Antioxidants & redox signaling最新文献

{"title":"Thioredoxin-1 Downregulation in the SNpc Exacerbates the Cognitive Impairment Induced by MPTP.","authors":"Xianwen Zhang, Fang Yan, Xiong Jie He, Yali Chen, Rou Gu, Xianghuan Dong, Yonghang Wei, Liping Bai, Jie Bai","doi":"10.1089/ars.2024.0630","DOIUrl":"https://doi.org/10.1089/ars.2024.0630","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Parkinson's disease (PD) is characterized by dopaminergic (DAergic) neuron degeneration in the substantia nigra pars compacta (SNpc). Thioredoxin-1 (Trx-1) is a redox protein that protects neurons from various injuries. Our study revealed that Trx-1 overexpression improved the learning and memory impairments induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the role of the specific transmission of signals from the SNpc to the hippocampus regulated by Trx-1 in cognition deficits associated with PD is still unknown. <b><i>Results:</i></b> We observed that Trx-1 downregulation in the SNpc aggravated cognitive dysfunction induced by MPTP. Importantly, we observed that the SNpc directly projects to the hippocampus. We found that the loss of DAergic neurons in the SNpc induced by MPTP resulted in a decrease in dopamine D1 receptor (D1R) expression in the hippocampus, which was promoted by Trx-1 downregulation in the SNpc. The levels of phosphorylated extracellular signal-regulated kinase (p-ERK1/2), phosphorylated cAMP-response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and postsynaptic density protein 95 (PSD95) in the hippocampus were decreased by MPTP and further decreased by Trx-1 downregulation in the SNpc. Finally, the number of synapses in the hippocampus was decreased by MPTP in the hippocampus and further reduced by Trx-1 downregulation in the SNpc. <b><i>Innovation:</i></b> Trx-1 downregulation accelerated the loss of DAergic neurons in the SNpc, leading to a decrease in the number dopaminergic projections to the hippocampus, subsequently inhibiting the D1R-ERK1/2-CREB-BDNF pathway in the hippocampus, and ultimately impairing hippocampus-dependent cognition. <b><i>Conclusions:</i></b> These results indicate that a decrease in Trx-1 level in the SNpc plays a critical regulatory role in cognitive dysfunction in individuals with PD by decreasing the hippocampal D1R signaling pathway. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707900","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":"Exosomal Prolactin-Induced Protein Inhibits the Activation of cGMP/PKG Pathway Mediated by ATP2B2 to Promote Myocardial Fibrosis in Atrial Fibrillation.","authors":"Yue Wei, Xiang Li, Zimo Sha, Jingmeng Liu, Guanhua Wu, Taojie Zhou, Changjian Lin, Yun Xie, Yangyang Bao, Qingzhi Luo, Tianyou Ling, Wenqi Pan, Yucai Xie, Ning Zhang, Qi Jin, Liqun Wu","doi":"10.1089/ars.2024.0723","DOIUrl":"https://doi.org/10.1089/ars.2024.0723","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Myocardial fibrosis is an important medium for atrial fibrillation (AF). Exosomes have been demonstrated to affect the development of AF. This study explored the molecular mechanism of exosomes from patients with AF (AF-exo) mediating myocardial fibrosis and thus affecting the development of AF. <b><i>Results:</i></b> Prolactin-induced protein (PIP) is highly expressed in AF-exo. AF-exo promoted the proliferation and activation of cardiac fibroblasts (CFs) as well as the migration and endothelial-to-mesenchymal transition (EndMT) of human umbilical vein endothelial cells (HUVECs). However, the effect of AF-exo on CFs and HUVECs was mitigated by PIP-specific short hairpin RNA (shPIP). Adeno-associated virus (AAV)-shPIP reduced the incidence and duration of AF in rats, and improved myocardial fibrosis and collagen deposition. ATPase plasma membrane Ca²⁺ transporting 2 (ATP2B2) overexpression or inhibition reverses the role of PIP or shPIP in CFs, HUVECs, and AF rats. Activation of the cyclic guanosine monophosphate/protein kinase G (cGMP/PKG) pathway is beneficial to alleviate myocardial fibrosis, but this effect is mitigated by shATP2B2. <b><i>Innovation:</i></b> Our investigation substantiates the pivotal role of the PIP/ATP2B2 axis in both HUVEC myocardial fibrosis and EndMT progression. Our findings suggest that AF-exo can suppress the activation of the cGMP/PKG pathway mediated by ATP2B2 through exosomal PIP, thus promoting myocardial fibrosis, indicating potential targets for novel antifibrotic drug development targeting either PIP or ATP2B2. <b><i>Conclusion:</i></b> Exosomal PIP can inhibit the activation of cGMP/PKG pathway mediated by ATP2B2, thus promoting the development of AF. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647227","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":"Ferroptosis Mediates the Progression of Hyperuricemic Nephropathy by Activating RAGE Signaling.","authors":"Qiang Wang, Yuemei Xi, Hairong Zhao, De Xie, Linqian Yu, Yunbo Yan, Jiayu Chen, Qian Zhang, Meng Liang, Jidong Cheng","doi":"10.1089/ars.2024.0672","DOIUrl":"https://doi.org/10.1089/ars.2024.0672","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Hyperuricemic nephropathy (HN) represents a prevalent complication of hyperuricemia, typified by tubular dysfunction, inflammation, and progressive renal fibrosis with unclear mechanisms. Ferroptosis, an iron-dependent regulated cell death, is implicated in multiple diseases, but has rarely been linked to HN. In this study, we aim to explore the possible role of ferroptosis in HN and its underlying mechanisms. <b><i>Results:</i></b> We showed that urate oxidase knockout mice, a model of hyperuricemia, exhibited renal impairment with elevated uric acid, creatinine, and blood urea nitrogen levels, accompanied by increased iron deposition and decreased glutathione peroxidase 4 (GPX4) and xCT expressions, suggesting ferroptosis involvement. Ferroptosis inhibitor Ferrostatin-1 (Fer-1) ameliorated renal injury, inflammatory cell infiltration, and fibrosis in these mice. Mechanistically, Fer-1 restored antioxidant protein levels, normalized ferroptosis-associated protein expressions, diminished iron overload and lipid peroxidation, and suppressed inflammatory markers and mitogen-activated protein kinase signaling. <i>In vitro</i>, monosodium urate crystals induced ferroptosis in human kidney 2 cells, characterized by increased lipid peroxidation and iron accumulation. Notably, receptor for advanced glycation end products (RAGE) inhibition alleviated renal injury, inflammation, and fibrosis albeit without directly diminishing ferroptosis. These findings were validated in human hyperuricemia-related kidney disease samples showing increased iron deposition, decreased GPX4, and elevated RAGE expression. <b><i>Innovation and Conclusion:</i></b> This study suggests that ferroptosis may play a role in the development of renal injury, inflammation, and fibrosis in HN, potentially mediated through RAGE signaling. While RAGE inhibition improved renal injury, it did not directly affect ferroptosis, indicating a complex and context-dependent role of RAGE in kidney injury. These findings highlight ferroptosis and its associated pathways, including RAGE signaling, as potential therapeutic targets for HN. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584354","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":"Bach1 Deficiency Ameliorates Radiation Pneumonitis via Activating TFAM Signaling Pathway.","authors":"Jianfeng Huang, Yanli Zhang, Fengjuan Jiang, Yaru Zhang, Shengpeng Li, Shuai He, Jiaojiao Sun, Dan Chen, Qingfeng Pang, Yaxian Wu","doi":"10.1089/ars.2024.0742","DOIUrl":"https://doi.org/10.1089/ars.2024.0742","url":null,"abstract":"<p><p><b><i>Aims:</i></b> BTB and CNC homology 1 (Bach1) is a transcription factor that mediates oxidative stress and inflammation and participates in the progression of diseases such as atherosclerosis, colitis, and acute lung injury. In this study, we aimed to explore the role of Bach1 in radiation pneumonitis (RP) and elucidate its underlying mechanism. <b><i>Results:</i></b> Bach1 expression was significantly elevated in the lung tissues of RP mice. Deletion of the Bach1 gene markedly ameliorated X-ray-induced RP by reducing inflammation and oxidative stress. <i>In vitro</i> experiments demonstrated that Bach1 deficiency mitigated radiation-induced oxidative damage and inflammation in bone marrow-derived macrophages. Conversely, Bach1 overexpression exacerbated oxidative stress and inflammation in radiation-treated macrophages. Mechanistically, using the JASPAR database, electromobility shift assays, and luciferase reporter assays, we revealed that Bach1 inhibited mRNA expression of mitochondrial transcription factor A (<i>TFAM</i>) by directly binding to its promoter region. <b><i>Innovation and Conclusion:</i></b> Our findings indicate that silencing of Bach1 protects against RP by upregulating the mRNA expression of <i>TFAM</i>, which, in turn, enhances mitochondrial function and reduces inflammation and oxidative stress. This study provides valuable insights into potential therapeutic strategies for patients with RP through Bach1 inhibition. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584353","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":"The Dual Role of Active Site Hydroxylated Residue in Peroxiredoxin Sulfinylation Catalysis.","authors":"Julie Mathieu, Alexandre Kriznik, Christophe Charron, Romain Perchat-Varlet, Benjamin Selles, Sophie Rahuel-Clermont","doi":"10.1089/ars.2024.0685","DOIUrl":"https://doi.org/10.1089/ars.2024.0685","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Peroxiredoxins (Prx) are ubiquitous Cys peroxidases regulated by sulfinylation, a modification that occurs when the sulfenic acid generated on the catalytic Cys by peroxide reduction reacts with a second molecule of peroxide. In the Prx1 family, sulfinylation sensitivity is controlled by competition between a structural transition from a fully folded (FF) to locally unfolded (LU) conformation and the chemical step of sulfinylation. The initial peroxide reduction relies on a conserved catalytic hydroxylated residue that allows peroxide optimal activation. This study aimed at investigating the role of this catalytic residue in sulfinylation. <b><i>Results:</i></b> Sulfenate attack on peroxide was favored by one order of magnitude when a catalytic Thr was present, for yeast cytosolic Prx1-type enzymes, human Prx1 and yeast mitochondrial Prx, a Prx6-type enzyme. Furthermore, pKa determination supported the notion of electrostatic interaction between the catalytic hydroxyl and sulfenate intermediate. Finally, FF-LU transition kinetics was faster with a catalytic Thr, supporting that the hydroxyl group proximity to the nascent sulfenate group also promotes the FF-LU transition. <b><i>Innovation:</i></b> We identify a major mechanism that activates sulfinylation in hyperoxidation-sensitive Prxs from the Prx1 and Prx6 families. Furthermore, we show that the catalytic hydroxylated residue holds a dual role in regulating hyperoxidation sensitivity, by activating the sulfinylation reaction, while also promoting the competing FF to LU transition, thus acting as an important regulatory determinant. <b><i>Conclusion:</i></b> The present work sets the basis for investigating other instances of Cys proteins regulated by sulfinylation, a modification increasingly recognized in cell redox regulation and signaling. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595837","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":"Anti-Inflammatory Effects of Hydrogen Sulfide in Axes Between Gut and Other Organs.","authors":"Weizhuo Lu, Jiyue Wen","doi":"10.1089/ars.2023.0531","DOIUrl":"10.1089/ars.2023.0531","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Hydrogen sulfide (H₂S), a ubiquitous small gaseous signaling molecule, plays a critical role in various diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ischemic stroke, and myocardial infarction (MI) <i>via</i> reducing inflammation, inhibiting oxidative stress, and cell apoptosis. <b><i>Recent Advances:</i></b> Uncontrolled inflammation is closely related to pathological process of ischemic stroke, RA, MI, and IBD. Solid evidence has revealed the axes between gut and other organs like joint, brain, and heart, and indicated that H₂S-mediated anti-inflammatory effect against IBD, RA, MI, and ischemic stroke might be related to regulating the functions of axes between gut and other organs. <b><i>Critical Issues:</i></b> We reviewed endogenous H₂S biogenesis and the H₂S-releasing donors, and revealed the anti-inflammatory effects of H₂S in IBD, ischemic stroke, RA, and MI. Importantly, this review outlined the potential role of H₂S in the gut-joint axis, gut-brain axis, and gut-heart axis as a gasotransmitter. <b><i>Future Direction:</i></b> The rate, location, and timing of H₂S release from its donors determine its potential success or failure as a useful therapeutic agent and should be focused on in the future research. Therefore, there is still a need to explore internal and external sources monitoring and controlling H₂S concentration. Moreover, more efficient H₂S-releasing compounds are needed; a better understanding of their chemistry and properties should be further developed. <i>Antioxid. Redox Signal.</i> 42, 341-360.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"341-360"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798974","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":"Dual Oxygen-Responsive Control by RegSR of Nitric Oxide Reduction in the Soybean Endosymbiont <i>Bradyrhizobium diazoefficiens</i>.","authors":"Andrea Jiménez-Leiva, Raquel A Juárez-Martos, Juan J Cabrera, María J Torres, Socorro Mesa, María J Delgado","doi":"10.1089/ars.2024.0710","DOIUrl":"10.1089/ars.2024.0710","url":null,"abstract":"<p><p><b><i>Aims:</i></b> To investigate the role of the RegSR-NifA regulatory cascade in the oxygen control of nitric oxide (NO) reduction in the soybean endosymbiont <i>Bradyrhizobium diazoefficiens</i>. <b><i>Results:</i></b> We have performed an integrated study of <i>norCBQD</i> expression and NO reductase activity in <i>regR</i>, <i>regS</i>₁, <i>regS</i>₂, <i>regS</i>_1/2, and <i>nifA</i> mutants in response to microoxia (2% O₂) or anoxia. An activating role of RegR and NifA was observed under anoxia. In contrast, under microaerobic conditions, RegR acts as a repressor by binding to a RegR box located between the -10 and -35 regions within the <i>norCBQD</i> promoter. In addition, both RegS₁ and RegS₂ sensors cooperated with RegR in repressing <i>norCBQD</i> genes. <b><i>Innovation:</i></b> NO is a reactive gas that, at high levels, acts as a potent inhibitor of symbiotic nitrogen fixation. In this paper, we report new insights into the regulation of NO reductase, the major enzyme involved in NO removal in rhizobia. This knowledge will be crucial for the development of new strategies and management practices in agriculture, in particular, for improving legume production. <b><i>Conclusion:</i></b> Our results demonstrate, for the first time, a dual control of the RegSR two-component regulatory system on <i>norCBQD</i> genes control in response to oxygen levels. <i>Antioxid. Redox Signal.</i> 42, 408-420.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"408-420"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045346","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":"Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.","authors":"Samar Farha, Kewal Asosingh, Paul M Hassoun, John Barnard, Suzy Comhair, Andrew Reichard, Nicholas Wanner, Milena Radeva, Micheala A Aldred, Gerald J Beck, Erika Berman-Rosenzweig, Barry A Borlaug, J Emanuel Finet, Robert P Frantz, Gabriele Grunig, Anna R Hemnes, Nicholas Hill, Evelyn M Horn, Christine Jellis, Jane A Leopold, Reena Mehra, Margaret M Park, Franz P Rischard, W H Wilson Tang, Serpil C Erzurum","doi":"10.1089/ars.2024.0557","DOIUrl":"10.1089/ars.2024.0557","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status. Mitochondrial transmembrane potential, superoxide production, and mass were measured by flow cytometry in fresh platelets. Metabolomics analysis was performed on plasma samples. Global arginine bioavailability was calculated as the ratio of arginine/(ornithine+citrulline). <b><i>Results:</i></b> Global arginine bioavailability is consistently lower than controls in all PH groups. Although the mitochondrial mass is similar across all PH groups and controls, superoxide production and transmembrane potential vary across groups. Mitochondrial superoxide is higher in group 1 PAH and lowest in group 3 compared with other groups, while transmembrane potential is lower in group 1 PAH than controls or group 3. The alterations in mitochondrial functions of group 1 PAH are associated with changes in fatty acid metabolism. Mitochondrial transmembrane potential in group 1 PAH is associated with transplant-free survival. <b><i>Conclusion:</i></b> While alterations in mitochondrial function are found in all PH groups, group 1 PAH has a unique mitochondrial phenotype with greater superoxide and lower transmembrane potential linked to fatty acid metabolism, and clinically to survival. <i>Antioxid. Redox Signal.</i> 42, 361-377.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"361-377"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798984","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":"Mitochondrial-Derived Signaling Mediates Differentiation of Parietal Epithelial Cells into Podocytes.","authors":"Minzhou Wang, Wangshu Wu, Jiayue Lu, Renhua Lu, Lulin Min, Ahui Song, Bingru Zhao, Ying Li, Kewei Xie, Leyi Gu","doi":"10.1089/ars.2024.0580","DOIUrl":"10.1089/ars.2024.0580","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Parietal epithelial cells (PECs) are potential stem cells within the glomerulus, migrating into site of podocyte loss to differentiate into podocytes. Little is known about the mechanism mediating differentiation of PECs into podocytes. <b><i>Results:</i></b> <i>In vitro</i> differentiation of PECs into podocytes led to upregulation of podocyte markers such as Wilms' tumor gene 1 (WT-1), Forkhead box C1 (FOXC1), synaptopodin and podocin, accompanied by increased mitochondrial abundance. Preincubation with a mitochondrial reactive oxygen species (ROS) inhibitor prevented all these events in PECs. <i>In vivo</i>, adriamycin (ADR)-treated mice exhibited albuminuria, decreased WT1 positive cells, and claudin-1 expressed in glomerular capillary tuft, as well as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) overproduction in PECs. Expression of the ROS-related molecule nuclear factor erythroid 2-related factor 2 (Nrf2) and its target protein Brahma-related gene 1 (Brg1) increased during differentiation of PECs into podocytes. Suppressing Nrf2 or Brg1 reduced the differentiation of PECs, whereas overexpression had the opposite effect. Brg1 directly regulated WT-1 transcription in PECs. Activation of Nrf2 with bardoxolone-methyl (CDDO-Me) resulted in less proteinuria and more WT1 positive cells in ADR mice. PECs conditional human Nrf2 knock-in mice showed increased WT1 cell numbers. <b><i>Conclusion:</i></b> It concluded that mitochondria-derived ROS mediated differentiation of PECs into podocytes <i>via</i> Nrf2 and Brg1 signaling. <i>Antioxid. Redox Signal.</i> 42, 393-407.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"393-407"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103734","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":"H₂S Donor SPRC Ameliorates Cardiac Aging by Suppression of JMJD3, a Histone Demethylase.","authors":"Sha Li, Qixiu Li, Hong Xiang, Chenye Wang, Qi Zhu, Danping Ruan, Yi Zhun Zhu, Yicheng Mao","doi":"10.1089/ars.2024.0605","DOIUrl":"10.1089/ars.2024.0605","url":null,"abstract":"<p><p><b><i>Aims:</i></b> S-propargyl-cysteine (SPRC) is an endogenous hydrogen sulfide (H₂S) donor obtained by modifying the structure of S-allyl cysteine in garlic. This study aims to investigate the effect of SPRC on mitigating cardiac aging and the involvement of jumonji domain-containing protein 3 (JMJD3), a histone demethylase, which represents the primary risk factor in major aging related diseases, in this process, elucidating the preliminary mechanism through which SPRC regulation of JMJD3 occurs. <b><i>Results:</i></b> <i>In vitro</i>, SPRC mitigated the elevated levels of reactive oxygen species, senescence-associated β-galactosidase, p53, and p21, reversing the decline in mitochondrial membrane potential, which represented a reduction in cellular senescence. <i>In vivo</i>, SPRC improved Dox-induced cardiac pathological structure and function. Overexpression of JMJD3 accelerated cardiomyocytes and cardiac senescence, whereas its knockdown <i>in vitro</i> reduced the senescence phenotype. The potential binding site of the upstream transcription factor of JMJD3, sheared X box binding protein 1 (XBP1s), was determined using online software. SPRC promoted the expression of cystathionine γ-lyase (CSE), which subsequently inhibited the IRE1α/XBP1s signaling pathway and decreased JMJD3 expression. <b><i>Innovations:</i></b> This study is the first to establish JMJD3 as a crucial regulator of cardiac aging. SPRC can alleviate cardiac aging by upregulating CSE and inhibiting endoplasmic reticulum stress pathways, which in turn suppress JMJD3 expression. <b><i>Conclusions:</i></b> JMJD3 plays an essential role in cardiac aging regulation, whereas SPRC can suppress the expression of JMJD3 by upregulating CSE, thus delaying cardiac aging, which suggests that SPRC may serve as an aging protective agent, and pharmacological targeting of JMJD3 may also be a promising therapeutic approach in age-related heart diseases. <i>Antioxid. Redox Signal.</i> 42, 301-320.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"301-320"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103733","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}