Ginsenoside Rg1 protection against 尾-amyloid peptide-induced neuronal apoptosis via estrogen receptor 伪 and glucocorticoid receptor-dependent anti-protein nitration pathway

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• 作者：Jiaying Wu^a ; Zongfu Pan^a ; Zhiqiang Wang^a ; Wenjie Zhu^a ; Yuanyuan Shen^b ; Rong Cui^a ; Jiazhen Lin^a ; Hao Yu^a ; Qiongque Wang^a ; Jianchang Qian^a ; Yongping Yu^a ; Danyan Zhu^a ; ; Yijia Lou^a ; ^{yijialou@zju.edu.cn}
• 关键词：尾-Amyloid ; Receptor nuclear translocation ; Ginsenoside Rg1 ; Protein tyrosine nitration ; ERK1/2 phosphorylation
• 刊名：Neuropharmacology
• 出版年：2012
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：September, 2012
• 卷：63
• 期：3
• 页码：349-361
• 文件大小：3071 K

摘要

Ginsenoside Rg1 (Rg1) acts as a neuroprotective agent against various insults, however, the underlying mechanism has not been fully elucidated yet. Here, we report that Rg1 protects primary rat cerebrocortical neurons against 尾-amyloid peptide_25-35 (A尾_25-35) injury via estrogen receptor 伪 (ER伪) and glucocorticoid receptor (GR)-dependent anti-protein nitration pathway. In primary rat cerebrocortical neuron cultures under basal conditions, Rg1 leads to nuclear translocation of ER伪 and GR, induces related responsive gene PR, pS₂ and MKP-1, SGK transcription. Meantime, Rg1 also increases the basal level of ERK1/2 phosphorylation. In the presence of toxic level of A尾_25-35, Rg1 maintains ERK1/2 phosphorylation, attenuates iNOS expression, NO production, and inhibits NF-魏B nuclear translocation, protein nitration and cell death. The聽antiapoptotic effects of Rg1 via both ER伪 and GR were abolished by small interfering RNAs (siRNA). ERK1/2 phosphorylation inhibitor U0126 can block downstream iNOS expression and NO generation. Interestingly, the anti-protein nitration effect of Rg1 is well matched with ER伪 and GR activation, although its anti-ROS production effect is in an ER伪- and GR-independent manner. These results suggest that Rg1 ameliorates A尾_25-35-induced neuronal apoptosis at least in part by two complementary ER伪- and GR-dependent downstream pathways: (1) upregulation of ERK1/2 phosphorylation followed by inhibiting iNOS expression, NO generation and protein tyrosine nitration. (2) reduction NF-魏B nuclear translocation. These data provide new understanding into the mechanisms of Rg1 anti-apoptotic functions after A尾_25-35 exposure, suggesting that ER伪 and GR-dependent anti-protein tyrosine nitration pathway might take an important role in the neuroprotective effect of Rg1.