NEUROPROTECTION OF ETHANOL AGAINST ISCHEMIA/REPERFUSION-INDUCED BRAIN INJURY THROUGH DECREASING c-Jun N-TERMINAL KINASE 3 (JNK3) ACTIVATION BY ENHANCING GABA RELEASE
NEUROPROTECTION OF ETHANOL AGAINST ISCHEMIA/REPERFUSION-INDUCED BRAIN INJURY THROUGH DECREASING c-Jun N-TERMINAL KINASE 3 (JNK3) ACTIVATION BY ENHANCING GABA RELEASE
复制标题
通过增强 GABA 释放来降低 c-Jun N 末端激酶 3 (JNK3) 的激活，从而对乙醇进行神经保护，防止缺血/再灌注引起的脑损伤
DOI：
10.1016/j.neuroscience.2010.02.018
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发表时间：
2010-06-02
期刊：
影响因子：
3.3
通讯作者：
Zhang, G. -Y.
中科院分区：
文献类型：
--
作者：
Qi, S. -H.;Liu, Y.;Zhang, G. -Y.
我们的最新研究表明，乙醇可以通过激活嗜离子性谷氨酸受体Kainate Family (Gluk1)-kainate （KA）受体和γ -氨基丁酸（GABA）受体来减轻脑缺血/再灌注诱导的脑损伤。然而，乙醇神经保护作用的可能机制尚不清楚。在这项研究中，我们报道了乙醇通过增加GABA的释放，然后降低c-Jun n -末端激酶3 （JNK3）的激活，对缺血性脑损伤具有神经保护作用。电生理记录表明，乙醇增强突触前神经元的GABA释放，释放的GABA随后抑制KA受体介导的全细胞电流。此外，我们的数据显示，乙醇可以抑制脑缺血诱导的Gluk2-PSD-95-MLK3（突触后密度蛋白-95，PSD-95和混合谱系激酶3，MLK3）模块的组装增加和MLK3-MKK4/7- jnk（丝裂原活化蛋白激酶4/7，MKK4/7）级联的激活。预处理GABA(A)受体拮抗剂双库兰和VGCC（电压门控钙通道[VGCC]）的拮抗剂（CdCl2）可以破坏乙醇的神经保护作用。结果表明，在缺血-再灌注过程中，乙醇可能激活突触前Gluk1-KA并促进Ca2+依赖性GABA的释放。释放的GABA激活突触后GABAA受体，抑制缺血去极化，减少突触后Gluk2-KA受体激活诱导的信号模块Gluk2-PSD-95-MLK3的关联。乙醇抑制JNK3凋亡通路（MLK3/MKK4/7/JNK3/c-Jun/Fas-L）可能对缺血性脑损伤具有神经保护作用。(c) 2010 ibro。Elsevier Ltd.出版。版权所有。
Our latest study indicated that ethanol could attenuate cerebral ischemia/reperfusion-induced brain injury through activating Ionotropic glutamate receptors Kainate Family (Gluk1)-kainate (KA) receptors and gamma-aminobutyric acid (GABA) receptors. However, the possible mechanism of the neuroprotective effects of ethanol remains unclear. In this study we report that ethanol shows neuroprotective effects against ischemic brain injury through enhancing GABA release and then decreasing c-Jun N-terminal kinase 3 (JNK3) activation. Electrophysiologic recording indicated that ethanol enhances GABA release from presynaptic neurons and the released GABA subsequently inhibits the KA receptor mediated whole-cell currents. Moreover, our data show that ethanol can inhibit the increased assembly of the Gluk2-PSD-95-MLK3 (postsynaptic density protein-95, PSD-95 and mixed-lineage kinase 3, MLK3) module induced by cerebral ischemia and the activation of the MLK3-MKK4/7-JNK (mitogen-activated protein kinase kinase 4/7, MKK4/7) cascade. Pretreatment of the GABA(A) receptor antagonist bicuculline and antagonist of VGCC (a broad-spectrum blocker of the voltage-gated calcium channel [VGCC]) Chromic (CdCl2) can demolish the neuroprotective effects of ethanol. The results suggest that during ischemia-reperfusion, ethanol may activate presynaptic Gluk1-KA and facilitate Ca2+-dependent GABA release. The released GABA activates postsynaptic GABAA receptors, which suppress the ischemic depolarization and decrease the association of signaling module Gluk2-PSD-95-MLK3 induced by the activation of postsynaptic Gluk2-KA receptors. There is a raised possibility that ethanol inhibiting the JNK3 apoptotic pathway (MLK3/MKK4/7/JNK3/c-Jun/Fas-L) performs a neuroprotective function against ischemic brain injury. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.