PI3K-Akt inactivation induced CHOP expression in endoplasmic reticulum-stressed cells
PI3K-Akt inactivation induced CHOP expression in endoplasmic reticulum-stressed cells
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DOI：
10.1016/j.bbrc.2005.12.007
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发表时间：
2006-02-03
影响因子：
3.1
通讯作者：
Nomura, Y
中科院分区：
文献类型：
--
作者：
Hyoda, K;Hosoi, T;Nomura, Y
损伤内质网（ER）功能的应激信号可导致ER中未折叠蛋白的积累，从而导致细胞死亡。最近的研究表明，ER应激有助于几种疾病，如神经退行性疾病或糖尿病。在本研究中，我们发现Akt下调对于诱导CHOP表达是重要的，CHOP是一种ER应激诱导的转录因子。处理衣霉素或毒胡萝卜素，ER应激诱导剂，引起Akt的去磷酸化从12至24小时，并诱导细胞死亡。有趣的是，单独用PI3K抑制剂处理诱导CHOP表达并引起细胞死亡。然而，MEK 1抑制剂既不诱导CHOP表达也不诱导细胞死亡。这些结果表明，ER应激导致Akt失活诱导CHOP表达并导致细胞死亡。因此，Akt在内质网应激状态中起着重要作用，可能对理解内质网应激相关疾病具有重要意义。(c)2005年爱思唯尔公司All rights reserved.
Stress signals that impair the function of the endoplasmic reticulum (ER) can lead to an accumulation of unfolded proteins in the ER causing cell death. Recent studies have indicated that ER stress contributes to several diseases such as neurodegenerative disorders or diabetes. In the present study, we found that Akt down-regulation is important for inducing CHOP expression, an ER stress-induced transcription factor. Treatment with tunicamycin or thapsigargin, ER stress inducers, caused dephosphorylation of Akt from 12 to 24 h and induced cell death. Interestingly, treatment with a PI3K inhibitor alone induced CHOP expression and caused cell death. However, a MEK 1 inhibitor induced neither CHOP expression nor cell death. These results indicate that the inactivation of Akt by ER stress induces CHOP expression and causes cell death. Therefore, Akt plays an important role in ER stressed condition and may have important implications for understanding ER stress-related diseases. (c) 2005 Elsevier Inc. All rights reserved.