Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2
Phosphoinositide 3-kinase accelerates autophagic cell death during glucose deprivation in the rat cardiomyocyte-derived cell line H9c2
复制标题
DOI：
10.1038/sj.onc.1207197
复制
发表时间：
2003-11-20
期刊：
影响因子：
8
通讯作者：
Mizukami, Y
中科院分区：
文献类型：
--
作者：
Aki, T;Yamaguchi, K;Mizukami, Y
我们研究了大鼠心肌细胞来源的H9c2细胞在缺糖过程中的细胞死亡。电子显微镜分析显示，在缺糖过程中，自噬空泡堆积。添加3-甲基腺嘌呤或LY294002，它们可以抑制自噬小体的形成，减少细胞死亡，而caspase抑制剂Z-VAD-FMK对细胞死亡略有影响。因此，缺糖过程中的细胞死亡不是I型程序性细胞死亡(凋亡性细胞死亡)，而是11型程序性细胞死亡(自噬细胞死亡)。此外，我们发现胰岛素样生长因子-I和腺病毒介导的野生型I型PI 3-激酶的过表达都加速了葡萄糖剥夺时细胞的死亡和自噬空泡的积累，而显性负性PI 3-K则减少了这些现象。结果表明，IGF-I/PI 3-激酶在缺糖时加速自噬空泡的积累和随后的自噬细胞死亡，揭示了IGF-I/PI 3-K在两种不同类型的程序性细胞死亡(凋亡性和自噬细胞死亡)中的相反作用。
We investigated cell death during glucose deprivation in rat cardiomyocyte-derived H9c2 cells. Electron microscopic analysis revealed accumulation of autophagic vacuoles during glucose deprivation. The addition of 3-methyladenine or LY294002, which are known to inhibit autophagosome formation, reduced cell death while Z-VAD-FMK, a caspase inhibitor, slightly affected cell death. Thus, cell death during glucose deprivation is not type I programmed cell death (apoptotic cell death) but type 11 programmed cell death (autophagic cell death). Moreover, we found that both insulin-like growth factor-I and the adenovirus-mediated overexpression of wild-type class I PI 3-kinase accelerated cell death as well as accumulation of autophagic vacuoles during glucose deprivation while dominant-negative PI 3-kinase reduced these phenomena. The results indicate that IGF-I/PI 3-kinase accelerates the accumulation of autophagic vacuoles and subsequent autophagic cell death during glucose deprivation, revealing the opposing role of IGF-I/PI 3-kinase in two distinct types of programmed cell death (apoptotic and autophagic cell death).