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作 者:黄欣[1] 赵彤[1] 赵华[1] 熊雷[1] 刘朝晖[1] 吴丽颖[1] 朱玲玲[1] 范明[1]
机构地区:[1]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
出 处:《生理学报》2008年第3期437-441,共5页Acta Physiologica Sinica
基 金:the National Basic Research Program of China (No. 2006CB504100, 2006CB943703);National NaturalScience Foundation of China (No. 30670792)
摘 要:本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。Extracellular signal-regulated kinase 1/2 (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 pathway. NSCs were isolated 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 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 20μmol/L PD98059, the growth of NSCs was also inhibited with time-dependence. These data indicate that ERK1/2 is essential for the proliferation of NSCs derived from mouse embryonic cortex.
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