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

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

Acta biochimica et biophysica Sinica 2021 Jan 12

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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. © The Author(s) 2021. Published by Oxford University Press on behalf of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

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. iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis. Acta biochimica et biophysica Sinica. 2021 Jan 12;53(1):102-111