铁死亡在心肌缺血再灌注损伤中作用研究进展

Role of ferroptosis in myocardial ischemia-reperfusion injury

铁死亡是一种铁依赖的程序性细胞死亡方式,铁死亡诱导的内质网应激在铁死亡与其他类型的细胞死亡之间发挥重要串联作用。铁死亡诱导内质网应激过程中的未折叠蛋白质反应,随后激活PERK-eIF2α-ATF4-CHOP信号通路。C/EBP同源蛋白信号通路可介导内质网应激凋亡过程,其在心肌缺血再灌注损伤过程中发挥重要作用。p53上调凋亡调控因子的过程是p53非依赖性的,同时参与铁死亡与细胞凋亡间的协同关系。本文就内质网应激介导的PERK-eIF2α-ATF4-CHOP-PUMA途径在铁死亡和心肌缺血再灌注过程中作用的研究进展作一综述。

Ferroptosis is an iron-dependent method of programmed cell death. It has been found that ferroptosis-induced endoplasmic reticulum stress(ERS) plays an important tandem role between iron death and other types of cell death. Ferroptosis induces an unfolded protein response during ERS, followed by activating PERK-eIF2α-ATF4-CHOP signaling pathway. The C/EBP homologous protein(CHOP) signaling pathway mediates ERS apoptosis, functioning in the ischemia-reperfusion injury process. p53 upregulated modulator of apoptosis(PUMA) is p53-independent, and is involved in the synergistic relationship between iron death and apoptosis. This paper reviews the role of ERS-mediated PERK-eIF2α-ATF4-CHOP-PUMA pathway in ferroptosis and myocardial ischemia-reperfusion.