17Beta-estradiol differentially protects cortical pericontusional zone from programmed cell death after traumatic cerebral contusion at distinct stages via non-genomic and genomic pathways
17Beta-estradiol differentially protects cortical pericontusional zone from programmed cell death after traumatic cerebral contusion at distinct stages via non-genomic and genomic pathways
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DOI：
10.1016/j.mcn.2011.07.004
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发表时间：
2011-11-01
影响因子：
3.5
通讯作者：
Wang, Yun-Jie
中科院分区：
文献类型：
--
作者：
Bao, Yi-Jun;Li, Li-Zhuo;Wang, Yun-Jie
外伤性脑挫伤的挫伤周围区是药物干预的靶点。本课题组前期研究表明，17 β-雌二醇通过上调雌激素受体（ER）α mRNA的诱导和蛋白表达，抑制caspase-3的激活，对创伤性脑挫伤后PCZ具有保护作用，提示17 β-雌二醇的保护作用可能与基因组信号通路有关。最近的研究表明，17 β-雌二醇还作用于细胞核/膜ER，激活非基因组信号通路，调节细胞功能，并在脑中发挥保护作用。目前尚不清楚17 β-雌二醇的基因组和非基因组途径如何以及是否参与PCZ的神经保护作用。我们目前的研究表明，17 β-雌二醇在早期激活ERK 1/2和Akt，并在晚期诱导ER α和Survivin mRNA，通过抑制caspase-3的激活来调节其保护作用。这些结果表明，17 β-雌二醇通过基因组和非基因组信号通路在创伤性脑挫伤后PCZ中差异发挥其保护作用。(C)2011 Elsevier Inc. All rights reserved.
Pericontusional zone (PCZ) of traumatic cerebral contusion is a target of pharmacological intervention. Our previous study indicated that 17beta-estradiol has a protective role in PCZ after traumatic cerebral contusion via the upregulation of estrogen receptor (ER) alpha mRNA induction and protein expression as well as inhibition of caspase-3 activation, suggesting that genomic signaling pathway is implicated in the protective effect of 17beta-estrodiol. Recent findings demonstrated that 17beta-estradiol also acts on the extranuclear/membrane ER to activate non-genomic signaling pathway to regulate cellular functions and exert the protective effect in the brain. It is still unclear how and whether genomic and non-genomic pathways of 17beta-estradiol are involved in the neuroprotection in PCZ. Our current study demonstrates that 17beta-estradiol activates ERK1/2 and Akt at the early stage and induces ERalpha and survivin mRNA at the late stage to modulate its protection via the suppression of caspase-3 activation in PCZ. These findings suggest that 17beta-estrodiol differentially plays its protective roles via genomic and non-genomic signaling pathways in PCZ after traumatic cerebral contusion. (C) 2011 Elsevier Inc. All rights reserved.