Antioxidants & redox signaling最新文献

{"title":"Intervention of Asprosin Attenuates Oxidative Stress and Neointima Formation in Vascular Injury.","authors":"Fen Zheng, Chao Ye, Jian-Zhen Lei, Rui Ge, Na Li, Jin-Hua Bo, Ai-Dong Chen, Feng Zhang, Hong Zhou, Jue-Jin Wang, Qi Chen, Yue-Hua Li, Guo-Qing Zhu, Ying Han","doi":"10.1089/ars.2023.0383","DOIUrl":"10.1089/ars.2023.0383","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Asprosin, a newly discovered hormone, is linked to insulin resistance. This study shows the roles of asprosin in vascular smooth muscle cell (VSMC) proliferation, migration, oxidative stress, and neointima formation of vascular injury. <b><i>Methods:</i></b> Mouse aortic VSMCs were cultured, and platelet-derived growth factor-BB (PDGF-BB) was used to induce oxidative stress, proliferation, and migration in VSMCs. Vascular injury was induced by repeatedly moving a guidewire in the lumen of the carotid artery in mice. <b><i>Results:</i></b> Asprosin overexpression promoted VSMC oxidative stress, proliferation, and migration, which were attenuated by toll-like receptor 4 (TLR4) knockdown, antioxidant (N-Acetylcysteine, NAC), NADPH oxidase 1 (NOX1) inhibitor ML171, or NOX2 inhibitor GSK2795039. Asprosin overexpression increased NOX1/2 expressions, whereas asprosin knockdown increased heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1) expressions. Asprosin inhibited nuclear factor E2-related factor 2 (Nrf2) nuclear translocation. Nrf2 activator sulforaphane increased HO-1 and NQO-1 expressions and prevented asprosin-induced NOX1/2 upregulation, oxidative stress, proliferation, and migration. Exogenous asprosin protein had similar roles to asprosin overexpression. PDGF-BB increased asprosin expressions. PDGF-BB-induced oxidative stress, proliferation, and migration were enhanced by Nrf2 inhibitor ML385 but attenuated by asprosin knockdown. Vascular injury increased asprosin expression. Local asprosin knockdown in the injured carotid artery promoted HO-1 and NQO-1 expressions but attenuated the NOX1 and NOX2 upregulation, oxidative stress, neointima formation, and vascular remodeling in mice. <b><i>Innovation and Conclusion:</i></b> Asprosin promotes oxidative stress, proliferation, and migration of VSMCs <i>via</i> TLR4-Nrf2-mediated redox imbalance. Inhibition of asprosin expression attenuates VSMC proliferation and migration, oxidative stress, and neointima formation in the injured artery. Asprosin might be a promising therapeutic target for vascular injury. <i>Antioxid. Redox Signal.</i> 41, 488-504.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"488-504"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178282","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 Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1.","authors":"Yanli Liu, Yue Wu, Yu Zhu, Qinghui Li, Xiaoyong Peng, Zisen Zhang, Lei Liu, Liangming Liu, Tao Li","doi":"10.1089/ars.2022.0167","DOIUrl":"10.1089/ars.2022.0167","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction. <b><i>Results:</i></b> Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mitochondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure and activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure and hemodynamic disorders and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor mitochondrial division inhibitor-1 can significantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy, and apoptosis and then protect circulation and vital organ functions, prolonging animal survival. <b><i>Innovation:</i></b> Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. <b><i>Conclusion:</i></b> Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction due to the mitochondrial structure and bioenergetics impairment.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"462-478"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046157","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":"Network of Extracellular Traps in the Pathogenesis of Sterile Chronic Inflammatory Diseases: Role of Oxidative Stress and Potential Clinical Applications.","authors":"Mangala Hegde, Sosmitha Girisa, Thulasidharan Nair Devanarayanan, Mohammed S Alqahtani, Mohamed Abbas, Gautam Sethi, Ajaikumar B Kunnumakkara","doi":"10.1089/ars.2023.0329","DOIUrl":"10.1089/ars.2023.0329","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"396-427"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103256","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":"Targeting Peroxisome Proliferator-Activated Receptor-β/δ, Reactive Oxygen Species and Redox Signaling with Phytocompounds for Cancer Therapy.","authors":"Charanjit Kaur, Sanjeev Kumar Sahu, Keshav Bansal, Lindsay K DeLiberto, Jie Zhang, Devesh Tewari, Anupam Bishayee","doi":"10.1089/ars.2023.0442","DOIUrl":"10.1089/ars.2023.0442","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Peroxisome proliferator-activated receptors (PPARs) have a moderately preserved amino-terminal domain, an extremely preserved DNA-binding domain, an integral hinge region, and a distinct ligand-binding domain that are frequently encountered with the other nuclear receptors. PPAR-β/δ is among the three nuclear receptor superfamily members in the PPAR group. <b><i>Recent Advances:</i></b> Emerging studies provide an insight on natural compounds that have gained increasing attention as potential anticancer agents due to their ability to target multiple pathways involved in cancer development and progression. <b><i>Critical Issues:</i></b> Modulation of PPAR-β/δ activity has been suggested as a potential therapeutic strategy for cancer management. This review focuses on the ability of bioactive phytocompounds to impact reactive oxygen species (ROS) and redox signaling by targeting PPAR-β/δ for cancer therapy. The rise of ROS in cancer cells may play an important part in the initiation and progression of cancer. However, excessive levels of ROS stress can also be toxic to the cells and cancer cells with increased oxidative stress are likely to be more vulnerable to damage by further ROS insults induced by exogenous agents, such as phytocompounds and therapeutic agents. Therefore, redox modulation is a way to selectively kill cancer cells without causing significant toxicity to normal cells. However, use of antioxidants together with cancer drugs may risk the effect of treatment as both act through opposite mechanisms. <b><i>Future Directions:</i></b> It is advisable to employ more thorough and detailed methodologies to undertake mechanistic explorations of numerous phytocompounds. Moreover, conducting additional clinical studies is recommended to establish optimal dosages, efficacy, and the impact of different phytochemicals on PPAR-β/δ.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"342-395"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650182","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":"Increased Neuronal Nitric Oxide Synthase in Alzheimer's Disease Mediates Spontaneous Calcium Signaling and Divergent Glutamatergic Calcium Responses.","authors":"Rachelle Balez, Claire H Stevens, Kerstin Lenk, Simon Maksour, Kuldip Sidhu, Greg Sutherland, Lezanne Ooi","doi":"10.1089/ars.2023.0395","DOIUrl":"10.1089/ars.2023.0395","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"255-277"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650181","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":"Glutamine Mitigates Oxidative Stress-Induced Matrix Degradation, Ferroptosis, and Pyroptosis in Nucleus Pulposus Cells via Deubiquitinating and Stabilizing Nrf2.","authors":"Jiajun Wu, Weitao Han, Yangyang Zhang, Shuangxing Li, Tianyu Qin, Zhengqi Huang, Chao Zhang, Ming Shi, Yuliang Wu, Wanli Zheng, Bo Gao, Kang Xu, Wei Ye","doi":"10.1089/ars.2023.0384","DOIUrl":"10.1089/ars.2023.0384","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Intervertebral disc degeneration (IDD) is closely related to low back pain, which is a prevalent age-related problem worldwide; however, the mechanism underlying IDD is unknown. Glutamine, a free amino acid prevalent in plasma, is recognized for its anti-inflammatory and antioxidant properties in various diseases, and the current study aims to clarify the effect and mechanism of glutamine in IDD. <b><i>Results:</i></b> A synergistic interplay was observed between pyroptosis and ferroptosis within degenerated human disc specimens. Glutamine significantly mitigated IDD in both <i>ex vivo</i> and <i>in vivo</i> experimental models. Moreover, glutamine protected nucleus pulposus (NP) cells after tert-butyl hydroperoxide (TBHP)-induced pyroptosis, ferroptosis, and extracellular matrix (ECM) degradation <i>in vitro</i>. Glutamine protected NP cells from TBHP-induced ferroptosis by promoting the nuclear factor erythroid 2-related factor 2 (Nrf2) accumulation by inhibiting its ubiquitin-proteasome degradation and inhibiting lipid oxidation. <b><i>Innovation and Conclusions:</i></b> A direct correlation is evident in the progression of IDD between the processes of pyroptosis and ferroptosis. Glutamine suppressed oxidative stress-induced cellular processes, including pyroptosis, ferroptosis, and ECM degradation through deubiquitinating Nrf2 and inhibiting lipid oxidation in NP cells. Glutamine is a promising novel therapeutic target for the management of IDD.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"278-295"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179236","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":"Building an Understanding of Proteostasis in Reproductive Cells: The Impact of Reactive Carbonyl Species on Protein Fate.","authors":"Shannon P Smyth, Brett Nixon, David A Skerrett-Byrne, Nathan D Burke, Elizabeth G Bromfield","doi":"10.1089/ars.2023.0314","DOIUrl":"10.1089/ars.2023.0314","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Stringent regulation of protein homeostasis pathways, under both physiological and pathological conditions, is necessary for the maintenance of proteome fidelity and optimal cell functioning. However, when challenged by endogenous or exogenous stressors, these proteostasis pathways can become dysregulated with detrimental consequences for protein fate, cell survival, and overall organism health. Most notably, there are numerous somatic pathologies associated with a loss of proteostatic regulation, including neurodegenerative disorders, type 2 diabetes, and some cancers. <b><i>Recent Advances:</i></b> Lipid oxidation-derived reactive carbonyl species (RCS), such as 4-hydroxynonenal (4HNE) and malondialdehyde, are relatively underappreciated purveyors of proteostatic dysregulation, which elicit their effects <i>via</i> the nonenzymatic post-translational modification of proteins. Emerging evidence suggests that a subset of germline proteins can serve as substrates for 4HNE modification. Among these, prevalent targets include succinate dehydrogenase, heat shock protein A2 and A-kinase anchor protein 4, all of which are intrinsically associated with fertility. <b><i>Critical Issues:</i></b> Despite growing knowledge in this field, the RCS adductomes of spermatozoa and oocytes are yet to be comprehensively investigated. Furthermore, the manner by which RCS-mediated adduction impacts protein fate and drives cellular responses, such as protein aggregation, requires further examination in the germline. Given that RCS-protein adduction has been attributed a role in infertility, there has been sparked research investment into strategies to prevent lipid peroxidation in germ cells. <b><i>Future Directions:</i></b> An increased depth of knowledge regarding the mechanisms and substrates of RCS-mediated protein modification in reproductive cells may reveal important targets for the development of novel therapies to improve fertility and pregnancy outcomes for future generations.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"296-321"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797191","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":"Thrombosis and Aging: Fibrin Clot Properties and Oxidative Stress.","authors":"Małgorzata Konieczyńska, Joanna Natorska, Anetta Undas","doi":"10.1089/ars.2023.0365","DOIUrl":"10.1089/ars.2023.0365","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Aging is a complex process associated with an increased risk of many diseases, including thrombosis. This review summarizes age-related prothrombotic mechanisms in clinical settings of thromboembolism, focusing on the role of fibrin structure and function modified by oxidative stress. <b><i>Recent Advances:</i></b> Aging affects blood coagulation and fibrinolysis <i>via</i> multiple mechanisms, including enhanced oxidative stress, with an imbalance in the oxidant/antioxidant mechanisms, leading to loss of function and accumulation of oxidized proteins, including fibrinogen. Age-related prothrombotic alterations are multifactorial involving enhanced platelet activation, endothelial dysfunction, and changes in coagulation factors and inhibitors. Formation of more compact fibrin clot networks displaying impaired susceptibility to fibrinolysis represents a novel mechanism, which might contribute to atherothrombosis and venous thrombosis. Alterations to fibrin clot structure/function are at least in part modulated by post-translational modifications of fibrinogen and other proteins involved in thrombus formation, with a major impact of carbonylation. Fibrin clot properties are also involved in the efficacy and safety of therapy with oral anticoagulants, statins, and/or aspirin. <b><i>Critical Issues:</i></b> Since a prothrombotic state is observed in very elderly individuals free of diseases associated with thromboembolism, the actual role of activated blood coagulation in health remains elusive. It is unclear to what extent oxidative modifications of coagulation and fibrinolytic proteins, in particular fibrinogen, contribute to a prothrombotic state in healthy aging. <b><i>Future Directions:</i></b> Ongoing studies will show whether novel therapies that may alter oxidative stress and fibrin characteristics are beneficial to prevent atherosclerosis and thromboembolic events associated with aging.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"233-254"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797277","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 Cell-Derived Cholesterol Crystals Promote Endothelial Inflammation in Early Atherogenesis.","authors":"Xia Wang, Wenxia Fu, Guo Zhou, Huanhuan Huo, Xin Shi, Hao Wang, Yinghua Wang, Xiying Huang, Linghong Shen, Long Li, Ben He","doi":"10.1089/ars.2023.0498","DOIUrl":"10.1089/ars.2023.0498","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"201-215"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179235","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":"Low Expression of Lipoic Acid Synthase Aggravates Silica-Induced Pulmonary Fibrosis by Inhibiting the Differentiation of Tregs in Mice.","authors":"Sensen Yan, Yingzheng Zhao, Jingyi Yan, Yabo Guan, Mengdi Lyu, Guangcui Xu, Xuesi Yang, Yichun Bai, Sanqiao Yao","doi":"10.1089/ars.2023.0387","DOIUrl":"10.1089/ars.2023.0387","url":null,"abstract":"<p><p><b><i>Aims:</i></b> In addition to reducing the respiratory function, crystalline silica (SiO₂) disturbs the immune response by affecting immune cells during the progression of silicosis. Regulatory T cell (Treg) differentiation may play a key role in the abnormal polarization of T helper cell (Th)1 and Th2 cells in the development of silicosis-induced fibrosis. Alpha-lipoic acid (ALA) has immunomodulatory effects by promoting Tregs differentiation. Thus, ALA may have a therapeutic potential for treating autoimmune disorders in patients with silicosis. However, little is known regarding whether ALA regulates the immune system during silicosis development. <b><i>Results:</i></b> We found that the expression levels of collagen increased, and the antioxidant capacity was lower in the <i>Lias^-/-</i>+SiO₂ group than in the <i>Lias</i>^+<i>/+</i>+SiO₂ group. The proportion of Tregs decreased in the peripheral blood and spleen tissue in mice exposed to SiO₂. The proportion of Tregs in the <i>Lias^-/-</i>+SiO₂ group was significantly lower than that in the <i>Lias^+/+</i>+SiO₂ group. Supplementary exogenous ALA attenuates the accumulation of inflammatory cells and extracellular matrix in lung tissues. ALA promotes the immunological balance between Th17 and Treg responses during the development of silicosis-induced fibrosis. <b><i>Innovation and Conclusion:</i></b> Our findings confirmed that low expression of lipoic acid synthase aggravates SiO₂-induced silicosis, and that supplementary exogenous ALA has therapeutic potential by improving Tregs in silicosis fibrosis.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"216-232"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797206","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}