NAC通过不同机制抑制激动剂依赖和非依赖的过表达mGlu_(1a)介导的细胞凋亡  

N-acetylcysteine protects against apoptosis induced by overexpressed mGlu_(1a) in agonist-dependent and-independent pathways

作　　者：王舒婷[1,2] 夏宁[1,2] 袁记方[1,2] 张红[1,2] 

机构地区：[1]首都医科大学神经生物学系,教育部神经变性疾病重点实验室,北京100069 [2]首都医科大学细胞生物学系,北京100069

出　　处：《疾病监测》2013年第3期172-177,共6页Disease Surveillance

基　　金：国家自然科学基金项目(No.81171886;30973406);北京市自然科学基金资助项目(No.5102011)~~

摘　　要：目的探测N-乙酰半胱氨酸(NAC)对于组成型和诱导型表达mGlu1a所介导的兴奋性毒性的影响。方法在过表达mGlu1a的HEK293细胞中,通过免疫印迹法,MTT法,胎盘蓝排斥法,酶联免疫吸附实验,二氯荧光素检测法及HPLC等方法,探测了NAC对mGlu1a下游信号分子活性,细胞活力和凋亡,受体表面表达以及细胞内氧化应激的影响。结果发现受体的组成型和诱导型活性通过不同机制,参与了NAC对于mGlu1a所介导的兴奋性毒性的抑制。在以上两种情况下,NAC均可以通过降低ROS调节细胞内氧化还原电势。结论在不同生理刺激条件下,mGlu1a的活性对于疾病的发生可能起着不同的作用,尤其是对mGlu1a高表达所产生的效应,为探究与mGluI相关疾病的发生提供了理论依据。Objective To investigate the effects of N-acetylcysteine （ NAC ） on constitutive （agonist-independent） and agonist-stimulated mGluta-mediated excitotoxicity associated with mGlU1a overexpression in HEK293 cells. Methods The signaling pathways, cell viability, the surface expression of mGlu1a and the intracellular oxidative stress were detected by western blot, MTr, trypan blue-exclusion assay, Elisa, Fluorescence-based Detection of Cellular ROS and HPLC methods. Results In mGlUl^-transfected cells and mGlu^a-transfected, DHPG-induced ceils, NAC inhibited the excitotoxicity of mGlUla by different mechanisms. Under two conditions, NAC prohibited the production of ROS and modulated the intracellular glutathione redox potential. Conclusion This study further suggested that the complex effects of mGlu1a activity under different conditions might play different role in the progress of many diseases, especially in terms of the effects of increased receptor expression.

关 键 词：Ⅰ组代谢型谷氨酸受体 N-乙酰半胱氨酸 细胞凋亡 ERK 

分 类 号：R96[医药卫生—药理学]