Antioxidants & redox signaling最新文献

{"title":"Exosomal Prolactin-Induced Protein Inhibits the Activation of cGMP/PKG Pathway Mediated by ATP2B2 to Promote Myocardial Fibrosis in Atrial Fibrillation.","authors":"Yue Wei, Xiang Li, Zimo Sha, Jingmeng Liu, Guanhua Wu, Taojie Zhou, Changjian Lin, Yun Xie, Yangyang Bao, Qingzhi Luo, Tianyou Ling, Wenqi Pan, Yucai Xie, Ning Zhang, Qi Jin, Liqun Wu","doi":"10.1089/ars.2024.0723","DOIUrl":"10.1089/ars.2024.0723","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Myocardial fibrosis is an important medium for atrial fibrillation (AF). Exosomes have been demonstrated to affect the development of AF. This study explored the molecular mechanism of exosomes from patients with AF (AF-exo) mediating myocardial fibrosis and thus affecting the development of AF. <b><i>Results:</i></b> Prolactin-induced protein (PIP) is highly expressed in AF-exo. AF-exo promoted the proliferation and activation of cardiac fibroblasts (CFs) as well as the migration and endothelial-to-mesenchymal transition (EndMT) of human umbilical vein endothelial cells (HUVECs). However, the effect of AF-exo on CFs and HUVECs was mitigated by PIP-specific short hairpin RNA (shPIP). Adeno-associated virus (AAV)-shPIP reduced the incidence and duration of AF in rats, and improved myocardial fibrosis and collagen deposition. ATPase plasma membrane Ca²⁺ transporting 2 (ATP2B2) overexpression or inhibition reverses the role of PIP or shPIP in CFs, HUVECs, and AF rats. Activation of the cyclic guanosine monophosphate/protein kinase G (cGMP/PKG) pathway is beneficial to alleviate myocardial fibrosis, but this effect is mitigated by shATP2B2. <b><i>Innovation:</i></b> Our investigation substantiates the pivotal role of the PIP/ATP2B2 axis in both HUVEC myocardial fibrosis and EndMT progression. Our findings suggest that AF-exo can suppress the activation of the cGMP/PKG pathway mediated by ATP2B2 through exosomal PIP, thus promoting myocardial fibrosis, indicating potential targets for novel antifibrotic drug development targeting either PIP or ATP2B2. <b><i>Conclusion:</i></b> Exosomal PIP can inhibit the activation of cGMP/PKG pathway mediated by ATP2B2, thus promoting the development of AF. <i>Antioxid. Redox Signal.</i> 43, 14-36.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"14-36"},"PeriodicalIF":5.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathodal Transcranial Direct Current Stimulation Attenuates Cerebral Ischemia-Reperfusion Injury by Coordinating Mitophagy Inhibition and Nrf2 Activation Against Ferroptosis.","authors":"Xian-Dong Li, Yue-Xin Ning, Yi-Feng Pei, Jing-Yuan Niu, Jian Luo, Yi-Na Zhang, Zi-Ai Zhao, Xiao-Wen Hou, Qian-Kun Zhao, Tian-Ce Xu, Hui-Sheng Chen","doi":"10.1089/ars.2025.0914","DOIUrl":"https://doi.org/10.1089/ars.2025.0914","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Cathodal transcranial direct current stimulation (C-tDCS), a noninvasive physical therapy, has potential neuroprotective effects in acute ischemic stroke. However, the rational timing of its application and the underlying mechanisms remain inadequately understood. This study aims to investigate its neuroprotective effects and the involved mechanisms. <b><i>Results:</i></b> Our <i>in vivo</i> results indicated that C-tDCS applied during the reperfusion phase but not during the ischemic phase significantly improved neurological outcomes, reduced infarct volume, and mitigated histopathological damage in middle cerebral artery occlusion/reperfusion rats. C-tDCS during the reperfusion phase suppressed ferroptosis, activated nuclear factor erythroid 2-related factor 2 (Nrf2), and inhibited mitophagy. <i>In vitro</i>, the ferroptosis inducer RSL3 negated the protective effects of cathodal direct current stimulation on HT22 neuronal cells subjected to oxygen-glucose deprivation/reoxygenation injury. Furthermore, the Nrf2 inhibitor ML385 and the mitophagy activator FCCP reversed the inhibitory effects of C-tDCS on ferroptosis, with FCCP also affecting Nrf2 activation by C-tDCS. <b><i>Innovation and Conclusions:</i></b> These results demonstrate that C-tDCS during reperfusion attenuates cerebral ischemia-reperfusion injury by coordinating mitophagy inhibition and Nrf2 activation to counteract ferroptosis, which provides new evidence for its potential translational clinical applications. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504731","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":"Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular Reactive Oxygen Species in Prolactin-Secreting Pituitary Adenoma.","authors":"Linpeng Xu, Zhuowei Lei, Quanji Wang, Qian Jiang, Biao Xing, Xingbo Li, Xiang Guo, Zihan Wang, Sihan Li, Yimin Huang, Ting Lei","doi":"10.1089/ars.2024.0611","DOIUrl":"10.1089/ars.2024.0611","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Dopamine agonists (DAs) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. <b><i>Results:</i></b> Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to bromocriptine (BRC) both <i>in vitro</i> and <i>in vivo</i>. Mechanistically, we demonstrated that intracellular reactive oxygen species (ROS) function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NFE2-like bZIP transcription factor 2 (NRF2) expression, which regulates intracellular ROS levels, thereby enhancing cell viability and conferring DA resistance to pituitary adenoma (PA) cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. <b><i>Conclusion and Innovation:</i></b> We demonstrated that AR plays a crucial role in mediating DA resistance in PRL adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas. <i>Antioxid. Redox Signal.</i> 42, 954-972.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"954-972"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364066","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":"Human Umbilical Cord Mesenchymal Stem Cells Alleviate Diabetic Nephropathy by Inhibiting Ferroptosis via the JNK/KEAP1/NRF2 Signaling Pathway.","authors":"Yuexin Zhu, Changqing Dong, Zhiheng Xu, Yan Lou, Na Tian, Yucan Guan, Ping Nie, Manyu Luo, Ping Luo","doi":"10.1089/ars.2024.0575","DOIUrl":"10.1089/ars.2024.0575","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Diabetic nephropathy (DN) is a major cause of end-stage renal disease, with no therapeutic interventions available to control its progression. Ferroptosis, an iron-dependent regulated cell death characterized by lipid peroxidation, plays a pivotal role in the pathogenesis of DN. Human umbilical cord mesenchymal stem cells (hUCMSCs) are an effective treatment modality for DN; however, the underlying mechanism of action remains unclear. The aim of the present study was to investigate whether hUCMSCs alleviate DN via inhibiting ferroptosis and its molecular mechanisms in type 2 diabetic mice and high-glucose and palmitate-stimulated human renal tubular epithelial cell (HK-11) models. <b><i>Results:</i></b> Our findings revealed that hUCMSCs improved the renal structure and function and tubular injuries. HUCMSC treatment can inhibit ferroptosis by decreasing iron content, reducing reactive oxygen species, malondialdehyde and 4-hydroxynonenal generation, decreasing the expression of positive ferroptosis mediator transferrin receptor 1 and long-chain acyl-CoA synthetase 4, and enhancing the expression of negative ferroptosis mediators (<i>i.e.,</i> ferritin heavy chain, glutathione peroxidase 4, and system Xc-cystine/glutamate reverse transporter). Mechanistically, hUCMSC treatment inhibited c-Jun N-terminal kinase (JNK) and Kelch-like ECH-associated protein 1 (KEAP1) activation while increasing the expression of nuclear factor erythroid 2-related factor 2 (NRF2). Furthermore, pretreatment of HK-11 cells with NRF2 siRNA, the JNK inhibitor SP600125, or the JNK agonist anisomycin demonstrated the regulation of the JNK/KEAP1/NRF2 signaling pathway by hUCMSCs. <b><i>Innovation and Conclusion:</i></b> HUCMSCs inhibit ferroptosis in DN via the JNK/KEAP1/NRF2 signaling pathway, providing a new perspective and scientific evidence for treating DN. <i>Antioxid. Redox Signal.</i> 42, 807-826.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"807-826"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738142","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":"Pathomechanistic Synergy Between Particulate Matter and Traffic Noise-Induced Cardiovascular Damage and the Classical Risk Factor Hypertension.","authors":"Marin Kuntic, Omar Hahad, Sadeer Al-Kindi, Matthias Oelze, Jos Lelieveld, Andreas Daiber, Thomas Münzel","doi":"10.1089/ars.2024.0659","DOIUrl":"10.1089/ars.2024.0659","url":null,"abstract":"<p><p><b><i>Significance:</i></b> In all modern urbanized and industrialized societies, noncommunicable diseases, such as cardiovascular disease (CVD), are becoming a more important cause of morbidity and mortality. Classical risk factors for CVDs, such as hypertension, are reinforced by behavioral risk factors, <i>e.g.</i>, smoking and diet, and environmental risk factors, <i>e.g.</i>, transportation noise and air pollution. <b><i>Recent Advances:</i></b> Both transportation noise and air pollution have individually been shown to increase the risk for CVD in large cohorts. Insights from animal studies have revealed pathophysiologic mechanisms by which these stressors influence the cardiovascular system. Noise primarily causes annoyance and sleep disturbance, promoting the release of stress hormones. Air pollution primarily damages the lung, where it causes local inflammation and an increase in oxidative stress, which can propagate to the circulation and remote organs. <b><i>Critical Issues:</i></b> Both noise and air pollution converge at the vascular level, where the inflammatory state and oxidative stress cause dysfunction in vascular signaling and promote atherosclerotic plaque formation and thrombosis. Both inflammation and oxidative stress are key aspects of traditional cardiovascular risk factors, such as arterial hypertension. The similarities among the mechanisms of environmental risk factor-induced CVD and hypertension indicate that a complex interplay between them can drive the onset and progression of CVDs, leading to synergistic health impacts. <b><i>Future Directions:</i></b> Our present overview of the negative effects of noise and air pollution on the cardiovascular system provides a mechanistic link to the traditional CVD risk factor, hypertension, which could be used to protect patients with preexisting CVD better. <i>Antioxid. Redox Signal.</i> 42, 827-847.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"827-847"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316602","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":"Epigenetic Control of Redox Pathways in Cancer Progression.","authors":"Vandit Shah, Hiu Yan Lam, Charlene Hoi-Mun Leong, Reo Sakaizawa, Jigna S Shah, Alan Prem Kumar","doi":"10.1089/ars.2023.0465","DOIUrl":"10.1089/ars.2023.0465","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Growing evidence indicates the importance of redox reactions homeostasis, mediated predominantly by reactive oxygen species (ROS) in influencing the development, differentiation, progression, metastasis, programmed cell death, tumor microenvironment, and therapeutic resistance of cancer. Therefore, reviewing the ROS-linked epigenetic changes in cancer is fundamental to understanding the progression and prevention of cancer. <b><i>Recent Advances:</i></b> We review in depth the molecular mechanisms involved in ROS-mediated epigenetic changes that lead to alteration of gene expression by altering DNA, modifying histones, and remodeling chromatin and noncoding RNA. <b><i>Critical Issues:</i></b> In cancerous cells, alterations of the gene-expression regulatory elements could be generated by the virtue of imbalance in tumor microenvironment. Various oxidizing agents and mitochondrial electron transport chain are the major pathways that generate ROS. ROS plays a key role in carcinogenesis by activating pro-inflammatory signaling pathways and DNA damage. This loss of ROS-mediated epigenetic regulation of the signaling pathways may promote tumorigenesis. We address all such aspects in this review. <b><i>Future Directions:</i></b> Developments in this growing field of epigenetics are expected to contribute to further our understanding of human health and diseases such as cancer and to test the clinical applications of redox-based therapy. Recent studies of the cancer-epigenetic landscape have revealed pervasive deregulation of the epigenetic factors in cancer. Thus, the study of interaction between ROS and epigenetic factors in cancer holds a great promise in the development of effective and targeted treatment modalities. <i>Antioxid. Redox Signal.</i> 42, 848-867.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"848-867"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-196a-5p Secreted by Bone Marrow Mesenchymal Stem Cells Inhibits Ferroptosis and Promotes Drug Resistance of Acute Myeloid Leukemia.","authors":"Bingjie Fan, Li Wang, Tianzhen Hu, Lin Zheng, Jishi Wang","doi":"10.1089/ars.2024.0882","DOIUrl":"10.1089/ars.2024.0882","url":null,"abstract":"<p><p><b><i>Background:</i></b> Ferroptosis is a nonapoptotic type of cell death characterized by an increase in lipid reactive oxygen species (ROS). Acute myeloid leukemia (AML)-derived bone marrow mesenchymal stem cells (AML-BMSCs) support the progression and drug resistance of AML by secreting various bioactive substances, including exosomes. However, the role of BMSCs in regulating lipid metabolism and ferroptosis in AML remains unexplored. <b><i>Results:</i></b> Exosomes secreted by AML-BMSCs increased the expression of miR-196a-5p in AML cells. MiR-196a-5p promoted the proliferation of AML cells, reduced lipid ROS and ferroptosis, and was associated with poor prognosis in AML patients. Mechanistically, miR-196a-5p inhibited the expression level of neural precursor cell expressed developmentally down-regulated 4-like (NEDD4L). Co-immunoprecipitation (CO-IP) analysis showed that NEDD4L was bound to long-chain acyl-CoA synthetase (ACSL)3 and promoted ubiquitin-mediated degradation of ACSL3 protein. In addition, we also demonstrated that AML-BMSCs highly expressed Ras-associated binding protein 7A (RAB7A), which was associated with exosomal miR-196a-5p release. Importantly, cytarabine (Ara-C) activated the expression of RAB7A and promoted the secretion of exosomal miR-196a-5p, which weakened the ubiquitination of ACSL3 by NEDD4L, leading to ferroptosis inhibition and Ara-C resistance in AML. <b><i>Innovation:</i></b> This is the first time that exosomes secreted by BMSCs (BMSCs-exos) have been linked to ferroptosis in AML cells, thereby expanding our understanding of the mechanism of drug resistance in AML cells. High miR-196a-5p expression reduced lipid ROS levels and ferroptosis in AML cells by inhibiting NEDD4L-mediated ubiquitination of ACSL3. <b><i>Conclusion:</i></b> This study identified a new network through which BMSCs-exos regulate ferroptosis in AML cells. We combined BMSCs and AML cells to provide new ideas for drug research targeting exosome secretion and ferroptosis. <i>Antioxid. Redox Signal.</i> 42, 933-953.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"933-953"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101030","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":"Remote Organ Damage Induced by Stroke: Molecular Mechanisms and Comprehensive Interventions.","authors":"Jie Wang, Sen Gao, Yue Cui, Xun-Zhi Liu, Xiang-Xin Chen, Chun-Hua Hang, Wei Li","doi":"10.1089/ars.2024.0720","DOIUrl":"10.1089/ars.2024.0720","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Damage after stroke is not only limited to the brain but also often occurs in remote organs, including the heart, lung, liver, kidney, digestive tract, and spleen, which are frequently affected by complex pathophysiological changes. The organs in the human body are closely connected, and signals transmitted through various molecular substances could regulate the pathophysiological changes of remote organs. <b><i>Recent Advances:</i></b> The latest studies have shown that inflammatory response plays an important role in remote organ damage after stroke, and can aggravate remote organ damage by activating oxidative stress, sympathetic axis, and hypothalamic axis, and disturbing immunological homeostasis. Remote organ damage can also cause damage to the brain, aggravating inflammatory response and oxidative damage. <b><i>Critical Issues:</i></b> Therefore, an in-depth exploration of inflammatory and oxidative mechanisms and adopting corresponding comprehensive intervention strategies have become necessary to reduce damage to remote organs and promote brain protection. <b><i>Future Directions:</i></b> The comprehensive intervention strategy involves multifaceted treatment methods such as inflammation regulation, antioxidants, and neural stem cell differentiation. It provides a promising treatment alternative for the comprehensive recovery of stroke patients and an inspiration for future research and treatment. The various organs of the human body are interconnected at the molecular level. Only through comprehensive intervention at the molecular and organ levels can we save remote organ damage and protect the brain after stroke to the greatest extent. <i>Antioxid. Redox Signal.</i> 42, 885-904.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"885-904"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762522","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":"Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease.","authors":"Siobhan M Craige, Gaganpreet Kaur, Jacob M Bond, Amada D Caliz, Shashi Kant, John F Keaney","doi":"10.1089/ars.2024.0706","DOIUrl":"10.1089/ars.2024.0706","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Endothelial cells (ECs) line the entire vasculature system and serve as both barriers and facilitators of intra- and interorgan communication. Positioned to rapidly sense internal and external stressors, ECs dynamically adjust their functionality. Endothelial dysfunction occurs when the ability of ECs to react to stressors is impaired, which precedes many cardiovascular diseases (CVDs). While EC reactive oxygen species (ROS) have historically been implicated as mediators of endothelial dysfunction, more recent studies highlight the central role of ROS in physiological endothelial signaling. <b><i>Recent Advances:</i></b> New evidence has uncovered that EC ROS are fundamental in determining how ECs interact with their environment and respond to stress. EC ROS levels are mediated by external factors such as diet and pathogens, as well as inherent characteristics, including sex and location. Changes in EC ROS impact EC function, leading to changes in metabolism, cell communication, and potentially disrupted signaling in CVDs. <b><i>Critical Issues:</i></b> Current endothelial biology concepts integrate the dual nature of ROS, emphasizing the importance of EC ROS in physiological stress adaptation and their contribution to CVDs. Understanding the discrete, localized signaling of EC ROS will be critical in preventing adverse cardiovascular outcomes. <b><i>Future Directions:</i></b> Exploring how the EC ROS environment alters EC function and cross-cellular communication is critical. Considering the inherent heterogeneity among EC populations and understanding how EC ROS contribute to this diversity and the role of sexual dimorphism in the EC ROS environment will be fundamental for developing new effective cardiovascular treatment strategies. <i>Antioxid. Redox Signal.</i> 42, 905-932.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"905-932"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103732","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":"Adverse Effects of Nrf2 in Different Organs and the Related Diseases.","authors":"Xuemei Jin, Long Chen, Yuelan Yang, Rongshao Tan, Chunjie Jiang","doi":"10.1089/ars.2024.0586","DOIUrl":"10.1089/ars.2024.0586","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Under normal physiological conditions, Nrf2 undergoes ubiquitination and subsequent proteasome degradation to maintain its basal activity. Oxidative stress can trigger Nrf2 activation, prompting its translocation to the nucleus where it functions as a transcription factor, activating various antioxidant pathways, and conferring antioxidant properties. <b><i>Recent Advances:</i></b> While extensive research has shown Nrf2's protective role in various diseases, emerging evidence suggests that Nrf2 activation can also produce harmful effects. <b><i>Critical Issues:</i></b> This review examines the pathological contexts in which Nrf2 assumes different roles, emphasizing the mechanisms and conditions that result in adverse outcomes. <b><i>Future Directions:</i></b> Persistent Nrf2 activation may have deleterious consequences, necessitating further investigation into the specific conditions and mechanisms through which Nrf2 exerts its harmful effects. <i>Antioxid. Redox Signal.</i> 42, 973-985.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"973-985"},"PeriodicalIF":5.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891543","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}