iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis
iASPP protects the heart from ischemia injury by inhibiting p53 expression and cardiomyocyte apoptosis
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iASPP 通过抑制 p53 表达和心肌细胞凋亡来保护心脏免受缺血损伤
DOI：
10.1093/abbs/gmaa104
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发表时间：
2021
影响因子：
3.7
通讯作者：
Pan Zhenwei
中科院分区：
文献类型：
--
作者：
Yagudin Timur;Zhao Yue;Gao Haiyu;Zhang Yang;Yang Ying;Zhang Xiaofang;Ma Wenbo;Daba Tolessa Muleta;Ishmetov Vladimir;Kang Kai;Yang Baofeng;Pan Zhenwei
目前，迫切需要阐明急性心肌梗死的分子机制，以促进新疗法的发展。p53凋亡刺激蛋白抑制剂（Inhibitor of apoptosis-stimulating protein of p53, iASPP）是ASPP家族的一员，是一种进化保存下来的p53抑制剂，参与许多细胞过程，包括癌细胞的凋亡。本研究的目的是探讨iASPP在急性心肌梗死中的可能作用。iASPP蛋白水平在体内缺血心脏和体外过氧化氢暴露心肌细胞中明显降低。iASPP的过表达减少了冠状动脉结扎24 h小鼠的梗死面积和心肌细胞凋亡。超声心动图显示心脏功能得到改善，射血分数和缩短分数增加。相反，iASPP基因敲低会加重心脏损伤，表现为心功能受损、梗死面积增大和细胞凋亡率升高。在机制上，iASPP的过表达抑制了细胞凋亡的关键调控因子p53和Bax的表达，而iASPP的下调则增加了p53和Bax的表达。综上所述，我们的研究结果表明iASPP是心肌细胞凋亡的重要调节因子，它代表了心肌梗死治疗的潜在靶点。
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.