which prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS, soluble guanylate cyclase (sGC and calcium activated potassium (KCa channels we demonstrated that tocomin increased NO mediated relaxation, without affecting the contribution of endothelium-dependent hyperpolarization type relaxation to the endothelium-dependent relaxation. The beneficial actions of tocomin in this diet-induced model of obesity suggests that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity.

Acute Exercise and Oxidative Stress: CrossFit™ vs. Treadmill Bout

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Kliszczewicz Brian

2015-09-01

Full Text Available CrossFit™, a popular high-intensity training modality, has been the subject of scrutiny, with concerns of elevated risk of injury and health. Despite these concerns empirical evidence regarding physiologic stresses including acute oxidative stress is lacking. Therefore, the purpose of this investigation was to examine the acute redox response to a CrossFit™ bout. Furthermore, these findings were compared to a high-intensity treadmill bout as a point of reference. Ten males 26.4 ± 2.7 yrs having three or more months of CrossFit™ experience participated in the present study. Blood plasma was collected at four time points: Pre-exercise (PRE, immediately-post-exercise (IPE, 1 hr-post (1-HP and 2 hr-post (2-HP, to examine oxidative damage and antioxidant capacity. Regarding plasma oxidative damage, CrossFit™ and Treadmill elicited a time-dependent increase of lipid peroxides 1-HP (CrossFit™=+143%,Treadmill=+115% and 2-HP (CrossFit™=+256%,Treadmill+167%. Protein Carbonyls were increased IPE in CF only (+5%, while a time-dependent decrease occurred 1-HP (CrossFit™=−16%,Treadmill=−8% and 2-HP (CF=−16%,TM=−1% compared to IPE. Regarding antioxidant capacity, Ferric Reducing Antioxidant Power also demonstrated a time-dependent increase within CrossFit™ and Treadmill: IPE (CrossFit™=+25%,Treadmill=+17%, 1-HP (CrossFit™=+26%,Treadmill=+4.8%, 2-HP (CrossFit™=+20%,Treadmill=+12%. Total Enzymatic Antioxidant Capacity showed a time-dependent decrease in IPE (CrossFit™= −10%,Treadmill=−12%, 1-HP (CrossFit™= −12%,Treadmill=−6%, 2-HP (CrossFit™= −7%,Treadmill=−11%. No trial-dependent differences were observed in any biomarker of oxidative stress. The CrossFit™ bout elicited an acute blood oxidative stress response comparable to a traditional bout of high-intensity treadmill running. Results also confirm that exercise intensity and the time course of exercise recovery influence oxidative responses.

Acute Exercise and Oxidative Stress: CrossFit™ vs. Treadmill Bout

Science.gov (United States)

Kliszczewicz, Brian; Quindry, C. John; Blessing, L. Daniel; Oliver, D. Gretchen; Esco, R. Michael; Taylor, J. Kyle

2015-01-01

CrossFit™, a popular high-intensity training modality, has been the subject of scrutiny, with concerns of elevated risk of injury and health. Despite these concerns empirical evidence regarding physiologic stresses including acute oxidative stress is lacking. Therefore, the purpose of this investigation was to examine the acute redox response to a CrossFit™ bout. Furthermore, these findings were compared to a high-intensity treadmill bout as a point of reference. Ten males 26.4 ± 2.7 yrs having three or more months of CrossFit™ experience participated in the present study. Blood plasma was collected at four time points: Pre-exercise (PRE), immediately-post-exercise (IPE), 1 hr-post (1-HP) and 2 hr-post (2-HP), to examine oxidative damage and antioxidant capacity. Regarding plasma oxidative damage, CrossFit™ and Treadmill elicited a time-dependent increase of lipid peroxides 1-HP (CrossFit™=+143%, Treadmill=+115%) and 2-HP (CrossFit™=+256%, Treadmill+167%). Protein Carbonyls were increased IPE in CF only (+5%), while a time-dependent decrease occurred 1-HP (CrossFit™=−16%, Treadmill=−8%) and 2-HP (CF=−16%, TM=−1%) compared to IPE. Regarding antioxidant capacity, Ferric Reducing Antioxidant Power also demonstrated a time-dependent increase within CrossFit™ and Treadmill: IPE (CrossFit™=+25%, Treadmill=+17%), 1-HP (CrossFit™=+26%, Treadmill=+4.8%), 2-HP (CrossFit™=+20%, Treadmill=+12%). Total Enzymatic Antioxidant Capacity showed a time-dependent decrease in IPE (CrossFit™=−10%, Treadmill=−12%), 1-HP (CrossFit™=−12%, Treadmill=−6%), 2-HP (CrossFit™=−7%, Treadmill=−11%). No trial-dependent differences were observed in any biomarker of oxidative stress. The CrossFit™ bout elicited an acute blood oxidative stress response comparable to a traditional bout of high-intensity treadmill running. Results also confirm that exercise intensity and the time course of exercise recovery influence oxidative responses. PMID:26557192

Oxidative stress and histopathological changes induced by ...

African Journals Online (AJOL)

These authors contributed equally to this work. Abstract: ... Oxidative stress has been proposed as a pos- sible mechanism involved .... to the Natural Health Institute of Health Guidelines for. Animal Care and ..... Journal of American College of.

Overexpression of catalase in mice reduces age-related oxidative stress and maintains sperm production.

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Selvaratnam, Johanna; Robaire, Bernard

2016-11-01

Advanced paternal age is associated with increased complications in pregnancy and genetic diseases in offspring. Oxidative stress is a major contributor to the damage accumulated in sperm during aging. Complex networks of antioxidants regulate reactive oxygen species (ROS) in the testis. While mounting evident shows that redox dysfunction compromises the quality of developing male germ cells, the mechanisms by which aging causes this remain unclear. Furthermore, therapies to successfully alleviate aging-associated loss in germ cell quality are limited. The antioxidant catalase (CAT) has been used in aging-associated pathologies to alleviate oxidative stress. We used mice overexpressing CAT (MCAT) to determine whether CAT overexpression alleviates the redox dysfunction observed with aging. We found that MCAT mice did not exhibit the age-dependent loss of spermatozoa, nor did they show aging associated loss in testicular germ and Sertoli cells seen in wild type (WT). Low overall ROS and reduced peroxynitrite levels were detected in spermatocytes from aged MCAT mice, following exposure to the pro-oxidant tert-butyl hydroperoxide. Germ cells from young MCATs showed elevated levels of DNA-damage repair markers, γ-H2AX and 53BP1, but this response was lost with aging. Finally, we found oxidative stress induced 8-oxodG lesions to increase in sperm with aging; these lesions were significantly reduced in aged MCAT and these mice showed no decrease in the age-dependent number of pups per litter. Thus we conclude that aged MCAT mice generate sperm at the same rate as young mice; these sperm are protected from oxidative stress associated damage. Copyright © 2016 Elsevier Inc. All rights reserved.

Helicobacter Catalase Devoid of Catalytic Activity Protects the Bacterium against Oxidative Stress*♦

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Benoit, Stéphane L.; Maier, Robert J.

2016-01-01

Catalase, a conserved and abundant enzyme found in all domains of life, dissipates the oxidant hydrogen peroxide (H2O2). The gastric pathogen Helicobacter pylori undergoes host-mediated oxidant stress exposure, and its catalase contains oxidizable methionine (Met) residues. We hypothesized catalase may play a large stress-combating role independent of its classical catalytic one, namely quenching harmful oxidants through its recyclable Met residues, resulting in oxidant protection to the bacterium. Two Helicobacter mutant strains (katAH56A and katAY339A) containing catalase without enzyme activity but that retain all Met residues were created. These strains were much more resistant to oxidants than a catalase-deletion mutant strain. The quenching ability of the altered versions was shown, whereby oxidant-stressed (HOCl-exposed) Helicobacter retained viability even upon extracellular addition of the inactive versions of catalase, in contrast to cells receiving HOCl alone. The importance of the methionine-mediated quenching to the pathogen residing in the oxidant-rich gastric mucus was studied. In contrast to a catalase-null strain, both site-change mutants proficiently colonized the murine gastric mucosa, suggesting that the amino acid composition-dependent oxidant-quenching role of catalase is more important than the well described H2O2-dissipating catalytic role. Over 100 years after the discovery of catalase, these findings reveal a new non-enzymatic protective mechanism of action for the ubiquitous enzyme. PMID:27605666

Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

Science.gov (United States)

Carini, Francesco; Mazzola, Margherita; Rappa, Francesca; Jurjus, Abdo; Geagea, Alice Gerges; Al Kattar, Sahar; Bou-Assi, Tarek; Jurjus, Rosalyn; Damiani, Provvidenza; Leone, Angelo; Tomasello, Giovanni

2017-09-01

One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The Role of Oxidative Stress and Antioxidants in Liver Diseases

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Sha Li

2015-11-01

Full Text Available A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

Oxidative stress and Parkinson’s Disease

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Javier eBlesa

2015-07-01

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

Genotoxicity and oxidative stress of microwave radiation role of ascorbic acid

International Nuclear Information System (INIS)

Desouky, O.S.; Abdel Karim, M.A.; Deiaa El Deen, D.A.; Nayal, N.A.

2005-01-01

Radiofrequency fields and especially microwaves are very important part of electromagnetic spectrum that can produce generations of reactive oxygen species, and thus can affect DNA and cause chromosomal aberrations. So this effect can be diminished by the supplement of an antioxidant such as ascorbic acid. In this study, the proposed protective role of ascorbic acid was tested against the EMF induced chromosomal aberrations and lipid peroxidation. The present study proved that EMF had a clastogenic effect on the bone marrow cells of mice, either with the exposure to EMF; 950 MHz or frequency EMF; 2450 MHz. This effect was evidenced by structural and numerical chromosomal aberrations. The study also proved that EMF had an effect on oxidative stress, evidenced by increase in the level of lipid peroxide, in a dose dependent manner. So, the mechanism of EMF induced chromosomal aberrations can be explained by this oxidative stress induced by EMF exposure. The present study showed that ascorbic acid had a protective effect against both EMF induced chromosomal aberrations and oxidative stress, when it is applied concomitantly with EMF exposure either at frequency of 950 MHz or 2450 MHz. this is evident by decreases in the level of lipid peroxide and decrease in chromosomal aberrations

Insights into the mechanisms underlying mercury-induced oxidative stress in gills of wild fish (Liza aurata) combining "1H NMR metabolomics and conventional biochemical assays

International Nuclear Information System (INIS)

Cappello, Tiziana; Brandão, Fátima; Guilherme, Sofia; Santos, Maria Ana; Maisano, Maria; Mauceri, Angela; Canário, João; Pacheco, Mário; Pereira, Patrícia

2016-01-01

Oxidative stress has been described as a key pathway to initiate mercury (Hg) toxicity in fish. However, the mechanisms underlying Hg-induced oxidative stress in fish still need to be clarified. To this aim, environmental metabolomics in combination with a battery of conventional oxidative stress biomarkers were applied to the gills of golden grey mullet (Liza aurata) collected from Largo do Laranjo (LAR), a confined Hg contaminated area, and São Jacinto (SJ), selected as reference site (Aveiro Lagoon, Portugal). Higher accumulation of inorganic Hg and methylmercury was found in gills of fish from LAR relative to SJ. Nuclear magnetic resonance (NMR)-based metabolomics revealed changes in metabolites related to antioxidant protection, namely depletion of reduced glutathione (GSH) and its constituent amino acids, glutamate and glycine. The interference of Hg with the antioxidant protection of gills was corroborated through oxidative stress endpoints, namely the depletion of glutathione peroxidase and superoxide dismutase activities at LAR. The increase of total glutathione content (reduced glutathione + oxidized glutathione) at LAR, in parallel with GSH depletion aforementioned, indicates the occurrence of massive GSH oxidation under Hg stress, and an inability to carry out its regeneration (glutathione reductase activity was unaltered) or de novo synthesis. Nevertheless, the results suggest the occurrence of alternative mechanisms for preventing lipid peroxidative damage, which may be associated with the enhancement of membrane stabilization/repair processes resulting from depletion in the precursors of phosphatidylcholine (phosphocholine and glycerophosphocholine), as highlighted by NMR spectroscopy. However, the observed decrease in taurine may be attributable to alterations in the structure of cell membranes or interference in osmoregulatory processes. Overall, the novel concurrent use of metabolomics and conventional oxidative stress endpoints demonstrated to

Proteomic Characterization of Armillaria mellea Reveals Oxidative Stress Response Mechanisms and Altered Secondary Metabolism Profiles

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Cassandra Collins

2017-09-01

Full Text Available Armillaria mellea is a major plant pathogen. Yet, the strategies the organism uses to infect susceptible species, degrade lignocellulose and other plant material and protect itself against plant defences and its own glycodegradative arsenal are largely unknown. Here, we use a combination of gel and MS-based proteomics to profile A. mellea under conditions of oxidative stress and changes in growth matrix. 2-DE and LC-MS/MS were used to investigate the response of A. mellea to H2O2 and menadione/FeCl3 exposure, respectively. Several proteins were detected with altered abundance in response to H2O2, but not menadione/FeCl3 (i.e., valosin-containing protein, indicating distinct responses to these different forms of oxidative stress. One protein, cobalamin-independent methionine synthase, demonstrated a common response in both conditions, which may be a marker for a more general stress response mechanism. Further changes to the A. mellea proteome were investigated using MS-based proteomics, which identified changes to putative secondary metabolism (SM enzymes upon growth in agar compared to liquid cultures. Metabolomic analyses revealed distinct profiles, highlighting the effect of growth matrix on SM production. This establishes robust methods by which to utilize comparative proteomics to characterize this important phytopathogen.

Channel length dependence of negative-bias-illumination-stress in amorphous-indium-gallium-zinc-oxide thin-film transistors

Energy Technology Data Exchange (ETDEWEB)

Um, Jae Gwang; Mativenga, Mallory; Jang, Jin, E-mail: jjang@khu.ac.kr [Advanced Display Research Center, Department of Information Display, Kyung Hee University, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Migliorato, Piero [Advanced Display Research Center, Department of Information Display, Kyung Hee University, Dongdaemun-gu, Seoul 130-701 (Korea, Republic of); Electrical Engineering Division, Department of Engineering, Cambridge University, Cambridge CB3 0FA (United Kingdom)

2015-06-21

We have investigated the dependence of Negative-Bias-illumination-Stress (NBIS) upon channel length, in amorphous-indium-gallium-zinc-oxide (a-IGZO) thin-film transistors (TFTs). The negative shift of the transfer characteristic associated with NBIS decreases for increasing channel length and is practically suppressed in devices with L = 100-μm. The effect is consistent with creation of donor defects, mainly in the channel regions adjacent to source and drain contacts. Excellent agreement with experiment has been obtained by an analytical treatment, approximating the distribution of donors in the active layer by a double exponential with characteristic length L{sub D} ∼ L{sub n} ∼ 10-μm, the latter being the electron diffusion length. The model also shows that a device with a non-uniform doping distribution along the active layer is in all equivalent, at low drain voltages, to a device with the same doping averaged over the active layer length. These results highlight a new aspect of the NBIS mechanism, that is, the dependence of the effect upon the relative magnitude of photogenerated holes and electrons, which is controlled by the device potential/band profile. They may also provide the basis for device design solutions to minimize NBIS.

Low Stress Mechanical Properties of Plasma-Treated Cotton Fabric Subjected to Zinc Oxide-Anti-Microbial Treatment

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Chi-Wai Kan

2013-01-01

Full Text Available Cotton fabrics are highly popular because of their excellent properties such as regeneration, bio-degradation, softness, affinity to skin and hygroscopic properties. When in contact with the human body, cotton fabrics offer an ideal environment for microbial growth due to their ability to retain oxygen, moisture and warmth, as well as nutrients from spillages and body sweat. Therefore, an anti-microbial coating formulation (Microfresh and Microban together with zinc oxide as catalyst was developed for cotton fabrics to improve treatment effectiveness. In addition, plasma technology was employed in the study which roughened the surface of the materials, improving the loading of zinc oxides on the surface. In this study, the low stress mechanical properties of plasma pre-treated and/or anti-microbial-treated cotton fabric were studied. The overall results show that the specimens had improved bending properties when zinc oxides were added in the anti-microbial coating recipe. Also, without plasma pre-treatment, anti-microbial-treatment of cotton fabric had a positive effect only on tensile resilience, shear stress at 0.5° and compressional energy, while plasma-treated specimens had better overall tensile properties even after anti-microbial treatment.

Mechanisms of Response to Salt Stress in Oleander (Nerium oleander L.

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Dinesh Kumar

2016-11-01

Full Text Available Elucidating the mechanisms of abiotic stress tolerance in different species will help to develop more resistant plant varieties, contributing to improve agricultural production in a climate change scenario. Basic responses to salt stress, dependent on osmolyte accumulation and activation of antioxidant systems, have been studied in Nerium oleander, a xerophytic species widely used as ornamental. Salt strongly inhibited growth, but the plants survived one-month treatments with quite high NaCl concentrations, up to 800 mM, indicating the the species is relatively resistant to salt stress, in addition to drought. Levels of proline, glycine betaine and soluble sugars increased only slightly in the presence of salt; however, soluble sugar absolute contents were much higher than those of the other osmolytes, suggesting a functional role of these compounds in osmotic adjustment, and the presence of constitutive mechanisms of response to salt stress. High salinity generated oxidative stress in the plants, as shown by the increase of malondialdehyde levels. Antioxidant systems, enzymatic and non-enzymatic, are generally activated in response to salt stress; in oleander, they do not seem to include total phenolics or flavonoids, antioxidant compounds which did not accumulate significantly in salt-trated plants

The Role of Oxidative Stress in Aging and Dementia

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Joana Teixeira

2014-12-01

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

Rat Aquaporin-5 Is pH-Gated Induced by Phosphorylation and Is Implicated in Oxidative Stress

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Claudia Rodrigues

2016-12-01

Full Text Available Aquaporin-5 (AQP5 is a membrane water channel widely distributed in human tissues that was found up-regulated in different tumors and considered implicated in carcinogenesis in different organs and systems. Despite its wide distribution pattern and physiological importance, AQP5 short-term regulation was not reported and mechanisms underlying its involvement in cancer are not well defined. In this work, we expressed rat AQP5 in yeast and investigated mechanisms of gating, as well as AQP5’s ability to facilitate H2O2 plasma membrane diffusion. We found that AQP5 can be gated by extracellular pH in a phosphorylation-dependent manner, with higher activity at physiological pH 7.4. Moreover, similar to other mammalian AQPs, AQP5 is able to increase extracellular H2O2 influx and to affect oxidative cell response with dual effects: whereas in acute oxidative stress conditions AQP5 induces an initial higher sensitivity, in chronic stress AQP5 expressing cells show improved cell survival and resistance. Our findings support the involvement of AQP5 in oxidative stress and suggest AQP5 modulation by phosphorylation as a novel tool for therapeutics.

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

Science.gov (United States)

Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

2017-12-15

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical

Time-dependent effect of p-Aminophenol (PAP) toxicity in renal slices and development of oxidative stress

International Nuclear Information System (INIS)

Harmon, R. Christopher; Terneus, Marcus V.; Kiningham, Kinsley K.; Valentovic, Monica

2005-01-01

p-Aminophenol (PAP), a metabolite of acetaminophen, is nephrotoxic. This study investigated PAP-mediated changes as a function of time that occur prior to loss of membrane integrity. Experiments further evaluated the development of oxidative stress by PAP. Renal slices from male Fischer 344 (F344) rats (N = 4-6) were exposed to 0.1, 0.25, and 0.5 mM PAP for 15-120 min under oxygen and constant shaking at 37 o C. Pyruvate-stimulated gluconeogenesis, adenine nucleotide levels, and total glutathione (GSH) levels were diminished in a concentration- and time-dependent manner prior to detection of a rise in lactate dehydrogenase (LDH) leakage. Glutathione disulfide (GSSG) levels were increased by PAP suggesting the induction of oxidative stress. Western blot analysis confirmed a rise in 4-hydroxynonenal (4-HNE)-adducted proteins in tissues exposed to 0.1 and 0.25 mM PAP for 90 min. The appearance of 4-HNE-adducted proteins at the 0.1 mM concentration of PAP occurred prior to development of increased LDH leakage. Pretreatment with 1 mM glutathione (GSH) for 30 min only partially reduced PAP toxicity as LDH values were less severely depleted relative to tissues not pretreated with GSH. In contrast, pretreatment for 15 min with 2 mM ascorbic acid completely protected against PAP toxicity. Further studies showed that ascorbic acid pretreatment prevented PAP-mediated depletion of GSH. In summary, PAP rapidly depletes GSH and adenine nucleotides and inhibits gluconeogenesis prior to a rise in LDH leakage. PAP induces oxidative stress as indicated by an increase in GSSG and 4-HNE-adducted proteins. Ascorbic acid pretreatment prevents PAP toxicity by maintaining GSH status

Oxidative Stress Associated with Neuronal Apoptosis in Experimental Models of Epilepsy

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Marisela Méndez-Armenta

2014-01-01

Full Text Available Epilepsy is considered one of the most common neurological disorders worldwide. Oxidative stress produced by free radicals may play a role in the initiation and progression of epilepsy; the changes in the mitochondrial and the oxidative stress state can lead mechanism associated with neuronal death pathway. Bioenergetics state failure and impaired mitochondrial function include excessive free radical production with impaired synthesis of antioxidants. This review summarizes evidence that suggest what is the role of oxidative stress on induction of apoptosis in experimental models of epilepsy.

Oxidative stress markers imbalance in late-life depression.

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Diniz, Breno S; Mendes-Silva, Ana Paula; Silva, Lucelia Barroso; Bertola, Laiss; Vieira, Monica Costa; Ferreira, Jessica Diniz; Nicolau, Mariana; Bristot, Giovana; da Rosa, Eduarda Dias; Teixeira, Antonio L; Kapczinski, Flavio

2018-03-20

Oxidative stress has been implicated in the pathophysiology of mood disorders in young adults. However, there is few data to support its role in the elderly. The primary aim of this study was to evaluate whether subjects with late-life depression (LLD) presented with changes in oxidative stress response in comparison with the non-depressed control group. We then explored how oxidative stress markers associated with specific features of LLD, in particular cognitive performance and age of onset of major depressive disorder in these individuals. We included a convenience sample of 124 individuals, 77 with LLD and 47 non-depressed subjects (Controls). We measure the plasma levels of 6 oxidative stress markers: thiobarbituric acid reactive substances (TBARS), protein carbonil content (PCC), free 8-isoprostane, glutathione peroxidase (GPx) activity, glutathione reductase (GR) activity, and glutathione S-transferase (GST) activity. We found that participants with LLD had significantly higher free 8-isoprostane levels (p = 0.003) and lower glutathione peroxidase activity (p = 0.006) compared to controls. Free 8-isoprostane levels were also significantly correlated with worse scores in the initiation/perseverance (r = -0.24, p = 0.01), conceptualization (r = -0.22, p = 0.02) sub-scores, and the total scores (r = -0.21, p = 0.04) on the DRS. Our study provides robust evidence of the imbalance between oxidative stress damage, in particular lipid peroxidation, and anti-oxidative defenses as a mechanism related to LLD, and cognitive impairment in this population. Interventions aiming to reduce oxidative stress damage can have a potential neuroprotective effect for LLD subjects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

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Stier, Antoine; Massemin, Sylvie; Criscuolo, François

2014-12-01

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

Is There Still Any Role for Oxidative Stress in Mitochondrial DNA-Dependent Aging?

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Gábor Zsurka

2018-03-01

Full Text Available Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive oxygen species (ROS to mitochondria-related aging because it is probably caused by the nucleotide selectivity of mitochondrial DNA polymerase γ (POLG. In contrast to point mutations, the age-dependent accumulation of mitochondrial DNA deletions is, in light of recent experimental data, still explainable by the segregation of mutant molecules generated by the direct mutagenic effects of ROS (in particular, of HO· radicals formed from H2O2 by a Fenton reaction. The source of ROS remains controversial, because the mitochondrial contribution to tissue ROS production is probably lower than previously thought. Importantly, in the discussion about the potential role of oxidative stress in mitochondria-dependent aging, ROS generated by inflammation-linked processes and the distribution of free iron also require careful consideration.

Protective mechanism of agmatine pretreatment on RGC-5 cells injured by oxidative stress

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Y. Iizuka

2010-04-01

Full Text Available Agmatine has neuroprotective effects on retinal ganglion cells (RGCs as well as cortical and spinal neurons. It protects RGCs from oxidative stress even when it is not present at the time of injury. As agmatine has high affinity for various cellular receptors, we assessed protective mechanisms of agmatine using transformed RGCs (RGC-5 cell line. Differentiated RGC-5 cells were pretreated with 100 μM agmatine and consecutively exposed to 1.0 mM hydrogen peroxide (H2O2. Cell viability was determined by measuring lactate dehydrogenase (LDH, and the effects of selective alpha 2-adrenergic receptor antagonist yohimbine (0-500 nM and N-methyl-D-aspartic acid (NMDA receptor agonist NMDA (0-100 µM were evaluated. Agmatine’s protective effect was compared to a selective NMDA receptor antagonist MK-801. After a 16-h exposure to H2O2, the LDH assay showed cell loss greater than 50%, which was reduced to about 30% when agmatine was pretreated before injury. Yohimbine almost completely inhibited agmatine’s protective effect, but NMDA did not. In addition, MK-801 (0-100 µM did not significantly attenuate the H2O2-induced cytotoxicity. Our results suggest that neuroprotective effects of agmatine on RGCs under oxidative stress may be mainly attributed to the alpha 2-adrenergic receptor signaling pathway.

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

International Nuclear Information System (INIS)

Mohammad, Mohammad K.; Avila, Diana; Zhang, Jingwen; Barve, Shirish; Arteel, Gavin; McClain, Craig; Joshi-Barve, Swati

2012-01-01

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. -- Highlights: ► Human primary hepatocytes and cultured cell lines are used. ► Multiple cell death signaling pathways are activated by acrolein. ► Novel finding of

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

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

2012-11-15

Acrolein is a common environmental, food and water pollutant and a major component of cigarette smoke. Also, it is produced endogenously via lipid peroxidation and cellular metabolism of certain amino acids and drugs. Acrolein is cytotoxic to many cell types including hepatocytes; however the mechanisms are not fully understood. We examined the molecular mechanisms underlying acrolein hepatotoxicity in primary human hepatocytes and hepatoma cells. Acrolein, at pathophysiological concentrations, caused a dose-dependent loss of viability of hepatocytes. The death was apoptotic at moderate and necrotic at high concentrations of acrolein. Acrolein exposure rapidly and dramatically decreased intracellular glutathione and overall antioxidant capacity, and activated the stress-signaling MAP-kinases JNK, p42/44 and p38. Our data demonstrate for the first time in human hepatocytes, that acrolein triggered endoplasmic reticulum (ER) stress and activated eIF2α, ATF-3 and -4, and Gadd153/CHOP, resulting in cell death. Notably, the protective/adaptive component of ER stress was not activated, and acrolein failed to up-regulate the protective ER-chaperones, GRP78 and GRP94. Additionally, exposure to acrolein disrupted mitochondrial integrity/function, and led to the release of pro-apoptotic proteins and ATP depletion. Acrolein-induced cell death was attenuated by N-acetyl cysteine, phenyl-butyric acid, and caspase and JNK inhibitors. Our data demonstrate that exposure to acrolein induces a variety of stress responses in hepatocytes, including GSH depletion, oxidative stress, mitochondrial dysfunction and ER stress (without ER-protective responses) which together contribute to acrolein toxicity. Our study defines basic mechanisms underlying liver injury caused by reactive aldehyde pollutants such as acrolein. -- Highlights: ► Human primary hepatocytes and cultured cell lines are used. ► Multiple cell death signaling pathways are activated by acrolein. ► Novel finding of

Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

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Tonon Jair

2013-01-01

Full Text Available Abstract Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD. Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20 and 40 mg/mL (E40 papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

The flavoprotein Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells

International Nuclear Information System (INIS)

Nishimura, Akira; Kawahara, Nobuhiro; Takagi, Hiroshi

2013-01-01

Highlights: ► NO is produced from L-arginine in response to elevated temperature in yeast. ► Tah18 was first identified as the yeast protein involved in NO synthesis. ► Tah18-dependent NO synthesis confers tolerance to high-temperature on yeast cells. -- Abstract: Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. In the unicellular eukaryote yeast, NO may be involved in stress response pathways, but its role is poorly understood due to the lack of mammalian NO synthase (NOS) orthologues. Previously, we have proposed the oxidative stress-induced L-arginine synthesis and its physiological role under stress conditions in yeast Saccharomyces cerevisiae. Here, our experimental results indicated that increased conversion of L-proline into L-arginine led to NO production in response to elevated temperature. We also showed that the flavoprotein Tah18, which was previously reported to transfer electrons to the Fe–S cluster protein Dre2, was involved in NO synthesis in yeast. Gene knockdown analysis demonstrated that Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells. As it appears that such a unique cell protection mechanism is specific to yeasts and fungi, it represents a promising target for antifungal activity.

The Trypanosoma cruzi vitamin C dependent peroxidase confers protection against oxidative stress but is not a determinant of virulence.

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Martin C Taylor

2015-04-01

Full Text Available The neglected parasitic infection Chagas disease is rapidly becoming a globalised public health issue due to migration. There are only two anti-parasitic drugs available to treat this disease, benznidazole and nifurtimox. Thus it is important to identify and validate new drug targets in Trypanosoma cruzi, the causative agent. T. cruzi expresses an ER-localised ascorbate-dependent peroxidase (TcAPx. This parasite-specific enzyme has attracted interest from the perspective of targeted chemotherapy.To assess the importance of TcAPx in protecting T. cruzi from oxidative stress and to determine if it is essential for virulence, we generated null mutants by targeted gene disruption. Loss of activity was associated with increased sensitivity to exogenous hydrogen peroxide, but had no effect on susceptibility to the front-line Chagas disease drug benznidazole. This suggests that increased oxidative stress in the ER does not play a significant role in its mechanism of action. Homozygous knockouts could proceed through the entire life-cycle in vitro, although they exhibited a significant decrease in their ability to infect mammalian cells. To investigate virulence, we exploited a highly sensitive bioluminescence imaging system which allows parasites to be monitored in real-time in the chronic stage of murine infections. This showed that depletion of enzyme activity had no effect on T. cruzi replication, dissemination or tissue tropism in vivo.TcAPx is not essential for parasite viability within the mammalian host, does not have a significant role in establishment or maintenance of chronic infections, and should therefore not be considered a priority for drug design.

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

International Nuclear Information System (INIS)

Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

2013-01-01

This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P 450 inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

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Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

2013-10-28

This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

Evolution of thermal stress and failure probability during reduction and re-oxidation of solid oxide fuel cell

Science.gov (United States)

Wang, Yu; Jiang, Wenchun; Luo, Yun; Zhang, Yucai; Tu, Shan-Tung

2017-12-01

The reduction and re-oxidation of anode have significant effects on the integrity of the solid oxide fuel cell (SOFC) sealed by the glass-ceramic (GC). The mechanical failure is mainly controlled by the stress distribution. Therefore, a three dimensional model of SOFC is established to investigate the stress evolution during the reduction and re-oxidation by finite element method (FEM) in this paper, and the failure probability is calculated using the Weibull method. The results demonstrate that the reduction of anode can decrease the thermal stresses and reduce the failure probability due to the volumetric contraction and porosity increasing. The re-oxidation can result in a remarkable increase of the thermal stresses, and the failure probabilities of anode, cathode, electrolyte and GC all increase to 1, which is mainly due to the large linear strain rather than the porosity decreasing. The cathode and electrolyte fail as soon as the linear strains are about 0.03% and 0.07%. Therefore, the re-oxidation should be controlled to ensure the integrity, and a lower re-oxidation temperature can decrease the stress and failure probability.

Oxidative Stress Responses in the Human Fungal Pathogen, Candida albicans

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da Silva Dantas, Alessandra; Day, Alison; Ikeh, Mélanie; Kos, Iaroslava; Achan, Beatrice; Quinn, Janet

2015-01-01

Candida albicans is a major fungal pathogen of humans, causing approximately 400,000 life-threatening systemic infections world-wide each year in severely immunocompromised patients. An important fungicidal mechanism employed by innate immune cells involves the generation of toxic reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. Consequently, there is much interest in the strategies employed by C. albicans to evade the oxidative killing by macrophages and neutrophils. Our understanding of how C. albicans senses and responds to ROS has significantly increased in recent years. Key findings include the observations that hydrogen peroxide triggers the filamentation of this polymorphic fungus and that a superoxide dismutase enzyme with a novel mode of action is expressed at the cell surface of C. albicans. Furthermore, recent studies have indicated that combinations of the chemical stresses generated by phagocytes can actively prevent C. albicans oxidative stress responses through a mechanism termed the stress pathway interference. In this review, we present an up-date of our current understanding of the role and regulation of oxidative stress responses in this important human fungal pathogen. PMID:25723552

Insights into the mechanisms underlying mercury-induced oxidative stress in gills of wild fish (Liza aurata) combining {sup 1}H NMR metabolomics and conventional biochemical assays

Energy Technology Data Exchange (ETDEWEB)

Cappello, Tiziana, E-mail: tcappello@unime.it [Department of Biological and Environmental Sciences, University of Messina, 98166 Messina (Italy); Brandão, Fátima, E-mail: fatimabrandao@ua.pt [Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro (Portugal); Guilherme, Sofia; Santos, Maria Ana [Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro (Portugal); Maisano, Maria; Mauceri, Angela [Department of Biological and Environmental Sciences, University of Messina, 98166 Messina (Italy); Canário, João [Centro de Química Estrutural, Instítuto Superíor Técnico, Universidade de Lisboa, 1049-001 Lisbon (Portugal); Pacheco, Mário; Pereira, Patrícia [Department of Biology and CESAM, University of Aveiro, 3810-193 Aveiro (Portugal)

2016-04-01

Oxidative stress has been described as a key pathway to initiate mercury (Hg) toxicity in fish. However, the mechanisms underlying Hg-induced oxidative stress in fish still need to be clarified. To this aim, environmental metabolomics in combination with a battery of conventional oxidative stress biomarkers were applied to the gills of golden grey mullet (Liza aurata) collected from Largo do Laranjo (LAR), a confined Hg contaminated area, and São Jacinto (SJ), selected as reference site (Aveiro Lagoon, Portugal). Higher accumulation of inorganic Hg and methylmercury was found in gills of fish from LAR relative to SJ. Nuclear magnetic resonance (NMR)-based metabolomics revealed changes in metabolites related to antioxidant protection, namely depletion of reduced glutathione (GSH) and its constituent amino acids, glutamate and glycine. The interference of Hg with the antioxidant protection of gills was corroborated through oxidative stress endpoints, namely the depletion of glutathione peroxidase and superoxide dismutase activities at LAR. The increase of total glutathione content (reduced glutathione + oxidized glutathione) at LAR, in parallel with GSH depletion aforementioned, indicates the occurrence of massive GSH oxidation under Hg stress, and an inability to carry out its regeneration (glutathione reductase activity was unaltered) or de novo synthesis. Nevertheless, the results suggest the occurrence of alternative mechanisms for preventing lipid peroxidative damage, which may be associated with the enhancement of membrane stabilization/repair processes resulting from depletion in the precursors of phosphatidylcholine (phosphocholine and glycerophosphocholine), as highlighted by NMR spectroscopy. However, the observed decrease in taurine may be attributable to alterations in the structure of cell membranes or interference in osmoregulatory processes. Overall, the novel concurrent use of metabolomics and conventional oxidative stress endpoints demonstrated to

The naked mole-rat response to oxidative stress: just deal with it.

Science.gov (United States)

Lewis, Kaitlyn N; Andziak, Blazej; Yang, Ting; Buffenstein, Rochelle

2013-10-20

The oxidative stress theory of aging has been the most widely accepted theory of aging providing insights into why we age and die for over 50 years, despite mounting evidence from a multitude of species indicating that there is no direct relationship between reactive oxygen species (ROS) and longevity. Here we explore how different species, including the longest lived rodent, the naked mole-rat, have defied the most predominant aging theory. In the case of extremely long-lived naked mole-rat, levels of ROS production are found to be similar to mice, antioxidant defenses unexceptional, and even under constitutive conditions, naked mole-rats combine a pro-oxidant intracellular milieu with high, steady state levels of oxidative damage. Clearly, naked mole-rats can tolerate this level of oxidative stress and must have mechanisms in place to prevent its translation into potentially lethal diseases. In addition to the naked mole-rat, other species from across the phylogenetic spectrum and even certain mouse strains do not support this theory. Moreover, overexpressing or knocking down antioxidant levels alters levels of oxidative damage and even cancer incidence, but does not modulate lifespan. Perhaps, it is not oxidative stress that modulates healthspan and longevity, but other cytoprotective mechanisms that allow animals to deal with high levels of oxidative damage and stress, and nevertheless live long, relatively healthy lifespans. Studying these mechanisms in uniquely long-lived species, like the naked mole-rat, may help us tease out the key contributors to aging and longevity.

A thioredoxin-dependent peroxiredoxin Q from Corynebacterium glutamicum plays an important role in defense against oxidative stress.

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Tao Su

Full Text Available Peroxiredoxin Q (PrxQ that belonged to the cysteine-based peroxidases has long been identified in numerous bacteria, but the information on the physiological and biochemical functions of PrxQ remain largely lacking in Corynebacterium glutamicum. To better systematically understand PrxQ, we reported that PrxQ from model and important industrial organism C. glutamicum, encoded by the gene ncgl2403 annotated as a putative PrxQ, played important roles in adverse stress resistance. The lack of C. glutamicum prxQ gene resulted in enhanced cell sensitivity, increased ROS accumulation, and elevated protein carbonylation levels under adverse stress conditions. Accordingly, PrxQ-mediated resistance to adverse stresses mainly relied on the degradation of ROS. The physiological roles of PrxQ in resistance to adverse stresses were corroborated by its induced expression under adverse stresses, regulated directly by the stress-responsive ECF-sigma factor SigH. Through catalytical kinetic activity, heterodimer formation, and bacterial two-hybrid analysis, we proved that C. glutamicum PrxQ catalytically eliminated peroxides by exclusively receiving electrons from thioredoxin (Trx/thioredoxin reductase (TrxR system and had a broad range of oxidizing substrates, but a better efficiency for peroxynitrite and cumene hydroperoxide (CHP. Site-directed mutagenesis confirmed that the conserved Cys49 and Cys54 are the peroxide oxidation site and the resolving Cys residue, respectively. It was also discovered that C. glutamicum PrxQ mainly existed in monomer whether under its native state or functional state. Based on these results, a catalytic model of PrxQ is being proposed. Moreover, our result that C. glutamicum PrxQ can prevent the damaging effects of adverse stresses by acting as thioredoxin-dependent monomeric peroxidase could be further applied to improve the survival ability and robustness of the important bacterium during fermentation process.

Bioaccumulation and oxidative stress responses measured in the estuarine ragworm (Nereis diversicolor) exposed to dissolved, nano- and bulk-sized silver

International Nuclear Information System (INIS)

Cozzari, Margherita; Elia, Antonia Concetta; Pacini, Nicole; Smith, Brian D.; Boyle, David; Rainbow, Philip S.; Khan, Farhan R.

2015-01-01

The impact of Ag NPs on sediment-dwelling organisms has received relatively little attention, particularly in linking bioaccumulation to oxidative injury. The polychaete Nereis diversicolor was exposed to sediments spiked with dissolved Ag (added as AgNO 3 ), Ag NPs (63 ± 27 nm) and larger bulk Ag particles (202 ± 56 μm), for up to 11 days at sublethal concentrations (nominally 2.5, 5, 10 μg Ag g −1 sediment (dw)). There were concentration- and time-dependent differences in the accumulation of the three Ag forms, but all three forms elicited an oxidative stress response. In the cases of Ag NPs and bulk Ag particles, changes in antioxidant markers (glutathione, SOD, CAT, GPx, SeGPx, GST and GR) occurred without significant Ag accumulation. Differences in biomarker profiles between the three Ag forms suggest that the mechanism of oxidative stress caused by particulate Ag is distinct from that of dissolved Ag. - Highlights: • N. diversicolor exposed to dissolved, nano and bulk Ag via spiked sediments. • Concentration- and time-dependent differences in the accumulation patterns. • All three forms elicited an oxidative stress response. • Antioxidant markers changed without significant accumulation for particulate Ag. • Biomarker profile resulting from particulate Ag exposure different to dissolved Ag. - Exposure to different Ag forms leads to distinct oxidative stress biomarker profiles. Particulate Ag activates the oxidative stress response differently to dissolved Ag

Depletion of the Third Complement Component Ameliorates Age-Dependent Oxidative Stress and Positively Modulates Autophagic Activity in Aged Retinas in a Mouse Model

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Dorota Rogińska

2017-01-01

Full Text Available The aim of the study was to investigate the influence of complement component C3 global depletion on the biological structure and function of the aged retina. In vivo morphology (OCT, electrophysiological function (ERG, and the expression of selected oxidative stress-, apoptosis-, and autophagy-related proteins were assessed in retinas of 12-month-old C3-deficient and WT mice. Moreover, global gene expression in retinas was analyzed by RNA arrays. We found that the absence of active C3 was associated with (1 alleviation of the age-dependent decrease in retinal thickness and gradual deterioration of retinal bioelectrical function, (2 significantly higher levels of antioxidant enzymes (catalase and glutathione reductase and the antiapoptotic survivin and Mcl-1/Bak dimer, (3 lower expression of the cellular oxidative stress marker—4HNE—and decreased activity of proapoptotic caspase-3, (4 ameliorated retinal autophagic activity with localization of ubiquitinated protein conjugates commonly along the retinal pigment epithelium (RPE layer, and (5 significantly increased expression of several gene sets associated with maintenance of the physiological functions of the neural retina. Our findings shed light on mechanisms of age-related retinal alterations by identifying C3 as a potential therapeutic target for retinal aging.

Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.

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Findeisen, Hannes M; Pearson, Kevin J; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; de Cabo, Rafael; Bruemmer, Dennis

2011-04-14

Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.

Sex-dependent effects of high-fat-diet feeding on rat pancreas oxidative stress.

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Gómez-Pérez, Yolanda; Gianotti, Magdalena; Lladó, Isabel; Proenza, Ana M

2011-07-01

The objective of the study was to investigate whether sex differences in oxidative stress-associated insulin resistance previously reported in rats could be attributed to a possible sex dimorphism in pancreas redox status. Fifteen-month-old male and female Wistar rats were fed a control diet or a high-fat diet for 14 weeks. Serum glucose, lipids, and hormone levels were measured. Insulin immunohistochemistry and morphometric analysis of islets were performed. Pancreas triglyceride content, oxidative damage, and antioxidant enzymatic activities were determined. Lipoprotein lipase, hormone-sensitive lipase, and uncoupling protein 2 (UCP2) levels were also measured. Male rats showed a more marked insulin resistance profile than females. In control female rats, pancreas Mn-superoxide dismutase activity and UCP2 levels were higher, and oxidative damage was lower compared with males. High-fat-diet feeding decreased pancreas triglyceride content in female rats and UCP2 levels in male rats. High-fat-diet female rats showed larger islets than both their control and sex counterparts. These results confirm the existence of a sex dimorphism in pancreas oxidative status in both control and high-fat-diet feeding situations, with female rats showing higher protection against oxidative stress, thus maintaining pancreatic function and contributing to a lower risk of insulin resistance.

Stress-dependent crystal structure of lanthanum strontium cobalt ferrite by in situ synchrotron X-ray diffraction

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Geiger, Philipp T.; Khansur, Neamul H.; Riess, Kevin; Martin, Alexander; Hinterstein, Manuel; Webber, Kyle G.

2018-02-01

Lanthanum strontium cobalt ferrite La1-xSrxCo1-yFeyO3-δ (LSCF) is one of the most studied mixed ionic-electronic conductor materials due to electrical and transport properties, which are attractive for intermediate temperature solid oxide fuel cells (SOFCs), oxygen permeation membranes, and catalysis. The integration of such materials, however, depends on the thermal as well as mechanical behavior. LSCF exhibits nonlinear hysteresis during compressive stress-strain measurements, marked by a remanent strain and coercive stress, i.e., ferroelasticity. However, the origin of ferroelastic behavior has not been investigated under high compressive stress. This study, therefore, investigates the microscopic origin of stress-induced mechanical behavior in polycrystalline (La0.6Sr0.4)0.95Co0.2Fe0.8O3-δ using in situ synchrotron x-ray diffraction. The data presented here reveals that the strain response originates from the intrinsic lattice strain as well as the extrinsic domain switching strain without any apparent change in crystallographic symmetry. A comparison of the calculated microscopic strain contribution with that of a macroscopic measurement indicates a significant change in the relative contributions of intrinsic and extrinsic strain depending on the applied stress state, i.e., under maximum stress and after unloading. Direct evidence of the microscopic origin of stress-strain response outlined in this paper may assist in guiding materials design with the improved mechanical reliability of SOFCs.

Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants

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Christophe Loix

2017-10-01

Full Text Available Cadmium (Cd pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule.

Tanshinol Attenuates the Deleterious Effects of Oxidative Stress on Osteoblastic Differentiation via Wnt/FoxO3a Signaling

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Yajun Yang

2013-01-01

Full Text Available There is now increasing evidence which suggests a pivotal role for oxidative stress in the development and progression of osteoporosis. We confirm herein the protective effects of natural antioxidant Tanshinol against oxidative stress in osteoblastic differentiation and the underlying mechanism. Our results show that hydrogen peroxide (H2O2 leads to accumulation of reactive oxygen species (ROS, decrease in cell viability, cell cycle arrest and apoptosis in a caspase-3-dependent manner, and inhibition of osteoblastic differentiation. Tanshinol reverses these deleterious consequence triggered by oxidative stress. Moreover, under the condition of oxidative stress, Tanshinol suppresses the activation of FoxO3a transcription factor and expressions of its target genes Gadd45a and catalase (CAT and simultaneously counteracts the inhibition of Wnt signalling and expressions of target genes Axin2, alkaline phosphatase (ALP, and Osteoprotegerin (OPG. The findings are further consolidated using FoxO3a siRNA interference and overexpression of Tcf4. The results illustrate that Tanshinol attenuates oxidative stress via down-regulation of FoxO3a signaling, and rescues the decrease of osteoblastic differentiation through upregulation of Wnt signal under oxidative stress. The present findings suggest that the beneficial effects of Tanshinol may be adopted as a novel therapeutic approach in recently recognized conditions of niche targeting osteoporosis.

Photobiomodulation Therapy Decreases Oxidative Stress in the Lung Tissue after Formaldehyde Exposure: Role of Oxidant/Antioxidant Enzymes

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Rodrigo Silva Macedo

2016-01-01

Full Text Available Formaldehyde is ubiquitous pollutant that induces oxidative stress in the lung. Several lung diseases have been associated with oxidative stress and their control is necessary. Photobiomodulation therapy (PBMT has been highlighted as a promissory treatment, but its mechanisms need to be better investigated. Our objective was to evaluate the effects of PBMT on the oxidative stress generated by FA exposure. Male Wistar rats were submitted to FA exposure of 1% or vehicle (3 days and treated or not with PBMT (1 and 5 h after each FA exposure. Rats treated only with laser were used as control. Twenty-four hours after the last FA exposure, we analyzed the effects of PBMT on the generation of nitrites and hydrogen peroxide, oxidative burst, glutathione reductase, peroxidase, S-transferase enzyme activities, the gene expression of nitric oxide, cyclooxygenase, superoxide dismutase, the catalase enzyme, and heme oxygenase-1. PBMT reduced the generation of nitrites and hydrogen peroxide and increased oxidative burst in the lung cells. A decreased level of oxidant enzymes was observed which were concomitantly related to an increased level of antioxidants. This study provides new information about the antioxidant mechanisms of PBMT in the lung and might constitute an important tool for lung disease treatment.

Acute Exercise and Oxidative Stress: CrossFit(™) vs. Treadmill Bout.

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Kliszczewicz, Brian; Quindry, C John; Blessing, L Daniel; Oliver, D Gretchen; Esco, R Michael; Taylor, J Kyle

2015-09-29

CrossFit(™), a popular high-intensity training modality, has been the subject of scrutiny, with concerns of elevated risk of injury and health. Despite these concerns empirical evidence regarding physiologic stresses including acute oxidative stress is lacking. Therefore, the purpose of this investigation was to examine the acute redox response to a CrossFit(™) bout. Furthermore, these findings were compared to a high-intensity treadmill bout as a point of reference. Ten males 26.4 ± 2.7 yrs having three or more months of CrossFit(™) experience participated in the present study. Blood plasma was collected at four time points: Pre-exercise (PRE), immediately-post-exercise (IPE), 1 hr-post (1-HP) and 2 hr-post (2-HP), to examine oxidative damage and antioxidant capacity. Regarding plasma oxidative damage, CrossFit(™) and Treadmill elicited a time-dependent increase of lipid peroxides 1-HP (CrossFit(™)=+143%, Treadmill=+115%) and 2-HP (CrossFit(™)=+256%, Treadmill+167%). Protein Carbonyls were increased IPE in CF only (+5%), while a time-dependent decrease occurred 1-HP (CrossFit(™)=-16%, Treadmill=-8%) and 2-HP (CF=-16%, TM=-1%) compared to IPE. Regarding antioxidant capacity, Ferric Reducing Antioxidant Power also demonstrated a time-dependent increase within CrossFit(™) and Treadmill: IPE (CrossFit(™)=+25%, Treadmill=+17%), 1-HP (CrossFit(™)=+26%, Treadmill=+4.8%), 2-HP (CrossFit(™)=+20%, Treadmill=+12%). Total Enzymatic Antioxidant Capacity showed a time-dependent decrease in IPE (CrossFit(™)=-10%, Treadmill=-12%), 1-HP (CrossFit(™)=-12%, Treadmill=-6%), 2-HP (CrossFit(™)=-7%, Treadmill=-11%). No trial-dependent differences were observed in any biomarker of oxidative stress. The CrossFit(™) bout elicited an acute blood oxidative stress response comparable to a traditional bout of high-intensity treadmill running. Results also confirm that exercise intensity and the time course of exercise recovery influence oxidative responses.

Rhesus monkey lens as an in vitro model for studying oxidative stress

International Nuclear Information System (INIS)

Zigler, J.S. Jr.; Lucas, V.A.; Du, X.Y.

1989-01-01

Lenses from young rhesus monkeys were incubated in the presence of H 2 O 2 or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that the mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses

Inhibition of Myeloperoxidase by N-Acetyl Lysyltyrosylcysteine Amide Reduces Oxidative Stress-Mediated Inflammation, Neuronal Damage, and Neural Stem Cell Injury in a Murine Model of Stroke.

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Yu, Guoliang; Liang, Ye; Zheng, Shikan; Zhang, Hao

2018-02-01

Recent studies suggest that myeloperoxidase (MPO)-dependent oxidative stress plays a significant role in brain injury in stroke patients. We previously showed that N -acetyl lysyltyrosylcysteine amide (KYC), a novel MPO inhibitor, significantly decreased infarct size, blood-brain barrier leakage, infiltration of myeloid cells, loss of neurons, and apoptosis in the brains of middle cerebral artery occlusion (MCAO) mice. Inhibition of MPO also noticeably reduced neurologic severity scores of MCAO mice. Thus, our data support the idea that MPO-dependent oxidative stress plays a detrimental role in tissue injury in ischemic stroke. However, the mechanisms of MPO-induced injury in stroke are still largely unknown. Here, we present new evidence showing that KYC treatment greatly reduced inflammation by decreasing the number of proinflammatory M1 microglial cells and N1 neutrophils in the brains of MCAO mice. KYC also markedly reduced the expression of high-mobility group box 1, receptor for advanced glycation end products, and nuclear factor- κ B in the brains of MCAO mice. Both neurons and neural stem cells (NSCs) were oxidatively injured by MPO-dependent oxidative stress in MCAO mice. Inhibiting MPO-dependent oxidative stress with KYC significantly reduced oxidative injury and apoptosis in neurons and NSCs. KYC treatment also protected transplanted exogenous NSCs in the brains of MCAO mice. Thus, our studies suggest that MPO-dependent oxidative stress directly injures brain tissues by oxidizing neurons and NSCs and increasing inflammation during stroke. Inhibition of MPO activity with KYC preserves neuronal function and helps the brain recover from injury after stroke. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

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

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

2016-01-01

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

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

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Namrata eChaudhari

2014-07-01

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

Haptoglobin is required to prevent oxidative stress and muscle atrophy.

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Enrico Bertaggia

Full Text Available BACKGROUND: Oxidative stress (OS plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/- to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD, OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

The role of oxidative stress in nervous system aging.

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Catrina Sims-Robinson

Full Text Available While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1(-/- mice, a mouse model of increased oxidative stress. Sod1(-/- mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1(+/+ mice at 30 months and the Sod1(-/- mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.

The role of oxidative stress in nervous system aging.

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Sims-Robinson, Catrina; Hur, Junguk; Hayes, John M; Dauch, Jacqueline R; Keller, Peter J; Brooks, Susan V; Feldman, Eva L

2013-01-01

While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1(-/-)) mice, a mouse model of increased oxidative stress. Sod1(-/-) mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1(+/+) mice at 30 months and the Sod1(-/-) mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.

Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

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Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

2016-01-01

Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

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Yaling eFeng

2016-05-01

Full Text Available Preeclampsia (PE and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

Piracetam improves mitochondrial dysfunction following oxidative stress

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Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

2005-01-01

Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

Oxidative stress and histopathological changes induced by ...

African Journals Online (AJOL)

Background: Methyl-thiophanate (MT), a fungicide largely used in agriculture throughout the world including Tunisia, protects many vegetables, fruits and field crops against a wide spectrum of fungal diseases. Oxidative stress has been proposed as a possible mechanism involved in MT toxicity on non-target organism.

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

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Wilking, Melissa; Ndiaye, Mary; Mukhtar, Hasan

2013-01-01

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

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

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Bruder-Nascimento, Thiago, E-mail: bruderthiago@usp.br [Departamento de Farmacologia - Instituto de Biociências de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Campos, Dijon Henrique Salome [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil)

2015-03-15

Stress is associated with cardiovascular diseases. This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca{sup 2+} flux was also evaluated. Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca{sup 2+} was decreased in the aorta of stressed rats. Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca{sup 2+}-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

Oxidative stress as a mechanism of diabetes in diabetic BB prone rats: effect of secoisolariciresinol diglucoside (SDG).

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Prasad, K

2000-06-01

Secoisolariciresinol diglucoside (SDG) isolated from flaxseed has antioxidant activity and has been shown to prevent hypercholesterolemic atherosclerosis. An investigation was made of the effects of SDG on the development of diabetes in diabetic prone BioBreeding rats (BBdp rats), a model of human type I diabetes [insulin dependent diabetes mellitus (IDDM)] to determine if this type of diabetes is due to oxidative stress and if SDG can prevent the incidence of diabetes. The rats were divided into three groups: Group I, BioBreeding normal rats (BBn rats) (n = 10); group II, BBdp untreated (n = 11); and group III, BBdp treated with SDG 22 mg/kg body wt, orally) (n = 14). Oxidative stress was determined by measuring lipid peroxidation product malondialdehyde (MDA) an index of level of reactive oxygen species in blood and pancreas; and pancreatic chemiluminescence (Pancreatic-CL), a measure of antioxidant reserve. Incidence of diabetes was 72.7% in untreated and 21.4% in SDG-treated group as determined by glycosuria and hyperglycemia. SDG prevented the development of diabetes by approximately 71%. Development of diabetes was associated with an increase in serum and pancreatic MDA and a decrease in antioxidant reserve. Prevention in development of diabetes by SDG was associated with a decrease in serum and pancreatic-MDA and an increase in antioxidant reserve. These results suggest that IDDM is mediated through oxidative stress and that SDG prevents the development of diabetes.

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

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

2017-06-18

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

[Role of green tea in oxidative stress prevention].

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Metro, D; Muraca, U; Manasseri, L

2006-01-01

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

Effect of Free Radicals & Antioxidants on Oxidative Stress: A Review

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Ashok Shinde

2012-01-01

Full Text Available Recently free radicals have attracted tremendous importance in the field of medicine including dentistry and molecular biology. Free radicals can be either harmful or helpful to the body. When there is an imbalance between formation and removal of free radicals then a condition called as oxidative stress is developed in body. To counteract these free radicals body has protective antioxidant mechanisms which have abilities to lower incidence of various human morbidities and mortalities. Many research groups in the past have tried to study and confirm oxidative stress. Many authors also have studied role of antioxidants in reducing oxidative stress. They have come across with controversial results and furthermore it is not yet fully confirmed whether oxidative stress increases the need for dietary antioxidants. Recently, an association between periodontitis and cardiovascular disease has received considerable attention. Various forms of antioxidants have been introduced as an approach to fight dental diseases and improve general gingival health. The implication of oxidative stress in the etiology of many chronic and degenerative diseases suggests that antioxidant therapy represents a promising avenue for treatment. This study was conducted with the objective of reviewing articles relating to this subject. A Pub Med search of all articles containing key words free radicals, oxidative stress, and antioxidants was done. A review of these articles was undertaken.

Oxidative stress in resuscitation and in ventilation of newborns.

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Gitto, E; Pellegrino, S; D'Arrigo, S; Barberi, I; Reiter, R J

2009-12-01

The lungs of newborns are especially prone to oxidative damage induced by both reactive oxygen and reactive nitrogen species. Yet, these infants are often 1) exposed to high oxygen concentrations, 2) have infections or inflammation, 3) have reduced antioxidant defense, and 4) have high free iron levels which enhance toxic radical generation. Oxidative stress has been postulated to be implicated in several newborn conditions with the phrase "oxygen radical diseases of neonatology" having been coined. There is, however, reason to believe that oxidative stress is increased more when resuscitation is performed with pure oxygen compared with ambient air and that the most effective ventilatory strategy is the avoidance of mechanical ventilation with the use of nasopharyngeal continuous positive airway pressure whenever possible. Multiple ventilation strategies have been attempted to reduce injury and improve outcomes in newborn infants. In this review, the authors summarise the scientific evidence concerning oxidative stress as it relates to resuscitation in the delivery room and to the various modalities of ventilation.

Diabetes and Alzheimer Disease, Two Overlapping Pathologies with the Same Background: Oxidative Stress

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Sergio Rosales-Corral

2015-01-01

Full Text Available There are several oxidative stress-related pathways interconnecting Alzheimer’s disease and type II diabetes, two public health problems worldwide. Coincidences are so compelling that it is attractive to speculate they are the same disorder. However, some pathological mechanisms as observed in diabetes are not necessarily the same mechanisms related to Alzheimer’s or the only ones related to Alzheimer’s pathology. Oxidative stress is inherent to Alzheimer’s and feeds a vicious cycle with other key pathological features, such as inflammation and Ca2+ dysregulation. Alzheimer’s pathology by itself may lead to insulin resistance in brain, insulin resistance being an intervening variable in the neurodegenerative disorder. Hyperglycemia and insulin resistance from diabetes, overlapping with the Alzheimer’s pathology, aggravate the progression of the neurodegenerative processes, indeed. But the same pathophysiological background is behind the consequences, oxidative stress. We emphasize oxidative stress and its detrimental role in some key regulatory enzymes.

Tetrahydrocannabinol Induces Brain Mitochondrial Respiratory Chain Dysfunction and Increases Oxidative Stress: A Potential Mechanism Involved in Cannabis-Related Stroke

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Valérie Wolff

2015-01-01

Full Text Available Cannabis has potential therapeutic use but tetrahydrocannabinol (THC, its main psychoactive component, appears as a risk factor for ischemic stroke in young adults. We therefore evaluate the effects of THC on brain mitochondrial function and oxidative stress, key factors involved in stroke. Maximal oxidative capacities Vmax (complexes I, III, and IV activities, Vsucc (complexes II, III, and IV activities, Vtmpd (complex IV activity, together with mitochondrial coupling (Vmax/V0, were determined in control conditions and after exposure to THC in isolated mitochondria extracted from rat brain, using differential centrifugations. Oxidative stress was also assessed through hydrogen peroxide (H2O2 production, measured with Amplex Red. THC significantly decreased Vmax (−71%; P<0.0001, Vsucc (−65%; P<0.0001, and Vtmpd (−3.5%; P<0.001. Mitochondrial coupling (Vmax/V0 was also significantly decreased after THC exposure (1.8±0.2 versus 6.3±0.7; P<0.001. Furthermore, THC significantly enhanced H2O2 production by cerebral mitochondria (+171%; P<0.05 and mitochondrial free radical leak was increased from 0.01±0.01 to 0.10±0.01% (P<0.001. Thus, THC increases oxidative stress and induces cerebral mitochondrial dysfunction. This mechanism may be involved in young cannabis users who develop ischemic stroke since THC might increase patient’s vulnerability to stroke.

Effect of oxidative stress on homer scaffolding proteins.

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Igor Nepliouev

Full Text Available Homer proteins are a family of multifaceted scaffolding proteins that participate in the organization of signaling complexes at the post-synaptic density and in a variety of tissues including striated muscle. Homer isoforms form multimers via their C-terminal coiled coil domains, which allows for the formation of a polymeric network in combination with other scaffolding proteins. We hypothesized that the ability of Homer isoforms to serve as scaffolds would be influenced by oxidative stress. We have found by standard SDS-PAGE of lysates from adult mouse skeletal muscle exposed to air oxidation that Homer migrates as both a dimer and monomer in the absence of reducing agents and solely as a monomer in the presence of a reducing agent, suggesting that Homer dimers exposed to oxidation could be modified by the presence of an inter-molecular disulfide bond. Analysis of the peptide sequence of Homer 1b revealed the presence of only two cysteine residues located adjacent to the C-terminal coiled-coil domain. HEK 293 cells were transfected with wild-type and cysteine mutant forms of Homer 1b and exposed to oxidative stress by addition of menadione, which resulted in the formation of disulfide bonds except in the double mutant (C246G, C365G. Exposure of myofibers from adult mice to oxidative stress resulted in decreased solubility of endogenous Homer isoforms. This change in solubility was dependent on disulfide bond formation. In vitro binding assays revealed that cross-linking of Homer dimers enhanced the ability of Homer 1b to bind Drebrin, a known interacting partner. Our results show that oxidative stress results in disulfide cross-linking of Homer isoforms and loss of solubility of Homer scaffolds. This suggests that disulfide cross-linking of a Homer polymeric network may contribute to the pathophysiology seen in neurodegenerative diseases and myopathies characterized by oxidative stress.

α,β-Unsaturated aldehyde pollutant acrolein suppresses cardiomyocyte contractile function: Role of TRPV1 and oxidative stress.

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Wu, Zhenbiao; He, Emily Y; Scott, Glenda I; Ren, Jun

2015-01-01

Air pollution is associated with an increased prevalence of heart disease and is known to trigger a proinflammatory response via stimulation of transient receptor potential vanilloid cation channels (TRPV1, also known as the capsaicin receptor). This study was designed to examine the effect of acrolein, an essential α,β-unsaturated aldehyde pollutant, on myocardial contractile function and the underlying mechanism involved with a focus on TRPV1 and oxidative stress. Cardiomyocyte mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), maximal velocity of shortening/relengthening (± dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR90 ), fura-2 fluorescence intensity (FFI) and intracellular Ca(2+) decay. Changes in apoptosis and TRPV1 were evaluated using Western blot analysis. The degree of oxidative stress was assessed using the ratio between reduced and oxidized glutathione. Results obtained revealed that exposure of cardiomyocytes to acrolein acutely compromised contractile and intracellular Ca(2+) properties including depressed PS, ± dL/dt and ΔFFI, as well as prolonged TR90 and intracellular Ca(2+) decay. In addition, acrolein exposure upregulated TRPV1 associated with an increase in both apoptosis and oxidative stress. However, the acrolein-induced cardiomyocyte contractile and intracellular Ca(2+) anomalies, as well as apoptosis (as evidenced by Bcl-2, Bax, FasL, Caspase-3 and -8), were negated by the reactive oxygen species (ROS) scavenger glutathione or the TRPV1 antagonist capsazepine. Collectively these data suggest that the α,β-unsaturated aldehyde pollutant acrolein may play a role in the pathogenesis and sequelae of air pollution-induced heart disease via a TRPV1- and oxidative stress-dependent mechanism. © 2013 Wiley Periodicals, Inc.

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

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Liu, Dexiang; Ke, Zunji; Luo, Jia

2017-09-01

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

Mechanical properties of phosphorene nanoribbons and oxides

International Nuclear Information System (INIS)

Hao, Feng; Chen, Xi

2015-01-01

Mechanical properties of phosphorene nanoribbons and oxides are investigated by using density functional theory. It is found that the ideal strength of nanoribbon decreases in comparison with that of 2D phosphorene. The Young's modulus of armchair nanoribbon has a remarkable size effect because of the edge relaxations. The analysis of the stress-strain relation indicates that, owing to chemisorbed oxygen atoms, the ideal strength and Young's modulus of 2D phosphorene oxide are greatly reduced along the zigzag direction, especially upon high oxidation ratios. In addition, strain and oxidation have significant impacts on phonon dispersion

Mechanical properties of phosphorene nanoribbons and oxides

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Hao, Feng [Department of Earth and Environmental Engineering, Columbia University, New York, New York 10027 (United States); Chen, Xi, E-mail: xichen@columbia.edu [International Center for Applied Mechanics, SV Laboratory, School of Aerospace, Xi' an Jiaotong University, Xi' an 710049 (China); Department of Earth and Environmental Engineering, Columbia University, New York, New York 10027 (United States)

2015-12-21

Mechanical properties of phosphorene nanoribbons and oxides are investigated by using density functional theory. It is found that the ideal strength of nanoribbon decreases in comparison with that of 2D phosphorene. The Young's modulus of armchair nanoribbon has a remarkable size effect because of the edge relaxations. The analysis of the stress-strain relation indicates that, owing to chemisorbed oxygen atoms, the ideal strength and Young's modulus of 2D phosphorene oxide are greatly reduced along the zigzag direction, especially upon high oxidation ratios. In addition, strain and oxidation have significant impacts on phonon dispersion.

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

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Hideki Wanibuchi

2013-10-01

Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

Heat indicators of oxidative stress, inflammation and metal transport show dependence of cadmium pollution history in the liver of female zebrafish.

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Zhu, Qing-Ling; Guo, Sai-Nan; Yuan, Shuang-Shuang; Lv, Zhen-Ming; Zheng, Jia-Lang; Xia, Hu

2017-10-01

Environmental stressors such as high temperature and metal exposure may occur sequentially, simultaneously, previously in aquatic ecosystems. However, information about whether responses to high temperature depend on Cd exposure history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5 (group 2) and 5μg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was subjected to Cd-free water maintained at 26°C and 32°C for 7days respectively. 26 indicators were used to compare differences between 26°C and 32°C in the liver of female zebrafish, including 5 biochemical indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL-6, IL-1β, TNF-α, iNOS and NF-κB), 8 molecular indicators of metal transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1). All biochemical indicators were unchanged in group 1 and changed in group 2 and 3. Contrarily, differences were observed in almost all of molecular indicators of inflammation and metal transport in group 1, about half in group 2, and few in group 3. We also found that all molecular indicators of oxidative stress in group 2 and fewer in group 1 and 3 were significantly affected by heat. Our data indicated that heat indicators of oxidative stress, inflammation and metal transport showed dependence of previous cadmium exposure in the liver of zebrafish, emphasizing metal pollution history should be carefully considered when evaluating heat stress in fish. Copyright © 2017. Published by Elsevier B.V.

Association of Oxidative Stress with Psychiatric Disorders.

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

2016-01-01

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

The flavoprotein Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells

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Nishimura, Akira; Kawahara, Nobuhiro [Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192 (Japan); Takagi, Hiroshi, E-mail: hiro@bs.naist.jp [Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192 (Japan)

2013-01-04

Highlights: Black-Right-Pointing-Pointer NO is produced from L-arginine in response to elevated temperature in yeast. Black-Right-Pointing-Pointer Tah18 was first identified as the yeast protein involved in NO synthesis. Black-Right-Pointing-Pointer Tah18-dependent NO synthesis confers tolerance to high-temperature on yeast cells. -- Abstract: Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. In the unicellular eukaryote yeast, NO may be involved in stress response pathways, but its role is poorly understood due to the lack of mammalian NO synthase (NOS) orthologues. Previously, we have proposed the oxidative stress-induced L-arginine synthesis and its physiological role under stress conditions in yeast Saccharomyces cerevisiae. Here, our experimental results indicated that increased conversion of L-proline into L-arginine led to NO production in response to elevated temperature. We also showed that the flavoprotein Tah18, which was previously reported to transfer electrons to the Fe-S cluster protein Dre2, was involved in NO synthesis in yeast. Gene knockdown analysis demonstrated that Tah18-dependent NO synthesis confers high-temperature stress tolerance on yeast cells. As it appears that such a unique cell protection mechanism is specific to yeasts and fungi, it represents a promising target for antifungal activity.

Physical exercise and oxidative stress in muscular dystrophies: is there a good balance?

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Chico, L; Ricci, G; Cosci O Di Coscio, M; Simoncini, C; Siciliano, G

2017-07-01

The effect of oxidative stress on muscle damage inducted by physical exercise is widely debated. It is generally agreed that endurance and intense exercise can increase oxidative stress and generate changes in antioxidant power inducing muscle damage; however, regular and moderate exercise can be beneficial for the health improving the antioxidant defense mechanisms in the majority of cases. Growing evidences suggest that an increased oxidative/nitrosative stress is involved in the pathogenesis of several muscular dystrophies (MDs). Notably, physical training has been considered useful for patients with these disorders. This review will focus on the involvement of oxidative stress in MDs and on the possible effects of physical activities to decrease oxidative damage and improve motor functions in MDs patients.

NO accumulation alleviates H2 O2 -dependent oxidative damage induced by Ca(NO3 )2 stress in the leaves of pumpkin-grafted cucumber seedlings.

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Li, Lin; Shu, Sheng; Xu, Qing; An, Ya-Hong; Sun, Jin; Guo, Shi-Rong

2017-05-01

Nitric oxide (NO) and hydrogen peroxide (H 2 O 2 ), two important signaling molecules, are stimulated in plants by abiotic stresses. In this study, we investigated the role of NO and its interplay with H 2 O 2 in the response of self-grafted (S-G) and salt-tolerant pumpkin-grafted (Cucurbita maxima × C. moschata) cucumber seedlings to 80 mM Ca(NO 3 ) 2 stress. Endogenous NO and H 2 O 2 production in S-G seedlings increased in a time-dependent manner, reaching maximum levels after 24 h of Ca(NO 3 ) 2 stress. In contrast, a transient increase in NO production, accompanied by H 2 O 2 accumulation, was observed at 2 h in rootstock-grafted plants. N w -Nitro-l-Arg methyl ester hydrochloride (l-NAME), an inhibitor of nitric oxide synthase (NOS), tungstate, an inhibitor of nitrate reductase (NR), and 2-(4-carboxyphenyl)-4,4,5,5-tetramethy-limidazoline-1-oxyl-3-oxide (cPTIO), a scavenger of NO, were found to significantly inhibit NO accumulation induced by salt stress in rootstock-grafted seedlings. H 2 O 2 production was unaffected by these stress conditions. Ca(NO 3 ) 2 stress-induced NO accumulation was blocked by pretreatment with an H 2 O 2 scavenger (dimethylthiourea, DMTU) and an inhibitor of NADPH oxidase (diphenyleneiodonium, DPI). In addition, maximum quantum yield of PSII (Fv/Fm), as well as the activities and transcript levels of antioxidant enzymes, were significantly decreased by salt stress in rootstock grafted seedlings after pretreatment with these above inhibitors; antioxidant enzyme transcript levels and activities were higher in rootstock-grafted seedlings compared with S-G seedlings. These results suggest that rootstock grafting could alleviate the oxidative damage induced by Ca(NO 3 ) 2 stress in cucumber seedlings, an effect that may be attributable to the involvement of NO in H 2 O 2 -dependent antioxidative metabolism. © 2016 Scandinavian Plant Physiology Society.

Oxidative/nitrosative stress and antidepressants: targets for novel antidepressants.

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Lee, Seung-Yup; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un

2013-10-01

The brain is an organ predisposed to oxidative/nitrosative stress. This is especially true in the case of aging as well as several neurodegenerative diseases. Under such circumstances, a decline in the normal antioxidant defense mechanisms leads to an increase in the vulnerability of the brain to the deleterious effects of oxidative damage. Highly reactive oxygen/nitrogen species damage lipids, proteins, and mitochondrial and neuronal genes. Unless antioxidant defenses react appropriately to damage inflicted by radicals, neurons may experience microalteration, microdysfunction, and degeneration. We reviewed how oxidative and nitrosative stresses contribute to the pathogenesis of depressive disorders and reviewed the clinical implications of various antioxidants as future targets for antidepressant treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.

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Gharib, Mohamed; Tao, Huan; Fungwe, Thomas V; Hajri, Tahar

2016-01-01

Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

Acute and sub-lethal exposure to copper oxide nanoparticles causes oxidative stress and teratogenicity in zebrafish embryos.

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Ganesan, Santhanamari; Anaimalai Thirumurthi, Naveenkumar; Raghunath, Azhwar; Vijayakumar, Savitha; Perumal, Ekambaram

2016-04-01

Nano-copper oxides are a versatile inorganic material. As a result of their versatility, the immense applications and usage end up in the environment causing a concern for the lifespan of various beings. The ambiguities surround globally on the toxic effects of copper oxide nanoparticles (CuO-NPs). Hence, the present study endeavored to study the sub-lethal acute exposure effects on the developing zebrafish embryos. The 48 hpf LC50 value was about 64 ppm. Therefore, we have chosen the sub-lethal dose of 40 and 60 ppm for the study. Accumulation of CuO-NPs was evidenced from the SEM-EDS and AAS analyzes. The alterations in the AChE and Na(+)/K(+)-ATPase activities disrupted the development process. An increment in the levels of oxidants with a concomitant decrease in the antioxidant enzymes confirmed the induction of oxidative stress. Oxidative stress triggered apoptosis in the exposed embryos. Developmental anomalies were observed with CuO-NPs exposure in addition to oxidative stress in the developing embryos. Decreased heart rate and hatching delay hindered the normal developmental processes. Our work has offered valuable data on the connection between oxidative stress and teratogenicity leading to lethality caused by CuO-NPs. A further molecular mechanism unraveling the uncharted connection between oxidative stress and teratogenicity will aid in the safe use of CuO-NPs. Copyright © 2015 John Wiley & Sons, Ltd.

Oxidative stress in tumor microenvironment——Its role in angiogenesis

Institute of Scientific and Technical Information of China (English)

Armando ROJAS; Raúl SILVA; Héctor FIGUEROA; Miguel A MORALES

2008-01-01

The tumor angiogenesis process is believed to be dependent on an "angiogenic switch" formed by a cascade of biologic events as a consequence of the "cross-talk" between tumor cells and several components of local microenvironment including endothelial cells, macrophages, mast cells and stromal components. Oxidative stress represents an important stimulus that widely contributes to this angiogenic switch, which is particularly relevant in lungs,where oxidative stress is originated from different sources including the incomplete reduction of oxygen during respiration,exposure to hypoxia/reoxygenation, stimulated resident or chemoattracted immune ceils to lung tissues, as well as by a variety of chemicals compounds. In the present review we highlight the role of oxidative stress in tumor angiogenesis as a key signal linked to other relevant actors in this complex process.

Anti-oxidative effects of Rooibos tea (Aspalathus linearis on immobilization-induced oxidative stress in rat brain.

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In-Sun Hong

Full Text Available Exposure to chronic psychological stress may be related to increased reactive oxygen species (ROS or free radicals, and thus, long-term exposure to high levels of oxidative stress may cause the accumulation of oxidative damage and eventually lead to many neurodegenerative diseases. Compared with other organs, the brain appears especially susceptible to excessive oxidative stress due to its high demand for oxygen. In the case of excessive ROS production, endogenous defense mechanisms against ROS may not be sufficient to suppress ROS-associated oxidative damage. Dietary antioxidants have been shown to protect neurons against a variety of experimental neurodegenerative conditions. In particular, Rooibos tea might be a good source of antioxidants due to its larger proportion of polyphenolic compounds. An optimal animal model for stress should show the features of a stress response and should be able to mimic natural stress progression. However, most animal models of stress, such as cold-restraint, electric foot shock, and burn shock, usually involve physical abuse in addition to the psychological aspects of stress. Animals subjected to chronic restraint or immobilization are widely believed to be a convenient and reliable model to mimic psychological stress. Therefore, in the present study, we propose that immobilization-induced oxidative stress was significantly attenuated by treatment with Rooibos tea. This conclusion is demonstrated by Rooibos tea's ability to (i reverse the increase in stress-related metabolites (5-HIAA and FFA, (ii prevent lipid peroxidation (LPO, (iii restore stress-induced protein degradation (PD, (iv regulate glutathione metabolism (GSH and GSH/GSSG ratio, and (v modulate changes in the activities of antioxidant enzymes (SOD and CAT.

Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

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Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

2018-02-20

The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

Peptidoglycan recognition proteins kill bacteria by inducing oxidative, thiol, and metal stress.

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Des Raj Kashyap

2014-07-01

Full Text Available Mammalian Peptidoglycan Recognition Proteins (PGRPs are a family of evolutionary conserved bactericidal innate immunity proteins, but the mechanism through which they kill bacteria is unclear. We previously proposed that PGRPs are bactericidal due to induction of reactive oxygen species (ROS, a mechanism of killing that was also postulated, and later refuted, for several bactericidal antibiotics. Here, using whole genome expression arrays, qRT-PCR, and biochemical tests we show that in both Escherichia coli and Bacillus subtilis PGRPs induce a transcriptomic signature characteristic of oxidative stress, as well as correlated biochemical changes. However, induction of ROS was required, but not sufficient for PGRP killing. PGRPs also induced depletion of intracellular thiols and increased cytosolic concentrations of zinc and copper, as evidenced by transcriptome changes and supported by direct measurements. Depletion of thiols and elevated concentrations of metals were also required, but by themselves not sufficient, for bacterial killing. Chemical treatment studies demonstrated that efficient bacterial killing can be recapitulated only by the simultaneous addition of agents leading to production of ROS, depletion of thiols, and elevation of intracellular metal concentrations. These results identify a novel mechanism of bacterial killing by innate immunity proteins, which depends on synergistic effect of oxidative, thiol, and metal stress and differs from bacterial killing by antibiotics. These results offer potential targets for developing new antibacterial agents that would kill antibiotic-resistant bacteria.

Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

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Sin Bond Leung

2013-01-01

Full Text Available Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction.

Salidroside Improves Homocysteine-Induced Endothelial Dysfunction by Reducing Oxidative Stress

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Leung, Sin Bond; Zhang, Huina; Lau, Chi Wai; Huang, Yu; Lin, Zhixiu

2013-01-01

Hyperhomocysteinemia is associated with an increased risk for cardiovascular diseases through increased oxidative stress. Salidroside is an active ingredient of the root of Rhodiola rosea with documented antioxidative, antihypoxia and neuroprotective properties. However, the vascular benefits of salidroside against endothelial dysfunction have yet to be explored. The present study, therefore, aimed to investigate the protective effect of salidroside on homocysteine-induced endothelial dysfunction. Functional studies on the rat aortas were performed to delineate the vascular effect of salidroside. DHE imaging was used to evaluate the reactive oxygen species (ROS) level in aortic wall and endothelial cells. Western blotting was performed to assess the protein expression associated with oxidative stress and nitric oxide (NO) bioavailability. Exposure to homocysteine attenuated endothelium-dependent relaxations in rat aortas while salidroside pretreatment rescued it. Salidroside inhibited homocystein-induced elevation in the NOX2 expression and ROS overproduction in both aortas and cultured endothelial cells and increased phosphorylation of eNOS which was diminished by homocysteine. The present study shows that salidroside is effective in preserving the NO bioavailability and thus protects against homocysteine-induced impairment of endothelium-dependent relaxations, largely through inhibiting the NOX2 expression and ROS production. Our results indicate a therapeutic potential of salidroside in the management of oxidative-stress-associated cardiovascular dysfunction. PMID:23589720

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

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

2016-07-01

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

Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial.

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Beckman, Joshua A; Goldfine, Allison B; Leopold, Jane A; Creager, Mark A

2016-12-01

Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus. Copyright © 2016 the American Physiological Society.

Sodium nitroprusside (SNP) alleviates the oxidative stress induced ...

African Journals Online (AJOL)

Yomi

2012-04-03

Apr 3, 2012 ... salinity stress has previously been extensively studied;. *Corresponding author. ... unfortunately, the adaption mechanism to alkalinity in plants is short of ..... of NO in hydrogen peroxide-dependent induction of abiotic stress ...

Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism.

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Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K; Lehtonen, Jukka Y A

2016-04-20

As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Electro-mechanical coupling of semiconductor film grown on stainless steel by oxidation

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Lin, M. C.; Wang, G.; Guo, L. Q.; Qiao, L. J.; Volinsky, Alex A.

2013-09-01

Electro-mechanical coupling phenomenon in oxidation film on stainless steel has been discovered by using current-sensing atomic force microscopy, along with the I-V curves measurements. The oxidation films exhibit either ohmic, n-type, or p-type semiconductor properties, according to the obtained I-V curves. This technique allows characterizing oxidation films with high spatial resolution. Semiconductor properties of oxidation films must be considered as additional stress corrosion cracking mechanisms.

The Role of Oxidative Stress in Nervous System Aging

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Sims-Robinson, Catrina; Hur, Junguk; Hayes, John M.; Dauch, Jacqueline R.; Keller, Peter J.; Brooks, Susan V.; Feldman, Eva L.

2013-01-01

While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1−/−) mice, a mouse model of increased oxidative stress. Sod1−/− mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1+/+ mice at 30 months and the Sod1−/− mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging. PMID:23844146

Prenatal irradiation: nitric oxide and oxidative stress roles in radiation-induced apoptosis of the developing central nervous system

International Nuclear Information System (INIS)

Sanjurjo, Julieta

2001-01-01

. Apoptosis was measured by flow cytometry. Cellular response to radiation injury was clearly dependent on the dose, with a significant increase in apoptosis death from 0,4 Gy on, measured 20 hours post irradiation and increasing in a linear way with total dose. Furthermore, apoptosis of cortical cells was dependant on developmental age. That is, it depends on both the proliferation rate and the differentiation stage, being maximal at day 15 of gestational age and decreasing to day 19. The time-course evolution of apoptosis revealed a significant increase from 4 hours post irradiation for a 2 Gy fixed dose, showing that though it is an early event, it continues to happen with an augmentation of apoptotic cells number to 20 hours post irradiation. Several mechanisms have been proposed for the etiology of neuronal apoptosis. Nitric oxide (NO) production and oxidative stress have been implicated in the neuronal injury seen in different neuro degenerative disorders. It is well-known that the excessive stimulation of glutamate receptors could mediate neuronal death by NO and superoxide anion, whose combination form peroxynitrite, a potent neurotoxic molecule. In spite of that, cortical cultures treatment with nitric oxide synthase (NOS) inhibitors, L-NAME and N-Arginine and with NMDA receptor antagonist MK801 produced a statistically significant increase of radiation-induced apoptosis at every concentration and incubation times tested. Because of this, NMDA receptors blockade could be implicated in NOS activity reduction and thus, in a minor NO production rate. Nitric oxide could be playing a protective role in this system. In some cases NO could potentate Reactive Oxygen Species (ROS) toxicity, but in other circumstances it could have direct or indirect antioxidant actions in biologic systems subjected to oxidative stress due to excessive ROS production, mainly protecting biologic membranes from lipid peroxidation. Besides NO actions, it is evident that radiation

Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells

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Müller Sylke

2009-05-01

Full Text Available Abstract Background Plasmodium falciparum-parasitized red blood cells (RBCs are equipped with protective antioxidant enzymes and heat shock proteins (HSPs. The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Methods Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70–2/70–3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. Results In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of

Co-ordinated stage-dependent enhancement of Plasmodium falciparum antioxidant enzymes and heat shock protein expression in parasites growing in oxidatively stressed or G6PD-deficient red blood cells.

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Akide-Ndunge, Oscar Bate; Tambini, Elisa; Giribaldi, Giuliana; McMillan, Paul J; Müller, Sylke; Arese, Paolo; Turrini, Francesco

2009-05-29

Plasmodium falciparum-parasitized red blood cells (RBCs) are equipped with protective antioxidant enzymes and heat shock proteins (HSPs). The latter are only considered to protect against thermal stress. Important issues are poorly explored: first, it is insufficiently known how both systems are expressed in relation to the parasite developmental stage; secondly, it is unknown whether P. falciparum HSPs are redox-responsive, in view of redox sensitivity of HSP in eukaryotic cells; thirdly, it is poorly known how the antioxidant defense machinery would respond to increased oxidative stress or inhibited antioxidant defense. Those issues are interesting as several antimalarials increase the oxidative stress or block antioxidant defense in the parasitized RBC. In addition, numerous inhibitors of HSPs are currently developed for cancer therapy and might be tested as anti-malarials. Thus, the joint disruption of the parasite antioxidant enzymes/HSP system would interfere with parasite growth and open new perspectives for anti-malaria therapy. Stage-dependent mRNA expression of ten representative P. falciparum antioxidant enzymes and hsp60/70-2/70-3/75/90 was studied by quantitative real-time RT-PCR in parasites growing in normal RBCs, in RBCs oxidatively-stressed by moderate H2O2 generation and in G6PD-deficient RBCs. Protein expression of antioxidant enzymes was assayed by Western blotting. The pentosephosphate-pathway flux was measured in isolated parasites after Sendai-virus lysis of RBC membrane. In parasites growing in normal RBCs, mRNA expression of antioxidant enzymes and HSPs displayed co-ordinated stage-dependent modulation, being low at ring, highest at early trophozoite and again very low at schizont stage. Additional exogenous oxidative stress or growth in antioxidant blunted G6PD-deficient RBCs indicated remarkable flexibility of both systems, manifested by enhanced, co-ordinated mRNA expression of antioxidant enzymes and HSPs. Protein expression of

[Biological consequences of oxidative stress induced by pesticides].

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Grosicka-Maciąg, Emilia

2011-06-17

Pesticides are used to protect plants and numerous plant products. They are also utilized in several industrial branches. These compounds are highly toxic to living organisms. In spite of close supervision in the use of pesticides there is a serious risk that these agents are able to spread into the environment and contaminate water, soil, food, and feedstuffs. Recently, more and more studies have been focused on understanding the toxic mechanisms of pesticide actions. The data indicate that the toxic action of pesticides may include the induction of oxidative stress and accumulation of free radicals in the cell. Long-lasting or acute oxidative stress disturbs cell metabolism and is able to produce permanent changes in the structure of proteins, lipids, and DNA. The proteins that are oxidized may lose or enhance their activity. Moreover, the proteins oxidized are able to form aggregates that inhibit the systems responsible for protein degradation and lead to alterations of proteins in the cell. Once oxidized, lipids have the capacity to damage and depolarize cytoplasmic membranes. Free oxygen radicals are harmful to DNA including damage to single nitric bases, DNA strand breaks and adduct production. Many studies indicate that oxidative stress may accelerate development of numerous diseases including cancer and neurodegenerative ones such as Alzheimer’s and Parkinson’s disease and may also be responsible for infertility.

Chlorobenzene induces oxidative stress in human lung epithelial cells in vitro

International Nuclear Information System (INIS)

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

2010-01-01

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

Effects of silver nanoparticles to soil invertebrates: Oxidative stress biomarkers in Eisenia fetida

International Nuclear Information System (INIS)

Gomes, Susana I.L.; Hansen, Ditte; Scott-Fordsmand, Janeck J.; Amorim, Mónica J.B.

2015-01-01

Silver nanoparticles (Ag-NPs) are among the most produced NPs worldwide having several applications in consumer products. Ag-NPs are known to cause oxidative stress in several organisms and cell lines, however comparatively less information is available regarding their effects on soil living invertebrates. The purpose of this study was to investigate if Ag-NPs cause oxidative stress on soil invertebrates. The model soil species Eisenia fetida was used. Our results showed that total glutathione (TG) is the first mechanism triggered by Ag-NPs, followed by glutathione peroxidase (GPx) and glutathione reductase (GR), however oxidative damage was observed for higher doses and exposure time (increased lipid peroxidation, LPO). AgNO 3 exposure caused impairment in GPx and glutathione-S-transferase (GST), probably as result of the higher bioavailability of Ag in the salt-form. The current results indicate that effects are partly caused by Ag ions released from Ag-NPs, but specific particle effects cannot be excluded. - Highlights: • Oxidative stress of Ag-NPs and AgNO 3 was assessed in Eisenia fetida. • Both Ag forms induced oxidative damage (LPO) via different mechanisms. • Ag-NPs activated total glutathione, followed by GPx and GR. • AgNO 3 impaired GPx and GST. • Overall results indicated effects from Ag ionization and NPs specific effects. - Oxidative stress to Ag in Eisenia fetida occurs via different mechanisms for Ag nanoparticles and AgNO 3

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

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Radha Ananthakrishnan

2013-10-01

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

Endothelial cell oxidative stress and signal transduction

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ROCIO FONCEA

2000-01-01

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

The sex differences in nature of vascular endothelial stress: nitrergic mechanisms

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Sindeev, Sergey; Gekaluyk, Artem; Ulanova, Maria; Agranovich, Ilana; Sharref, Ali Esmat; Semyachkina-Glushkovskaya, Oxana

2016-04-01

Here we studied the role of nitric oxide in cardiovascular regulation in male and female hypertensive rats under normal and stress conditions. We found that the severity of hypertension in females was lower than in males. Hypertensive females demonstrated more favorable pattern of cardiovascular responses to stress. Nitric oxide blockade by NG-nitro-L-arginine methyl ester (L-NAME) increased the mean arterial pressure and decreased the heart rate more effectively in females than in males. During stress, L-NAME modified the stress-induced cardiovascular responses more significantly in female compared with male groups. Our data show that hypertensive females demonstrated the more effective nitric oxide control of cardiovascular activity under normal and especially stress conditions than male groups. This sex differences may be important mechanism underlying greater in females vs. males stress-resistance of cardiovascular system and hypertension formation.

A role for ethanol-induced oxidative stress in controlling lineage commitment of mesenchymal stromal cells through inhibition of wnt/beta-catenin signaling

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The mechanisms by which chronic ethanol intake induces bone loss remain unclear. In females, the skeletal response to ethanol varies depending on physiologic status (viz. cycling, pregnancy, lactation). Ethanol-induced oxidative stress appears to be a key event leading to skeletal toxicity. In the c...

Loss of Trx-2 enhances oxidative stress-dependent phenotypes in Drosophila.

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Tsuda, Manabu; Ootaka, Ryousuke; Ohkura, Chiaki; Kishita, Yoshihito; Seong, Ki-Hyeon; Matsuo, Takashi; Aigaki, Toshiro

2010-08-04

Overexpression of thioredoxin (TRX) confers oxidative stress resistance and extends lifespan in mammals and insects. However, less is known about phenotypes associated with loss of TRX. We investigated loss-of-function phenotypes of Trx-2 in Drosophila, and found that the mutant flies are hyper-susceptible to paraquat, a free radical generator, but not to hydrogen peroxide. They contain a high amount of protein carbonyl, which dramatically increases with age. Trx-2 mutants express high levels of anti-oxidant genes, such as superoxide dismutase, catalase, and glutathione synthetase. This is the first demonstration of biochemical and physiological consequences caused by loss of Trx-2 in Drosophila. Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

2017-01-01

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

Oxidative stress and male reproductive health

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Robert J Aitken

2014-02-01

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

Cytochrome P450s: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress.

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Bhattacharyya, Sudip; Sinha, Krishnendu; Sil, Parames C

2014-01-01

Cytochrome monooxygenases P450 enzymes (CYPs) are terminal oxidases, belonging to the multi-gene family of heme-thiolate enzymes and located in multiple sites of ER, cytosol and mitochondria. CYPs act as catalysts in drugs metabolism. This review highlights the mitochondrial and microsomal CYPs metabolic functions, CYPs mediated ROS generation and its feedback, bioactivation of drugs and related hypersensitivity, metabolic disposition as well as the therapeutic approaches. CYPs mediated drugs bioactivation may trigger oxidative stress and cause pathophysiology. Almost all drugs show some adverse reactions at high doses or accidental overdoses. Drugs lead to hypersensitivity reactions while metabolic predisposition to drug hypersensitivity exaggerates it. Mostly different intermediate bioactive products of CYPs mediated drug metabolism is the principal issue in this respect. On the other hand, CYPs are the main source of ROS. Their generation and feedback are of major concern of this review. Besides drug metabolism, CYPs also contribute significantly to carcinogen metabolism. Ultimately other enzymes in drug metabolism and antioxidant therapy are indispensible. Importance of this field: In a global sense, understanding of exact mechanism can facilitate pharmaceutical industries' challenge of developing drugs without toxicity. Ultimate message: This review would accentuate the recent advances in molecular mechanism of CYPs mediated drug metabolism and complex cross-talks between various restorative novel strategies evolved by CYPs to sustain the redox balance and limit the source of oxidative stress.

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

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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...

Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury

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

2013-01-01

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

Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

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Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

2015-11-01

Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Oxidative stress and regulation of Pink1 in zebrafish (Danio rerio.

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Madhusmita Priyadarshini

Full Text Available Oxidative stress-mediated neuronal dysfunction is characteristic of several neurodegenerative disorders, including Parkinson's disease (PD. The enzyme tyrosine hydroxylase (TH catalyzes the formation of L-DOPA, the rate-limiting step in the biosynthesis of dopamine. A lack of dopamine in the striatum is the most characteristic feature of PD, and the cause of the most dominant symptoms. Loss of function mutations in the PTEN-induced putative kinase (PINK1 gene cause autosomal recessive PD. This study explored the basic mechanisms underlying the involvement of pink1 in oxidative stress-mediated PD pathology using zebrafish as a tool. We generated a transgenic line, Tg(pink1:EGFP, and used it to study the effect of oxidative stress (exposure to H2O2 on pink1 expression. GFP expression was enhanced throughout the brain of zebrafish larvae subjected to oxidative stress. In addition to a widespread increase in pink1 mRNA expression, mild oxidative stress induced a clear decline in tyrosine hydroxylase 2 (th2, but not tyrosine hydroxylase 1 (th1 expression, in the brain of wild-type larvae. The drug L-Glutathione Reduced (LGR has been associated with anti-oxidative and possible neuroprotective properties. Administration of LGR normalized the increased fluorescence intensity indicating pink1 transgene expression and endogenous pink1 mRNA expression in larvae subjected to oxidative stress by H2O2. In the pink1 morpholino oliogonucleotide-injected larvae, the reduction in the expression of th1 and th2 was partially rescued by LGR. The pink1 gene is a sensitive marker of oxidative stress in zebrafish, and LGR effectively normalizes the consequences of mild oxidative stress, suggesting that the neuroprotective effects of pink1 and LGR may be significant and useful in drug development.

Protective effect of Rhus coriaria fruit extracts against hydrogen peroxide-induced oxidative stress in muscle progenitors and zebrafish embryos

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Fadia Najjar

2017-12-01

Full Text Available Background and Purpose Oxidative stress is involved in normal and pathological functioning of skeletal muscle. Protection of myoblasts from oxidative stress may improve muscle contraction and delay aging. Here we studied the effect of R. coriaria sumac fruit extract on human myoblasts and zebrafish embryos in conditions of hydrogen peroxide-induced oxidative stress. Study Design and Methods Crude ethanolic 70% extract (CE and its fractions was obtained from sumac fruits. The composition of sumac ethyl acetate EtOAc fraction was studied by 1H NMR. The viability of human myoblasts treated with CE and the EtOAc fraction was determined by trypan blue exclusion test. Oxidative stress, cell cycle and adhesion were analyzed by flow cytometry and microscopy. Gene expression was analyzed by qPCR. Results The EtOAc fraction (IC50 2.57 µg/mL had the highest antioxidant activity and exhibited the best protective effect against hydrogen peroxide-induced oxidative stress. It also restored cell adhesion. This effect was mediated by superoxide dismutase 2 and catalase. Pre-treatment of zebrafish embryos with low concentrations of the EtOAc fraction protected them from hydrogen peroxide-induced death in vivo. 1H NMR analysis revealed the presence of gallic acid in this fraction. Conclusion Rhus coriaria extracts inhibited or slowed down the progress of skeletal muscle atrophy by decreasing oxidative stress via superoxide dismutase 2 and catalase-dependent mechanisms.

Clinical Relevance of Biomarkers of Oxidative Stress

DEFF Research Database (Denmark)

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

2015-01-01

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

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

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

2017-02-01

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

ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis

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Diane DeZwaan-McCabe

2017-05-01

Full Text Available The unfolded protein response (UPR, induced by endoplasmic reticulum (ER stress, regulates the expression of factors that restore protein folding homeostasis. However, in the liver and kidney, ER stress also leads to lipid accumulation, accompanied at least in the liver by transcriptional suppression of metabolic genes. The mechanisms of this accumulation, including which pathways contribute to the phenotype in each organ, are unclear. We combined gene expression profiling, biochemical assays, and untargeted lipidomics to understand the basis of stress-dependent lipid accumulation, taking advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid accumulation in both organs. These findings provide evidence for both direct and indirect regulation of peripheral metabolism by ER stress.

ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis.

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DeZwaan-McCabe, Diane; Sheldon, Ryan D; Gorecki, Michelle C; Guo, Deng-Fu; Gansemer, Erica R; Kaufman, Randal J; Rahmouni, Kamal; Gillum, Matthew P; Taylor, Eric B; Teesch, Lynn M; Rutkowski, D Thomas

2017-05-30

The unfolded protein response (UPR), induced by endoplasmic reticulum (ER) stress, regulates the expression of factors that restore protein folding homeostasis. However, in the liver and kidney, ER stress also leads to lipid accumulation, accompanied at least in the liver by transcriptional suppression of metabolic genes. The mechanisms of this accumulation, including which pathways contribute to the phenotype in each organ, are unclear. We combined gene expression profiling, biochemical assays, and untargeted lipidomics to understand the basis of stress-dependent lipid accumulation, taking advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid accumulation in both organs. These findings provide evidence for both direct and indirect regulation of peripheral metabolism by ER stress. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Soft-food diet induces oxidative stress in the rat brain.

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Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il

2012-02-02

Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of post-stress hydrogen annealing on MOS oxides after 60Co irradiation or Fowler-Nordheim injection

International Nuclear Information System (INIS)

Saks, N.S.; Stahlbush, R.E.; Mrstik, B.J.; Rendell, R.W.; Klein, R.B.

1993-01-01

Changes in interface trap density D it have been determined in MOSFETs as a function of time during hydrogen annealing at 295K. Large increases in D it are observed during H 2 annealing in MOSFETs previously stressed by either 60 Co irradiation or Fowler-Nordheim electron injection. The annealing behavior is very similar for both types of stress, which suggests that the D it creation mechanism involves similar chemistry for hydrogen reactions. Studies of the time dependence of D it creation as a function of MOSFET gate length show that the time dependence is limited primarily by lateral diffusion of molecular hydrogen (H 2 ) through the gate oxide. An activation energy of 0.57 eV, which is consistent with H 2 diffusion, is obtained from the temperature dependence

Oxidative stress and the effect of parasites on a carotenoid-based ornament.

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Mougeot, F; Martínez-Padilla, J; Blount, J D; Pérez-Rodríguez, L; Webster, L M I; Piertney, S B

2010-02-01

Oxidative stress, the physiological condition whereby the production of reactive oxygen and nitrogen species overwhelms the capacity of antioxidant defences, causes damage to key bio-molecules. It has been implicated in many diseases, and is proposed as a reliable currency in the trade-off between individual health and ornamentation. Whether oxidative stress mediates the expression of carotenoid-based signals, which are among the commonest signals of many birds, fish and reptiles, remains controversial. In the present study, we explored interactions between parasites, oxidative stress and the carotenoid-based ornamentation of red grouse Lagopus lagopus scoticus. We tested whether removing nematode parasites influenced both oxidative balance (levels of oxidative damage and circulating antioxidant defences) and carotenoid-based ornamentation. At the treatment group level, parasite purging enhanced the size and colouration of ornaments but did not significantly affect circulating carotenoids, antioxidant defences or oxidative damage. However, relative changes in these traits among individuals indicated that males with a greater number of parasites prior to treatment (parasite purging) showed a greater increase in the levels of circulating carotenoids and antioxidants, and a greater decrease in oxidative damage, than those with initially fewer parasites. At the individual level, a greater increase in carotenoid pigmentation was associated with a greater reduction in oxidative damage. Therefore, an individual's ability to express a carotenoid-based ornament appeared to be linked to its current oxidative balance and susceptibility to oxidative stress. Our experimental results suggest that oxidative stress can mediate the impact of parasites on carotenoid-based signals, and we discuss possible mechanisms linking carotenoid-based ornaments to oxidative stress.

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

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Lačković Maja

2013-01-01

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

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

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

2013-01-15

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

Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training.