Redox Report最新文献

{"title":"Effects of α subunit substitutions on the oxidation of βCys93 and the stability of sickle cell hemoglobin.","authors":"Wayne Hicks,&nbsp;Fantao Meng,&nbsp;Tigist Kassa,&nbsp;Abdu I Alayash","doi":"10.1080/13510002.2020.1834250","DOIUrl":"https://doi.org/10.1080/13510002.2020.1834250","url":null,"abstract":"<p><p>The β subunit substitutions, F41Y and K82D, in sickle cell hemoglobin (Hb) (βE6 V) provides significant resistance to oxidative stress by shielding βCys93 from the oxidizing ferryl heme. We evaluated the oxidative resistance of βCys93 to hydrogen peroxide (H₂O₂) in α subunit mutations in βE6 V (at both the putative and lateral contact regions) that included (1) αH20Q/βE6 V; (2) αH50Q/βE6 V; (3) αH20Q/H50Q/βE6 V; (4) αH20R/βE6 V; and (5) αH20R/H50Q/βE6 V. Estimation by mass spectrometry of irreversible oxidation of βCys93 to cysteic acid (CA) was unchanged or moderately increased in the single mutants harboring a H20Q or H50Q substitution when compared to control (βE6 V). The introduction of Arg (R) singularly or in combination with Q enhanced the pseudoperoxidative cycle by slightly decreasing the ferryl in favor of ferrous and ferric species after treatment with H₂O₂. Higher rates for heme loss from the ferric forms of the Q species to the receptor high affinity recombinant apomyglobin were observed in contrast to the R mutants and control. Because of their improved solubility, a combination of Q and R substitutions together with mutations carrying redox active variants (F41Y/K82D) may provide dual antioxidant and antisickling targets in the design of gene therapy-based candidates.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"95-103"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1834250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38493905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Codeine-induced sperm DNA damage is mediated predominantly by oxidative stress rather than apoptosis.","authors":"Ayodeji Folorunso Ajayi,&nbsp;Roland Eghoghosoa Akhigbe","doi":"10.1080/13510002.2020.1752003","DOIUrl":"https://doi.org/10.1080/13510002.2020.1752003","url":null,"abstract":"<p><p><b>ABSTRACT</b><b>Background:</b> Opioids have been implicated to induce infertility. Although codeine remains the most used opioid for recreational purpose, no study has documented its effect on sperm quality. Elucidating the effect of codeine on sperm cells and the associated mechanisms may provide an insight into preventing drug-induced sperm damage. Twenty-one New Zealand white rabbits were randomized into three groups; control and codeine-treated. The codeine-treated groups received either 4 or 10mg/kg b.w of codeine for six weeks.<b>Results:</b> Codeine treatment led to significant decrease in sperm count, motility, viability, normal morphology, and sperm membrane integrity. This was associated with significant rise in sperm DNA fragmentation, oxidative damage, and caspase 3 activity. The percentage of sperm DNA fragmentation correlates positively with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, and caspase 3 activity, a biomarker of apoptosis. The observed correlation was stronger between sperm DNA fragmentation and oxidative DNA damage than sperm DNA fragmentation and caspase 3 activity.<b>Conclusion:</b> This study revealed that chronic codeine exposure causes sperm DNA fragmentation and poor sperm quality primarily via oxidative stress rather than activation of caspase 3-dependent apoptosis. Findings of the present study may explain drug-induced male factor infertility, particularly, those associated with opioid use.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"33-40"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1752003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37836299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renin angiotensin system blockage by losartan neutralize hypercholesterolemia-induced inflammatory and oxidative injuries.","authors":"Abdulaziz M S AlSaad,&nbsp;Fawaz Alasmari,&nbsp;Hatem M Abuohashish,&nbsp;Mohamed Mohany,&nbsp;Mohammed M Ahmed,&nbsp;Salim S Al-Rejaie","doi":"10.1080/13510002.2020.1763714","DOIUrl":"https://doi.org/10.1080/13510002.2020.1763714","url":null,"abstract":"<p><p><b>ABSTRACT</b><b>Objectives:</b> This study explores the protective role of losartan (LT) against oxidative and inflammatory damages in different physiological systems including heart, liver, and kidney tissue in hypercholesterolemic rats.<b>Methods:</b> After induction of hypercholesterolemia by high cholesterol diet for 6 weeks, LT was administered for 4 weeks. In serum, the levels of lipoproteins, aminotransferases, creatine kinases, urea, apoptosis, and inflammatory markers were measured. In cardiac, hepatic, and renal tissues, lipid peroxidation product and GSH as well as antioxidant enzymatic activities were assayed. Finally, histopathological assessment evaluated the structural damage in cardiac, hepatic, and renal tissues.<b>Results:</b> Serum markers of cardiac, hepatic, and renal toxicities including creatine kinases, aminotransferases, and urea were attenuated by LT in hypercholesterolemic animals. Moreover, LT markedly corrected the elevated levels of lipoproteins, apoptosis, and inflammatory biomarkers. Hypercholesterolemia-induced lipid peroxidation, low GSH levels, and diminished activities of antioxidant enzymes were prominently improved in LT treated animals. Histopathological alterations by hypercholesterolemia in heart, liver, and kidney tissues were ameliorated by LT.<b>Conclusion:</b> This study confirmed the pathological enrollment of renin-angiotensin system in hypercholesterolemia-associated metabolic alterations. LT had a significant cardiac, hepatic, and renal protective role against these impairments through down-regulation of oxidative damage, inflammation and necrosis.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"51-58"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1763714","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37925065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early onset of renal oxidative stress in small for gestational age newborn pigs.","authors":"Hitesh Soni,&nbsp;Taisiya Yakimkova,&nbsp;Anberitha T Matthews,&nbsp;Paul K Amartey,&nbsp;Robert W Read,&nbsp;Randal K Buddington,&nbsp;Adebowale Adebiyi","doi":"10.1080/13510002.2019.1596429","DOIUrl":"https://doi.org/10.1080/13510002.2019.1596429","url":null,"abstract":"<p><strong>Objective: </strong>Oxidative stress, a common feature in cardiovascular and renal disease is associated with the causes and consequences of fetal growth restriction. Hence, renal redox status is likely an early determinant of morbidity in small-for-gestational-age (SGA) infants. In this study, we examined renal oxidative stress in naturally-farrowed SGA newborn pigs.</p><p><strong>Methods: </strong>We studied SGA newborn pigs with 52% less body weight and 59% higher brain/liver weight ratio compared with their appropriate-for-gestational-age (AGA) counterparts.</p><p><strong>Results: </strong>The kidneys of the SGA newborn pigs weighed 56% less than the AGA group. The glomerular cross-sectional area was also smaller in the SGA group. SGA newborn pigs exhibited increased renal lipid peroxidation, reduced kidney and urine total antioxidant capacity, and increased renal nitrotyrosine immunostaining. Whereas the protein expression level of NADPH oxidase (NOX)2 was unchanged, NOX4 expression was significantly higher in SGA kidneys. The level of serum potassium was lower, but serum sodium and creatinine were similar in SGA compared with AGA newborn pigs. The serum concentrations of C-reactive protein and NGAL, the biomarkers of inflammation and early acute kidney injury were significantly elevated in the SGA group.</p><p><strong>Conclusion: </strong>Early induction of oxidative stress may contribute to the onset of kidney injury in growth-restricted infants.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"10-16"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1596429","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37262408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol improves osteogenic differentiation of senescent bone mesenchymal stem cells through inhibiting endogenous reactive oxygen species production <i>via</i> AMPK activation.","authors":"Ting Zhou,&nbsp;Yurong Yan,&nbsp;Chenchen Zhao,&nbsp;Yao Xu,&nbsp;Qiong Wang,&nbsp;Na Xu","doi":"10.1080/13510002.2019.1658376","DOIUrl":"https://doi.org/10.1080/13510002.2019.1658376","url":null,"abstract":"<p><p><b>Objective:</b> Resveratrol has been confirmed to improve bone quality and delay osteoporosis, but the mechanisms have not been thoroughly elucidated. In this report, we investigated the osteogenic differentiation effect of resveratrol on senescent bone mesenchymal stem cells (BMSCs) and the involvement of AMP-activated protein kinase (AMPK)/ reactive oxygen species (ROS) signaling pathway. <b>Methods:</b> Cell senescence, viability, and osteogenic differentiation of BMSCs influenced by resveratrol were investigated and ROS production and AMPK expression were detected. <b>Results:</b> Cell senescence, characterized by senescence β-galactosidase staining and senescence-related genes (p16, p21, and p53) expression, was attenuated by resveratrol. Cell viability, extracellular matrix calcification, and osteogenic-related genes expression were significantly enhanced after resveratrol treatment. ROS production in BMSCs was inhibited while AMPK expression was up-regulated by resveratrol. Inhibition of AMPK expression by compound C reduced resveratrol-prompted osteogenesis and ROS production down-regulation. <b>Conclusion:</b> These results provide a potential mechanism involving AMPK activation/ROS inhibition signaling pathway in osteogenic differentiation of BMSCs enhanced by resveratrol. It suggests that development of therapy towards ROS is an effective way for osteoporosis treatment.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"62-69"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1658376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41211005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protection of cholinergic and antioxidant system contributes to the effect of Vitamin D₃ ameliorating memory dysfunction in sporadic dementia of Alzheimer's type.","authors":"Marilia Valvassori Rodrigues,&nbsp;Jessié Martins Gutierres,&nbsp;Fabiano Carvalho,&nbsp;Thauan Faccin Lopes,&nbsp;Vitor Antunes,&nbsp;Pauline da Costa,&nbsp;Maria Estér Pereira,&nbsp;Maria Rosa Chitolina Schetinger,&nbsp;Vera M Morsch,&nbsp;Cinthia Melazzo de Andrade","doi":"10.1080/13510002.2019.1617514","DOIUrl":"10.1080/13510002.2019.1617514","url":null,"abstract":"<p><strong>Objective: </strong>Investigate Vitamin D₃ (VD₃) effect on the Acetylcholinesterase (AChE), oxidative damage and behavioral tests in animals subjected to Intracerebroventicular injection of Streptozotocin (ICV-STZ) simulating a Sporadic Dementia of Alzheimer's Type (SDAT) and treated with VD₃ (21 days).</p><p><strong>Methods: </strong>Animals were divided into eight groups: Vehicle, VD12.5 μg/kg, VD42 μg/kg, VD125 μg/kg, STZ, STZ+VD12.5 μg/kg, STZ+VD42 μg/kg, STZ+VD125 μg/kg.</p><p><strong>Results: </strong>VD₃ prevented the increase in AChE in groups of VD42 µg/kg and VD125 µg/kg; in AChE of synaptossomes and TBARS levels prevented the increase in group VD125 µg/kg; in ROS levels there was not a significant difference; for the Carbonyl Content all doses prevented the increase. Total Thiols prevent the decrease in VD42 µg/kg and VD125 µg/kg, and Reduced Glutathione prevented the decrease in VD125 µg/kg, Oxidized Glutathione prevented the increase in VD125 µg/kg. In relation to behavioral tests, the VD₃ prevented the increase in time to find (days 2 and 3), in the time to find the platform (day 3) and in time spent in the quadrant (day 2). However, in relation to crossings there was not difference in groups. These results indicated the therapeutic effect of the VD₃ in model of STZ in rats.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"34-40"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1617514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37249950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant potential of theaflavin ameliorates the activities of key enzymes of glucose metabolism in high fat diet and streptozotocin - induced diabetic rats.","authors":"Kirubananthan Gothandam,&nbsp;Vijayan Siva Ganesan,&nbsp;Thangaraj Ayyasamy,&nbsp;Sundaram Ramalingam","doi":"10.1080/13510002.2019.1624085","DOIUrl":"https://doi.org/10.1080/13510002.2019.1624085","url":null,"abstract":"<p><p><b>Objectives:</b> The present study was to evaluate the effect of theaflavin on the activities of key enzymes of carbohydrate metabolism in high fat diet and streptozotocin - induced diabetic rats. <b>Methods:</b> Diabetes was induced in male albino Wistar rats by feeding them with high fat diet comprising of standard laboratory rat chow 84.3%, lard 5%, egg yolk powder 10%, cholesterol 0.2% and bile salt 0.5% for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (40 mg/kg b.w). <b>Results:</b> Theaflavin (100 mg/kg b.w /day) was administered orally to diabetic rats for 30 days. At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats. <b>Discussion:</b> Oral administration of theaflavin to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The results of the present study suggest that theaflavin exhibits antidiabetic effect through its antioxidant activity.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"41-50"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1624085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37288542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoke exposure induces ROS-mediated autophagy by regulating sestrin, AMPK, and mTOR level in mice.","authors":"Ana Lucia Bernardo Carvalho Morsch,&nbsp;Elvis Wisniewski,&nbsp;Thais Fernandes Luciano,&nbsp;Vitor Hugo Comin,&nbsp;Gustavo de Bem Silveira,&nbsp;Scherolin de Oliveira Marques,&nbsp;Anand Thirupathi,&nbsp;Paulo Cesar Silveira Lock,&nbsp;Claudio Teodoro De Souza","doi":"10.1080/13510002.2019.1601448","DOIUrl":"https://doi.org/10.1080/13510002.2019.1601448","url":null,"abstract":"<p><p>Many pathological conditions linked to cigarette smoking are caused by the production of reactive oxygen species (ROS). The present study was conducted to analyze the effect of ROS on the lungs of Swiss mice exposed to cigarette smoking, focusing on autophagy-mediated mechanisms, and investigate the involvement of SESN2, AMPK, and mTOR signaling. Mice were exposed to cigarette smoke (CS) for 7, 15, 30, 45, and 60 days; the control group was not exposed to CS. Only mice exposed to CS for 45 days were selected for subsequent N-acetylcysteine (NAC) supplementation and smoke cessation analyses. Exposure to CS increased the production of ROS and induced molecular changes in the autophagy pathway, including an increase in phosphorylated AMPK and ULK1, reduction in phosphorylated mTOR, and increases in SESN2, ATG12, and LC3B levels. NAC supplementation reduced ROS levels and reversed all molecular changes observed upon CS treatment, suggesting the involvement of oxidative stress in inducing autophagy upon CS exposure. When exposure to CS was stopped, there were decreases in the levels of oxidative stress, AMPK and ULK1 phosphorylation, and autophagy-initiating molecules and increase in mTOR phosphorylation. In conclusion, these results suggest the involvement of ROS, SESN2, AMPK, and mTOR in the CS-induced autophagic process in the lung.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"27-33"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1601448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37292174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomics and phosphoproteomics study of LCMT1 overexpression and oxidative stress: overexpression of LCMT1 arrests H₂O₂-induced lose of cells viability.","authors":"Xinhang Wang,&nbsp;Shen Tang,&nbsp;Fu Qin,&nbsp;Yuyang Liu,&nbsp;Ziwei Liang,&nbsp;Haiqing Cai,&nbsp;Laiming Mo,&nbsp;Deqiang Xiao,&nbsp;Songcao Guo,&nbsp;Yiqiang Ouyang,&nbsp;Bin Sun,&nbsp;Cailing Lu,&nbsp;Xiyi Li","doi":"10.1080/13510002.2019.1595332","DOIUrl":"https://doi.org/10.1080/13510002.2019.1595332","url":null,"abstract":"<p><strong>Objectives: </strong>Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase, is also known to be a target of ROS. The methylation of PP2A can be catalyzed by leucine carboxyl methyltransferase-1 (LCMT1), which regulates PP2A activity and substrate specificity.</p><p><strong>Methods: </strong>In the previous study, we have showed that LCMT1-dependent PP2Ac methylation arrests H₂O₂-induced cell oxidative stress damage. To explore the possible protective mechanism, we performed iTRAQ-based comparative quantitative proteomics and phosphoproteomics studies of H₂O₂-treated vector control and LCMT1-overexpressing cells.</p><p><strong>Results: </strong>A total of 4480 non-redundant proteins and 3801 unique phosphopeptides were identified by this means. By comparing the H₂O₂-regulated proteins in LCMT1-overexpressing and vector control cells, we found that these differences were mainly related to protein phosphorylation, gene expression, protein maturation, the cytoskeleton and cell division. Further investigation of LCMT1 overexpression-specific regulated proteins under H₂O₂ treatment supported the idea that LCMT1 overexpression induced ageneral dephosphorylation of proteins and indicated increased expression of non-erythrocytic hemoglobin, inactivation of MAPK3 and regulation of proteins related to Rho signal transduction, which were known to be linked to the regulation of the cytoskeleton.</p><p><strong>Discussion: </strong>These data provide proteomics and phosphoproteomics insights into the association of LCMT1-dependent PP2Ac methylation and oxidative stress and indirectly indicate that the methylation of PP2A plays an important role against oxidative stress.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"1-9"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1595332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37078890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis C virus core or NS3/4A protein expression preconditions hepatocytes against oxidative stress and endoplasmic reticulum stress.","authors":"W Alfredo Ríos-Ocampo,&nbsp;Toos Daemen,&nbsp;Manon Buist-Homan,&nbsp;Klaas Nico Faber,&nbsp;María-Cristina Navas,&nbsp;Han Moshage","doi":"10.1080/13510002.2019.1596431","DOIUrl":"https://doi.org/10.1080/13510002.2019.1596431","url":null,"abstract":"<p><strong>Objectives: </strong>The occurrence of oxidative stress and endoplasmic reticulum (ER) stress in hepatitis C virus (HCV) infection has been demonstrated and play an important role in liver injury. During viral infection, hepatocytes must handle not only the replication of the virus, but also inflammatory signals generating oxidative stress and damage. Although several mechanisms exist to overcome cellular stress, little attention has been given to the adaptive response of hepatocytes during exposure to multiple noxious triggers.</p><p><strong>Methods: </strong>In the present study, Huh-7 cells and hepatocytes expressing HCV Core or NS3/4A proteins, both inducers of oxidative and ER stress, were additionally challenged with the superoxide anion generator menadione to mimic external oxidative stress. The production of reactive oxygen species (ROS) as well as the response to oxidative stress and ER stress were investigated.</p><p><strong>Results: </strong>We demonstrate that hepatocytes diminish oxidative stress through a reduction in ROS production, ER-stress markers (HSPA5 [GRP78], sXBP1) and apoptosis (caspase-3 activity) despite external oxidative stress. Interestingly, the level of the autophagy substrate protein p62 was downregulated together with HCV Core degradation, suggesting that hepatocytes can overcome excess oxidative stress through autophagic degradation of one of the stressors, thereby increasing cell survival. Duscussion: In conclusion, hepatocytes exposed to direct and indirect oxidative stress inducers are able to cope with cellular stress associated with viral hepatitis and thus promote cell survival.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"24 1","pages":"17-26"},"PeriodicalIF":3.8,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2019.1596431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37088872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}