Antioxidants & redox signaling最新文献

{"title":"Adeno-Associated Virus-Mediated <i>Dickkopf-1</i> Gene Transduction Reduces Silica-Induced Oxidative Stress and Silicosis in Mouse Lung.","authors":"Jia Ma, Jiaqi Wang, Ruiting Sun, Zheqing Hu, Zhaojun Wang, Jing Xue, Shuang Wu, Wenfeng Hu, Jing Wang, Liyuan Yang, Qian Cai, Jiali Yang, Juan Chen, Xiaoming Liu","doi":"10.1089/ars.2024.0646","DOIUrl":"https://doi.org/10.1089/ars.2024.0646","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Silicosis is a lung disease caused by inhalation of silica particles. Both silica-induced oxidative stress and aberrant activation of the Wnt/β-catenin signaling pathway are potential targets in the treatment of pulmonary fibrosis. Dickkopf-1 (Dkk1), an inhibitor of the Wnt/β-catenin signaling pathway, plays regulatory roles in cell fate determination and immune responses. Our previous study demonstrated that adenoviral vector-mediated <i>Dkk1</i> gene transfer alleviated the silica-induced mouse silicosis. However, the mechanism of therapeutic action of Dkk1 in silicosis is yet completely understood; together with the drawbacks of adenoviral vectors in gene therapy, we investigated the therapeutic effect and mechanisms of Dkk1 by employing an adeno-associated virus (AAV) vector in a silicosis mouse model. <b><i>Results:</i></b> The AAV vector could efficiently transduce the <i>Dkk1</i> gene in silicotic lung during both the early and the late phases of disease, resulting in an alleviation of silicotic lesions, improvement of pulmonary compliance, and radiological findings. Mechanistic studies further demonstrated that the transduction of <i>Dkk1</i> inhibited the silica-activated Wnt/β-catenin signaling and reduced the silica-induced reactive oxygen species-producing enzyme NADPH oxidase 4, oxidative stress regulator nuclear factor erythroid 2-related factor 2, and signaling molecules binding immunoglobulin protein and C/EBP homologous protein. In addition, shRNA-mediated downregulation of <i>Dkk1</i> exacerbated the progression of silicosis in mice, whereas the treatment of ROS scavenger n-acetylcysteine showed a comparable mitigation of silicosis that was seen in the AAV-Dkk1 treatment. <b><i>Innovation and Conclusion:</i></b> This study provides an insight into the mechanism by which Dkk1 inhibits the silica-induced Wnt signaling and oxidative stress to mitigate the pathogenesis of lung silicosis and evidence of the potential of AAV-mediated Dkk1 gene transfer as an alternative approach in silicosis treatment. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613514","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":"Nrf2-Dependent Adaptation to Oxidative Stress Protects Against Progression of Diabetic Nephropathy.","authors":"Eugene Lee, Jae-Hun Ahn, Byeong-Cheol Kang, Hyun Soon Lee","doi":"10.1089/ars.2023.0431","DOIUrl":"https://doi.org/10.1089/ars.2023.0431","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Adaptation to oxidative stress is essential for maintaining protein and redox homeostasis in mammalian cells. Palmitic acid (PA) plays a central role in oxidative stress and immunoproteasome regulation in podocytes and diabetes, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial impact on diabetes. The role of Nrf2 in adaptation to oxidative stress and regulation of immunoproteasome by PA and EPA/DHA in podocytes and diabetic kidneys is not well defined. The present study describes the effect of PA- and EPA/DHA-induced oxidative stress in regulating Nrf2/immuoproteasome pathway in a model system relevant to diabetic nephropathy (DN). <b><i>Results:</i></b> Short PA exposure to podocytes promotes the upregulation of antioxidant proteins and immunoproteasome mediated by Nrf2, leading to acute transient oxidative stress adaptation. Both short- and long-term incubation of EPA or DHA in podocytes induced oxidative stress and activation of Nrf2, causing persistent oxidative stress adaptation. Long PA exposure to podocytes decreased the Nrf2 activity, and EPA/DHA attenuated these effects of PA. In <i>db/db</i> mice, feeding of EPA/DHA-rich fish oil increased oxidative stress in kidneys and induced renal cortical Nrf2 nuclear translocation and immunoproteasome overexpression, inhibiting the progression of DN. <b><i>Innovation and Conclusion:</i></b> We demonstrate an oxidative stress adaptation mechanism by PA and EPA/DHA regulated by Nrf2 in podocytes and kidneys of type 2 diabetes. This work provides an important insight into the pathogenetic mechanisms of DN by PA-induced oxidative stress. We conclude that activation of Nrf2-immunoproteasome signaling pathway by EPA/DHA plays a crucial role in abrogating the proteotoxic stress in DN. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613515","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":"Meta-Analysis of Antioxidant Mutants Reveals Common Alarm Signals for Shaping Abiotic Stress-Induced Transcriptome in Plants.","authors":"Shefali Mishra, Thumballi Ramabhatta Ganapathi, Girdhar Kumar Pandey, Christine Helen Foyer, Ashish Kumar Srivastava","doi":"10.1089/ars.2023.0361","DOIUrl":"10.1089/ars.2023.0361","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"42-55"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10402523","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":"A Novel lncRNA FUAT1/TNS4 Axis Confers Chemoresistance by Suppressing Reactive Oxygen Species-Mediated Apoptosis in Gastric Cancer.","authors":"Mingliang Liu, Hehe Li, Xiaoling Li, Boyu Pan, Jian Zhang, Ya Pan, Miaomiao Shen, Liren Liu","doi":"10.1089/ars.2023.0298","DOIUrl":"10.1089/ars.2023.0298","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"24-41"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144961","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":"YTHDF2 Promotes Cardiac Ferroptosis <i>via</i> Degradation of SLC7A11 in Cardiac Ischemia-Reperfusion Injury.","authors":"Ping Pang, Wei Si, Han Wu, Jiaming Ju, Kuiwu Liu, Chunlei Wang, Yingqiong Jia, Hongtao Diao, Linghua Zeng, Weitao Jiang, Yang Yang, Yuting Xiong, Xue Kong, Zhengwei Zhang, Feng Zhang, Jinglun Song, Ning Wang, Baofeng Yang, Yu Bian","doi":"10.1089/ars.2023.0291","DOIUrl":"10.1089/ars.2023.0291","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"889-905"},"PeriodicalIF":5.9,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949607","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":"Advances in Antioxidant Nanomedicines for Imaging and Therapy of Alzheimer's Disease.","authors":"Ikram Hasan, Bing Guo, Jian Zhang, Chunqi Chang","doi":"10.1089/ars.2022.0107","DOIUrl":"10.1089/ars.2022.0107","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Reactive oxygen species (ROS) are crucial signaling molecules in the regulation of numerous physiological activities including the formation and function of the central nervous system (CNS). So far, many functional antioxidant nanomedicines with ROS scavenging capability to reduce oxidative stress in Alzheimer's disease (AD) have been developed for both imaging and therapy of AD. <b><i>Recent Advances:</i></b> This review focuses on the most recent advances in antioxidant nanomedicines such as ROS-scavenging nanoparticles (NPs), NPs with intrinsic antioxidant activity, and drug-loaded antioxidant NPs for AD theranostics. In addition to antioxidant nanomedicines, the emerging phototherapy treatment paradigms and the promising preclinic drug carriers, such as exosomes and liposomes, are also introduced. <b><i>Critical Issues:</i></b> In general, excessive generation of ROS can cause lipid peroxidation, oxidative DNA, as well as protein damage, aggravating pathogenic alterations, accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain. These negative factors further cause cell death, which is the beginning of AD. <b><i>Future Directions:</i></b> We anticipate that this review will help researchers in the area of preclinical research and clinical translation of antioxidant nanomedicines for AD imaging and therapy.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"863-888"},"PeriodicalIF":5.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10756774","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":"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":"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}