Akt up- and down-regulation in response to endoplasmic reticulum stress
Akt up- and down-regulation in response to endoplasmic reticulum stress
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DOI：
10.1016/j.brainres.2007.03.052
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发表时间：
2007-06-04
期刊：
影响因子：
2.9
通讯作者：
Ozawa, Koichiro
中科院分区：
文献类型：
--
作者：
Hosoi, Toru;Hyoda, Kanae;Ozawa, Koichiro
内质网（ER）应激与中枢神经系统疾病如阿尔茨海默病、帕金森病和脑缺血的发病机制有关。在本研究中，我们发现，Akt激活的双重调节ER应激原代培养的胶质细胞。我们观察到，Akt激活增加短期暴露于ER应激，但下调长期暴露于ER应激。ER应激诱导的Akt活化是通过磷脂酰肌醇3-激酶（PI 3 K）介导的，因为PI 3 K抑制剂LY 294002和渥曼青霉素抑制Akt活化。此外，Akt被定位在ER中，如通过免疫组织化学评估的，并且ER应激增加了微粒体定位的Akt活化。这些结果表明Akt在损害ER功能的应激条件下起重要作用。(c)2007 Elsevier B. V.保留所有权利。
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. (c) 2007 Elsevier B.V. All rights reserved.