G蛋白偶联受体激酶5在稳定表达α-Synuclein的SHSY5Y细胞中的基因表达调控功能  

Function of G Protein-Coupled Receptor Kinase 5 in h α-Synucle in Overexpressing SHSY5Y Cells

作　　者：刘鹏[1] 王晓映[1] 高宁[1] 朱华[1] 代小伟[1] 黄澜[1] 徐艳峰[1] 马春梅[1] 秦川[1] 

机构地区：[1]中国医学科学院实验动物研究所北京协和医学院比较医学中心卫生部人类疾病比较医学重点实验室,北京100021

出　　处：《中国比较医学杂志》2010年第2期6-11,共6页Chinese Journal of Comparative Medicine

基　　金：863项目:2006AA02A115和2004AA215262

摘　　要：目的观测G蛋白偶联受体激酶5(G protein-coupled receptor kinase,GRK5)在稳定表达hα-synuclein(人突触核蛋白)的SHSY5Y细胞的胞核、胞浆中的表达情况并对其在帕金森病中的可能作用进行研究。方法应用Western blotting、组蛋白去乙酰化酶(histone deacetylase,HDAC)活性检测技术以及shRNA干扰技术等对稳定表达hα-synuclein的SHSY5Y细胞中GRK5的表达及其亚细胞分布、胞核内GRK5蛋白的功能进行研究。结果发现GRK5蛋白在过表达hα-synuclein的细胞核以及细胞浆内均表达增加,胞核中的GRK5蛋白通过影响组蛋白去乙酰化酶的活性对bcl-2基因的转录和表达进行调控。结论帕金森模型中GRK5通过对bcl-2基因的表达进行调控发挥作用。Objective To investigate the expression levels of GRK5 in hα-synuclein overexpressing SHSY5Y cells and to clarify its role in（Parkinson＇s） disease.Methods／The protein expression levels of GRK5 in hα-synuclein overexpressing cells were measured by Western blotting.Western blotting,HDAC assay and RNAi techniques were used to detect the function of GRK5 in cytosol and in nuclei.Results Both the expression levels of GRK5 of cytoplasmic and nuclear distribution showed an increase induced by hα-synuclein overexpression in vitro. Nuclear accumulation of GRK5 inhibits blc-2 transcription and expression.Conclusions／G-protein-coupled receptor kinase 5 is upregulated in（Parkinson＇s） disease.It plays a role via regulating the bcl-2 expression in the pathogenesis of Parkinson＇s disease.

关 键 词：G蛋白偶联受体激酶5 帕金森病 Α-SYNUCLEIN 

分 类 号：R-33[医药卫生]