Insulin modulates induction of glucose-regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells
Insulin modulates induction of glucose-regulated protein 78 during endoplasmic reticulum stress via augmentation of ATF4 expression in human neuroblastoma cells
复制标题
DOI：
10.1016/j.febslet.2010.07.040
复制
发表时间：
2010-08-20
期刊：
影响因子：
3.5
通讯作者：
Inageda, Kiyoshi
中科院分区：
文献类型：
--
作者：
Inageda, Kiyoshi
观察胰岛素对内质网应激的影响。胰岛素保护内质网应激诱导的细胞死亡，并增加葡萄糖调节蛋白78(GRP78)的mRNA和蛋白水平。胰岛素还可显著增加细胞核内激活的转录因子4(ATF4)蛋白，这一作用可被磷脂酰肌醇3-激酶(PI-3)抑制剂LY294002抑制。胰岛素增加ATF4蛋白的表达不是由于转录或翻译上调，而是一种翻译后机制。SiRNA下调ATF4基因可显著抑制胰岛素对GRP78的诱导作用。这些结果表明，胰岛素调节内质网应激诱导的GRP78表达是通过上调ATF4来实现的。(C)2010年欧洲生化学会联合会。爱思唯尔出版公司版权所有。
The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose-regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor-4 (ATF4) protein in the nucleus, which was inhibited by LY294002, a phosphatidylinositol 3-kinase (PI-3 kinase) inhibitor. The increase of ATF4 protein by insulin was not due to transcriptional or translational up-regulation but to a post-translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress-induced GRP78 expression occurs via ATF4 up-regulation. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.