globalchange  > 气候变化与战略
DOI: 10.1016/j.scib.2021.04.008
论文题名:
Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2
作者: Ma L.; Shi H.; Li Y.; Gao W.; Guo J.; Zhu J.; Dong Z.; Sun A.; Zou Y.; Ge J.
刊名: Science Bulletin
ISSN: 20959273
出版年: 2021
语种: 英语
中文关键词: Acetylation ; Hypertrophic preconditioning ; IDH2 ; Ischemia/reperfusion injury ; SIRT3
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resistant to subsequent ischemic stress, short-term transverse aortic constriction (TAC) was performed in mice and then withdrawn for several days by aortic debanding, followed by subsequent myocardial exposure to ischemia/reperfusion (I/R).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
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资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/170353
Appears in Collections:气候变化与战略

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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

Recommended Citation:
Ma L.,Shi H.,Li Y.,et al. Hypertrophic preconditioning attenuates myocardial ischemia/reperfusion injury through the deacetylation of isocitrate dehydrogenase 2[J]. Science Bulletin,2021-01-01
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