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JNK抑制剂SP600125对低钾诱导的小脑颗粒神经元凋亡的保护作用 被引量：2

A Specific Inhibitor of JNK Protects Cerebellar Granule Neurons from Apoptosis Induced by Low Potassium
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摘要 [目的]研究特异性c-Jun氨基末端激酶(JNK)抑制剂SP600125对低钾诱导的小脑颗粒神经元凋亡的保护作用。[方法]把体外培养的小脑颗粒神经元从含去极化浓度钾离子(KCl 25mmol/L)的培养基中转移至低钾培养基(KCl 5mmol/L)中诱导神经元凋亡。以Western blot法检测JNK和c-Jun的磷酸化水平。[结果]低钾(KCl 5 mmol/L)磷酸化并激活JNK,诱导c-Jun磷酸化和小脑颗粒神经元凋亡。SP600125通过抑制c-Jun磷酸化而浓度依赖性地促进低钾环境中培养的小脑颗粒神经元的存活。其保护作用的半数有效量(ED_(50))为1.01μmol/L。[结论]SP600125通过特异性地抑制JNK活性而对低钾培养的小脑颗粒神经元具有保护作用;提示JNK是介导低钾诱导的小脑颗粒神经元凋亡的关键激酶,它可能可以作为干扰神经元凋亡的药物的作用靶点。 [Objective] To study the effect of SP600125,a specific c-Jun NHz-terminal protein ki-nase (JNK) inhibitor, on apoptosis of cerebellar granule neurons induced by low potassium. [Methods] Apoptosis was induced by switching the cerebellar granule neurons (CGNs) from a culture medium containing K+ 25 mmol/L to a medium containing K+ 5 mmol/L . The phosphorylation levels of JNK and c-Jun were measured using Western blot. [Results ] Low potassium resulted in JNK phosphorylation and activation, c-Jun phosphorylation and apoptosis of cerebellar granule neurons. SP600125 improved the survival of cerebellar granule neurons cultured in low potassium medium by blocking c-Jun phosphorylation and apoptosis in a dose-dependent manner. The half effective dose (ED50) of its protective action was 1.01μmol/L. [Conclusion] SP600125 protects granule neurons from apoptosis induced by low potassium via inhibiting the activity of JNK. It suggests that JNK is a key kinase mediating potassium-withdrawal-induced apoptosis on cerebellar granule neurons, and inhibition of JNK activity may represent a new and effective strategy to protect neurons from apoptosis in neu-rodegenerative disorder.
作者 王文雅 谢元斌 刘炜 朱振宇 黎明涛
机构地区 中山大学中山医学院药理学教研室蛋白质组学实验室 中山大学中山医学院生化教研室
出处 《中山大学学报（医学科学版）》 CAS CSCD 北大核心 2003年第4期316-320,共5页 Journal of Sun Yat-Sen University:Medical Sciences
基金 国家自然科学基金(30170299) 广东省自然科学基金(021803 010697) 广州市科委重点攻关项目(2002Z3-E4031)
关键词 c-Jun 氨基末端激酶 SP600125 细胞凋亡 小脑颗粒神经元 神经保护 apoptosis/drug effects neurons protein kinases kinase inhibitor c-Jun SP600125
分类号 R338.2 [医药卫生—人体生理学]
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参考文献10

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同被引文献22

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引证文献2

中山大学学报（医学科学版）
2003年 第4期

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