LncRNA-6395 promotes myocardial ischemia-reperfusion injury in mice through increasing p53 pathway

被引:0
|
作者
Lin-feng Zhan
Qi Zhang
Lu Zhao
Xue Dong
Xin-yu Pei
Li-li Peng
Xiao-wen Zhang
Bo Meng
Wen-di Shang
Zhen-wei Pan
Chao-qian Xu
Yan-jie Lu
Ming-yu Zhang
机构
[1] Harbin Medical University,Department of Pharmacology (State
[2] Harbin Medical University,Province Key Laboratories of Biomedicine
来源
Acta Pharmacologica Sinica | 2022年 / 43卷
关键词
myocardial I/R injury; H; O; lncRNA; apoptosis; p53; ubiquitination; neonatal mouse ventricular cardiomyocytes;
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摘要
Myocardial ischemia-reperfusion (I/R) injury is a pathological process characterized by cardiomyocyte apoptosis, which leads to cardiac dysfunction. Increasing evidence shows that abnormal expression of long noncoding RNAs (lncRNAs) plays a crucial role in cardiovascular diseases. In this study we investigated the role of lncRNAs in myocardial I/R injury. Myocardial I/R injury was induced in mice by ligating left anterior descending coronary artery for 45 min followed by reperfusion for 24 h. We showed that lncRNA KnowTID_00006395, termed lncRNA-6395 was significantly upregulated in the infarct area of mouse hearts following I/R injury as well as in H2O2-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Overexpression of lncRNA-6395 led to cell apoptosis and the expression change of apoptosis-related proteins in NMVCs, whereas knockdown of lncRNA-6395 attenuated H2O2-induced cell apoptosis. LncRNA-6395 knockout mice (lncRNA-6395+/−) displayed improved cardiac function, decreased plasma LDH activity and infarct size following I/R injury. We demonstrated that lncRNA-6395 directly bound to p53, and increased the abundance of p53 protein through inhibiting ubiquitination-mediated p53 degradation and thereby facilitated p53 translocation to the nucleus. More importantly, overexpression of p53 canceled the inhibitory effects of lncRNA-6395 knockdown on cardiomyocyte apoptosis, whereas knockdown of p53 counteracted the apoptotic effects of lncRNA-6395 in cardiomyocytes. Taken together, lncRNA-6395 as an endogenous pro-apoptotic factor, regulates cardiomyocyte apoptosis and myocardial I/R injury by inhibiting degradation and promoting sub-cellular translocation of p53.
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页码:1383 / 1394
页数:11
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