MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification.

IF 1.5 4区医学 Q3 PERIPHERAL VASCULAR DISEASE Clinical and Experimental Hypertension Pub Date : 2023-12-31 Epub Date: 2023-10-17 DOI:10.1080/10641963.2023.2271196

Yan Wang, Hongying Zhou, Jin Wu, Shanshan Ye

{"title":"MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification.","authors":"Yan Wang, Hongying Zhou, Jin Wu, Shanshan Ye","doi":"10.1080/10641963.2023.2271196","DOIUrl":null,"url":null,"abstract":"Background: Mitsugumin 53 (MG53) is a membrane repair factor that is associated with acute myocardial infarction. This study aimed to investigate the effects of MG53 on cardiomyocyte injury and the posttranslational modification of MG53.Methods: Cardiomyocyte injury was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The succinylation and ubiquitination levels of MG53 were examined by immunoprecipitation (IP) and western blot. The relationship between MG53 and KAT3B or SIRT7 was assessed by co-IP and immunofluorescence.Results: The results showed that overexpression of MG53 inhibited inflammation response and apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R). Succinylation and protein levels of MG53 were downregulated in H/R-induced cells, which was inhibited by SIRT7 and promoted by KAT3B. SIRT7 aggravated and KAT3B alleviated MG53-mediated cardiomyocyte injury. Moreover, MG53 was succinylated and ubiquitinated at K130.Conclusion: SIRT7 inhibited/KAT3B promoted succinylation of MG53 at K130 sites, which suppressed ubiquitination of MG53 and upregulated its protein levels, thereby alleviating H/R-induced cardiomyocyte injury. The findings suggested that MG53 may be a potential therapy for myocardial infarction.","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Hypertension","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10641963.2023.2271196","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/17 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Mitsugumin 53 (MG53) is a membrane repair factor that is associated with acute myocardial infarction. This study aimed to investigate the effects of MG53 on cardiomyocyte injury and the posttranslational modification of MG53.

Methods: Cardiomyocyte injury was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The succinylation and ubiquitination levels of MG53 were examined by immunoprecipitation (IP) and western blot. The relationship between MG53 and KAT3B or SIRT7 was assessed by co-IP and immunofluorescence.

Results: The results showed that overexpression of MG53 inhibited inflammation response and apoptosis of cardiomyocytes induced by hypoxia/reoxygenation (H/R). Succinylation and protein levels of MG53 were downregulated in H/R-induced cells, which was inhibited by SIRT7 and promoted by KAT3B. SIRT7 aggravated and KAT3B alleviated MG53-mediated cardiomyocyte injury. Moreover, MG53 was succinylated and ubiquitinated at K130.

Conclusion: SIRT7 inhibited/KAT3B promoted succinylation of MG53 at K130 sites, which suppressed ubiquitination of MG53 and upregulated its protein levels, thereby alleviating H/R-induced cardiomyocyte injury. The findings suggested that MG53 may be a potential therapy for myocardial infarction.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

MG53通过琥珀酰化和泛素化修饰减轻缺氧/复氧诱导的心肌细胞损伤。

背景：Mitsugumin53（MG53）是一种与急性心肌梗死相关的膜修复因子。本研究旨在探讨MG53对心肌细胞损伤的影响以及MG53的翻译后修饰。方法：采用酶联免疫吸附法和流式细胞术评价心肌细胞损伤。通过免疫沉淀（IP）和蛋白质印迹检测MG53的琥珀酰化和泛素化水平。通过co-IP和免疫荧光评估MG53与KAT3B或SIRT7之间的关系。结果：MG53的过表达抑制了缺氧/复氧（H/R）诱导的心肌细胞的炎症反应和凋亡。在H/R诱导的细胞中，琥珀酰化和MG53的蛋白水平下调，SIRT7抑制这种下调，KAT3B促进这种下调。SIRT7加重，KAT3B减轻MG53介导的心肌细胞损伤。结论：SIRT7抑制/KAT3B促进了MG53在K130位点的琥珀酰化，抑制了MG53的泛素化并上调了其蛋白水平，从而减轻了H/R诱导的心肌细胞损伤。研究结果提示MG53可能是一种潜在的心肌梗死治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Clinical and Experimental Hypertension 医学-外周血管病

CiteScore

3.90

自引率

0.80%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical and Experimental Hypertension is a reputable journal that has converted to a full Open Access format starting from Volume 45 in 2023. While previous volumes are still accessible through a Pay to Read model, the journal now provides free and open access to its content. It serves as an international platform for the exchange of up-to-date scientific and clinical information concerning both human and animal hypertension. The journal publishes a wide range of articles, including full research papers, solicited and unsolicited reviews, and commentaries. Through these publications, the journal aims to enhance current understanding and support the timely detection, management, control, and prevention of hypertension-related conditions. One notable aspect of Clinical and Experimental Hypertension is its coverage of special issues that focus on the proceedings of symposia dedicated to hypertension research. This feature allows researchers and clinicians to delve deeper into the latest advancements in this field. The journal is abstracted and indexed in several renowned databases, including Pharmacoeconomics and Outcomes News (Online), Reactions Weekly (Online), CABI, EBSCOhost, Elsevier BV, International Atomic Energy Agency, and the National Library of Medicine, among others. These affiliations ensure that the journal's content receives broad visibility and facilitates its discoverability by professionals and researchers in related disciplines.