大鼠海马脑缺血后，细胞外信号调节激酶5（ERK5）的激活由N-甲基-D-天冬氨酸受体和L型电压门控钙通道通过Src介导，且涉及氧化应激。

Activation of ERK5 is mediated by N-methyl-D-aspartate receptor and L-type voltage-gated calcium channel via Src involving oxidative stress after cerebral ischemia in rat hippocampus.

作者信息

Wang Rui-min, Zhang Quan-guang, Zhang Guang-yi

机构信息

Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huai-Hai Road, Xuzhou, Jiangsu 221002, China.

出版信息

Neurosci Lett. 2004 Feb 26;357(1):13-6. doi: 10.1016/j.neulet.2003.11.061.

DOI:10.1016/j.neulet.2003.11.061

PMID:15036602

Abstract

Activation (phosphorylation) and the possible mechanism of extracellular signal-regulated kinase 5 (ERK5) were evaluated after cerebral ischemia-reperfusion (I/R) in the hippocampus in a four-vessel occlusion model of Sprague-Dawley rats. Western blotting showed that ERK5 was strongly activated from 10 min to 1 day and peaked at 30 min of reperfusion after 15 min ischemia. Pretreatment with N-acetylcysteine, a free radical scavenger, effectively inhibited ERK5 activation in a dose-dependent manner. Consistently, ERK5 activation was significantly suppressed by genistein (protein-tyrosine kinase inhibitor), PP2 (specific inhibitor of Src family kinases), nifedipine (L-VGCC blocker) and dextromethorphan (NMDA receptor antagonist), but not 6,7-dinitroquinoxaline-2, 3(1H, 4H)-dione (AMPA receptor antagonist). These results suggested that ERK5 could be significantly activated by I/R, which might be mediated by NMDA receptor and L-VGCC through Src kinase pathway involving oxidative stress in rat hippocampus.

摘要

在Sprague-Dawley大鼠四动脉闭塞模型中，评估了脑缺血再灌注（I/R）后海马中细胞外信号调节激酶5（ERK5）的激活（磷酸化）及其可能机制。蛋白质印迹法显示，在缺血15分钟后再灌注10分钟至1天期间ERK5被强烈激活，并在再灌注30分钟时达到峰值。用自由基清除剂N-乙酰半胱氨酸预处理可有效抑制ERK5的激活，且呈剂量依赖性。同样，染料木黄酮（蛋白酪氨酸激酶抑制剂）、PP2（Src家族激酶特异性抑制剂）、硝苯地平（L型电压门控钙通道阻滞剂）和右美沙芬（NMDA受体拮抗剂）可显著抑制ERK5的激活，但6,7-二硝基喹喔啉-2,3(1H,4H)-二酮（AMPA受体拮抗剂）则无此作用。这些结果表明，I/R可显著激活ERK5，这可能是由NMDA受体和L型电压门控钙通道通过Src激酶途径介导的，且涉及大鼠海马中的氧化应激。