Redox Biology最新文献_第5页

Monoamine oxidases: A missing link between mitochondria and inflammation in chronic diseases ? 单胺氧化酶：慢性疾病中线粒体与炎症之间缺失的联系？

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-11 DOI: 10.1016/j.redox.2024.103393

Lise Beucher, Claudie Gabillard-Lefort, Olivier R. Baris, Jeanne Mialet-Perez

{"title":"Monoamine oxidases: A missing link between mitochondria and inflammation in chronic diseases ?","authors":"Lise Beucher, Claudie Gabillard-Lefort, Olivier R. Baris, Jeanne Mialet-Perez","doi":"10.1016/j.redox.2024.103393","DOIUrl":"10.1016/j.redox.2024.103393","url":null,"abstract":"<div><div>The role of mitochondria spans from the regulation of the oxidative phosphorylation, cell metabolism and survival/death pathways to a more recently identified function in chronic inflammation. In stress situations, mitochondria release some pro-inflammatory mediators such as ATP, cardiolipin, reactive oxygen species (ROS) or mitochondrial DNA, that are believed to participate in chronic diseases and aging. These mitochondrial Damage-Associated Molecular Patterns (mito-DAMPs) can modulate specific receptors among which TLR9, NLRP3 and cGAS-STING, triggering immune cells activation and sterile inflammation. In order to counter the development of chronic diseases, a better understanding of the underlying mechanisms of low grade inflammation induced by mito-DAMPs is needed. In this context, monoamine oxidases (MAO), the mitochondrial enzymes that degrade catecholamines and serotonin, have recently emerged as potent regulators of chronic inflammation in obesity-related disorders, cardiac diseases, cancer, rheumatoid arthritis and pulmonary diseases. The role of these enzymes in inflammation embraces their action in both immune and non-immune cells, where they regulate monoamines levels and generate toxic ROS and aldehydes, as by-products of enzymatic reaction. Here, we discuss the more recent advances on the role and mechanisms of action of MAOs in chronic inflammatory diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103393"},"PeriodicalIF":10.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of MTH1 in oxidative stress and therapeutic targeting of cancer MTH1 在氧化应激和癌症靶向治疗中的作用

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-11 DOI: 10.1016/j.redox.2024.103394

Aaliya Taiyab , Anam Ashraf , Md Nayab Sulaimani , Aanchal Rathi , Anas Shamsi , Md Imtaiyaz Hassan

{"title":"Role of MTH1 in oxidative stress and therapeutic targeting of cancer","authors":"Aaliya Taiyab , Anam Ashraf , Md Nayab Sulaimani , Aanchal Rathi , Anas Shamsi , Md Imtaiyaz Hassan","doi":"10.1016/j.redox.2024.103394","DOIUrl":"10.1016/j.redox.2024.103394","url":null,"abstract":"<div><div>Cancer cells maintain high levels of reactive oxygen species (ROS) to drive their growth, but ROS can trigger cell death through oxidative stress and DNA damage. To survive enhanced ROS levels, cancer cells activate their antioxidant defenses. One such defense is MTH1, an enzyme that prevents the incorporation of oxidized nucleotides into DNA, thus preventing DNA damage and allowing cancer to proliferate. MTH1 levels are often elevated in many cancers, and thus, inhibiting MTH1 is an attractive strategy for suppressing tumor growth and metastasis. Targeted MTH1 inhibition can induce DNA damage in cancer cells, exploiting their vulnerability to oxidative stress and selectively targeting them for destruction. Targeting MTH1 is promising for cancer treatment because normal cells have lower ROS levels and are less dependent on these pathways, making the approach both effective and specific to cancer. This review aims to investigate the potential of MTH1 as a therapeutic target, especially in cancer treatment, offering detailed insights into its structure, function, and role in disease progression. We also discussed various MTH1 inhibitors that have been developed to selectively induce oxidative damage in cancer cells, though their effectiveness varies. In addition, this review provide deeper mechanistic insights into the role of MTH1 in cancer prevention and oxidative stress management in various diseases.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103394"},"PeriodicalIF":10.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HJURP inhibits sensitivity to ferroptosis inducers in prostate cancer cells by enhancing the peroxidase activity of PRDX1 HJURP 通过增强 PRDX1 的过氧化物酶活性来抑制前列腺癌细胞对铁变态诱导剂的敏感性

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-10 DOI: 10.1016/j.redox.2024.103392

Wenjie Lai , Weian Zhu , Jianjie Wu , Jiongduan Huang , Xiaojuan Li , Yun Luo , Yu Wang , Hengda Zeng , Mingqiang Li , Xiaofu Qiu , Xingqiao Wen

{"title":"HJURP inhibits sensitivity to ferroptosis inducers in prostate cancer cells by enhancing the peroxidase activity of PRDX1","authors":"Wenjie Lai , Weian Zhu , Jianjie Wu , Jiongduan Huang , Xiaojuan Li , Yun Luo , Yu Wang , Hengda Zeng , Mingqiang Li , Xiaofu Qiu , Xingqiao Wen","doi":"10.1016/j.redox.2024.103392","DOIUrl":"10.1016/j.redox.2024.103392","url":null,"abstract":"<div><div>Ferroptosis induction has emerged as a promising therapeutic approach for prostate cancer (PCa), either as a monotherapy or in combination with hormone therapy. Therefore, identifying the mechanisms regulating ferroptosis in PCa cells is essential. Our previous study demonstrated that HJURP, an oncogene upregulated in PCa cells, plays a role in tumor proliferation. Here, we expand these findings by elucidating a novel mechanism by which HJURP inhibits sensitivity to ferroptosis inducers in PCa cells via the PRDX1/reactive oxygen species (ROS) pathway <em>in vitro</em> and <em>in vivo</em>. Mechanistically, HJURP forms disulfide-linked intermediates with PRDX1 through Cys<sup>327</sup> and Cys<sup>457</sup> residues. This disulfide binding promotes PRDX1 redox cycling and inhibits its hyperoxidation. As a result, HJURP enhances the peroxidase activity of PRDX1, leading to a decrease in ROS levels and subsequently suppressing lipid peroxidation induced by ferroptosis inducers. These findings reveal the potential of HJURP/PRDX1 as novel therapeutic targets and biomarkers of ferroptosis in PCa patients.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103392"},"PeriodicalIF":10.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142416196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methionine oxidation of actin cytoskeleton attenuates traumatic memory retention via reactivating dendritic spine morphogenesis 肌动蛋白细胞骨架的蛋氨酸氧化可通过重新激活树突棘形态发生减轻创伤记忆的保持

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-09 DOI: 10.1016/j.redox.2024.103391

Cun-Dong Huang , Yu Shi , Fang Wang , Peng-Fei Wu , Jian-Guo Chen

{"title":"Methionine oxidation of actin cytoskeleton attenuates traumatic memory retention via reactivating dendritic spine morphogenesis","authors":"Cun-Dong Huang , Yu Shi , Fang Wang , Peng-Fei Wu , Jian-Guo Chen","doi":"10.1016/j.redox.2024.103391","DOIUrl":"10.1016/j.redox.2024.103391","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is characterized by hypermnesia of the trauma and a persistent fear response. The molecular mechanisms underlying the retention of traumatic memories remain largely unknown, which hinders the development of more effective treatments. Utilizing auditory fear conditioning, we demonstrate that a redox-dependent dynamic pathway for dendritic spine morphogenesis in the basolateral amygdala (BLA) is crucial for traumatic memory retention. Exposure to a fear-induced event markedly increased the reduction of oxidized filamentous actin (F-actin) and decreased the expression of the molecule interacting with CasL 1 (MICAL1), a methionine-oxidizing enzyme that directly oxidizes and depolymerizes F-actin, leading to cytoskeletal dynamic abnormalities in the BLA, which impairs dendritic spine morphogenesis and contributes to the persistence of fearful memories. Following fear conditioning, overexpression of MICAL1 in the BLA inhibited freezing behavior during fear memory retrieval via reactivating cytokinesis, whereas overexpression of methionine sulfoxide reductase B 1, a key enzyme that reduces oxidized F-actin monomer, increased freezing behavior during retrieval. Notably, intra-BLA injection of semaphorin 3A, an endogenous activator of MICAL1, rapidly disrupted fear memory within a short time window after conditioning. Collectively, our results indicate that redox modulation of actin cytoskeleton in the BLA is functionally linked to fear memory retention and PTSD-like memory.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103391"},"PeriodicalIF":10.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methionine restriction alleviates diabetes-associated cognitive impairment via activation of FGF21 通过激活 FGF21 限制蛋氨酸摄入可减轻糖尿病相关的认知障碍。

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-08 DOI: 10.1016/j.redox.2024.103390

Yuyu Zhang , Yajie Wang , Yiju Li , Jingxi Pang , Annika Höhn , Weixuan Dong , Rui Gao , Yan Liu , Da Wang , Yongbo She , Rui Guo , Zhigang Liu

{"title":"Methionine restriction alleviates diabetes-associated cognitive impairment via activation of FGF21","authors":"Yuyu Zhang , Yajie Wang , Yiju Li , Jingxi Pang , Annika Höhn , Weixuan Dong , Rui Gao , Yan Liu , Da Wang , Yongbo She , Rui Guo , Zhigang Liu","doi":"10.1016/j.redox.2024.103390","DOIUrl":"10.1016/j.redox.2024.103390","url":null,"abstract":"<div><div>Glucose metabolism disturbances may result in diabetes-associated cognitive decline (DACI). Methionine restriction (MR) diet has emerged as a potential dietary strategy for managing glucose homeostasis. However, the effects and underlying mechanisms of MR on DACI have not been fully elucidated. Here, we found that a 13-week MR (0.17 % methionine, <em>w</em>/<em>w</em>) intervention starting at 8 weeks of age improved peripheral insulin sensitivity in male db/db mice, a model for type 2 diabetes. Notably, MR significantly improved working as well as long-term memory in db/db mice, accompanied by increased PSD-95 level and reduced neuroinflammatory factors, malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG). We speculate that this effect may be mediated by MR activating hepatic fibroblast growth factor 21 (FGF21) and the brain FGFR1/AMPK/GLUT4 signaling pathway to enhance brain glucose metabolism. To further delineate the mechanism, we used intracerebroventricular injection of adeno-associated virus to specifically knock down FGFR1 in the brain to verify the role of FGFR1 in MR-mediated DACI. It was found that the positive effects of MR on DACI were offset, reflected in decreased cognitive function, impaired synaptic plasticity, upregulated neuroinflammation, and balanced enzymes regulating reactive oxygen species (Sod1, Sod2, Nox4). Of note, the FGFR1/AMPK/GLUT4 signaling pathway and brain glucose metabolism were inhibited. In summary, our study demonstrated that MR increased peripheral insulin sensitivity, activated brain FGFR1/AMPK/GLUT4 signaling through FGF21, maintained normal glucose metabolism and redox balance in the brain, and thereby alleviated DACI. These results provide new insights into the effects of MR diet on cognitive dysfunction caused by impaired brain energy metabolism.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103390"},"PeriodicalIF":10.7,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles 胰岛素氧化和氧化修饰会改变葡萄糖摄取、细胞代谢和炎症分泌情况。

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-05 DOI: 10.1016/j.redox.2024.103372

Ramona Clemen , Wiebke Dethloff , Julia Berner , Paul Schulan , Alice Martinet , Klaus Dieter Weltmann , Thomas von Woedtke , Tilman Grune , Kristian Wende , Sander Bekeschus

{"title":"Insulin oxidation and oxidative modifications alter glucose uptake, cell metabolism, and inflammatory secretion profiles","authors":"Ramona Clemen , Wiebke Dethloff , Julia Berner , Paul Schulan , Alice Martinet , Klaus Dieter Weltmann , Thomas von Woedtke , Tilman Grune , Kristian Wende , Sander Bekeschus","doi":"10.1016/j.redox.2024.103372","DOIUrl":"10.1016/j.redox.2024.103372","url":null,"abstract":"<div><div>Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103372"},"PeriodicalIF":10.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients 脂质组学和蛋白质组学的结合强调了红细胞膜脂质畸变在维持性血液透析患者心脑血管不良并发症发生过程中的作用

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-05 DOI: 10.1016/j.redox.2024.103389

Ke Zheng , Yujun Qian , Haiyun Wang , Dan Song , Hui You , Bo Hou , Fei Han , Yicheng Zhu , Feng Feng , Sin Man Lam , Guanghou Shui , Xuemei Li

{"title":"Combinatorial lipidomics and proteomics underscore erythrocyte lipid membrane aberrations in the development of adverse cardio-cerebrovascular complications in maintenance hemodialysis patients","authors":"Ke Zheng , Yujun Qian , Haiyun Wang , Dan Song , Hui You , Bo Hou , Fei Han , Yicheng Zhu , Feng Feng , Sin Man Lam , Guanghou Shui , Xuemei Li","doi":"10.1016/j.redox.2024.103389","DOIUrl":"10.1016/j.redox.2024.103389","url":null,"abstract":"<div><div>Patients on maintenance hemodialysis exhibit a notably higher risk of cardio-cerebrovascular complications that constitute the major cause of death. Preceding studies have reported conflicting associations between traditional lipid measures and clinical outcome in dialysis patients. In this prospective longitudinal study, we utilized quantitative lipidomics to elucidate, at molecular resolution, changes in lipidome profiles of erythrocyte and plasma samples collected from maintenance hemodialysis patients followed up for 86 months (≈7 years). Primary outcome was defined as cardiovascular-related deaths or new-onset cardio-cerebrovascular events. Cox regression model uncovered plasma/erythrocyte lipids associated with incident cardio-cerebrovascular events in the erythrocyte cohort (n = 117 patients, 37 events) and plasma cohort (n = 45 patients, 11 events), respectively. Both the erythrocyte lipid panel [PA 40:5, PI 34:2, PC 42:6, AUC = 0.83] and plasma lipid panel [PC O-34:1, GM3 18:1; O2/25:0, TG 44:1(16:1_28:0), AUC = 0.94] significantly improved the prediction of cardio-cerebrovascular-related outcome compared to the base model comprising age, sex and dialysis vintage alone. Our findings underscore the pathophysiological significance of anionic phospholipid accretion in erythrocytes in the development of cardio-cerebrovascular complications in dialysis patients. In particular, distorted membrane lipid asymmetry leads to compromised membrane deformability, aberrant cell-cell interactions and altered glutathione metabolism in the erythrocytes of high-risk individuals even at relatively early stage of hemodialysis. Our findings thus underscore the importance of maintaining the RBC pool to lower the risk of cardio-cerebrovascular complications in dialysis patients.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"78 ","pages":"Article 103389"},"PeriodicalIF":10.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142554009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1 通过靶向 PPT1 增强 Gpx1 棕榈酰化抑制血管生成

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-05 DOI: 10.1016/j.redox.2024.103376

Yidan Ma , Xinxin Yuan , Aodong Wei , Xiaopeng Li , Azim Patar , Shaobo Su , Songtao Wang , Gaoen Ma , Jiangli Zhu , Eryan Kong

{"title":"Enhancing Gpx1 palmitoylation to inhibit angiogenesis by targeting PPT1","authors":"Yidan Ma , Xinxin Yuan , Aodong Wei , Xiaopeng Li , Azim Patar , Shaobo Su , Songtao Wang , Gaoen Ma , Jiangli Zhu , Eryan Kong","doi":"10.1016/j.redox.2024.103376","DOIUrl":"10.1016/j.redox.2024.103376","url":null,"abstract":"<div><div>The significance of protein S-palmitoylation in angiogenesis has been largely overlooked, leaving various aspects unexplored. Recent identification of Gpx1 as a palmitoylated protein has generated interest in exploring its potential involvement in novel pathological mechanisms related to angiogenesis. In this study, we demonstrate that Gpx1 undergoes palmitoylation at cysteine-76 and -113, with PPT1 playing a crucial role in modulating the depalmitoylation of Gpx1. Furthermore, we find that PPT1-regulated depalmitoylation negatively impacts Gpx1 protein stability. Interestingly, inhibiting Gpx1 palmitoylation, either through expression of a non-palmitoylated Gpx1 mutant or by expressing PPT1, significantly enhances neovascular angiogenesis. Conversely, in PPT1-deficient mice, angiogenesis is notably attenuated compared to wild-type mice in an Oxygen-Induced Retinopathy (OIR) model, which mimics pathological angiogenesis. Physiologically, under hypoxic conditions, Gpx1 palmitoylation levels are drastically reduced, suggesting that increasing Gpx1 palmitoylation may have beneficial effects. Indeed, enhancing Gpx1 palmitoylation by inhibiting PPT1 with DC661 effectively suppresses retinal angiogenesis in the OIR disease model. Overall, our findings highlight the pivotal role of protein palmitoylation in angiogenesis and propose a novel mechanism whereby the PPT1-Gpx1 axis modulates angiogenesis, thereby providing a potential therapeutic strategy for targeting PPT1 to combat angiogenesis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103376"},"PeriodicalIF":10.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulation of cardiovascular diseases by histone deacetylases and NADPH oxidases 组蛋白去乙酰化酶和 NADPH 氧化酶对心血管疾病的调节。

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-04 DOI: 10.1016/j.redox.2024.103379

Hui Yan , Yidan Yin , Yichen Zhou , Zhanghang Li , Yuxing Li , Lingxuan Ren , Jiazheng Wen , Weirong Wang

引用次数: 0

Lipid peroxidation triggered by the degradation of xCT contributes to gasdermin D-mediated pyroptosis in COPD xCT降解引发的脂质过氧化是慢性阻塞性肺病中气敏剂D介导的脓毒症的诱因。

IF 10.7 1区生物学

Redox Biology Pub Date : 2024-10-03 DOI: 10.1016/j.redox.2024.103388

Tianhua Hou , Laiyu Zhu , Yan Zhang , Ying Tang , Yun Gao , Shucheng Hua , Xinxin Ci , Liping Peng

{"title":"Lipid peroxidation triggered by the degradation of xCT contributes to gasdermin D-mediated pyroptosis in COPD","authors":"Tianhua Hou , Laiyu Zhu , Yan Zhang , Ying Tang , Yun Gao , Shucheng Hua , Xinxin Ci , Liping Peng","doi":"10.1016/j.redox.2024.103388","DOIUrl":"10.1016/j.redox.2024.103388","url":null,"abstract":"<div><h3>Background</h3><div>Pyroptosis is an inflammatory form of regulated necrosis that has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the role of lipid peroxidation in pyroptosis and its underlying mechanisms in COPD remain unclear.</div></div><div><h3>Methods</h3><div>In vitro, human bronchial epithelial cells (Beas-2b cells) were exposed to cigarette smoke extract (CSE) for 24 h. In vivo, mice were exposed to cigarette smoke (CS) for 4 weeks. To investigate the role of xCT, we used siRNA and AAV6 to conditionally knock down xCT in vitro and in vivo, respectively.</div></div><div><h3>Results</h3><div>The administration of ferrostatin-1 (Fer-1), a ferroptosis inhibitor that inhibits lipid peroxidation, significantly reduced the cytotoxicity of CSE to Beas-2b cells and mitigated inflammatory exudation, lung injury and mucus hypersecretion in mice with CS-induced COPD. Fer-1 suppressed gasdermin D (GSDMD)-mediated pyroptosis caused by CS in vitro and in vivo. However, in Beas-2b cells and the lung epithelial cells of mice, conditional knockdown of xCT (a negative regulatory factor of lipid peroxidation) inhibited the xCT/GPx4 axis, leading to more severe lipid peroxidation and GSDMD-mediated pyroptosis during cigarette smoke exposure. Moreover, we found that CS promoted the degradation of xCT through the ubiquitin proteasome system (UPS) and that treatment with MG132 significantly inhibited the degradation of xCT and downregulated the expression of pyroptosis-related proteins.</div></div><div><h3>Conclusion</h3><div>The results of this study suggested that the ubiquitination-mediated degradation of xCT drives GSDMD-mediated pyroptosis in COPD and is a potential therapeutic target for COPD.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"77 ","pages":"Article 103388"},"PeriodicalIF":10.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0