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      The effect of voluntary wheel running on the antioxidant status is dependent on sociability conditions

      research-article
      a , * , a , b , a , a , c , a , a , a , a , a
      Pharmacology, Biochemistry, and Behavior
      Elsevier Inc.
      DTNB, 5,5-dithiobis-2-nitrobenzoic acid, ANOVA, Analysis of variance, CHP, Cumene peroxide, Ethylenediamine tetraacetic acid (EDTA), Ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (also known as Egtazic acid, EGTA) , GPx, Glutathione peroxidase, GR, Glutathione reductase, MDA, Malondialdehyde, NADH, Nicotinamide adenine dinucleotide, NADPH, Nicotinamide adenine dinucleotide phosphate, NPSH, Nonprotein thiols groups, GSSG, Oxidized glutathione, PA, Physical activity, GSH, Reduced glutathione, SIS, Social isolation stress, TST, Tail suspension test, TBARS, Thiobarbituric acid reactive species, Glutathione, Mitochondria, Oxidative stress, Physical activity, Voluntary wheel running, Social isolation stress

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          Abstract

          Voluntary wheel running is widely used as a physical activity (PA) model in rodents, but most studies investigate the beneficial effects of this intervention in socially isolated mice. Social isolation stress (SIS) is associated with vulnerability to oxidative stress and reduced mitochondrial activity. Thus, the aim of this study was to investigate the effects of free access to a running wheel for 21 days on the various markers of the cellular redox/antioxidant status as well as mitochondrial function of mice subjected to SIS or maintained in groups of 3 in the homecage. SIS increased thiobarbituric acid reactive substance (TBARS) levels in the cerebral cortex, and PA intervention was not able to reverse such alteration. PA reduced TBARS levels in the liver of grouped mice and gastrocnemius of socially isolated mice. PA increased nonprotein thiol (NPSH) levels in the cerebral cortex of grouped mice. Furthermore, socially isolated mice presented lower glutathione peroxidase (GPx) activity in the cerebellum and gastrocnemius, and glutathione reductase (GR) activity in the cerebral cortex and liver. By contrast, SIS induced higher GPx activity in the cerebral cortex and heart. PA reduced GPx (cerebral cortex) and GR (cerebral cortex and liver) activities of socially isolated mice. SIS caused higher activity of mitochondrial complexes I and II in the cerebral cortex, and the PA paradigm was not able to alter this effect. Interestingly, the PA produced antidepressant-like effect at both SIS and control groups. In conclusion, the results showed the influence of SIS for the effects of PA on the antioxidant status, but not on the mitochondrial function and emotionality.

          Highlights

          • PA intervention produces antioxidant responses dependent on sociability conditions.

          • SIS induces mitochondria function and antioxidant defense abnormalities.

          • Running produces antidepressant-like behavior and does not change the ambulation.

          • The distance travelled on the running wheel is correlated with immobility time in the TST.

          • The lipoperoxidation index is negatively correlated with time spent on the running wheel.

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          Most cited references106

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          Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes.

          Glutathione-dependent catalysis is a metabolic adaptation to chemical challenges encountered by all life forms. In the course of evolution, nature optimized numerous mechanisms to use glutathione as the most versatile nucleophile for the conversion of a plethora of sulfur-, oxygen- or carbon-containing electrophilic substances. This comprehensive review summarizes fundamental principles of glutathione catalysis and compares the structures and mechanisms of glutathione-dependent enzymes, including glutathione reductase, glutaredoxins, glutathione peroxidases, peroxiredoxins, glyoxalases 1 and 2, glutathione transferases and MAPEG. Moreover, open mechanistic questions, evolutionary aspects and the physiological relevance of glutathione catalysis are discussed for each enzyme family. It is surprising how little is known about many glutathione-dependent enzymes, how often reaction geometries and acid-base catalysts are neglected, and how many mechanistic puzzles remain unsolved despite almost a century of research. On the one hand, several enzyme families with non-related protein folds recognize the glutathione moiety of their substrates. On the other hand, the thioredoxin fold is often used for glutathione catalysis. Ancient as well as recent structural changes of this fold did not only significantly alter the reaction mechanism, but also resulted in completely different protein functions. Glutathione-dependent enzymes are excellent study objects for structure-function relationships and molecular evolution. Notably, in times of systems biology, the outcome of models on glutathione metabolism and redox regulation is more than questionable as long as fundamental enzyme properties are neither studied nor understood. Furthermore, several of the presented mechanisms could have implications for drug development. This article is part of a Special Issue entitled Cellular functions of glutathione. Copyright © 2012 Elsevier B.V. All rights reserved.
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            The changing faces of glutathione, a cellular protagonist.

            Glutathione (GSH) has been described for a long time just as a defensive reagent against the action of toxic xenobiotics (drugs, pollutants, carcinogens). As a prototype antioxidant, it has been involved in cell protection from the noxious effect of excess oxidant stress, both directly and as a cofactor of glutathione peroxidases. In addition, it has long been known that GSH is capable of forming disulfide bonds with cysteine residues of proteins, and the relevance of this mechanism ("S-glutathionylation") in regulation of protein function is currently receiving confirmation in a series of research lines. Rather paradoxically, however, recent studies have also highlighted the ability of GSH-and notably of its catabolites-to promote oxidative processes, by participating in metal ion-mediated reactions eventually leading to formation of reactive oxygen species and free radicals. A crucial role in these phenomena is played by membrane bound gamma-glutamyltransferase activity. The significance of GSH as a major factor in regulation of cell life, proliferation, and death, should be regarded as the integrated result of all these roles it can play.
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              Social relationships and health.

              Recent scientific work has established both a theoretical basis and strong empirical evidence for a causal impact of social relationships on health. Prospective studies, which control for baseline health status, consistently show increased risk of death among persons with a low quantity, and sometimes low quality, of social relationships. Experimental and quasi-experimental studies of humans and animals also suggest that social isolation is a major risk factor for mortality from widely varying causes. The mechanisms through which social relationships affect health and the factors that promote or inhibit the development and maintenance of social relationships remain to be explored.
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                Author and article information

                Contributors
                Journal
                Pharmacol Biochem Behav
                Pharmacol. Biochem. Behav
                Pharmacology, Biochemistry, and Behavior
                Elsevier Inc.
                0091-3057
                1873-5177
                20 August 2020
                20 August 2020
                : 173018
                Affiliations
                [a ]Department of Biochemistry, Federal University of Santa Catarina, 88040-900 Florianópolis, SC, Brazil
                [b ]Institute of Basic Health Sciences, Department of Biochemistry, Federal University of Rio Grande do Sul, 900035-003 Porto Alegre, RS, Brazil
                [c ]Department of Biological and Agronomic Sciences, Federal University of Santa Catarina, 89520-000 Curitibanos, SC, Brazil
                Author notes
                [* ]Corresponding author. mauricio.personal@ 123456gmail.com
                Article
                S0091-3057(20)30098-8 173018
                10.1016/j.pbb.2020.173018
                7438373
                bf7c7d9e-d6a3-4fd3-8067-91c4e015a95e
                © 2020 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 11 February 2020
                : 14 August 2020
                : 17 August 2020
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                dtnb, 5,5-dithiobis-2-nitrobenzoic acid,anova, analysis of variance,chp, cumene peroxide,ethylenediamine tetraacetic acid (edta), ethylene glycol-bis(β-aminoethyl ether)-n,n,n′,n′-tetraacetic acid (also known as egtazic acid, egta),gpx, glutathione peroxidase,gr, glutathione reductase,mda, malondialdehyde,nadh, nicotinamide adenine dinucleotide,nadph, nicotinamide adenine dinucleotide phosphate,npsh, nonprotein thiols groups,gssg, oxidized glutathione,pa, physical activity,gsh, reduced glutathione,sis, social isolation stress,tst, tail suspension test,tbars, thiobarbituric acid reactive species,glutathione,mitochondria,oxidative stress,physical activity,voluntary wheel running,social isolation stress

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