气候变化领域集成服务门户(CCPortal): Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2

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DOI	10.1016/j.scib.2021.04.008
	Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2
	Ma L.; Shi H.; Li Y.; Gao W.; Guo J.; Zhu J.; Dong Z.; Sun A.; Zou Y.; Ge J.
发表日期	2021
ISSN	20959273
英文摘要	To test the hypothesis that transient nonischemic stimulation of hypertrophy would render the heart resistant to subsequent ischemic stress, short-term transverse aortic constriction (TAC) was performed in mice and then withdrawn for several days by aortic debanding, followed by subsequent myocardial exposure to ischemia/reperfusion (I/R). Following I/R injury, the myocardial infarct size and apoptosis were markedly reduced, and contractile function was significantly improved in the TAC preconditioning group compared with the control group. Mechanistically, hypertrophic preconditioning remarkably alleviated I/R-induced oxidative stress, as evidenced by the increased reduced nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide phosphate (NADP) ratio, increase in the reduced glutathione (GSH)/oxidized glutathione (GSSH) ratio, and reduced mitochondrial reactive oxygen species (ROS) production. Moreover, TAC preconditioning inhibited caspase-3 activation and mitigated the mitochondrial impairment by deacetylating isocitrate dehydrogenase 2 (IDH2) via a sirtuin 3 (SIRT3)-dependent mechanism. In addition, the expression of a genetic deacetylation mimetic IDH2 mutant (IDH2 K413R) in cardiomyocytes, which increased IDH2 enzymatic activity and decreased mitochondrial ROS production, and ameliorated I/R injury, whereas the expression of a genetic acetylation mimetic (IDH2 K413Q) in cardiomyocytes abolished these protective effects of hypertrophic preconditioning. Furthermore, both the activity and expression of the SIRT3 protein were markedly increased in preconditioned mice exposed to I/R. Treatment with an adenovirus encoding SIRT3 partially emulated the actions of hypertrophic preconditioning, whereas genetic ablation of SIRT3 in mice blocked the cardioprotective effects of hypertrophic preconditioning. The present study identifies hypertrophic preconditioning as a novel endogenous self-defensive and cardioprotective strategy for cardiac I/R injury that induces IDH2 deacetylation through a SIRT3-dependent mechanism. A therapeutic strategy targeting IDH2 may be a promising treatment for cardiac ischemic injury. © 2021 Science China Press
关键词	Acetylation Hypertrophic preconditioning IDH2 Ischemia/reperfusion injury SIRT3
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207519
作者单位	Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, 200032, China; NHC Key Laboratory of Viral Heart Diseases, Shanghai, 200032, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, 200032, China; Institute of Biomedical Science, Fudan University, Shanghai, 200032, China; Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266101, China; Qingdao Municipal Key Laboratory of Hypertension (Key Laboratory of Cardiovascular Medicine), Qingdao, 266101, China; Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China; Jiangxi Hypertension Research Institute, Nanchang, 330006, China
推荐引用方式 GB/T 7714	Ma L.,Shi H.,Li Y.,et al. Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2[J],2021.
APA	Ma L..,Shi H..,Li Y..,Gao W..,Guo J..,...&Ge J..(2021).Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2.Science Bulletin.
MLA	Ma L.,et al."Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2".Science Bulletin (2021).