Redox Report最新文献

{"title":"Sulfur amino acid restriction and caloric restriction induce divergent redox metabolism-related adaptations in male F344 rats.","authors":"Dwight A L Mattocks, Naidu B Ommi, András K Ponti, Christopher Hine, John T Pinto, Sailendra N Nichenametla","doi":"10.1080/13510002.2026.2742750","DOIUrl":"10.1080/13510002.2026.2742750","url":null,"abstract":"<p><strong>Introduction: </strong>To discover novel mechanisms, we compared changes in redox metabolism markers induced by caloric restriction (CR) and sulfur amino acid restriction (SAAR).</p><p><strong>Methods: </strong>We fed 16-week-old male F344 rats either a control diet (CD, 0.86% methionine), a sulfur amino acid-restricted diet (SAAR, 0.17% methionine), or a control diet pair-fed to 60% of the CD's <i>ad libitum</i> intake (CR, caloric restriction). We quantified small redox molecule concentrations, mRNA levels, and protein levels of relevant markers.</p><p><strong>Results: </strong>Compared with CR, SAAR decreased the hepatic total free glutathione (tGSH), increased GSSG:tGSH, protein-bound GSH:tGSH, and lowered glucose-6-phosphate dehydrogenase levels, indicating a pro-oxidant milieu. SAAR and CR differentially affected the NADPH-generating enzymes. SAAR increased the cytosolic malic enzyme (ME1) without affecting mitochondrial ME3, while CR increased ME3, but not ME1. CR elevated cytosolic methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) without affecting mitochondrial MTHFD2, whereas SAAR increased MTHFD2 without affecting MTHFD1. Folate cycle changes include increases in <i>Aldh1l1</i> and <i>Aldh1l2</i> by SAAR and MTHFD1L by CR. SAAR, but not CR, upregulated the gene expression of compartment-specific (de)glutathionylation enzymes; both diets had distinct effects on glutathionylation of the hepatic proteome.</p><p><strong>Conclusions: </strong>SAAR and CR engage different pathways to generate compartment-specific NADPH. Protein glutathionylation may contribute to SAAR-induced benefits.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2742750"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170494","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":"Oxidative stress biomarkers and flavonoids in Alzheimer's disease: current clinical evidence and therapeutic perspectives.","authors":"Muhammad-Safuan Zainuddin, Narendra Pamidi, Adzzie Shazleen Azman, Kasthuri Bai Magalingam, Saatheeyavaane Bhuvanendran","doi":"10.1080/13510002.2026.2677396","DOIUrl":"10.1080/13510002.2026.2677396","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a major global neurodegenerative disorder associated with high morbidity and mortality, yet current treatments remain largely symptomatic and ineffective in halting neurodegeneration. Growing evidence links oxidative stress potentially being an early event in AD progression. Consequently, therapeutic strategies targeting oxidative stress-mediated cellular damage are increasingly attractive. This review summarizes clinical evidence of oxidative stress biomarkers in AD and examines the neuroprotective mechanisms of flavonoids against oxidative stress <i>in vivo</i>, together with current clinical findings. Despite inconsistencies among studies due to variations in detection methods, a consistent trend of elevated oxidative stress in AD is evident, correlating with disease severity. Although <i>in vivo</i> studies have demonstrated that flavonoids restore antioxidant defences and suppress neuroinflammation, convincing clinical evidence of their efficacy in AD patients remains limited. Overall, these findings emphasize oxidative stress as a therapeutic target requiring further validation efforts.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2677396"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13215411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148034632","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":"DMAMCL induces ferroptosis in neuroblastoma by targeting HMOX1 in MYCN-amplified subtypes whereas targeting STEAP3 in MYCN-nonamplified subtypes.","authors":"Yifan Ma, Simeng Zhang, Dongyang Zhang, Zhongyan Hua, Zhijie Li","doi":"10.1080/13510002.2026.2702136","DOIUrl":"10.1080/13510002.2026.2702136","url":null,"abstract":"<p><strong>Objectives: </strong>Neuroblastoma (NB) is a common pediatric extracranial solid tumor. Dimethylaminomicheliolide (DMAMCL), a prodrug of Micheliolide (MCL), shows antitumor activity against NB, but its mechanisms remain unclear. This study investigated the antitumor mechanisms of DMAMCL in NB.</p><p><strong>Methods: </strong>Key pathways/genes were identified by RNA-seq and ferroptosis PCR array. Ferroptosis was confirmed by indicators. Mechanisms were investigated using siRNAs, shRNAs, and overexpression plasmids <i>in vitro</i> and <i>in vivo</i>. Direct targets were screened by LiP-MS. Molecular biology experiments elucidated the mechanisms.</p><p><strong>Results: </strong>DMAMCL induced ferroptosis in NB <i>in vitro</i> and <i>in vivo</i>, upregulating <i>HMOX1</i>. <i>HMOX1</i> knockdown attenuated DMAMCL-induced ferroptosis and its overexpression triggered ferroptosis in <i>MYCN</i>-amplified NB cells but not in <i>MYCN</i>-nonamplified cells. DMAMCL-induced ferroptosis via <i>HMOX1</i> upregulation depended on MYCN levels. Mechanistically, DMAMCL bound to KEAP1 in <i>MYCN</i>-amplified NB cells, increasing nuclear NRF2 and upregulating HMOX1. In <i>MYCN-</i>nonamplified NB cells, DMAMCL upregulated STEAP3, increasing Fe²⁺ and lipid peroxidation to induce ferroptosis. STEAP3 overexpression induced ferroptosis and suppressed tumor growth.</p><p><strong>Disscusion: </strong>DMAMCL induces ferroptosis in NB through MYCN-associated dual pathways, activating the NRF2/HMOX1 axis via KEAP1 binding in <i>MYCN</i>-amplified cells, while upregulating STEAP3 in <i>MYCN</i>-nonamplified cells. This provides new insights for DMAMCL application in treating NB subtypes with different MYCN levels.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2702136"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437667","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":"The cysteine metabolic regulation through CSE-transsulfuration pathway is essential in iron-induced oxidative damage of heart.","authors":"Yong Zhang, Yijun Xin, Jie Zhou, Guang Yang, Siying Li","doi":"10.1080/13510002.2026.2684348","DOIUrl":"10.1080/13510002.2026.2684348","url":null,"abstract":"<p><strong>Objectives: </strong>Iron overload (IO) cardiomyopathy is a major cause of mortality in patients with iron overload disorders. This study investigates the role of cystathionine <i>γ</i>-lyase (CSE), a key enzyme in the transsulfuration pathway for cysteine and hydrogen sulfide (H₂S) production, in iron-induced oxidative cardiac injury.</p><p><strong>Methods: </strong>We investigated the effects of CSE on oxidative stress, metabolic dysregulation, and cardiac remodeling using <i>in vivo</i> mouse models of chronic iron overload and <i>in vitro</i> ferric citrate (FAC)-treated cardiomyocytes.</p><p><strong>Results: </strong>Genetic deletion of <i>Cth</i> (encoding CSE) in mice exacerbated iron overload-induced cardiac hypertrophy, systolic dysfunction, and interstitial fibrosis. These effects correlated with reduced expression of the cysteine transporter SLC7A11, impaired glutathione (GSH) synthesis, and suppression of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) antioxidant signaling pathway. Conversely, CSE overexpression in cardiomyocytes restored SLC7A11 stability, and suppressed reactive oxygen species (ROS) production through the Nrf2/HO-1/GPX4 pathway, thereby attenuating iron-mediated oxidative damage. Mechanistically, CSE deficiency disrupted both cysteine uptake via SLC7A11and cysteine production via transsulfuration pathway, inducing a self-reinforcing cycle of oxidative stress.</p><p><strong>Conclusion: </strong>These findings demonstrate that the CSE-transsulfuration pathway serves as a crucial regulator of cysteine metabolism and antioxidant signaling in cardiomyocytes, presenting a potential therapeutic target in iron-induced cardiomyopathy.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2684348"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164231","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":"Lipid droplets as redox-active organelles after spinal cord injury: lipid peroxidation, mitochondrial dysfunction, and neuroinflammation.","authors":"Yichen Zhang, Jie Li, Yinan Liu, Dong Guo","doi":"10.1080/13510002.2026.2720356","DOIUrl":"https://doi.org/10.1080/13510002.2026.2720356","url":null,"abstract":"<p><strong>Objectives: </strong>Spinal cord injury (SCI) causes myelin breakdown and membrane disruption, leading to the release and redistribution of cholesterol, fatty acids, and other lipids within the lesion. The resulting disruption of lipid homeostasis can promote sustained lipid peroxidation, neuroinflammation, and repair failure. In recent years, lipid droplets (LDs) have been recognized as highly dynamic organelles that coordinate lipid storage, mobilization, energy metabolism, and stress responses. However, the stage- and cell-specific roles of LDs in lipid-redox dysregulation after SCI remain poorly understood.</p><p><strong>Methods: </strong>This review summarizes the basic mechanisms of LD formation, lipolysis, and lipophagy, examines the regulation of lipid peroxidation by LDs, and discusses bidirectional LD-mitochondria crosstalk. We further integrate evidence on LD remodeling across microglia/macrophages, astrocytes, neurons, oligodendrocyte-lineage cells, and microvascular endothelial cells. We also consider how these cell-specific changes relate to lipid detoxification and transfer, neuronal oxidative injury, blood-spinal cord barrier dysfunction, and remyelination.</p><p><strong>Results: </strong>We propose that LDs are not passive markers of lipid deposition after SCI but stage- and cell-type-dependent redox-metabolic regulators. Early LD formation may buffer acute lipid overload, whereas persistent oxidative stress, mitochondrial dysfunction, and impaired LD turnover may convert LDs into pathological lipid reservoirs that amplify lipid peroxidation and neuroinflammation. Finally, we discuss therapeutic strategies aimed at limiting pathological lipid accumulation, restoring LD turnover and cholesterol efflux, suppressing lipid peroxidation, and preserving mitochondrial redox homeostasis.</p><p><strong>Discussion: </strong>Together, this review provides an integrated framework for understanding how LD remodeling links lipid metabolic imbalance to secondary injury and neural repair after SCI.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2720356"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797660","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":"A novel curcumin analog sAc15 alleviates LPS-induced acute lung injury by activating the PI3K/AKT/Nrf2 pathway in pulmonary epithelial cells.","authors":"Liqin Zhou, Zhiyi Tang, Yuting Lin, Tengfei Zhou, Mengya Shen, Yuxi Lin, Chengshui Chen, Chaolei Chen","doi":"10.1080/13510002.2026.2721883","DOIUrl":"10.1080/13510002.2026.2721883","url":null,"abstract":"<p><strong>Objectives: </strong>Acute lung injury (ALI) is driven by oxidative stress and disrupted redox homeostasis. While curcumin is a potent natural antioxidant, its clinical application is limited. We evaluated the protective capacity and underlying mechanisms of sAc15, a stable curcumin analog, in ALI models.</p><p><strong>Methods: </strong><i>In vivo</i>, mice were intratracheally instilled with lipopolysaccharide (LPS) to induce ALI. <i>In vitro</i>, Beas-2b cells were exposed to <i>t</i>-BHP for oxidative damage. Target engagement was evaluated via surface Plasmon resonance (SPR). Protective effects and mechanisms were evaluated via histopathology, ROS accumulation, apoptosis assays, network pharmacology, Western blotting, LY294002 and Nrf2-specific siRNA.</p><p><strong>Results: </strong>sAc15 exhibited broader safety margins and superior ROS suppression compared to natural curcumin. SPR established direct binding between sAc15 and recombinant Nrf2 (KD = 2.68 μM). <i>In vivo and in vitro</i>, sAc15 mitigated pulmonary inflammation, oxidative stress, mitochondrial dysfunction and apoptosis. Mechanistically, sAc15 promoting PI3K/AKT phosphorylation and upregulating the expression of Nrf2, HO-1 and NQO-1. Crucially, Nrf2 silencing or PI3K inhibition markedly attenuated sAc15-mediated cytoprotective, anti-apoptotic, and antioxidant benefits.</p><p><strong>Conclusion: </strong>sAc15 ameliorates ALI by activating the PI3K/AKT/Nrf2 axis to restore oxidative equilibrium, hightlighhting its promise as a therapeutic candidate for ALI/ARDS.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2721883"},"PeriodicalIF":6.9,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148797707","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":"The hippo-YAP1/TEAD1-SLC7A5 axis: uncovering a novel therapeutic target for oxalate-induced renal tubular ferroptosis.","authors":"Junyi Yang, Zhilong Ma, Wenlong Wan, Dongfeng Yuan, Jiabo Li, Yongqi Wang, Baokang Wang, Guoruiyu Lyu, Yang Xun, Xiao Yu","doi":"10.1080/13510002.2026.2643967","DOIUrl":"10.1080/13510002.2026.2643967","url":null,"abstract":"<p><strong>Objectives: </strong>To systematically investigate the regulatory mechanisms of ferroptosis in renal tubular epithelial cells under high oxalate stress, focusing on identifying key upstream signaling pathways and their therapeutic potential.</p><p><strong>Methods: </strong>We employed HK-2 cell cultures and Glyoxylate-induced mouse models of oxalate nephropathy. Multi-omics approaches including 4D-label-free proteomics, RNA-sequencing, and CUT&Tag were integrated to identify regulatory networks. Functional validation utilized genetic manipulation, pharmacological intervention, chromatin immunoprecipitation, and dual-luciferase reporter assays.</p><p><strong>Results: </strong>High oxalate dose-dependently induced renal tubular ferroptosis and activated the Hippo pathway, leading to YAP1 phosphorylation and inactivation. Proteomic and multi-omics analyses identified YAP1 as a key regulator and SLC7A5 as its direct transcriptional target via TEAD1. High oxalate disrupted YAP1/TEAD1 binding to the SLC7A5 promoter, downregulating SLC7A5. Functional rescue confirmed that SLC7A5 loss mediated ferroptosis under YAP1 inhibition. Mechanistically, SLC7A5 downregulation restricted leucine availability and suppressed mTOR signaling, while leucine supplementation or mTOR reactivation reversed ferroptosis, demonstrating that SLC7A5 regulates ferroptosis via the leucine/mTOR axis.</p><p><strong>Conclusion: </strong>We establish the Hippo-YAP1/TEAD1-SLC7A5 axis as a master regulatory pathway controlling oxalate-induced ferroptosis. This pathway represents a promising therapeutic target for oxalate nephropathy and provides fundamental insights into stress-responsive ferroptosis regulation in kidney disease.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2643967"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147463289","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":"Ligustroflavone alleviates chronic kidney disease by inhibiting ferroptosis through the GSK3β/NRF2 signaling pathway.","authors":"Wen Zhang, Shaofan Wang, Yaru Wang, Sutianyi Li, Mingyue Chen, Jiayu Song, Yunwen Yang","doi":"10.1080/13510002.2026.2636421","DOIUrl":"10.1080/13510002.2026.2636421","url":null,"abstract":"<p><strong>Objectives: </strong>Chronic kidney disease (CKD) is a global public health concern, characterized by a gradual decline in kidney function, with death of renal tubular epithelial cells (RTECs) as a key pathological mechanism. This study investigated the protective effect of ligustroflavone in CKD and its potential molecular mechanisms.</p><p><strong>Methods: </strong><i>In vivo</i>, the unilateral ureteral obstruction (UUO) and folic acid-induced nephropathy (FAN) mouse models were employed to assess the effects of ligustroflavone. <i>In vitro</i>, RTECs were treated with erastin. Western blotting, qRT-PCR, immunofluorescence (IF), and immunohistochemistry (IHC) were performed to detect renal tubular injury both <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Results: </strong><i>In vivo</i>, ligustroflavone treatment significantly improved renal tubular damage and interstitial fibrosis in mice. Furthermore, our results demonstrated that ligustroflavone alleviated ferroptosis of RTECs by inhibiting GSK3β activity and reducing lipid peroxidation in mice. <i>In vitro</i>, ligustroflavone treatment inhibited erastin-induced ferroptosis in RTECs. In addition, ligustroflavone inhibited activation of myofibroblasts induced by ferroptosis of RTECs. Mechanistically, ligustroflavone exerted it's protect effects through the GSK3β/NRF2 pathway by inhibiting GSK3β and activating NRF2, thereby promoting GPX4 expression and suppressing ferroptosis.</p><p><strong>Conclusions: </strong>In summary, ligustroflavone inhibits ferroptosis in RTECs and confers protection in CKD. These findings suggest that ligustroflavone holds promise as a potential therapeutic agent for CKD.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2636421"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12943817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147309633","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":"Increased levels of systemic iron content in adult-onset interleukin-6 knockout mice.","authors":"Fali Zhang, Cuizhen Zhang, Qianqian Luo, Jia Li, Xiaoyan Qiu, Zhongming Qian","doi":"10.1080/13510002.2025.2602306","DOIUrl":"10.1080/13510002.2025.2602306","url":null,"abstract":"<p><strong>Background: </strong>Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in multiple metabolic disorders. IL-6 is well recognized to induce hepcidin expression and decreased serum iron through the JAK2/STAT3 pathway under inflammatory conditions. Targeted inhibition of IL-6 represents a potential therapeutic regimen for multiple diseases. The current study aimed to explore the physiological concentration of IL-6 in sustaining systemic iron homeostasis.</p><p><strong>Methods: </strong>IL-6-knockout mice (IL-6-/-) were established in the current study. Western blot measured the expression of key iron-related proteins in liver, kidney, spleen and duodenum, as well as hepatic hepcidin mRNA expression. Serum iron and hematologic parameters were detected. ELISA and Masson's trichrome staining were performed to detect renal TGF-β1 expression and collagen deposition. Furthermore, bone marrow-derived and peritoneal macrophages were prepared to identify the iron recycling.</p><p><strong>Results: </strong>Serum iron and tissue iron content were markedly elevated in IL-6-/- mice. Mechanistically, decreased renal erythropoietin (EPO) synthesis contributed to iron utilization, macrophage-mediated recycling of iron was markedly reduced, thereby resulting in systemic iron accumulation. However, IL-6-/- mice displayed increased Hepcidin expression via p-ERK activation and a significant reduction in duodenal iron uptake.</p><p><strong>Conclusion: </strong>This study highlighted the critical role of IL-6 in iron homeostasis both in physiological and pathological situations.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2602306"},"PeriodicalIF":7.4,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768982","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":"Nrf2 de-SUMOylation alleviates myocardial ischemia-reperfusion injury (MIRI) by attenuating myocardial ferroptosis in mice.","authors":"Qinyun Shi, Weifeng Yao, Wenlong Zhang, Jiaqian Xu, Xiyu Wang, Xiangyun Wei, Shuming Hu, Qiuju Fan, Huan Yang, Xiaoling Wu, Rong Cai","doi":"10.1080/13510002.2026.2624946","DOIUrl":"10.1080/13510002.2026.2624946","url":null,"abstract":"<p><strong>Objectives: </strong>Reperfusion, an essential therapeutic strategy for salvaging ischemic myocardium in ischemic heart disease, paradoxically exacerbates myocardial injury. Ferroptosis is a pivotal mechanism underlying myocardial ischemia-reperfusion injury (MIRI). Nrf2 can regulate ferroptosis, which could undergo SUMOylation at lysine 110 (K110) and was subsequently de-SUMOylated by Senp1. This study aimed to determine whether Nrf2 de-SUMOylation could mitigate MIRI by inhibiting myocardial ferroptosis.</p><p><strong>Methods: </strong>Nrf2 K110R mice, mimicking Nrf2 de-SUMOylation, were generated. Mice cardiac morphology and function were observed by hematoxylin-eosin staining (HE) and echocardiography under normal and MIRI conditions. Ferroptosis inhibitor liproxstatin-1 (Lip-1) was used to demonstrate ferroptosis participation in Nrf2 de-SUMOylation regulated MIRI. <i>In vitro,</i> SUMO1/sentrin-specific protease 1 <i>Senp1</i> KO H9C2 cells were subjected to RSL₃-induced ferroptosis to explore underlying mechanism.</p><p><strong>Results: </strong>Nrf2 K110R mice showed normal cardiac morphology and function at baseline. However, de-SUMOylation of Nrf2 alleviated myocardial ferroptosis, resulting in a reduction of MIRI severity in MIRI mice. The administration of Lip-1 attenuated the differences in MIRI between Nrf2 wild-type and K110R mice. Mechanistically, Nrf2 de-SUMOylation was associated with a reduction in Transferrin receptor (Tfr) expression level, thereby mitigating ferroptosis in cardiomyocytes.</p><p><strong>Conclusion: </strong>This study highlighted the role of Nrf2 SUMOylation in promoting ferroptosis during MIRI and identified Nrf2 de-SUMOylation as a potential therapeutic target for MIRI.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"31 1","pages":"2624946"},"PeriodicalIF":6.9,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12885000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126338","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}