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细胞外信号调节激酶在小鼠神经干细胞增殖中的作用

黄欣, 赵彤, 赵华, 熊雷, 刘朝晖, 吴丽颖, 朱玲玲, 范明

军事医学科学院基础医学研究所脑保护与可塑性实验室.北京 100850

摘要

该文旨在探讨细胞外信号调节激酶(extracellular signal--regulated kinase1/2,ERK1/2)对小鼠神经干细胞增殖的影响。分离E14.5小鼠皮层神经干细胞,通过Western blot检测神经干细胞增殖过程中磷酸化ERK1/2的表达情况,以及不同浓度PD98059处理对神经干细胞ERK1/2磷酸化及神经球形成的影响,并用CCK--8法检测PD98059对神经干细胞增殖的影响。结果显示:ERK1/2在体外培养的神经干细胞增殖过程中被激活;PD98059显著抑制ERK1/2磷酸化及神经干细胞的成球率,且存在剂量效应依赖关系;加入PD98059后神经干细胞的生长被抑制。以上结果表明,ERK1/2在小鼠神经干细胞增殖中具有重要的作用,阻断ERK1/2信号通路后可抑制神经干细胞的增殖。

关键词： 神经干细胞; 细胞外信号调节激酶; PD98059; 增殖

Extracellular signal--regulated kinase 1/2 is essential for the proliferation of neural stem cells derived from embryonic cortex

Huang Xin, Zhao Tong, Zhao Hua, Xiong Lei, Liu Zhaohui, Wu Liying, Zhu Lingling, Fan Ming

Department of Brain Protection and Plasticity,Institute of Basic Medical Sciences.Beijing 100850

Abstract

Extracellular signal-regulated kinase1/2 (ERK1/2) pathway has been shown to be important for regulating cell proliferation and survival. The role of ERK1/2 signaling in the survival and growth of neural stem cells (NSCs) has not been addressed adequately. In this work, we aimed to provide evidence that proliferation of NSCs in vitro is controlled via ERK1/2-dependent pathways. Mouse NSCs were prepared from embryonic day 14.5 (E14.5) cortex of mouse forebrain. Cells were harvested at the desired times (1 d, 3 d and 5 d) and the total protein was extracted and analyzed by Western blot. It was observed that ERK1/2 signaling was activated during the proliferation of NSCs. In addition, mitogen-activated protein kinase kinase (MEK) inhibitor PD98059, which directly prohibited ERK1/2 phosphorylation, inhibited the formation of neurospheres, and this inhibitory effect was dose-dependent. After treatment with 20 μmol/L PD98059, the growth of NSCs was also reduced with time-dependence. These data indicate that the ERK1/2 is essential for the proliferation of NSCs derived from embryonic cortex in vitro.

Key words: neural stem cell;extracellular signal-regulated kinase;PD98059;cell proliferation

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引用本文：

黄欣, 赵彤, 赵华, 熊雷, 刘朝晖, 吴丽颖, 朱玲玲, 范明. 细胞外信号调节激酶在小鼠神经干细胞增殖中的作用[J]. 生理学报 2008; 60 (3): 437-441.

Huang Xin, Zhao Tong, Zhao Hua, Xiong Lei, Liu Zhaohui, Wu Liying, Zhu Lingling, Fan Ming. Extracellular signal--regulated kinase 1/2 is essential for the proliferation of neural stem cells derived from embryonic cortex. Acta Physiol Sin 2008; 60 (3): 437-441 (in Chinese with English abstract).