Redox Biology最新文献

{"title":"Alleviation of accelerated diabetic atherogenesis in STZ-treated apoE/NOX1 DKO mice, apoE−/−/tg-EC-DHFR mice, and by folic acid","authors":"Yixuan Zhang,&nbsp;Ji Youn Youn,&nbsp;Kai Huang,&nbsp;Yuhan Zhang,&nbsp;Hua Cai","doi":"10.1016/j.redox.2025.103570","DOIUrl":"10.1016/j.redox.2025.103570","url":null,"abstract":"<div><div>We and others have previously shown that uncoupling of endothelial nitric oxide synthase (eNOS) induces oxidative stress in diabetes, contributing to endothelial dysfunction. Activation of NADPH oxidase (NOX) isoform NOX1 by angiotensin II (Ang II) triggers eNOS uncoupling via deficiency in dihydrofolate reductase (DHFR) in streptozotocin (STZ)-induced type 1 diabetic mice. Presently, we investigated whether accelerated atherosclerosis is attenuated in apoE/NOX1 double knockout, and whether mice overexpressing DHFR in the endothelium (tg-EC-DHFR, generated in house) recouples eNOS to alleviate diabetic atherogenesis. At baseline, endothelial-specific DHFR overexpression recoupled eNOS and improved vasorelaxation in the aortas and mesenteric arteries of STZ-induced diabetic mice. Accelerated atherogenesis in STZ/high-fat diet (HFD) treated apoE^−/− mice was markedly abrogated in tg-EC-DHFR background, establishing an important role of endothelial DHFR in maintaining vascular function and protecting from diabetic atherogenesis. Moreover, by crossing apoE^−/− with NOX1 null mice (NOX1^-/y), we found that NOX1 deletion markedly diminished atherosclerotic lesion formation in HFD + STZ-treated apoE^−/−/NOX1^-/y mice, indicating that NOX1 lies upstream of eNOS uncoupling in facilitating diabetic atherogenesis. Oral administration with folic acid (FA), shown to upregulate DHFR, robustly attenuated atherosclerotic lesion formation in HFD + STZ-treated apoE^−/− mice similarly to NOX1 deletion. Taken together, our data for the first time demonstrate that endothelial DHFR plays an important role in the preservation of endothelial function and inhibition of atherosclerosis in diabetes, deficiency of which consequent to NOX1 activation mediates eNOS uncoupling driven lesion formation. Strategies targeting uncoupled eNOS prove to be robust treatment options for diabetic endothelial dysfunction and atherogenesis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103570"},"PeriodicalIF":10.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating neutrophil responses to stimuli: Comparative analysis of reactive species-dependent and independent mechanisms","authors":"Lorenna Rocha Reis ,&nbsp;Rafaela Oliveira Nascimento ,&nbsp;Mariana Pereira Massafera,&nbsp;Paolo Di Mascio,&nbsp;Graziella Eliza Ronsein","doi":"10.1016/j.redox.2025.103540","DOIUrl":"10.1016/j.redox.2025.103540","url":null,"abstract":"<div><div>Neutrophils play a critical role in immune response, using mechanisms as degranulation, phagocytosis, and the release of extracellular DNA together with microbicidal proteins, the so-called neutrophil extracellular traps (NETs), to combat pathogens. Multiple mechanisms might be involved in neutrophil's response to stimuli, but the biochemical characterization of each different pathway is still lacking. In this study, we used superoxide measurements, live-imaging microscopy and high-resolution proteomics to provide a thorough biochemical characterization of the neutrophil's response following activation by two well-known stimuli, namely phorbol-12-myristate-13-acetate (PMA), and ionomycin, a calcium ionophore. Our results demonstrated that although both stimuli induce extracellular DNA release, signals and mediators released by activated cells before this final event were distinct. Thus, PMA-treated neutrophils induce superoxide production, and degranulation of proteins from all granules, especially those derived from secretory vesicles and tertiary granules. On the other hand, ionomycin-treated neutrophils do not stimulate superoxide generation, but induce extensive protein citrullination (also known as arginine deimination), particularly modifying proteins related to actin cytoskeleton organization, nucleus stability, and the NADPH oxidase complex. Interestingly, many of the citrullinated proteins detected in this work were also found to act as autoantigens in autoimmune diseases such as rheumatoid arthritis. These striking differences show neutrophils' response to PMA and ionomycin are two distinct biochemical processes that point towards neutrophils diversification and plasticity responding to the environment. It also provides implications for understanding neutrophil-driven microbial response and potential roles in autoimmune diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103540"},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Succinate predisposes mice to atrial fibrillation by impairing mitochondrial function via SUCNR1/AMPK axis","authors":"Yudi Zhang ,&nbsp;Haoyu Gong ,&nbsp;Lingyan Jin ,&nbsp;Peng Liu ,&nbsp;Jiali Fan ,&nbsp;Xinghua Qin ,&nbsp;Qiangsun Zheng","doi":"10.1016/j.redox.2025.103576","DOIUrl":"10.1016/j.redox.2025.103576","url":null,"abstract":"<div><div>Atrial fibrillation (AF), a major public health concern, is associated with high rates of death and disability. Mitochondrial dysfunction has emerged as a key contributor to the pathophysiology of AF. Succinate, an essential Krebs cycle metabolite, is often elevated in the circulation of patients at risk for AF. However, its exact role in AF pathogenesis is still not well understood. To explore the association linking succinate overload and AF, we first established AF-susceptible mouse models of obesity and diabetes, confirming that circulating succinate levels were significantly elevated in these AF-prone mice. Next, we assessed AF vulnerability and atrial remodeling in succinate-treated mice (2 %/5 % for 7 weeks) or isolated primary atrial cells (0.5 mM for 24 h). Our results demonstrated that succinate overload increased AF susceptibility in mice and triggered adverse atrial remodeling, characterized by left atrial dilation, connexins lateralization, ion channel disturbances, and fibrosis. Moreover, succinate compromised atrial mitochondrial structure, leading to increased oxidative stress. Mechanistically, succinate overload upregulated the expression of its cognate receptor SUCNR1 (succinate receptor 1) and decreased AMPK (AMP-activated protein kinase) phosphorylation both <em>in vitro</em> and <em>in vivo</em>. AICAR (AMPK activator) maintained mitochondrial health to mitigate remodeling in succinate-exposed cells and prevented succinate-induced AF in obese and diabetic mice. In conclusion, succinate overload enhances AF vulnerability and atrial remodeling by impairing AMPK signaling and mitochondrial function. Succinate, therefore, represents an underappreciated contributor to AF pathogenesis and a potential biomarker.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103576"},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indoleamine 2,3-dioxygenase 1 drives epithelial cells ferroptosis in influenza-induced acute lung injury","authors":"Yongxin Zheng ,&nbsp;Yu Zhang ,&nbsp;Yubiao Chen ,&nbsp;Xiumei Deng ,&nbsp;Baiyun Liu ,&nbsp;Qiang Xu ,&nbsp;Chuyun Qian ,&nbsp;Zhihui Zhang ,&nbsp;Ke Wang ,&nbsp;Yuan Zeng ,&nbsp;Zhenting Liang ,&nbsp;Ling Sang ,&nbsp;Lingbo Nong ,&nbsp;Xiaoqing Liu ,&nbsp;Yonghao Xu ,&nbsp;Yimin Li ,&nbsp;Yongbo Huang","doi":"10.1016/j.redox.2025.103572","DOIUrl":"10.1016/j.redox.2025.103572","url":null,"abstract":"<div><div>Acute lung injury (ALI) is a life-threatening complication of influenza A virus (IAV) infection, characterized by high morbidity and mortality. Recent studies have implicated ferroptosis, a distinct form of regulated cell death characterized by iron-dependent lipid peroxidation, in the pathogenesis of IAV-induced ALI. However, the underlying mechanisms and key regulators of IAV-induced ferroptosis remain largely unknown. In this study, we found that IAV infection induces predominant ferroptosis in alveolar and bronchial epithelial cells, contributing to tissue damage and the development of acute lung injury. Treatment with the ferroptosis inhibitor ferrostatin-1 improved survival, mitigated weight loss, and alleviated lung injury in IAV-infected mice. Mechanistically, IAV-induced ferroptosis was associated with excess lipid peroxidation, nitrative stress, and disrupted iron metabolism. Targeted lipidomic analysis revealed that phospholipid peroxidation is a crucial mechanism in IAV-induced ferroptosis. Importantly, we identified indoleamine 2,3-dioxygenase 1 (IDO1) as a key regulator of IAV-induced ferroptosis. IDO1 knockdown inhibited IAV-induced cell death, and reduced intracellular reactive oxygen species, peroxynitrite, and inducible nitric oxide synthase expression. Furthermore, pharmacological inhibition of IDO1 with 1-methyl-tryptophan improved ALI phenotype in IAV-infected mice. These findings highlight the critical role of ferroptosis in IAV-induced ALI pathogenesis and identify IDO1 as a potential therapeutic target for the treatment of this life-threatening condition.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103572"},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between serum micronutrients and all-cause, cancer, and cardiovascular mortality in a national representative population: Mediated by inflammatory biomarkers","authors":"Chunliang Liu ,&nbsp;Harrison Wongsonegoro ,&nbsp;Tianchen Sheng ,&nbsp;Hao Fan ,&nbsp;Jianjun Zhang","doi":"10.1016/j.redox.2025.103573","DOIUrl":"10.1016/j.redox.2025.103573","url":null,"abstract":"<div><h3>Background</h3><div>Micronutrient intake was inversely associated with cancer and cardiovascular risk in previous studies, but obtained results were inconsistent and the biological mechanisms for this potential protective effect remain elusive. Therefore, we investigated the associations of serum vitamin C, 25(OH)D, α-tocopherol, β-carotene, lycopene, folate, and iron with all-cause, cancer, and cardiovascular mortality. We further evaluated whether these associations were mediated through altered inflammatory responses.</div></div><div><h3>Methods</h3><div>Data were obtained from 11,539 participants aged ≥40 years in the National Health and Nutrition Examination Survey (NHANES) in 2001–2006 and 2017–2018. Mortality status of the participants with an average follow-up of 10.5 years was ascertained from the linked mortality files of the National Death Index. Cox proportional hazards regression was performed to evaluate mortality risk in relation to serum micronutrients, while mediation analysis was used to assess the mediating effects of serum C-reactive protein and white blood cell count on the associations of interest.</div></div><div><h3>Results</h3><div>After adjustment for confounders, serum levels of vitamin C, 25(OH)D, β-carotene, and lycopene were associated with a reduced risk of death from all causes, cancer, and cardiovascular disease. For example, HRs (95 % CIs) for quartiles 2, 3, and 4 vs. quartile 1 of 25(OH)D were, respectively, 0.72 (0.62, 0.83), 0.70 (0.62, 0.79), and 0.66 (0.56, 0.78) (p-trend: &lt;0.0001) for all-cause mortality, 0.68 (0.52, 0.91), 0.54 (0.39, 0.73), and 0.48 (0.32, 0.71) (p-trend: 0.0001) for cancer mortality, and 0.64 (0.50, 0.83), 0.66 (0.53, 0.83), and 0.59 (0.42, 0.82) (p-trend: 0.0012) for cardiovascular mortality. Additionally, serum C-reactive protein significantly mediated 5.3%–20.4 %, 4.5%–18.1 %, and 3.3%–15.7 % of the associations of vitamin C, 25(OH)D, β-carotene, and lycopene with all-cause, cancer, and cardiovascular mortality, respectively.</div></div><div><h3>Conclusion</h3><div>This study suggested that serum levels of several antioxidants and vitamin D were inversely associated with all-cause, cancer, and cardiovascular mortality, mediated in part by mitigated inflammatory responses.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103573"},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactive oxygen species in tendon injury and repair","authors":"Damir Kračun ,&nbsp;Agnes Görlach ,&nbsp;Jess G. Snedeker ,&nbsp;Johanna Buschmann","doi":"10.1016/j.redox.2025.103568","DOIUrl":"10.1016/j.redox.2025.103568","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) are chemical moieties that in physiological concentrations serve as fast-acting signaling molecules important for cellular homeostasis. However, their excess either due to overproduction or inability of the antioxidant system to inactivate them results in oxidative stress, contributing to cellular dysfunction and tissue damage.</div><div>In tendons, which are hypovascular, hypocellular, and composed predominantly of extracellular matrix (ECM), particularly collagen I, ROS likely play a dual role: regulating cellular processes such as inflammation, proliferation, and ECM remodeling under physiological conditions, while contributing to tendinopathy and impaired healing when dysregulated.</div><div>This review explores the sources of ROS in tendons, including NADPH oxidases and mitochondria, and their role in key processes such as tissue adaptation to mechanical load and injury repair, also in systemic conditions such as diabetes. In addition, we integrate the emerging perspective that calcium signaling—mediated by mechanically activated ion channels—plays a central role in tendon mechanotransduction under daily mechanical loads. We propose that mechanical overuse (overload) may lead to hyperactivation of calcium channels, resulting in chronically elevated intracellular calcium levels that amplify ROS production and oxidative stress. Although direct evidence linking calcium channel hyperactivity, intracellular calcium dysregulation, and ROS generation under overload conditions is currently circumstantial, this review aims to highlight these connections and identify them as critical avenues for future research.</div><div>By framing ROS within the context of both adaptive and maladaptive responses to mechanical load, this review provides a comprehensive synthesis of redox biology in tendon injury and repair, paving the way for future work, including development of therapeutic strategies targeting ROS and calcium signaling to enhance tendon recovery and resilience.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103568"},"PeriodicalIF":10.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of the LKB1-AMPK-SLC7A11-GSH signaling pathway sensitizes NSCLC to albumin-bound paclitaxel via oxidative stress","authors":"Dade Rong ,&nbsp;Liangliang Gao ,&nbsp;Yiguan Chen ,&nbsp;Xiang-Zheng Gao ,&nbsp;Mingzhu Tang ,&nbsp;Haimei Tang ,&nbsp;Yuan Gao ,&nbsp;Guang Lu ,&nbsp;Zhi-Qiang Ling ,&nbsp;Han-Ming Shen","doi":"10.1016/j.redox.2025.103567","DOIUrl":"10.1016/j.redox.2025.103567","url":null,"abstract":"<div><div>Albumin-bound paclitaxel (nab-PTX) is an important chemotherapeutic drug used for the treatment of advanced and metastatic non-small cell lung cancer (NSCLC). One critical issue in its clinical application is the development of resistance; thus, a deeper understanding of the mechanisms underlying the primary resistance to nab-PTX is expected to help to develop effective therapeutic strategies to overcome resistance. In this study, we made an unexpected discovery that NSCLC with wild-type (WT) Liver kinase B1 (LKB1), an important tumor suppressor and upstream kinase of AMP-activated protein kinase (AMPK), is more resistant to nab-PTX than NSCLC with mutant <em>LKB1</em>. Mechanistically, LKB1 status does not alter the intracellular concentration of nab-PTX or affect its canonical pharmacological action in promoting microtubule polymerization. Instead, we found that LKB1 mediates AMPK activation, leading to increased expression of SLC7A11, a key amino acid transporter and intracellular level of glutathione (GSH), which then attenuates the production of reactive oxygen species (ROS) and apoptotic cell death induced by nab-PTX. On the other hand, genetic or pharmacological inhibition of AMPK in <em>LKB1</em>-WT NSCLC reduces the expression of SLC7A11 and intracellular GSH, increases ROS level, and eventually promotes the apoptotic cell death induced by nab-PTX <em>in vitro</em>. Consistently, the combination of nab-PTX with an AMPK inhibitor exhibits a greater therapeutic efficacy in <em>LKB</em>1-WT NSCLC using xenograft models <em>in vivo</em>. Taken together, our data reveal a novel role of LKB1-AMPK-SLC7A11-GSH signaling pathway in the primary resistance to nab-PTX, and provide a therapeutic strategy for the treatment of <em>LKB1</em>-WT NSCLC by targeting the LKB1-AMPK-SLC7A11-GSH pathway.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103567"},"PeriodicalIF":10.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 deficiency leads to inadequate beta cell adaptation during pregnancy and gestational diabetes","authors":"Fatema Haidery ,&nbsp;Luca Lambertini ,&nbsp;Isabelle Tse ,&nbsp;Sriya Dodda ,&nbsp;Adolfo Garcia-Ocaña ,&nbsp;Donald K. Scott ,&nbsp;Sharon Baumel-Alterzon","doi":"10.1016/j.redox.2025.103566","DOIUrl":"10.1016/j.redox.2025.103566","url":null,"abstract":"<div><div>The late stages of mammalian pregnancy are accompanied by a mild increase in insulin resistance likely due to enhanced glucose demand of the growing fetus. Therefore, as an adaptive process to maintain euglycemia during pregnancy, maternal β-cell mass expands leading to increased insulin release. Defects in functional β-cell adaptive expansion during pregnancy can lead to gestational diabetes mellitus (GDM). While the exact mechanisms that promote GDM are poorly understood, GDM is associated with inadequate functional β-cell mass expansion and with a systematic increase of oxidative stress. Here, we show that NRF2 levels are upregulated in mouse β-cells at gestational day 15 (GD15). Inducible β-cell-specific <em>Nrf2</em> deleted (βNrf2KO) mice display reduced β-cell proliferation, increased β-cell oxidative stress and lipid peroxidation, compromised β-cell function, and elevated β-cell death, leading to impaired β-cell mass expansion and dysregulated glucose homeostasis towards the end of pregnancy. Importantly, the gestational hormone 17-β-estradiol (E2) increases NRF2 levels, and downregulation of NRF2 suppresses E2-induced protection of β-cells against oxidative stress, suggesting that E2 exerts its antioxidant effects through activation of NRF2 signaling in β-cells. Collectively, these data highlight the critical role of NRF2 in regulating oxidative stress during the adaptive response of β-cells in pregnancy and identify NRF2 as a potential therapeutic target for GDM treatment.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103566"},"PeriodicalIF":10.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cleavage site heterogeneity at the pre-mRNA 3′-untranslated region regulates gene expression in oxidative stress response","authors":"Feba Shaji ,&nbsp;Jamshaid Ali ,&nbsp;Rakesh S. Laishram","doi":"10.1016/j.redox.2025.103565","DOIUrl":"10.1016/j.redox.2025.103565","url":null,"abstract":"<div><div>The endonucleolytic cleavage step of the eukaryotic mRNA 3′-end processing is considered imprecise, which leads to heterogeneity of cleavage site (CS) with hitherto unknown function. Contrary to popular belief, we show that this imprecision in the cleavage is tightly regulated, resulting in the CS heterogeneity (CSH) that controls gene expression in antioxidant response. CSH centres around a primary CS, followed by several subsidiary cleavages determined by CS's positions. Globally and using reporter antioxidant mRNA, we discovered an inverse relationship between the number of CS and the gene expression, with the primary CS exhibiting the highest cleavage efficiency. Strikingly, reducing CSH and increasing primary CS usage induces gene expression. Under oxidative stress (we employ three conditions that induce antioxidant response, tBHQ, H₂O₂, and NaAsO₂) conditions, there is a decrease in the CSH and an increase in the primary CS usage to induce antioxidant gene expression. Key oxidative stress response genes (<em>NQO1</em>, <em>HMOX1</em>, <em>PRDX1</em>, and <em>CAT</em>) also show higher CSH compared to the non-stress response genes and that the number of CSs are reduced to impart cellular response to oxidative stresses. Concomitantly, ectopic expression of one of the key antioxidant response gene (<em>NQO1</em>) driven by the primary CS but not from other subsidiary CSs, or reduction in CSH imparts tolerance to cellular oxidative stresses (H₂O₂, and NaAsO₂). Genome-wide CS analysis of stress response genes also shows a similar result. Compromised CSH or CSH-mediated gene control hampers cellular response to oxidative stress. We establish that oxidative stress induces affinity/strength of cleavage complex assembly, increasing the fidelity of cleavage at the primary CS, thereby reducing CSH inducing antioxidant response. Together, our study reports a novel cleavage imprecision- or CSH-mediated anti-oxidant response mechanism that is distinct and operates downstream but in concert with the transcriptional pathway of oxidative stress induction.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103565"},"PeriodicalIF":10.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-sulfur cluster proteins present the weak spot in non-thermal plasma-treated Escherichia coli","authors":"Marco Krewing,&nbsp;Kim Marie Weisgerber,&nbsp;Tim Dirks,&nbsp;Ivan Bobkov,&nbsp;Britta Schubert,&nbsp;Julia Elisabeth Bandow","doi":"10.1016/j.redox.2025.103562","DOIUrl":"10.1016/j.redox.2025.103562","url":null,"abstract":"<div><div>Non-thermal atmospheric pressure plasmas have an antiseptic activity beneficial in different medical applications. In a genome-wide screening, hydrogen peroxide and superoxide were identified as key species contributing to the antibacterial effects of plasma while [FeS] cluster proteins emerged as potential cellular targets. We investigated the impact of plasma treatment on [FeS] cluster homeostasis in <em>Escherichia coli</em> treated for 1 min with the effluent of a microscale atmospheric pressure plasma jet (μAPPJ). Mutants defective in [FeS] cluster synthesis and maintenance lacking the SufBC₂D scaffold protein complex or desulfurase IscS were hypersensitive to plasma treatment. Monitoring the activity of [FeS] cluster proteins of the tricarboxylic acid cycle (aconitase, fumarase, succinate dehydrogenase) and malate dehydrogenase (no [FeS] clusters), we identified cysteine, iron, superoxide dismutase, and catalase as determinants of plasma sensitivity. Survival rates, enzyme activity, and restoration of enzyme activity after plasma treatment were superior in mutants with elevated cysteine levels and in the wildtype under iron replete conditions. Mutants with elevated hydrogen peroxide and superoxide detoxification capacity over-expressing <em>sodA</em> and <em>katE</em> showed full protection from plasma-induced enzyme inactivation and survival rates increased from 34 % (controls) to 87 %. Our study indicates that metabolic and genetic adaptation of bacteria may result in plasma tolerance and resistance, respectively.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103562"},"PeriodicalIF":10.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}