 | Related Articles |
Ginsenoside Rg1 protection against ?-amyloid peptide-induced neuronal apoptosis via estrogen receptor ? and glucocorticoid receptor-dependent anti-protein nitration pathway.
Neuropharmacology. 2012 Sep;63(3):349-61
Authors: Wu J, Pan Z, Wang Z, Zhu W, Shen Y, Cui R, Lin J, Yu H, Wang Q, Qian J, Yu Y, Zhu D, Lou Y
Abstract
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 ?-amyloid peptide????? (A??????) injury via estrogen receptor ? (ER?) 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? and GR, induces related responsive gene PR, pS? and MKP-1, SGK transcription. Meantime, Rg1 also increases the basal level of ERK1/2 phosphorylation. In the presence of toxic level of A??????, Rg1 maintains ERK1/2 phosphorylation, attenuates iNOS expression, NO production, and inhibits NF-?B nuclear translocation, protein nitration and cell death. The antiapoptotic effects of Rg1 via both ER? 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? and GR activation, although its anti-ROS production effect is in an ER?- and GR-independent manner. These results suggest that Rg1 ameliorates A??????-induced neuronal apoptosis at least in part by two complementary ER?- 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-?B nuclear translocation. These data provide new understanding into the mechanisms of Rg1 anti-apoptotic functions after A?????? exposure, suggesting that ER? and GR-dependent anti-protein tyrosine nitration pathway might take an important role in the neuroprotective effect of Rg1.
PMID: 22534050 [PubMed - indexed for MEDLINE]
没有评论:
发表评论