Nitric oxide : biology and chemistry最新文献

{"title":"Corrigendum to “The impact of ciliary length on the mechanical response of osteocytes to fluid shear stress” [Nitric Oxide 155 2025 1–11]","authors":"Dong Ding , Ran Tian , Xiao Yang , Zhe Ren , Zhi-Cheng Jing , Xin-Tong Wu , Lian-Wen Sun","doi":"10.1016/j.niox.2025.09.001","DOIUrl":"10.1016/j.niox.2025.09.001","url":null,"abstract":"","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 38-39"},"PeriodicalIF":3.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004508","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":"Role of hydrogen sulfide in catalyzing the formation of NO-ferroheme","authors":"Laxman Poudel ,&nbsp;Thilini Karunarathna ,&nbsp;Stephen Baker ,&nbsp;Elmira Alipour ,&nbsp;Matthew R. Dent ,&nbsp;Jesús Tejero ,&nbsp;Mark T. Gladwin ,&nbsp;Anthony W. DeMartino ,&nbsp;Daniel B. Kim-Shapiro","doi":"10.1016/j.niox.2025.09.002","DOIUrl":"10.1016/j.niox.2025.09.002","url":null,"abstract":"<div><div>We recently demonstrated a rapid reaction between labile ferric heme and nitric oxide (NO) in the presence of reduced glutathione (GSH) or other small thiols in a process called thiol-catalyzed reductive nitrosylation, yielding a novel signaling molecule, labile nitrosyl ferrous heme (NO-ferroheme), which we and others have shown can regulate vasodilation and platelet homeostasis. Red blood cells (RBCs) contain high concentrations of GSH, and NO can be generated in the RBC via nitrite reduction and/or RBC endothelial nitric oxide synthase (eNOS) so that NO-ferroheme could, in principle, be formed in the RBC. NO-ferroheme may also form in other cells and compartments, including in plasma, where another small and reactive thiol species, hydrogen sulfide (H₂S/HS⁻), is also present and may catalyze NO-ferroheme formation akin to GSH. Here, we compare the reactivity of GSH and hydrogen sulfide with hemin in physiologically relevant media, including human serum albumin (HSA) and RBC membranes. Strikingly, hydrogen sulfide demonstrated a second-order rate constant over 10 times higher than GSH. We propose that the increased solubility of H₂S vs GSH in lipophilic environments – where labile heme is most readily found – and the increased steric hindrance of the bulkier GSH account for the faster reaction kinetics observed with hydrogen sulfide. Our findings suggest that the hydrogen sulfide-catalyzed reductive nitrosylation reaction produces thionitrous acid (HSNO), which readily undergoes further reactions with excess hydrogen sulfide to form nitrosopersulfide (SSNO⁻) and polysulfides. These results suggest a common theme in thiol-catalyzed reductive nitrosylation of labile ferric heme that could play an important role in NO signaling.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 40-50"},"PeriodicalIF":3.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008359","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":"Distribution and activation of nitrergic neurons in response to aversive stimulus exposure in the Tropidurus hispidus lizard: Involvement of glutamatergic circuitry","authors":"Katty Anne Amador de Lucena Medeiros ,&nbsp;Auderlan Mendonça de Gois ,&nbsp;Rodolfo Silva dos Santos ,&nbsp;Milena Caroline Nunes Monteiro ,&nbsp;Heitor Franco Santos ,&nbsp;Marina Freire de Souza ,&nbsp;Thassya Fernanda Oliveira dos Santos ,&nbsp;Marco Aurelio M. Freire ,&nbsp;Mariza Bortolanza ,&nbsp;Elaine Del-Bel ,&nbsp;José Ronaldo Santos ,&nbsp;Murilo Marchioro","doi":"10.1016/j.niox.2025.08.005","DOIUrl":"10.1016/j.niox.2025.08.005","url":null,"abstract":"<div><h3>Introduction</h3><div>Fear is a response to real aversive stimuli. Studies on phylogenetically distant species like reptiles can offer valuable insights into the neural mechanisms of fear.</div></div><div><h3>Objective</h3><div>To investigate the activation and distribution of nitrergic neurons in the telencephalon of <em>Tropidurus hispidus</em> lizards and evaluate the role of glutamatergic modulation via NMDA receptors following exposure to an aversive stimulus.</div></div><div><h3>Methods</h3><div>Lizards were exposed to a live cat, and 24 h later, NADPH-diaphorase histochemistry was performed in the telencephalon to quantify neuron number and optical density. In the second stage, animals received i.c.v. injections of the NMDA receptor antagonist AP5 (1.25, 2.5, or 5.0 μg/μl), followed by cat exposure and histochemical analysis.</div></div><div><h3>Results</h3><div>Exposure to the cat led to increased freezing time in lizards. These animals also showed an increased number of nitrergic neurons in the dorsal cortex, anterior dorsal ventricular ridge (ADVR), and dorsolateral amygdala, as well as elevated integrated optical density (IOD) in the striatum, ADVR, dorsolateral amygdala and lateral amygdaloid nucleus. The AP5 1.25 and 5.0 μg/μl groups exhibited some head or limb movements even in the presence of the cat. The 1.25 μg/μl group showed reduced neuron counts and IOD in the dorsolateral amygdala; the 2.5 μg/μl and 5.0 μg/μl groups showed reduced IOD and neuron counts in the striatum.</div></div><div><h3>Conclusion</h3><div><em>Tropidurus hispidus</em> lizards show fear-like behavior and decreased exploration after aversive stimuli, with nitric oxide in the telencephalon – particularly in the striatum and dorsolateral amygdala – modulating this response via NMDA receptor activation.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 23-37"},"PeriodicalIF":3.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926561","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":"Divergent roles of endothelial and red blood cell nitric oxide synthase in regulating cardiovascular function during anemia","authors":"Vithya Yogathasan ,&nbsp;Patricia Wischmann ,&nbsp;Isabella Solga ,&nbsp;Lilly Jäger ,&nbsp;Stefanie Becher ,&nbsp;Miriam M. Cortese-Krott ,&nbsp;Norbert Gerdes ,&nbsp;Malte Kelm ,&nbsp;Christian Jung ,&nbsp;Ramesh Chennupati","doi":"10.1016/j.niox.2025.08.004","DOIUrl":"10.1016/j.niox.2025.08.004","url":null,"abstract":"<div><h3>Background</h3><div>Red blood cells (RBCs) express functional endothelial nitric oxide synthase (eNOS), which regulates blood pressure (BP) independently of eNOS in endothelial cells (ECs) and provides cardioprotection during acute myocardial infarction (AMI). The functional role of RBC- and EC- eNOS in anemia remains unknown. This study evaluated the effects of RBC- or EC-specific eNOS deletion on hemodynamics and cardiac function in blood loss anemia.</div></div><div><h3>Methods</h3><div>and resultsAnemia was induced in EC- or RBC-specific eNOS knockout (KO) mice and their respective controls. In vivo flow-mediated dilation (FMD) was preserved in RBC-eNOS-KO mice under both baseline and anemic conditions but was impaired in EC-eNOS-KO mice compared to their respective controls. Wire myograph analysis of aortic rings showed preserved endothelium-dependent relaxation (EDR) in anemic RBC-eNOS-KO mice, while EDR was abolished in anemic EC-eNOS-KO mice relative to controls. Miller catheter BP measurements revealed elevated systolic and diastolic BP in EC-eNOS-KO mice under both baseline and anemic conditions. Both systolic and diastolic BP were increased in RBC-eNOS-KO mice compared to controls, whereas these parameters remained unchanged in anemic RBC-eNOS-KO mice compared to their respective controls. Echocardiography demonstrated preserved cardiac function across all genotypes at baseline, 3 days post-anemia, and 24 h post-reperfused AMI. However, infarct size was significantly increased in anemic RBC-eNOS-KO mice compared to controls.</div></div><div><h3>Conclusions</h3><div>Anemia mitigates the BP elevation caused by RBC-eNOS deletion, while hypertension persists in the absence of endothelial eNOS, highlighting vascular eNOS as the predominant regulator of BP under anemic conditions. RBC-eNOS limits infarct size under anemic conditions.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906965","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":"Corrigendum to “Catestatin alleviates PASMC phenotypic switching-mediated pulmonary arterial remodeling in a rat model of MCT-induced pulmonary arterial hypertension by promoting endothelium-derived NO synthesis” [Nitric Oxide158 (2025) 93–105]","authors":"Zheyu Liu ,&nbsp;Bo Cui ,&nbsp;Hao Ju ,&nbsp;Tuantuan Tan ,&nbsp;Jinchun Wu ,&nbsp;Manqi Yang ,&nbsp;Saeed Kashkooli ,&nbsp;Mian Cheng ,&nbsp;Gang Wu ,&nbsp;Tao Liu","doi":"10.1016/j.niox.2025.08.002","DOIUrl":"10.1016/j.niox.2025.08.002","url":null,"abstract":"","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 132-133"},"PeriodicalIF":3.2,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963242","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":"Nitrate-dependent changes in the primary and lateral root growth in wheat seedlings require the coordinated action of auxin, calcium and nitric oxide","authors":"Sandeep B. Adavi ,&nbsp;Lekshmy Sathee ,&nbsp;Rakesh Pandey ,&nbsp;Prachi Yadav","doi":"10.1016/j.niox.2025.08.003","DOIUrl":"10.1016/j.niox.2025.08.003","url":null,"abstract":"<div><div>Nitrate (NO₃⁻), besides serving as a major N source, also acts as a signalling molecule in plant growth and development. Studies on NO₃⁻ dependent regulation of root growth in wheat (<em>Triticum aestivum</em>) are mostly limited to morphophysiological changes, while the underlying signalling mechanisms remain largely unexplored. To bridge this gap, the present study aims to get a mechanistic understanding of the NO₃⁻ dependent regulation of root growth in wheat seedlings. For this, uniformly germinated two days old wheat seedlings were exposed to nitric oxide (NO) donor sodium nitroprusside (SNP), auxin source Indole-3-butyric acid (IBA), calcium chloride as source of calcium (Ca²⁺), NO scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), polar auxin transport inhibitor 2,3,5-triiodobenzoic acid (TIBA) and calcium chelator ethylene glycol-bis (β-aminoethyl ether)-N,N,N′,N'-tetraacetic acid (EGTA) with NO₃⁻ as a major determinant. After seven days, root traits were analyzed, and a tissue localization assay was performed using Fluo-3 AM, DAF-FM, and salkowski reagents to visualize the distribution of Ca²⁺, NO, and indole-3-acetic acid (IAA) in root tissues, respectively. The study reveals that the cross-talk of nitric oxide (NO), auxin and calcium (Ca²⁺) modulates NO₃⁻ regulated root growth in wheat seedlings. The changes in cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt) are a major mediator in the regulation of root growth. High NO₃⁻ (5 mM) in combination with exogenous IBA and Ca²⁺ suppresses the root growth, with ethylene acting downstream of [Ca²⁺]_cyt. We observed a synergistic effect between NO and endogenous IAA (Indole-3-acetic acid) in lateral root (LR) growth. In LRs, the external NO₃⁻ enhances the NO production, which is further augmented by the elevated [Ca²⁺]_cyt levels. Our results indicate that endogenous IAA plays a pivotal role in regulating root hair development on LR with NO and [Ca²⁺]_cyt functioning downstream of the signalling cascade. However, the high NO₃⁻ was found to counteract the root hair formation by importing the shoot-derived auxin. These findings provide valuable insights into the intricate signalling interactions between nitric oxide, auxin, and calcium in NO₃⁻ regulated root development in wheat, with potential targets for enhancing nutrient uptake efficiency. Further work is necessary to identify downstream signalling components and examine how shoot-to-root signalling modulates the root architectures under different NO₃⁻ regimes.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"159 ","pages":"Pages 11-22"},"PeriodicalIF":3.2,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920295","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":"Potential role of brain nitric oxide in inhibiting α7 nicotinic acetylcholine receptor-mediated suppression of the micturition reflex in rats","authors":"Nobutaka Shimizu ,&nbsp;Takahiro Shimizu ,&nbsp;Mio Togo ,&nbsp;Youichirou Higashi ,&nbsp;Satoshi Fukata ,&nbsp;Keiji Inoue ,&nbsp;Motoaki Saito","doi":"10.1016/j.niox.2025.07.003","DOIUrl":"10.1016/j.niox.2025.07.003","url":null,"abstract":"<div><div>Brain nitric oxide (NO), produced by NO synthase (NOS), exerts both facilitatory and inhibitory effects on micturition. A functional relationship between NO and nicotinic acetylcholine receptors (nAChRs) has been indicated, and we previously reported that stimulation of brain α7 nAChR suppresses the micturition reflex in rats. In this study, we investigated which brain NOS isozyme is involved in micturition regulation and how NO influences α7 nAChR-mediated suppression. Cystometry was performed in urethane-anesthetized male rats using a bladder catheter. SNAP (NO donor), <span>l</span>-NAME (NOS inhibitor), 3-bromo-7-nitroindazole (neuronal NOS inhibitor), or BYK191023 (inducible NOS inhibitor) was administered intracerebroventricularly (icv) 3 h after the surgery. In some rats, the effects of pre-treated SNAP or <span>l</span>-NAME on PHA568487 (α7 nAChR agonist, icv)-induced responses were assessed. Intercontraction intervals (ICI)—the interval between two voiding bladder contractions—were recorded starting 1 h before the first icv administration. SNAP (30 nmol/rat) shortened ICI, whereas <span>l</span>-NAME (100 nmol/rat) and 3-bromo-7-nitroindazole (100 nmol/rat) prolonged ICI; BYK191023 had no effect. PHA568487 (1 nmol/rat) induced ICI prolongation, but this response was suppressed by SNAP (10 nmol/rat). At a lower dose (0.3 nmol/rat), PHA568487 had no effect on ICI unless <span>l</span>-NAME (30 nmol/rat) was pre-administered, which then revealed its significant ICI-prolonging effect. These findings suggest a possibility that brain endogenous NO, particularly from neuronal NOS, may be involved in the inhibition of brain α7 nAChR-mediated suppression of the micturition reflex in rats.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 116-123"},"PeriodicalIF":3.2,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725008","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":"Nitric oxide as a biomarker for patients with endometriosis: a systematic review and meta-analysis","authors":"Kelly Campara ,&nbsp;Patrícia Rodrigues ,&nbsp;Fernanda Tibolla Viero,&nbsp;Brenda da Silva,&nbsp;Gabriela Trevisan","doi":"10.1016/j.niox.2025.07.002","DOIUrl":"10.1016/j.niox.2025.07.002","url":null,"abstract":"<div><h3>Background</h3><div>Endometriosis causes pelvic pain, inflammation, and increased oxidative stress levels. To assist in the diagnosis of endometriosis and molecular mechanisms, we propose synthesize the studies that NO levels in different samples using a systematic review and metanalysis. We also evaluate NO levels in different stages of endometriosis.</div></div><div><h3>Material/methods</h3><div>The protocol was registered with PROSPERO (CRD42023397591). We searched for all articles published up to November 2023 that evaluated NO levels in patients with endometriosis compared to control patients. We used the Newcastle-Ottawa Scale (NOS) to estimate the quality of the articles and the risk of bias. Publication bias was assessed using the Egger test and Begg test.</div></div><div><h3>Results</h3><div>In this study, 5795 articles were found, after revision 14 studies with 666 control patients and 881 patients with endometriosis were included. NO levels in the combined analysis of all samples from endometriosis patients were increased compared to control patients. Patients with type III/IV endometriosis showed higher levels of NO compared to controls in peritoneal fluid and serum/plasma. The increase in NO levels in patients with type III/IV endometriosis has a high quality of evidence without publication bias.</div></div><div><h3>Conclusion</h3><div>Here we demonstrate the increase of NO in peritoneal fluid samples from endometriosis patients. Therefore, NO levels may be directly linked to the pathophysiology of endometriosis and can be involved in the severity of endometriosis and inflammatory mechanisms.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 106-115"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659732","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":"Catestatin alleviates PASMC phenotypic switching-mediated pulmonary arterial remodeling in a rat model of MCT-induced pulmonary arterial hypertension by promoting endothelium-derived no synthesis","authors":"Zheyu Liu ,&nbsp;Bo Cui ,&nbsp;Hao Ju ,&nbsp;Tuantuan Tan ,&nbsp;Jinchun Wu ,&nbsp;Manqi Yang ,&nbsp;Saeed Kashkooli ,&nbsp;Mian Cheng ,&nbsp;Gang Wu ,&nbsp;Tao Liu","doi":"10.1016/j.niox.2025.07.001","DOIUrl":"10.1016/j.niox.2025.07.001","url":null,"abstract":"<div><h3>Background</h3><div>Enhancing the nitric oxide (NO) signaling pathway is an effective strategy for treating pulmonary arterial hypertension (PAH). Previous research has found that Catestatin (CST) exerts a negative inotropic effect by upregulating NO production. However, the effect of CST on PAH remains unclear.</div></div><div><h3>Methods</h3><div>In vivo, PAH was induced in rats by monocrotaline (MCT) injection. After MCT administration, continuous CST treatment was applied to the experimental group. At study conclusion, echocardiographic, hemodynamic, and histological assessments were performed. In vitro, the effects of CST on rat pulmonary arterial endothelial dysfunction and phenotypic switching of rat pulmonary arterial smooth muscle cells (rPASMC) under PAH-like conditions were investigated. The role of NO in rPASMC phenotypic switching was also explored.</div></div><div><h3>Results</h3><div>In vivo experiments demonstrated that CST significantly improved right heart structure and function in rats with PAH, reduced pulmonary arterial pressure, and alleviated remodeling of the right ventricle and pulmonary arteries. These effects were likely mediated by upregulation of the eNOS/cGMP/PKG pathway. In vitro, CST promoted endothelial NO synthesis via the PI3K/Akt/eNOS pathway, but had no significant impact on the proliferation or migration of rPASMCs. In contrast, exogenous NO effectively inhibited rPASMC phenotypic switching by arresting the cell cycle at the G0/G1 phase.</div></div><div><h3>Conclusion</h3><div>CST enhances endothelial NO synthesis through the PI3K/Akt/eNOS pathway, which subsequently acts on rPASMCs to inhibit their phenotypic switching via the NO/cGMP/PKG signaling pathway, thereby alleviating pulmonary arterial remodeling in PAH.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 93-105"},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144601089","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":"SIRT3 sulfhydrylation by hydrogen sulphide: A novel approach to prevent ferroptosis and atrial fibrosis","authors":"Zi-Zhu Zhang ,&nbsp;Xiu-Heng Wang ,&nbsp;Zhi-Hong Ning ,&nbsp;Yun Ou ,&nbsp;Jia-Yan Yang ,&nbsp;Hui-Fang Tang ,&nbsp;Zhi-Sheng Jiang ,&nbsp;Heng-Jing Hu","doi":"10.1016/j.niox.2025.06.006","DOIUrl":"10.1016/j.niox.2025.06.006","url":null,"abstract":"<div><h3>Background</h3><div>Hydrogen sulfide (H₂S) has been shown to counteract ferroptosis and atrial fibrosis, yet the underlying mechanisms remain incompletely understood. This study aims to investigate how H₂S regulates ferroptosis to alleviate atrial fibrosis.</div></div><div><h3>Methods</h3><div>In vivo and in vitro models of atrial fibrosis were established using Angiotensin II (Ang-II) to modulate the expression of SIRT3, β-catenin, and ferroptosis markers. Western blotting was employed to analyze changes in proteins related to ferroptosis and fibrosis. Histological evaluations, including Hematoxylin and Eosin (HE), and Masson's staining were performed to assess atrial fibrosis. Cardiac ultrasound was used to assess left atrial function in vivo. In vitro, reactive oxygen species (ROS) levels and iron staining were used to monitor ferroptosis and oxidative stress.</div></div><div><h3>Results</h3><div>In atrial tissue from patients with AF, significant increases in ferroptosis markers and atrial fibrosis were observed. In both animal and cell models of atrial fibrosis, reduced sulfhydrylated SIRT3 and elevated β-catenin expression were associated with increased ferroptosis and fibrosis markers. Treatment with NaHS, a donor of H₂S, reversed these changes, reducing both ferroptosis and fibrosis. Importantly, inhibition of sulfhydrylated SIRT3 further upregulated β-catenin, exacerbating ferroptosis and fibrosis. However, blocking β-catenin effectively alleviated Ang–II–induced ferroptosis and fibrosis in the atrial fibrosis model.</div></div><div><h3>Conclusion</h3><div>H₂S alleviates atrial fibrosis and inhibits ferroptosis by upregulating SIRT3 sulfhydrylation and antagonizing the Wnt/β-catenin signaling pathway. These findings suggest that targeting the H₂S-SIRT3-β-catenin signaling axis may offer a promising therapeutic strategy for atrial fibrosis and associated arrhythmias.</div></div>","PeriodicalId":19357,"journal":{"name":"Nitric oxide : biology and chemistry","volume":"158 ","pages":"Pages 82-92"},"PeriodicalIF":3.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507134","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}