کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8262651 | 1400119 | 2017 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3β pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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![عکس صفحه اول مقاله: Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3β pathway Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3β pathway](/preview/png/8262651.png)
چکیده انگلیسی
Oxidative stress and apoptosis are thought to be broadly involved in the pathogenesis of Parkinson's disease. We previously reported that Mesencephalic astrocyte-derived neurotrophic factor (MANF) possesses anti-oxidation and anti-apoptotic effects against 6-OHDA-induced neurotoxicity, but the specific molecular mechanism remains unclear. In this study, we showed that MANF up-regulates the expression of nuclear factor erythroid 2-related factor (Nrf2) and promotes its translocation into the nucleus. The anti-oxidation and anti-apoptotic effects of MANF could be partially blocked by inhibitor or shRNA-mediated knockdown of Nrf2. Furthermore, MANF activated phospoinositide-3-kinase (PI3K)/Akt signaling and suppressed glycogen synthase kinase (GSK3β) activation. PI3K inhibitor (LY49002) abolished effects of MANF on AKT phosphorylation, GSK3β inactivation, Nrf2 nuclear translocation and subsequently abrogated MANF-mediates cytoprotection. Collectively, our findings indicated that MANF-mediated protection against 6-OHDA-induced cytotoxicity by potentiating the Nrf2-related survival mechanism through the PI3K/Akt/GSK3β pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Gerontology - Volume 100, 15 December 2017, Pages 77-86
Journal: Experimental Gerontology - Volume 100, 15 December 2017, Pages 77-86
نویسندگان
Jingxing Zhang, Weifang Tong, Hui Sun, Ming Jiang, Yijue Shen, Yigang Liu, Hua Gu, Jia Guo, Jianmin Fang, Lingjing Jin,