iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis  

作　　者：Timur Yagudin Yue Zhao Haiyu Gao Yang Zhang Ying Yang Xiaofang Zhang Wenbo Ma Tolessa Muleta Daba Vladimir Ishmetov Kai Kang Baofeng Yang Zhenwei Pan 

机构地区：[1]Department of Pharmacology(The Key Laboratory of Cardiovascular Research,Ministry of Education)at College of Pharmacy,Harbin Medical University,Harbin 150086,China [2]Department of Cardiovascular Surgery,The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China [3]Department of Hospital Surgery,Bashkir State Medical University,Ufa 450008,Russian Federation [4]Department of Cardiovascular Surgery in Clinic,Hospital of Bashkir State Medical University,Ufa 450059,Russian Federation

出　　处：《Acta Biochimica et Biophysica Sinica》2021年第1期102-111,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Key R&D Program of China(No.2017YFC1307404 to Zhenwei Pan,Harbin Medical Univerisity);the National Natural Science Foundation of China(No.81730012 to Baofeng Yang,Harbin Medical University and No.81870295 to Zhenwei Pan,Harbin Medical Univerisity);Funds for Distinguished Young Scholars of Heilongjiang Province(to Zhenwei Pan,Harbin Medical Univerisity);Yu Weihan Excellent Youth Foundation of Harbin Medical University(No.001000004 to Zhenwei Pan,Harbin Medical Univerisity).

摘　　要：Currently, there remains a great need to elucidate the molecular mechanism of acute myocardial infarction in order to facilitate the development of novel therapy. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the ASPP family proteins and an evolutionarily preserved inhibitor of p53 that is involved in many cellular processes, including apoptosis of cancer cells. The purpose of this study was to investigate the possible role of iASPP in acute myocardial infarction. The protein level of iASPP was markedly reduced in the ischemic hearts in vivo and hydrogen peroxide-exposed cardiomyocytes in vitro. Overexpression of iASPP reduced the infarct size and cardiomyocyte apoptosis of mice subjected to 24 h of coronary artery ligation. Echocardiography showed that cardiac function was improved as indicated by the increase in ejection fraction and fractional shortening. In contrast, knockdown of iASPP exacerbated cardiac injury as manifested by impaired cardiac function, increased infarct size, and apoptosis rate. Mechanistically, overexpression of iASPP inhibited, while knockdown of iASPP increased the expressions of p53 and Bax, the key regulators of apoptosis. Taken together, our results suggested that iASPP is an important regulator of cardiomyocyte apoptosis, which represents a potential target in the therapy of myocardial infarction.

关 键 词：IASPP myocardial infarction apoptosis P53 

分 类 号：R542.2[医药卫生—心血管疾病]