Aβ_(31-35)-induced neuronal apoptosis is mediated by JNK-dependent extrinsic apoptosis pathway  

JNK激活的外源性凋亡途径介导Aβ_(31-35)诱导的神经元凋亡(英文)

作　　者：李灵敏[1] 刘青华[1] 乔建天[2] 张策[2] 

机构地区：[1]山西医科大学病理教研室,太原030001 [2]山西医科大学生理教研室,太原030001

出　　处：《Neuroscience Bulletin》2009年第6期361-366,共6页神经科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China (No. 30572085);Natural Science Foundation of Shanxi Province, China(No. 2007011111)

摘　　要：Objective To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Aβ31-35-induced apoptosis of cultured cortical neurons. Methods Cultured cortical neurons were treated with Aβ31-35 （25 μmol/L） for 4 h, 8 h, 16 h and 24 h, respectively. Caspase activities were measured using a spectrophotometer. Levels of c-Jun phosphorylation （p-c-Jun） and Fas ligand （FasL） expression were assessed by immunocytochemistry method and quantified using Image-pro plus11.0 image processing and analysis software. Results Treatment with Aβ31-35 （25 μmol/L） for 24 h induced significant increases in the activities of caspase-3 and caspase-8 in the cortical neurons. Besides, Aβ31-35 could time-dependently enhance the expression of p-c-Jun protein. Moreover, SP600125 application （100 nmol/L） could completely abolish Aβ31-35 neurotoxicity. The increase in FasL expression was detected at 8 h, 16 h and 24 h after Aβ31-35 treatment, and SP600125 （100 nmol/L） significantly inhibited FasL expression. Conclusion JNK-c-Jun-FasL-caspase-dependent extrinsic apoptotic pathway plays a critical role in mediating Aβ31-35-induced apoptosis of cultured neurons.目的探讨JNK信号通路在Aβ31-35诱导的神经元凋亡过程中的作用。方法经老化处理的Aβ31-35(终浓度为25μmol/L)制备AD细胞模型,采用生物比色法检测caspase-3和caspase-8的活性。采用免疫细胞化学技术观察不同时间点磷酸化c-Jun(p-c-Jun)及Fas ligand(FasL)蛋白的表达情况,并用IPP11.0图像分析软件进行定量分析。结果Aβ31-35孵育24h能显著提高神经元内caspase-3和caspase-8的活性。Aβ31-35孵育4h时p-c-Jun蛋白表达水平开始升高,在8h升高最显著,呈现一定的时间依赖性;JNK特异性抑制剂SP600125能抑制Aβ31-35对p-c-Jun蛋白表达的诱导作用。Aβ31-35孵育8h时出现FasL蛋白表达的升高,而SP600125则能抑制这一作用。结论JNK激活的外源性凋亡途径在Aβ31-35诱导的神经元凋亡过程中发挥一定的作用。

关 键 词：Aβ31-35 NEUROTOXICITY CASPASE JNK pathway 

分 类 号：Q42[生物学—神经生物学]