过表达OGCP对鱼藤酮和突变型Parkin致HEK293细胞毒性的保护作用  

Protective Effect of Over-expression OGCP on HEK293 Cells Treated by Rotenone and Mutant Parkin Protein

作　　者：王春喻[1,2] 唐北沙[2] 张海南[1] 汤建光[1] 郭纪锋[2] 严新翔[2] 谭利明[1] 

机构地区：[1]中南大学湘雅二医院神经内科,长沙410011 [2]中南大学湘雅医院神经内科,长沙410008

出　　处：《四川大学学报（医学版）》2010年第4期604-608,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(批准号30370515;30570638);国家863计划(项目编号2004AA227040);国家973计划(项目编号2006cb500700);国家十五科技公关计划(项目编号2004BA720A03)资助项目

摘　　要：目的研究α-酮戊二酸载体蛋白(2-oxoglutarate carrier protein,OGCP)和Parkin对HEK293细胞功能的影响。方法采用流式细胞术检测经鱼藤酮、OGCP和/或Parkin处理的HEK293细胞细胞凋亡、线粒体膜电位和细胞内活性氧水平。结果①野生型Parkin和OGCP能够提高经鱼藤酮诱导的HEK293细胞的线粒体膜电位,降低细胞内活性氧和细胞凋亡率,而突变型Parkin(R42P和T240R)则降低HEK293细胞尤其是经鱼藤酮诱导的HEK293细胞的线粒体膜电位,增加细胞内活性氧,促进细胞凋亡;②此外,还发现OGCP可以抑制由于Parkin突变(R42P和T240R)导致的线粒体膜电位降低和活性氧增加,减少Parkin突变(R42P和T240R)导致的细胞凋亡。结论①Parkin蛋白和OGCP可能与维持线粒体正常功能相关;②过表达突变型Parkin(R42P和T240R)蛋白可能抑制线粒体功能,促进细胞凋亡;③过表达OGCP可能对鱼藤酮和突变型Parkin蛋白细胞毒性有一定的保护作用。Objective To study the effect of α-ketoglutarate carrier protein(2-oxoglutarate carrier protein,OGCP) and the Parkin protein on HEK293 cell function.Methods The cell apoptosis rate,mitochondrial membrane potential and intracellular reactive oxygen species of HEK293 cells treated with rotenone,OGCP and / or Parkin protein were detected by using flow cytometry methods(FCM).Results ① Over-expression wild-type Parkin protein and /or OGCP can increase mitochondrial membrane potential of HEK293 cells induced by rotenone,reduce intracellular reactive oxygen species and cell apoptosis rate of HEK293 cells induced by rotenone,while over-expression mutant Parkin(R42P and T240R) protein can decrease the mitochondrial membrane potential of HEK293 cells,especially the HEK293 cells induced by rotenone,but increase intracellular reactive oxygen species and promote apoptosis.② In addition,we also found that OGCP can inhibit the increasing of mitochondrial membrane potential and reactive oxygen species and decreasing of cell apoptosis caused by mutant Parkin protein(R42P and T240R).Conclsuion ① Parkin protein and OGCP may be associated with the maintenance of normal function of mitochondria.② Over-expression of mutant parkin(R42P and T240R) protein may inhibit mitochondrial function and promote apoptosis.③ Over-expression OGCP has protective effect on cell toxicity caused by rotenone and mutant parkin protein.

关 键 词：OGCP PARKIN 细胞凋亡 

分 类 号：R346[医药卫生—基础医学]