Akt up- and down-regulation in response to endoplasmic reticulum stress

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• 作者：Toru Hosoi ; Kanae Hyoda ; Yasunobu Okuma ; Yasuyuki Nomura ; Koichiro Ozawa
• 关键词：Endoplasmic reticulum stress ; Phosphatidylinositol 3-kinase ; Akt ; Glial cell
• 刊名：Brain Research
• 出版年：2007
• 出版时间：4 June 2007
• 年：2007
• 卷：1152
• 期：Complete
• 页码：27-31
• 全文大小：462 K

文摘

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of CNS diseases such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia. In the present study, we found that Akt activation is regulated dually by ER stress in primary cultured glial cells. We observed that Akt activation was increased by short-term exposure to ER stress but was down-regulated by long-term exposure to ER stress. ER stress-induced Akt activation was mediated through phosphatidylinositol 3-kinase (PI3K) because the PI3K inhibitors, LY294002 and wortmannin, inhibited Akt activation. Moreover, Akt was localized in the ER, as assessed by immunohistochemistry, and ER stress increased microsomally localized Akt activation. These results suggest that Akt plays an important role in stress conditions, which impair ER function.