PERK通路在心肌缺血再灌注损伤中的研究进展

Research advance in PERK pathway in myocardial ischemia reperfusion injury

蛋白激酶R样内质网激酶(PERK)是内质网上的一种应激感受器,具有丝氨酸-苏氨酸激酶活性,它既能激活细胞存活信号传导途径,也能促进细胞凋亡。在内质网应激(ERS)的早期阶段激活PERK结构域,导致真核细胞翻译起始因子2α(e IF2α)磷酸化,减少转录启动和蛋白折叠,维持内质网内环境稳态。晚期磷酸化e IF2α则通过转录激活因子4(ATF4)导致促凋亡蛋白C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)及半胱氨酸天冬氨酸蛋白水解酶12(caspase-12)的过度表达,导致细胞凋亡。PERK通路作为ERS主要信号通路之一,在心肌缺血再灌注损伤(MIRI)的发生、发展中扮演着重要角色,了解其在MIRI中的作用,可能为改善缺血性心脏病治疗效果提供新的思路。

Protein kinase R-like ER kinase（ PERK） is a stress receptor on the endoplasmic reticulum with serine-threonine kinase activity,which can promote apoptosis and activate cell survival signaling pathway. Activating the PERK kinase domain in the early stages of endoplasmic reticulum stress（ ERS） leads to phosphorylation of e IF2α,reducing transcriptional initiation and protein folding,and maintaining homeostasis in the endoplasmic reticulum. Advanced phosphorylation of e IF2α through the activation of ATF4 induces apoptosis protein CHOP and caspase-12 overexpression and further leads to apoptosis. As one of the significant signaling pathways of ERS,PERK pathway plays an important role in the development and progression of myocardial ischemia-reperfusion injury（ MIRI）. Therefore,understanding the action of PERK in MIRI might be helpful to improve the therapeutic effects on ischemic heart disease.