Antioxidants & redox signaling最新文献

{"title":"A Minimal Kynurenine Pathway Was Preserved for Rhodoquinone but Not for <i>De Novo</i> NAD⁺ Biosynthesis in Parasitic Worms: The Essential Role of NAD⁺ Rescue Pathways.","authors":"Rosina Comas-Ghierra, Abdulkareem Alshaheeb, Melanie R McReynolds, Jennifer N Shepherd, Gustavo Salinas","doi":"10.1089/ars.2023.0293","DOIUrl":"10.1089/ars.2023.0293","url":null,"abstract":"<p><p><b><i>Aims:</i></b> To determine the role of the kynurenine (KYN) pathway in rhodoquinone (RQ) and <i>de novo</i> NAD⁺ biosynthesis and whether NAD⁺ rescue pathways are essential in parasitic worms (helminths). <b><i>Results:</i></b> We demonstrate that RQ, the key electron transporter used by helminths under hypoxia, derives from the tryptophan (Trp) catabolism even in the presence of a minimal KYN pathway. We show that of the KYN pathway genes only the kynureninase and tryptophan/indoleamine dioxygenases are essential for RQ biosynthesis. Metabolic labeling with Trp revealed that the lack of the formamidase and kynurenine monooxygenase genes did not preclude RQ biosynthesis in the flatworm <i>Mesocestoides corti</i>. In contrast, a minimal KYN pathway prevented <i>de novo</i> NAD⁺ biosynthesis, as revealed by metabolic labeling in <i>M. corti</i>, which also lacks the 3-hydroxyanthranilate 3,4-dioxygenase gene. Our results indicate that most helminths depend solely on NAD⁺ rescue pathways, and some lineages rely exclusively on the nicotinamide salvage pathway. Importantly, the inhibition of the NAD⁺ recycling enzyme nicotinamide phosphoribosyltransferase with FK866 led cultured <i>M. corti</i> to death. <b><i>Innovation:</i></b> We use comparative genomics of more than 100 hundred helminth genomes, metabolic labeling, HPLC-mass spectrometry targeted metabolomics, and enzyme inhibitors to define pathways that lead to RQ and NAD⁺ biosynthesis in helminths. We identified the essential enzymes of these pathways in helminth lineages, revealing new potential pharmacological targets for helminthiasis. <b><i>Conclusion:</i></b> Our results demonstrate that a minimal KYN pathway was evolutionary maintained for RQ and not for <i>de novo</i> NAD⁺ biosynthesis in helminths and shed light on the essentiality of NAD⁺ rescue pathways in helminths.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"737-750"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10107928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights Into Antioxidant Strategies to Counteract Radiation-Induced Male Infertility.","authors":"Maria Angélica Spadella, Erick J R Silva, Agnaldo Bruno Chies, Laine Andreotti de Almeida","doi":"10.1089/ars.2023.0282","DOIUrl":"10.1089/ars.2023.0282","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Radiotherapy, which employs ionizing radiation to destroy or prevent the multiplication of tumor cells, has been increasingly used in the treatment of neoplastic diseases, especially cancers. However, radiation collaterally leads to prolonged periods of sperm count suppression, presumably due to impaired spermatogenesis by depleting the germ cell pool, which has long-term side effects for male reproduction. <b><i>Recent Advances:</i></b> Studies of antioxidant compounds as a potential strategy for male fertility preservation have been performed mainly from animal models, aiming to prevent and restore the male germinal tissue and its function, particularly against the oxidative stress effects of radiation. Evidence in preclinical and clinical trials has shown that inhibitors of the renin-angiotensin system and other drugs, such as statins and metformin, are candidates for ameliorating radiation-induced damage to several tissues, including the testis and prostate. <b><i>Critical Issues:</i></b> Research for developing an ideal radioprotective agent is challenging due to toxicity in the normal tissue, tumor radioresistance, cellular response to radiation, costs, regulation, and timeline development. Moreover, male radioprotection experiments in humans, mainly clinical trials, are scarce and use few individuals. This scenario is reflected in the slow progress of innovation in the radioprotection field. <b><i>Future Directions:</i></b> Expanding human studies to provide clues on the efficacy and safety of radioprotective compounds in the human reproductive system is necessary. Drug repurposing, frequently used in clinical practice, can be a way to shorten the development pipeline for innovative approaches for radioprotection or radiomitigation of the repercussions of radiotherapy in the male reproductive system.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"776-801"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Measurement and Imaging of Redox Status with Electron Paramagnetic Resonance.","authors":"Boris Epel, Joseph P Y Kao, Sandra S Eaton, Gareth R Eaton, Howard J Halpern","doi":"10.1089/ars.2022.0216","DOIUrl":"10.1089/ars.2022.0216","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Fundamental to the application of tissue redox status to human health is the quantification and localization of tissue redox abnormalities and oxidative stress and their correlation with the severity and local extent of disease to inform therapy. The centrality of the low-molecular-weight thiol, glutathione, in physiological redox balance has long been appreciated, but direct measurement of tissue thiol status <i>in vivo</i> has not been possible hitherto. Recent advances in instrumentation and molecular probes suggest the feasibility of real-time redox assessment in humans. <b><i>Recent Advances:</i></b> Recent studies have demonstrated the feasibility of using low-frequency electron paramagnetic resonance (EPR) techniques for quantitative imaging of redox status in mammalian tissues <i>in vivo</i>. Rapid-scan (RS) EPR spectroscopy and imaging, new disulfide-dinitroxide spin probes, and novel analytic techniques have led to significant advances in direct, quantitative imaging of thiol redox status. <b><i>Critical Issues:</i></b> While novel RS EPR imaging coupled with first-generation molecular probes has demonstrated the feasibility of imaging thiol redox status <i>in vivo</i>, further technical advancements are desirable and ongoing. These include developing spin probes that are tailored for specific tissues with response kinetics tuned to the physiological environment. Equally critical are RS instrumentation with higher signal-to-noise ratio and minimal signal distortion, as well as optimized imaging protocols for image acquisition with sparsity adapted to image information content. <b><i>Future Directions:</i></b> Quantitative images of tissue glutathione promise to enable acquisition of a general image of mammalian and potentially human tissue health.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"850-862"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9402060","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":"Hypothalamic Glucose Hypersensitivity-Induced Insulin Secretion in the Obese Zücker Rat Is Reversed by Central Ghrelin Treatment.","authors":"Lionel Carneiro, Claire Fenech, Fabienne Liénard, Sylvie Grall, Besma Abed, Joulia Haydar, Camille Allard, Lucie Desmoulins, Romain Paccoud, Marie-Claude Brindisi, Thomas Mouillot, Laurent Brondel, Xavier Fioramonti, Luc Pénicaud, Agnès Jacquin-Piques, Corinne Leloup","doi":"10.1089/ars.2022.0031","DOIUrl":"10.1089/ars.2022.0031","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Part of hypothalamic (mediobasal hypothalamus [MBH]) neurons detect changes in blood glucose levels that in turn coordinate the vagal control of insulin secretion. This control cascade requires the production of mitochondrial reactive oxygen species (mROS), which is altered in models of obesity and insulin resistance. Obese, insulin-resistant Zücker rats are characterized by hypothalamic hypersensitivity to glucose. This initiates an abnormal vagus-induced insulin secretion, associated with an overproduction of mROS in response to a low glucose dose. Here, we hypothesized that ghrelin, known to buffer reactive oxygen species (ROS) <i>via</i> mitochondrial function, may be a major component of the hypothalamic glucose hypersensitivity in the hypoghrelinemic obese Zücker rat. <b><i>Results:</i></b> Hypothalamic glucose hypersensitivity-induced insulin secretion of Zücker obese rats was reversed by ghrelin pretreatment. The overproduction of MBH mROS in response to a low glucose load no longer occurred in obese rats that had previously received the cerebral ghrelin infusion. This decrease in mROS production was accompanied by a normalization of oxidative phosphorylation (OXPHOS). Conversely, blocking the action of ghrelin with a growth hormone secretagogue receptor antagonist in a model of hyperghrelinemia (fasted rats) completely restored hypothalamic glucose sensing-induced insulin secretion that was almost absent in this physiological situation. Accordingly, ROS signaling and mitochondrial activity were increased by the ghrelin receptor antagonist. <b><i>Innovation:</i></b> These results demonstrate for the first time that ghrelin addressed only to the brain could have a protective effect on the defective control of insulin secretion in the insulin-resistant, hypoghrelinemic obese subject. <b><i>Conclusions:</i></b> Ghrelin, through its action on OXPHOS, modulates mROS signaling in response to cerebral hyperglycemia and the consequent vagal control of insulin secretion. In insulin-resistant obese states, brain hypoghrelinemia could be responsible for the nervous defect in insulin secretion.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"837-849"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9421303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and Functional Diversity of the Peroxiredoxin 6 Enzyme Family.","authors":"Hamidur Rahaman, Khundrakpam Herojit, Laishram Rajendrakumar Singh, Reena Haobam, Aron B Fisher","doi":"10.1089/ars.2023.0287","DOIUrl":"10.1089/ars.2023.0287","url":null,"abstract":"<p><p><b>Significance:</b> Peroxiredoxins (Prdxs) with a single peroxidative cysteine (C_P) in a conserved motif PXXX(T/S)XXC_P within its thioredoxin fold, have been classified as the peroxiredoxin 6 (Prdx6 ) family. All Prdxs can reduce H₂O₂ and short chain hydroperoxides while Prdx6 in addition, can reduce phospholipid hydroperoxides (PLOOH) due to its ability to interact with peroxidized phospholipid substrate. The single C_P of Prdx6 uses various external electron donors including glutathione thioredoxin, and ascorbic acid for resolution of its peroxidized state and, therefore, its peroxidase activity. Prdx6 proteins also exhibit Ca²⁺-independent phospholipase A2 (PLA2), lysophosphatidylcholine acyltransferase (LPCAT), and chaperone activities that depend on cellular localization and the oxidation and oligomerisation states of the protein. Thus, Prdx6 is a \"moonlighting\" enzyme. <b>Recent Advance:</b> Physiologically, Prdx6s have been reported to play an important role in protection against oxidative stress, repair of peroxidized cell membranes, mammalian lung surfactant turnover, activation of some NADPH oxidases, the regulation of seed germination in plants, as an indicator of cellular levels of reactive O₂ species through Nrf-Klf9 activation, and possibly in male fertility, regulation of cell death through ferroptosis, cancer metastasis, and oxidative stress-related signalling pathways. <b>Critical Issues:</b> This review outlines Prdx6 enzyme unique structural features and explores its wide range of physiological functions. Yet, existing structural data falls short of fully revealing all of human Prdx6 multifunctional roles. Further endeavour is required to bridge this gap in its understanding. Although there are wide variations in both the structure and function of Prdx6 family members in various organisms, all Prdx6 proteins show the unique a long C-terminal extension that is also seen in Prdx1, but not in other Prdxs. <b>Future Directions:</b> As research data continues to accumulate, the potential for detailed insights into the role of C-terminal of Prdx6 in its oligomerisation and activities. There is a need for thorough exploration of structural characteristics of the various biological functions. Additionally, uncovering the interacting partners of Prdx6 and understanding its involvement in signalling pathways will significantly contribute to a more profound comprehension of its role.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"759-775"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Chemical-Induced Reactive Oxygen Species Generation and Immunotoxicity: A Comprehensive Review.","authors":"Leonard Clinton D'Souza, Jagdish Gopal Paithankar, Helga Stopper, Ashutosh Pandey, Anurag Sharma","doi":"10.1089/ars.2022.0117","DOIUrl":"10.1089/ars.2022.0117","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Reactive oxygen species (ROS), the reactive oxygen-carrying chemicals moieties, act as pleiotropic signal transducers to maintain various biological processes/functions, including immune response. Increased ROS production leads to oxidative stress, which is implicated in xenobiotic-induced adverse effects. Understanding the immunoregulatory mechanisms and immunotoxicity is of interest to developing therapeutics against xenobiotic insults. <b><i>Recent Advances:</i></b> While developmental studies have established the essential roles of ROS in the establishment and proper functioning of the immune system, toxicological studies have demonstrated high ROS generation as one of the potential mechanisms of immunotoxicity induced by environmental chemicals, including heavy metals, pesticides, aromatic hydrocarbons (benzene and derivatives), plastics, and nanoparticles. Mitochondrial electron transport and various signaling components, including NADH oxidase, toll-like receptors (TLRs), NF-κB, JNK, NRF2, p53, and STAT3, are involved in xenobiotic-induced ROS generation and immunotoxicity. <b><i>Critical Issues:</i></b> With many studies demonstrating the role of ROS and oxidative stress in xenobiotic-induced immunotoxicity, rigorous and orthogonal approaches are needed to achieve in-depth and precise understanding. The association of xenobiotic-induced immunotoxicity with disease susceptibility and progression needs more data acquisition. Furthermore, the general methodology needs to be possibly replaced with high-throughput precise techniques. <b><i>Future Directions:</i></b> The progression of xenobiotic-induced immunotoxicity into disease manifestation is not well documented. Immunotoxicological studies about the combination of xenobiotics, age-related sensitivity, and their involvement in human disease incidence and pathogenesis are warranted. <i>Antioxid. Redox Signal.</i> 40, 691-714.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"691-714"},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox Regulation of Xenobiotics by Reactive Sulfur and Supersulfide Species.","authors":"Tianli Zhang, Takaaki Akaike, Tomohiro Sawa","doi":"10.1089/ars.2022.0172","DOIUrl":"10.1089/ars.2022.0172","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Routine exposure to xenobiotics is unavoidable during our lifetimes. Certain xenobiotics are hazardous to human health, and are metabolized in the body to render them less toxic. During this process, several detoxification enzymes cooperatively metabolize xenobiotics. Glutathione (GSH) conjugation plays an important role in the metabolism of electrophilic xenobiotics. <b><i>Recent Advances:</i></b> Recent advances in reactive sulfur and supersulfide (RSS) analyses showed that persulfides and polysulfides bound to low-molecular-weight thiols, such as GSH, and to protein thiols are abundant in both eukaryotes and prokaryotes. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to cell protection against oxidative stress and electrophilic stress. <b><i>Critical Issues:</i></b> In contrast to GSH conjugation to electrophiles that is aided by glutathione <i>S</i>-transferase (GST), persulfides and polysulfides can directly form conjugates with electrophiles without the catalytic actions of GST. The polysulfur bonds in the conjugates are further reduced by perthioanions and polythioanions derived from RSS to form sulfhydrated metabolites that are no longer electrophilic but rather nucleophilic, and differ from metabolites that are formed <i>via</i> GSH conjugation. <b><i>Future Directions:</i></b> In view of the abundance of RSS in cells and tissues, metabolism of xenobiotics that is mediated by RSS warrants additional investigations, such as studies of the impact of microbiota-derived RSS on xenobiotic metabolism. Metabolites formed from reactions between electrophiles and RSS may be potential biomarkers for monitoring exposure to electrophiles and for studying their metabolism by RSS. <i>Antioxid. Redox Signal.</i> 40, 679-690.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"679-690"},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10125657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SESN2-Mediated AKT/GSK-3β/NRF2 Activation to Ameliorate Adriamycin Cardiotoxicity in High-Fat Diet-Induced Obese Mice.","authors":"Ting Gao, Jie Wang, Mengjie Xiao, Jie Wang, Shudong Wang, Yufeng Tang, Jingjing Zhang, Guangping Lu, Hua Guo, Yuanfang Guo, Qingbo Liu, Jiahao Li, Junlian Gu","doi":"10.1089/ars.2022.0156","DOIUrl":"10.1089/ars.2022.0156","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Obese patients are highly sensitive to adriamycin (ADR)-induced cardiotoxicity. However, the potential mechanism of superimposed toxicity remains to be elucidated. Sestrin 2 (SESN2), a potential antioxidant, could attenuate stress-induced cardiomyopathy; therefore, this study aims to explore whether SESN2 enhances cardiac resistance to ADR-induced oxidative damage in high-fat diet (HFD)-induced obese mice. <b><i>Results:</i></b> The results revealed that obesity decreased SESN2 expression in ADR-exposed heart. And, HFD mice may predispose to ADR-induced cardiotoxicity, which was probably associated with inhibiting protein kinase B (AKT), glycogen synthase kinase-3 beta (GSK-3β) phosphorylation and subsequently blocking nuclear localization of nuclear factor erythroid-2 related factor 2 (NRF2), ultimately resulting in cardiac oxidative damage. However, these destructive cascades and cardiac oxidative damage effects induced by HFD/sodium palmitate combined with ADR were blocked by overexpression of SESN2. Moreover, the antioxidant effect of SESN2 could be largely abolished by sh-<i>Nrf2</i> or wortmannin. And sulforaphane, an NRF2 agonist, could remarkably reverse cardiac pathological and functional abnormalities caused by ADR in obese mice. <b><i>Innovation and Conclusion:</i></b> This study demonstrated that SESN2 might be a promising therapeutic target for improving anthracycline-related cardiotoxicity in obesity by upregulating activity of NRF2 <i>via</i> AKT/GSK-3β/Src family tyrosine kinase signaling pathway. <i>Antioxid. Redox Signal.</i> 40, 598-615.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"598-615"},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9923315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin 5 Alleviates Liver Ischemia/Reperfusion Injury by Regulating Mitochondrial Succinylation and Oxidative Stress.","authors":"Yan Hu, Xinyao Tian, Yan Zhao, Zhecheng Wang, Musen Lin, Ruimin Sun, Yue Wang, Zhanyu Wang, Guiru Li, Shusen Zheng, Jihong Yao","doi":"10.1089/ars.2022.0137","DOIUrl":"10.1089/ars.2022.0137","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Mitochondrial dysfunction is the primary mechanism of liver ischemia/reperfusion (I/R) injury. The lysine desuccinylase sirtuin 5 (SIRT5) is a global regulator of the mitochondrial succinylome and has pivotal roles in mitochondrial metabolism and function; however, its hepatoprotective capacity in liver I/R remains unclear. In this study, we established liver I/R model in SIRT5-silenced and SIRT5-overexpressed mice to examine the role and precise mechanisms of SIRT5 in liver I/R injury. <b><i>Results:</i></b> Succinylation was strongly enriched in liver mitochondria during I/R, and inhibiting mitochondrial succinylation significantly attenuated liver I/R injury. Importantly, the levels of the desuccinylase SIRT5 were notably decreased in liver transplant patients, as well as in mice subjected to I/R and in AML12 cells exposed to hypoxia/reoxygenation. Furthermore, SIRT5 significantly ameliorated liver I/R-induced oxidative injury, apoptosis, and inflammation by regulating mitochondrial oxidative stress and function. Intriguingly, the hepatoprotective effect of SIRT5 was mediated by PRDX3. Mechanistically, SIRT5 specifically desuccinylated PRDX3 at the K84 site, which enabled PRDX3 to alleviate mitochondrial oxidative stress during liver I/R. <b><i>Innovation:</i></b> This study denoted the new effect and mechanism of SIRT5 in regulating mitochondrial oxidative stress through lysine desuccinylation, thus preventing liver I/R injury. <b><i>Conclusions:</i></b> Our findings demonstrate for the first time that SIRT5 is a key mediator of liver I/R that regulates mitochondrial oxidative stress through the desuccinylation of PRDX3, which provides a novel strategy to prevent liver I/R injury. <i>Antioxid. Redox Signal.</i> 40, 616-631.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"616-631"},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9888944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress, Transfer RNA Metabolism, and Protein Synthesis.","authors":"Yasutoshi Akiyama, Pavel Ivanov","doi":"10.1089/ars.2022.0206","DOIUrl":"10.1089/ars.2022.0206","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Oxidative stress refers to excessive intracellular levels of reactive oxygen species (ROS) due to an imbalance between ROS production and the antioxidant defense system. Under oxidative stress conditions, cells trigger various stress response pathways to protect themselves, among which repression of messenger RNA (mRNA) translation is one of the key hallmarks promoting cell survival. This regulation process minimizes cellular energy consumption, enabling cells to survive in adverse conditions and to promote recovery from stress-induced damage. <b><i>Recent Advances:</i></b> Recent studies suggest that transfer RNAs (tRNAs) play important roles in regulating translation as a part of stress response under adverse conditions. In particular, research relying on high-throughput techniques such as next-generation sequencing and mass spectrometry approaches has given us detailed information on mechanisms such as individual tRNA dynamics and crosstalk among post-transcriptional modifications. <b><i>Critical Issues:</i></b> Oxidative stress leads to dynamic tRNA changes, including their localization, cleavage, and alteration of expression profiles and modification patterns. Growing evidence suggests that these changes not only are tightly regulated by stress response mechanisms, but also can directly fine-tune the translation efficiency, which contributes to cell- or tissue-specific response to oxidative stress. <b><i>Future Directions:</i></b> In this review, we describe recent advances in the understanding of the dynamic changes of tRNAs caused by oxidative stress. We also highlight the emerging roles of tRNAs in translation regulation under the condition of oxidative stress. In addition, we discuss future perspectives in this research field. <i>Antioxid. Redox Signal</i>. 40, 715-735.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"715-735"},"PeriodicalIF":5.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11001508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105402","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}