Ferroptosis-Induced Endoplasmic Reticulum Stress: Cross-talk between Ferroptosis and Apoptosis.
Ferroptosis-Induced Endoplasmic Reticulum Stress: Cross-talk between Ferroptosis and Apoptosis.
复制标题
DOI：
10.1158/1541-7786.mcr-18-0055
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Lee YJ
中科院分区：
文献类型：
--
作者：
Lee YS;Lee DH;Choudry HA;Bartlett DL;Lee YJ
自2012年被发现以来，由于谷胱甘肽依赖的抗氧化剂防御失败，铁下垂一直以脂质过氧化积聚为特征。它被认为是一种铁依赖的细胞程序性死亡形式，不同于其他形式的细胞死亡，如凋亡和坏死。尽管如此，关于铁链促进剂诱导的内质网(ER)应激反应及其在细胞死亡中的作用，人们知之甚少。最近的研究表明，铁性下垂诱导的内质网应激反应在铁性下垂和其他类型的细胞死亡之间的串扰中起着重要作用。铁链诱导剂诱导未折叠的蛋白质反应，随后内质网应激介导的PERK-eIF2α-ATF4-CHOP通路的激活。CHOP(C/EBP Homologous Protein，C/EBP同源蛋白)信号通路介导的非P53非依赖性PUMA(P53 Upregated Modelator Of Atotosis)的表达参与了铁下垂与细胞凋亡的协同作用。本文综述了近年来通过内质网应激介导的PERK-eIF2ATF4-CHOP-PUMA途径与铁性趋化因子相互作用的最新文献，并提示联合治疗可有效地提高肿瘤杀伤力作为一种新的癌症治疗策略。
Since its discovery in 2012, ferroptosis has been well-characterized by the accumulation of lipid peroxides due to the failure of glutathione-dependent antioxidant defenses. It is known as an iron-dependent form of programmed cell death, which is distinct from other forms of cell death such as apoptosis and necrosis. Nonetheless, little is known about the ferroptotic agent-induced endoplasmic reticulum (ER) stress response and its role in cell death. Recent studies reveal that the ferroptotic agent-induced ER stress response plays an important role in the crosstalk between ferroptosis and other types of cell death. Ferroptotic agents induce the unfolded protein response and subsequently ER stress-mediated activation of the PERK-eIF2α-ATF4-CHOP pathway. CHOP (C/EBP homologous protein) signaling pathway-mediated p53-independent PUMA (p53 upregulated modulator of apoptosis) expression is involved in the synergistic interaction between ferroptosis and apoptosis. This review highlights the recent literature on ferroptotic and apoptotic agent interactions through the ER stress-mediated PERK-eIF2α-ATF4-CHOP-PUMA pathway and implicates combined treatment to effectively enhance tumoricidal efficacy as a novel therapeutic strategy for cancer.