新基因NDRG2及其蛋白产物Ndrg2磷酸化修饰在心肌缺血/再灌注损伤中的作用

项目名称： 新基因NDRG2及其蛋白产物Ndrg2磷酸化修饰在心肌缺血/再灌注损伤中的作用

项目编号： No.81500183

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 童光

作者单位： 中国人民解放军南部战区总医院

项目金额： 18万元

中文摘要： 缺血再灌注损伤严重影响急性心肌梗死患者预后，其机制尚不明了。NDRG2是近年来发现的新基因，其功能与细胞生存相关。其在心肌细胞中高表达，但其在心肌细胞中功能尚未阐明。NDRG2表达在心肌缺血再灌注损伤中均发生明显变化，干扰其表达消除了胰岛素的心肌保护作用，表明其可能具有抗缺血再灌注损伤的作用。Ndrg2可被磷酸化修饰，在缺血再灌注损伤中，胰岛素增加了其磷酸化水平。因此，我们猜测磷酸化修饰可能是调节其在缺血再灌注损伤心肌功能的机制之一。本课题将首次应用基因敲除与磷酸化位点突变结合的方法明确 NDRG2及其蛋白产物Ndrg2磷酸化修饰在心肌缺血/再灌注损伤中的作用；从而发现新的心肌保护机制，为新的药物开发奠定基础。

中文关键词： N-MYC下游调节基因2；心肌细胞；缺血/再灌注；磷酸化

英文摘要： Ischemia/reperfusion(I/R) injury is a major contributor to mobidity and mortality in patient with acute myocardial infarct. The mechanism involved in I/R injury is not fully understood. NDRG2 is a novel gene and it is shown to be involved in cell survival. It is highly expressed in cardiomyocytes, however, its function in cardiomyocytes is largely unknown. Ischemia-reperfusion(I/R) significantly change its expression in cardiomyocytes. The silencing of NDRG2 alleviates the cardioprotection by Insulin. It is possible that NRDG2 is cardioprotective in I/R injury. NDRG2 can be phosphorylated and its phosphorylation level is shown to be significantly elevated by insulin in cardiomyocytes under I/R injury. We speculate that phosphorylation modified Ndrg2 function in cardiomyocytes during I/R injury. We plan to clarify the role of NDRG2 in cardiomyocytes I/R injury and the impact of phosphorylation on its function in cardiomyocytes under I/R injury.Our study will not only further understand the function of Ndrg2 in myocardial dysfunction, but also contribute to better understanding of the mechanism of I/R injury, and lay foundation for the development of novel medication for I/R injury.

英文关键词： NDRG2;cardiomyocyte;ischemia/reperfusion ;phosphorylation