JNK激酶介导mGluR1对细胞凋亡的不同效应  

The Different Effects of mGluR1 on Cell Apoptosis Mediated by JNK

作　　者：祝佳玮[1] 朱萍[2] 张松[3] 杨荟敏[1] 张晨光[1] 张红[1] 

机构地区：[1]首都医科大学细胞生物学系,北京100069 [2]中国科学院生物物理研究所结构与分子生物学研究中心,北京100101 [3]山西省分析测试中心,太原030006

出　　处：《中国生物化学与分子生物学报》2011年第3期228-236,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然基金资助项目(No.30873087;No.30973406);北京市自然科学基金资助项目(No.7082010;No.5102011);北京市教委资助项目(No.KM200910025001);北京市属高等学校人才强教计划资助项目(IHLB)~~

摘　　要：代谢型谷氨酸受体1(mGluR1)可以通过激活多条信号通路促进或抑制细胞凋亡.然而,导致这种生理功能差异的机制尚不明确.本研究选用两种细胞系,即大鼠神经胶质瘤细胞系(C6)和人胚胎肾细胞(HEK293)分别研究内源性和外源转染的mGluR1的激活对细胞凋亡的影响及其调节机制.结果显示,内源性mGluR1的活化能够激活PI3K/ERK/JNK通路,抑制凋亡试剂STS诱导的细胞凋亡;而外源转染的mGluR1的活化能够分别激活PI3K/ERK和JNK通路,同时促进STS诱导的应激损伤.HEK293细胞中,应用JNK通路抑制剂SP600125,能够部分抑制由mGluR1激活介导的caspase-3的剪切和细胞凋亡;而在C6细胞中阻断JNK通路,则加剧了由mGluR1活化而引起的细胞凋亡.本文结果提示:mGluR1通过不同信号通路影响细胞凋亡,其中JNK通路可能是调控细胞凋亡的关键途径.本文为受体激活对细胞凋亡能够产生不同的调控作用提供了相应的证据.Multiple signaling pathways are involved in the regulation of cell apoptosis by metabotropic glutamate receptor 1 （mGluR1）. The activation of mGluR1 can either promote or inhibit cell growth with mechanisms yet to be obscure. In this study,neurogliocytoma C6 and HEK293 cells were used to investigate the roles of mGluR1 on the cell growth and survival. In C6 cells,stimulation of endogenousm GluR1 with its agonist DHPG activated the cascade of PI3K （phosphoinositide 3 kinase） /ERK（extracellular signal-regulated kinase）/JNK （c-Jun N-terminal kinase）,and inhibited the apoptosis induced by proapoptotic agent staurosporine （STS）. In HEK293 cells with exogenously transfectedm GluR1,however,mGluR1 activation intensified STS-mediated injury with independent activation of PI3K /ERK and JNK. Inhibition of JNK signaling by its specific inhibitor SP600125 could partially reduced mGluR1-mediated caspase-3 cleavage and apoptosis in HEK293 cells,but not in C6 cells where augmented apoptosis was observed. Our data suggested that mGluR1 modulated cell apoptosis involved multiple signal pathways,and JNK could be a key regulator as shown by the different effects of JNK inhibition specific to cell lines. Our finding may provide additional insights about the receptor-triggered signaling for the differentially regulated apoptosis in different cell lines.

关 键 词：代谢型谷氨酸受体1 C-JUN氨基末端激酶 细胞凋亡 

分 类 号：Q2[生物学—细胞生物学]