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

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 imm...

Full description

Bibliographic Details
Main Authors: Yan Wang, Hongying Zhou, Jin Wu, Shanshan Ye
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Clinical and Experimental Hypertension
Subjects:
Online Access:http://dx.doi.org/10.1080/10641963.2023.2271196
_version_ 1827767375439593472
author Yan Wang
Hongying Zhou
Jin Wu
Shanshan Ye
author_facet Yan Wang
Hongying Zhou
Jin Wu
Shanshan Ye
author_sort Yan Wang
collection DOAJ
description 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.
first_indexed 2024-03-11T11:57:51Z
format Article
id doaj.art-81a39e6ab473422f97f92f91b4024b8f
institution Directory Open Access Journal
issn 1064-1963
1525-6006
language English
last_indexed 2024-03-11T11:57:51Z
publishDate 2023-12-01
publisher Taylor & Francis Group
record_format Article
series Clinical and Experimental Hypertension
spelling doaj.art-81a39e6ab473422f97f92f91b4024b8f2023-11-08T11:49:23ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062023-12-0145110.1080/10641963.2023.22711962271196MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modificationYan Wang0Hongying Zhou1Jin Wu2Shanshan Ye3The First People’s Hospital of Chun’an County(Chun’an branch of Zhejiang Provincial People’s Hospital)Zhejiang Provincial People’s HospitalThe First People’s Hospital of Chun’an County(Chun’an branch of Zhejiang Provincial People’s Hospital)Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical UniversityBackground 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.http://dx.doi.org/10.1080/10641963.2023.2271196mg53succinylationkat3bsirt7ubiquitinationhypoxia/reoxygenation
spellingShingle Yan Wang
Hongying Zhou
Jin Wu
Shanshan Ye
MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification
Clinical and Experimental Hypertension
mg53
succinylation
kat3b
sirt7
ubiquitination
hypoxia/reoxygenation
title MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification
title_full MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification
title_fullStr MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification
title_full_unstemmed MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification
title_short MG53 alleviates hypoxia/reoxygenation-induced cardiomyocyte injury by succinylation and ubiquitination modification
title_sort mg53 alleviates hypoxia reoxygenation induced cardiomyocyte injury by succinylation and ubiquitination modification
topic mg53
succinylation
kat3b
sirt7
ubiquitination
hypoxia/reoxygenation
url http://dx.doi.org/10.1080/10641963.2023.2271196
work_keys_str_mv AT yanwang mg53alleviateshypoxiareoxygenationinducedcardiomyocyteinjurybysuccinylationandubiquitinationmodification
AT hongyingzhou mg53alleviateshypoxiareoxygenationinducedcardiomyocyteinjurybysuccinylationandubiquitinationmodification
AT jinwu mg53alleviateshypoxiareoxygenationinducedcardiomyocyteinjurybysuccinylationandubiquitinationmodification
AT shanshanye mg53alleviateshypoxiareoxygenationinducedcardiomyocyteinjurybysuccinylationandubiquitinationmodification