Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival
Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival
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DOI：
10.1074/jbc.m609267200
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发表时间：
2007-02-16
影响因子：
4.8
通讯作者：
Yin, Xiao-Ming
中科院分区：
文献类型：
--
作者：
Ding, Wen-Xing;Ni, Hong-Min;Yin, Xiao-Ming
自噬是对不利环境和压力的细胞反应，但其在细胞存活中的重要性并不总是很清楚。在这里，我们表明可以在哺乳动物细胞中诱导自噬，例如A23187，衣霉素，Thapsigargin和Brefeldin A，从而导致内质网应激。内质网应激诱导的自噬对于清除多偶联的蛋白质聚集体和减少HCT116结肠癌细胞和DU145前列腺癌细胞的细胞液泡的重要性很重要，从而减轻内质网应激和保护细胞死亡。相反，相同化学物质诱导的自噬不能在正常的人类结肠细胞系和未转化的鼠类胚胎成纤维细胞中提供保护，而是在细胞死亡中造成保护。因此，自噬对内质网应激期间细胞存活的影响可能取决于细胞的状态，这可以用于肿瘤特异性治疗。
Autophagy is a cellular response to adverse environment and stress, but its significance in cell survival is not always clear. Here we show that autophagy could be induced in the mammalian cells by chemicals, such as A23187, tunicamycin, thapsigargin, and brefeldin A, that cause endoplasmic reticulum stress. Endoplasmic reticulum stress-induced autophagy is important for clearing polyubiquitinated protein aggregates and for reducing cellular vacuolization in HCT116 colon cancer cells and DU145 prostate cancer cells, thus mitigating endoplasmic reticulum stress and protecting against cell death. In contrast, autophagy induced by the same chemicals does not confer protection in a normal human colon cell line and in the non-transformed murine embryonic fibroblasts but rather contributes to cell death. Thus the impact of autophagy on cell survival during endoplasmic reticulum stress is likely contingent on the status of cells, which could be explored for tumor-specific therapy.