Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension
Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension
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DOI：
10.1016/j.mcn.2004.12.010
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发表时间：
2005-04-01
影响因子：
3.5
通讯作者：
Mandell, JW
中科院分区：
文献类型：
--
作者：
Heffron, DS;Mandell, JW
星形胶质细胞的星状突起在神经损伤后发生广泛的重塑。关于细胞内信号传导机制控制过程扩展的了解甚少。我们在一个简化的培养模型中测试了ERK和p38 MAP激酶途径的作用。在fgf2诱导的过程扩展之前，ERK发生了强烈的短暂磷酸化，p38 MAP激酶的适度激活表现出显著的基础活性。磷酸化的ERK主要在细胞质中发现，而活化的p38 MAP激酶则在细胞核中。特异性MEK抑制剂U0126完全阻断了过程扩展。相反，SB202190抑制p38 MAP激酶通路可刺激自发过程生长，并大大增强fgf2诱导的过程扩展。p38抑制作用在表达显性阴性p38 MAP激酶的腺病毒中重现。选择性阻断MAP激酶通路可以调节星形胶质细胞对损伤的反应，从而促进神经再生。(c) 2005爱思唯尔公司版权所有。
The stellate processes of astroglial cells undergo extensive remodeling in response to neural injury. Little is known about intracellular signaling mechanisms controlling process extension. We tested roles for the ERK and p38 MAP kinase pathways in a simplified culture model. FGF2-induced process extension was preceded by a strong and transient phosphorylation of ERK, and a modest activation of p38 MAP kinase, which exhibited significant basal activity. Phosphorylated ERK was found predominantly in the cytoplasm, whereas activated p38 MAP kinase was nuclear. Process extension was completely blocked by the specific MEK inhibitor U0126. Conversely, inhibition of the p38 MAP kinase pathway with SB202190 stimulated spontaneous process growth and greatly potentiated FGF2-induced process extension. The p38 inhibitor effect was reproduced with an adenovirus expressing dominant-negative p38 MAP kinase. Selective pharmacological blockade of MAP kinase pathways may enable modulation of the astroglial response to injury so as to promote neural regeneration. (c) 2005 Elsevier Inc. All rights reserved.