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Logo of neuroscibullNeuroscience Bulletin
 
Neurosci Bull. 2007 July; 23(4): 221–228.
Published online 2008 February 1. doi:  10.1007/s12264-007-0033-y
PMCID: PMC5550585

Language: English | Chinese

Involvement of MAPK/ERK kinase-ERK pathway in exogenous bFGF-induced Egr-1 binding activity enhancement in anoxia-reoxygenation injured astrocytes

MAPK/ERK 激酶-ERK 信号通路参与外源性 bFGF 对缺氧-复氧损伤后星形胶质细胞内 Egr-1 结合活性的调节

Abstract

Objective

Intravenous administration of basic fibroblast growth factor (bFGF) is effective to reduce the volume of cerebral infract due to ischemia. This study was designed to investigate the molecular mechanism, especially the signal transduction pathways, involved in this protective role of bFGF.

Methods

Anoxia-reoxygenation treated atrocytes were used to study the role of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MAPK/ERK kinase, MEK)-ERK signaling pathway after exogenous bFGF administration by Western blot. Electrophoretic mobile shift assay was used to detect the binding activity of early growth response factor-1 (Egr-1), an important transcription factor for endogenous bFGF.

Results

BFGF could protect some signal transduction proteins from the oxygen-derived free radicals induced degradation. ERK1/2 was activated and involved in Egr-1 binding activity enhancement induced by exogenous bFGF.

Conclusion

MEK-ERK MAPK cascade may be an important signal transduction pathway contributed to bFGF induced enhancement of Egr-1 binding activity in anoxia-reoxygenation injured astrocytes.

Keywords: extracellular signal-regulated kinase, mitogen-activated protein kinase, free radicals, fibroblast growth factor 2, early growth response protein 1, astrocyte

摘要

目的

静脉注射碱性成纤维细胞生长因子(basic fibroblast growth factor, bFGF)可以明显降低实验性脑缺血大鼠的脑梗死面积, 但该作用的分子机制尚不清楚。本文旨在研究外源性bFGF 作用的信号转导通路。

方法

缺氧-复氧损伤星形胶质细胞。Western blot 检测外源性 bFGF 作用后丝裂原活化蛋白激酶 / 细胞外信号调节激酶激酶(mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, MEK)-细胞外信号调节激酶(extracellular signal-regulated kinase, ERK) 信号通路活化。电泳变动迁移率分析实验检测外源性bFGF 作用后核转录因子早期生长反应因子-1(early growth respons factor 1, Egr-1)的结合活性变化。

结果

外源性bFGF可以保护胞外信号调节激酶MEK-ERK 信号通路蛋白不被氧自由基降解。MEK-ERK信号通路在外源性bFGF作用后活化。 这一信号通路进一步使Egr-1结合活性升高。

结论

外源性bFGF可能通过激活ERK信号通路, 促进内源性转录因子Egr-1 的结合活性升高, 进而促进内源性bFGF 的表达。

关键词: 细胞外信号调节激酶, 丝裂原活化蛋白激酶, 自由基, 碱性成纤维细胞生长因子, 早期生长反应因子-1, 星形胶质细胞

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