Antioxidants & redox signaling最新文献

{"title":"Cystathionine γ-Lyase Attenuates Vascular Smooth Muscle Cell Senescence via Foxm1-Gas1 Pathway to Mediate Arterial Stiffness.","authors":"Qian Lin, Changting Cui, Ying Zhao, Yuefeng Geng, Huimin Gao, Xiaodie Shao, Ling Cheng, Haitao Li, Bin Geng","doi":"10.1089/ars.2024.0602","DOIUrl":"10.1089/ars.2024.0602","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Arterial stiffness, a hallmark of vascular aging, significantly contributes to hypertension and impaired organ perfusion. Vascular smooth muscle cell (VSMC) dysfunction, particularly VSMC senescence and its interaction with stiffness, is crucial in the pathogenesis of arterial stiffness. Although hydrogen sulfide (H₂S) and its key enzyme cystathionine γ-lyase (CSE) are known to play roles in cardiovascular diseases, their effects on arterial stiffness are not well understood. <b><i>Methods & Results:</i></b> First, we observed a downregulation of CSE/H₂S in the aortic media during biological aging and angiotensin II (AngII)-induced aging. The VSMC-specific CSE knockout mice were created by loxp-cre (Tagln-cre) system and which exacerbated AngII-induced aortic aging and stiffness <i>in vivo</i> and VSMC senescence and stiffness <i>in vitro</i>. Conversely, the CSE agonist norswertianolin mitigated these effects. Next, we identified growth arrest-specific 1 (Gas1) as a crucial target of CSE/H₂S and found it to be a downstream target gene of forkhead box protein M1 (Foxm1). siRNA knockdown Foxm1 increased Gas1 transcription and reduced the protective effects of H₂S on VSMC senescence and stiffness. Finally, we demonstrated that CSE/H₂S sulfhydrates Foxm1 at the C210 site, regulating its nuclear translocation and activity, thus reducing VSMC senescence and stiffness. <b><i>Innovation:</i></b> Our findings highlight the protective role of CSE/H₂S in arterial stiffness, emphasizing the novel contributions of CSE, Gas1, and Foxm1 to VSMC senescence and stiffness. <b><i>Conclusion:</i></b> Endogenous CSE/H₂S in VSMCs reduces VSMC senescence and stiffness, thereby attenuating arterial stiffness and aging, partly through sulfhydration-mediated activation of Foxm1 and subsequent inhibition of Gas1 signaling pathways. <i>Antioxid. Redox Signal.</i> 42, 655-671.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"655-671"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124602","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":"Angiotensin-Converting Enzyme-Dependent Intrarenal Angiotensin II Contributes to CTP: Phosphoethanolamine Cytidylyltransferase Downregulation, Mitochondrial Membranous Disruption, and Reactive Oxygen Species Overgeneration in Diabetic Tubulopathy.","authors":"Xia-Qing Li, Zhang-Zhang Xiao, Ke Ma, Xia-Yun Liu, Huan-Huan Liu, Bo Hu, Qian Zhao, Hong-Yue Li, Rui-Chang Chen, Yu Meng, Liang-Hong Yin","doi":"10.1089/ars.2024.0637","DOIUrl":"10.1089/ars.2024.0637","url":null,"abstract":"<p><p><b><i>Aims:</i></b> The limited therapeutic options for diabetic tubulopathy (DT) in early diabetic kidney disease (DKD) reflect the difficulty of targeting renal tubular compartment. While renin-angiotensin-aldosterone system (RAS) inhibitors are commonly utilized in the management of DKD, how intrarenal RAS contributes to diabetic tubular injury is not fully understood. Mitochondrial disruption and reactive oxygen species (ROS) overgeneration have been involved in diabetic tubular injury. Herein, we aim to test the hypothesis that angiotensin-converting enzyme (ACE)-dependent intrarenal angiotensin II (AngII) disrupts tubular mitochondrial membranous homeostasis and causes excessive ROS generation in DT. <b><i>Results:</i></b> Mice suffered from renal tubular mitochondrial disruption and ROS overgeneration following high-fat diet/streptozocin-type 2 diabetic induction. Intrarenal AngII generation is ACE-dependent in DT. Local AngII accumulation in renal tissues was achieved by intrarenal artery injection. ACE-dependent intrarenal AngII-treated mice exhibit markedly elevated levels of makers of tubular injury. CTP: Phosphoethanolamine cytidylyltransferase (PCYT2), the primary regulatory enzyme for the biosynthesis of phosphatidylethanolamine, was enriched in renal tubules according to single-cell RNA sequencing. ACE-dependent intrarenal AngII-induced tubular membranous disruption, ROS overgeneration, and PCYT2 downregulation. The diabetic ambiance deteriorated the detrimental effect of ACE-dependent intrarenal AngII on renal tubules. Captopril, the ACE inhibitor (ACEI), showed efficiency in partially ameliorating ACE-dependent intrarenal AngII-induced tubular deterioration pre- and post-diabetic induction. <b><i>Innovation and Conclusion:</i></b> This study uncovers a critical role of ACE-dependent intrarenal AngII in mitochondrial membranous disruption, ROS overgeneration, and PCYT2 deficiency in diabetic renal tubules, providing novel insight into DT pathogenesis and ACEI-combined therapeutic targets. <i>Antioxid. Redox Signal.</i> 42, 767-786.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"767-786"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574798","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":"Exploring the Molecular Interplay Between Oxygen Transport, Cellular Oxygen Sensing, and Mitochondrial Respiration.","authors":"Sirsendu Jana, Abdu I Alayash","doi":"10.1089/ars.2023.0428","DOIUrl":"10.1089/ars.2023.0428","url":null,"abstract":"<p><p><b><i>Significance:</i></b> The mitochondria play a key role in maintaining oxygen homeostasis under normal oxygen tension (normoxia) and during oxygen deprivation (hypoxia). This is a critical balancing act between the oxygen content of the blood, the tissue oxygen sensing mechanisms, and the mitochondria, which ultimately consume most oxygen for energy production. <b><i>Recent Advances:</i></b> We describe the well-defined role of the mitochondria in oxygen metabolism with a special focus on the impact on blood physiology and pathophysiology. <b><i>Critical Issues:</i></b> Fundamental questions remain regarding the impact of mitochondrial responses to changes in overall blood oxygen content under normoxic and hypoxic states and in the case of impaired oxygen sensing in various cardiovascular and pulmonary complications including blood disorders involving hemolysis and hemoglobin toxicity, ischemia reperfusion, and even in COVID-19 disease. <b><i>Future Directions:</i></b> Understanding the nature of the crosstalk among normal homeostatic pathways, oxygen carrying by hemoglobin, utilization of oxygen by the mitochondrial respiratory chain machinery, and oxygen sensing by hypoxia-inducible factor proteins, may provide a target for future therapeutic interventions. <i>Antioxid. Redox Signal.</i> 42, 730-750.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"730-750"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021884","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":"Succinate Activates Uncoupling Protein 2 to Suppress Neuroinflammation and Confer Protection Following Intracerebral Hemorrhage.","authors":"Yecheng Wang, Caiyun Huang, Xiaoying Wang, Rong Cheng, Xue Li, Jiahao Wang, Lu Zhang, Fuhao Li, Hao Wang, Xinyu Li, Yi Li, Yiqing Xia, Jian Cheng, Xiaofan Pan, Jia Jia, Guo-Dong Xiao","doi":"10.1089/ars.2024.0573","DOIUrl":"10.1089/ars.2024.0573","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Succinate, a metabolite in the tricarboxylic acid cycle, is increasingly recognized to play essential roles in inflammation by functioning either as an intracellular or extracellular signaling molecule. However, the role and mechanisms of succinate in inflammation remain elusive. Here, we investigated the mechanism underlying the effects of succinate on neuroinflammation in intracerebral hemorrhage (ICH) models. [Figure: see text] <b><i>Results:</i></b> We unexpectedly found that succinate robustly inhibited neuroinflammation and conferred protection following ICH. Mechanistically, the oxidation of succinate by succinate dehydrogenase (SDH) drove reverse electron transport (RET) at mitochondrial complex I, leading to mitochondrial superoxide production in microglia. Complex I-derived superoxides, in turn, activated uncoupling protein 2 (UCP2). By using mice with specific deletion of UCP2 in microglia/macrophages, we showed that UCP2 was needed for succinate to inhibit neuroinflammation, confer protection, and activate downstream 5'-adenosine monophosphate-activated protein kinase (AMPK) following ICH. Moreover, knockdown of SDH, complex I, or AMPK abolished the therapeutic effects of succinate following ICH. <b><i>Innovation and Conclusion:</i></b> We provide evidence that driving complex I RET to activate UCP2 is a novel mechanism of succinate-mediated intracellular signaling and a mechanism underlying the inhibition of neuroinflammation by succinate. <i>Antioxid. Redox Signal.</i> 42, 687-710.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"687-710"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124603","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":"GPx3 Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglial Pyroptosis Through IRAK4/ROS/NLRP3 Axis.","authors":"Zhongyuan Liu, Jiawei Shi, Kewu Tu, Hao Ma, Jiayu Chen, Xin Xiang, Peiqian Zou, Congrui Liao, Ruoting Ding, Zucheng Huang, Xinqiang Yao, Jianting Chen, Liang Wang, Zhongmin Zhang","doi":"10.1089/ars.2024.0618","DOIUrl":"10.1089/ars.2024.0618","url":null,"abstract":"<p><p><b><i>Aim:</i></b> Spinal cord injury (SCI) is a catastrophic injury characterized by oxidative stress. Glutathione peroxidase 3 (GPx3) is an antioxidant enzyme that protects against immune responses in various diseases. However, the effects of GPx3 in SCI remains unclear. This study aimed to investigate the role of GPx3 in SCI and its underlying mechanisms. <b><i>Results:</i></b> We injected adeno-associated viruses to overexpress GPx3 in mice. Primary microglia and BV2 cells were used as <i>in vitro</i> models. We knocked down or overexpressed GPx3 in BV2 cells. Additionally, BV2 cells transfected with siIRAK4 were used to perform rescue experiments. A series of histological and molecular biological analyses were used to explore the role of GPx3 in SCI. Overexpression of GPx3 inhibited oxidative stress in mice, improving functional recovery after SCI. Similarly, LPS+ATP stimulation decreased GPx3 expression in microglia. Silencing of GPx3 elevated the generation of reactive oxygen species, increased the expression of IRAK4 and pro-inflammatory factors, and promoted pyroptosis in microglia. However, overexpression of GPx3 reversed these results. Moreover, silencing of IRAK4 alleviated these phenomena, which were upregulated by GPx3 deficiency. <b><i>Innovation and Conclusion:</i></b> Our results demonstrated that GPx3 plays a critical role in SCI by inhibiting microglial pyroptosis <i>via</i> the IRAK4/ROS/NLRP3 signaling pathway. <i>Antioxid. Redox Signal.</i> 42, 711-729.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"711-729"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078477","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 Potential of Targeting APE1/Ref-1 as a Therapeutic Intervention for Duchenne Muscular Dystrophy.","authors":"Hannah Lalunio, Nicole Stupka, Craig A Goodman, Alan Hayes","doi":"10.1089/ars.2024.0620","DOIUrl":"10.1089/ars.2024.0620","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Inflammation and oxidative stress play crucial roles in the development and progression of skeletal muscle diseases. This review aims to examine the existing evidence regarding the involvement and inhibition of APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1/redox factor 1) in diseases, then extrapolate this evidence to the context of skeletal muscle and discuss the potential beneficial effects of APE1/Ref-1 inhibition in ameliorating myopathy with a particular focus on dystrophic pathology. <b><i>Critical Issues:</i></b> Currently, therapeutic interventions targeting pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (NRF2), have shown limited efficacy in both clinical and preclinical settings. Thus, there is a need for a more comprehensive treatment approach. <b><i>Recent Advances:</i></b> APE1/Ref-1 is a multifunctional protein that was initially identified as being involved in DNA repair. However, newer research has revealed its additional role as a redox-sensitive regulator of transcription factors, including NF-κB and NRF2. Numerous studies have reported increased expression of APE1/Ref-1 in various disorders and have demonstrated the beneficial effects of inhibiting its redox function using the small molecular inhibitor, APX3330. Although these pathways are similarly dysregulated in neuromuscular disorders, the specific role of APE1/Ref-1 in skeletal muscle remains unclear, with only a limited number of studies noting its presence in this tissue. <b><i>Future Directions:</i></b> Further studies investigating the role of APE1/Ref-1 in skeletal muscle and identifying whether APE1/Ref-1 is up- or downregulated in dystrophic skeletal muscle would be required to determine whether upregulating or inhibiting the redox function of APE1/Ref-1 will alleviate chronic inflammation and heightened oxidative stress. <i>Antioxid. Redox Signal.</i> 42, 641-654.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"641-654"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2-Dependent Adaptation to Oxidative Stress Protects Against Progression of Diabetic Nephropathy.","authors":"Eugene Lee, Jae-Hun Ahn, Byeong-Cheol Kang, Hyun Soon Lee","doi":"10.1089/ars.2023.0431","DOIUrl":"10.1089/ars.2023.0431","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Adaptation to oxidative stress is essential for maintaining protein and redox homeostasis in mammalian cells. Palmitic acid (PA) plays a central role in oxidative stress and immunoproteasome regulation in podocytes and diabetes, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial impact on diabetes. The role of Nrf2 in adaptation to oxidative stress and regulation of immunoproteasome by PA and EPA/DHA in podocytes and diabetic kidneys is not well defined. The present study describes the effect of PA- and EPA/DHA-induced oxidative stress in regulating Nrf2/immuoproteasome pathway in a model system relevant to diabetic nephropathy (DN). <b><i>Results:</i></b> Short PA exposure to podocytes promotes the upregulation of antioxidant proteins and immunoproteasome mediated by Nrf2, leading to acute transient oxidative stress adaptation. Both short- and long-term incubation of EPA or DHA in podocytes induced oxidative stress and activation of Nrf2, causing persistent oxidative stress adaptation. Long PA exposure to podocytes decreased the Nrf2 activity, and EPA/DHA attenuated these effects of PA. In <i>db/db</i> mice, feeding of EPA/DHA-rich fish oil increased oxidative stress in kidneys and induced renal cortical Nrf2 nuclear translocation and immunoproteasome overexpression, inhibiting the progression of DN. <b><i>Innovation and Conclusion:</i></b> We demonstrate an oxidative stress adaptation mechanism by PA and EPA/DHA regulated by Nrf2 in podocytes and kidneys of type 2 diabetes. This work provides an important insight into the pathogenetic mechanisms of DN by PA-induced oxidative stress. We conclude that activation of Nrf2-immunoproteasome signaling pathway by EPA/DHA plays a crucial role in abrogating the proteotoxic stress in DN. <i>Antioxid. Redox Signal.</i> 42, 751-766.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"751-766"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear Factor Erythroid 2-Related Factor 2 Activator DDO-1039 Ameliorates Podocyte Injury in Diabetic Kidney Disease via Suppressing Oxidative Stress, Inflammation, and Ferroptosis.","authors":"Xing Liu, Xiuwen Zhai, Xiaoyu Wang, Xiaodong Zhu, Ziyue Wang, Zhengyu Jiang, Hao Bao, ZhaoHong Chen","doi":"10.1089/ars.2024.0653","DOIUrl":"10.1089/ars.2024.0653","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and podocyte injury is one of the major contributors to DKD. As a crucial transcriptional factor that regulates cellular response to oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is an attractive therapeutic target for DKD. In this study, we evaluated the therapeutic potential of DDO-1039, a novel small-molecule Nrf2 activator developed with protein-protein interaction strategy, on podocyte injury in DKD. <b><i>Results:</i></b> DDO-1039 treatment significantly increased Nrf2 protein level and Nrf2 nuclear translocation, thereby upregulating Nrf2 target genes [heme oxygenase 1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase modifier, and tyrosine-protein kinase receptor] both <i>in vitro</i> and <i>in vivo</i>. DDO-1039 attenuated glomerular sclerosis and podocyte injury in the high-fat diet/streptozotocin-induced (HFD/STZ) diabetic mice and db/db diabetic mice. It also significantly improved hyperglycemia in both diabetic mice and mitigated proteinuria in HFD/STZ mice. Meanwhile, DDO-1039 attenuated oxidative stress and inflammation as well as apoptosis <i>in vivo</i> and in podocytes stimulated with palmitic acid and high glucose. Interestingly, we identified podocyte protective factor Tyro3 as a novel Nrf2-regulated gene. In addition, podocyte ferroptosis is reduced <i>via</i> activation of glutathione peroxidase 4 by the novel Nrf2 activator. <b><i>Innovation and conclusion:</i></b> DDO-1039 activates the Nrf2-based cytoprotective system to mitigate podocyte injury in the context of diabetes, suggesting the potential of DDO-1039 in the treatment of DKD. <i>Antioxid. Redox Signal.</i> 42, 787-806.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"787-806"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891547","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":"Sulfur Dioxide Alleviates Aortic Dissection Through Inhibiting Vascular Smooth Muscle Cell Phenotype Switch, Migration, and Proliferation <i>via</i> miR-184-3p/Cyp26b1 Axis.","authors":"Jie He, Kan Huang, Xiaoping Fan, Guangqi Chang","doi":"10.1089/ars.2023.0471","DOIUrl":"10.1089/ars.2023.0471","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Abnormal migration and proliferation of vascular smooth muscle cells (VSMCs) are considered early events in the onset of thoracic aortic dissection (TAD). Endogenous sulfur dioxide (SO₂), primarily produced by aspartate aminotransferase (AAT1) in mammals, has been reported to inhibit the migration and proliferation of VSMCs. However, the role of SO₂ in the development of TAD remains unclear. <b><i>Results:</i></b> Endogenous SO₂ production was decreased in aortic samples from patients with TAD. Supplementation with SO₂ ameliorated β-aminopropionitrile-induced vascular injury in mice. Increasing the expression of SO₂ pathway might reverse the abnormal migration, proliferation, and phenotypic switching in VSMCs. MicroRNA sequencing revealed miR-184-3p as the miRNA with the most significant increased expression level after AAT1 knockdown, and Cyp26b1 was predicted to be its potential target. A decrease in the SO₂ pathway resulted in reduced Cyp26b1 expression, impairing VSMCs function, while restoring Cyp26b1 expression with miR-184-3p inhibitors could improve the VSMCs function. <b><i>Innovation:</i></b> This research extends the application of endogenous SO₂ to the aortic diseases and elucidates the role of miRNA in endogenous SO₂ regulatory network, highlighting its potential as a target for clinical practice. <b><i>Conclusion:</i></b> Endogenous SO₂ inhibits the migration and proliferation of VSMCs in TAD progression <i>via</i> the miR-184-3p/Cyp26b1 axis. <i>Antioxid. Redox Signal.</i> 42, 672-686.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"672-686"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998926","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":"Modes of Mitochondrial Reactive Oxygen Species Production in Inflammation.","authors":"Miguel González-Hernández, Laura Gallardo-Andalucía, Pablo Hernansanz-Agustín","doi":"10.1089/ars.2024.0737","DOIUrl":"https://doi.org/10.1089/ars.2024.0737","url":null,"abstract":"<p><p><b><i>Background:</i></b> Inflammation is one of the most important pathways in innate immunity and its relationship with redox biology is becoming increasingly clear in the last decades. However, the specific redox modes and pathways by which inflammation is produced are not yet well defined. <b><i>Significance:</i></b> In this review, we provide a general explanation of the reactive oxygen species (ROS) production and quenching modes occurring in mammalian mitochondria, as well as a summary of the most recent advances in mitochondrial redox biology and bioenergetics regarding sodium (Na⁺) homeostasis. In addition, we provide a collection of examples in which several inflammatory pathways have been associated with specific modes of either mitochondrial ROS production or quenching. <b><i>Innovation:</i></b> The role of Na⁺ in mitochondrial biology is being developed. Since its discovery as a second messenger, the research of its role in the immune system has emerged. Now, the role of Na⁺ in mitochondrial bioenergetics has recently been identified, which owns unprecedented applications. The potential implication of Na⁺ in inflammatory mechanisms grows as its role does not only cover ROS production and respiration but also the control through the management of mitochondrial membrane potential. <b><i>Future directions:</i></b> Na⁺ is becoming relevant for mitochondrial biology. Thus, processes regarding mitochondrial bioenergetics, redox state, or metabolism may probably need to include the study of Na⁺ in their road map. Some of these pathways are involved in inflammation and more are possibly to come. This review is expected to serve as a bridge between both fields. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969532","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}