GPR30 mediates estrogen rapid signaling and neuroprotection.
GPR30 mediates estrogen rapid signaling and neuroprotection.
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GPR30 介导雌激素快速信号传导和神经保护。
DOI：
10.1016/j.mce.2014.01.024
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发表时间：
2014-04-25
影响因子：
4.1
通讯作者：
Wang R
中科院分区：
文献类型：
--
作者：
Tang H;Zhang Q;Yang L;Dong Y;Khan M;Yang F;Brann DW;Wang R
G蛋白偶联雌激素受体-30（GPR 30），也称为G蛋白雌激素受体-1（GPER 1），是一种推定的雌激素核受体，其在大脑中的确切功能知之甚少。使用外源性给予GPR 30激动剂G1的研究表明，GPR 30可能在脑缺血中具有神经保护作用。然而，GPR 30在介导雌激素（E2）诱导的脑缺血神经保护中的生理作用仍不清楚。同样不清楚的是，GPR 30是否在脑缺血后通过E2介导快速信号传导中起作用，这被认为是其神经保护作用的基础。为了解决这些缺陷，在我们的知识，目前的研究探讨反义寡核苷酸（AS）敲低GPR 30在海马CA 1区E2-BSA诱导的神经保护和快速激酶信号在大鼠模型的全脑缺血（GCI）的影响。免疫组化结果显示，GPR 30在海马CA 1区和齿状回呈强阳性表达，在CA 3区表达较少。E2-BSA对GCI的海马CA 1区神经元产生了强大的神经保护作用，这种作用可被AS敲低GPR 30所消除。错义对照寡核苷酸对E2-BSA诱导的神经保护作用没有影响，表明该作用具有特异性。GPR 30激动剂G1也对GCI产生显著的神经保护作用。E2-BSA和G1也迅速增强了促生存激酶Akt和ERK的激活，同时降低了促凋亡JNK的激活。重要的是，AS敲低GPR 30显著减弱E2-BSA的这些快速激酶信号传导效应。总体而言，这些研究提供了证据证明GPR 30在介导海马中E2的快速信号传导和神经保护作用中的重要作用。
G-protein-coupled estrogen receptor-30 (GPR30), also known as G-protein estrogen receptor-1 (GPER1), is a putative extranuclear estrogen receptor whose precise functions in the brain are poorly understood. Studies using exogenous administration of the GPR30 agonist, G1 suggests that GPR30 may have a neuroprotective role in cerebral ischemia. However, the physiological role of GPR30 in mediating estrogen (E2)-induced neuroprotection in cerebral ischemia remains unclear. Also unclear is whether GPR30 has a role in mediating rapid signaling by E2 after cerebral ischemia, which is thought to underlie its neuroprotective actions. To address these deficits in our knowledge, the current study examined the effect of antisense oligonucleotide (AS) knockdown of GPR30 in the hippocampal CA1 region upon E2-BSA-induced neuroprotection and rapid kinase signaling in a rat model of global cerebral ischemia (GCI). Immunohistochemistry demonstrated that GPR30 is strongly expressed in the hippocampal CA1 region and dentate gyrus, with less expression in the CA3 region. E2-BSA exerted robust neuroprotection of hippocampal CA1 neurons against GCI, an effect abrogated by AS knockdown of GPR30. Missense control oligonucleotides had no effect upon E2-BSA-induced neuroprotection, indicating specificity of the effect. The GPR30 agonist, G1 also exerted significant neuroprotection against GCI. E2-BSA and G1 also rapidly enhanced activation of the prosurvival kinases, Akt and ERK, while decreasing proapototic JNK activation. Importantly, AS knockdown of GPR30 markedly attenuated these rapid kinase signaling effects of E2-BSA. As a whole, the studies provide evidence of an important role of GPR30 in mediating the rapid signaling and neuroprotective actions of E2 in the hippocampus.
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影响因子：
7.7
作者：
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通讯作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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