利培酮在U251细胞中调节PI3K-Akt-GSK3β信号通路的研究  

Regulation of PI3K-Akt-GSK3β signaling pathway in U251 cells by risperidone

作　　者：粱林辉 王英成[2] 韦锦学[2] 谷晓楚[1] 向波[1] 马小红[2] 李涛[2] 

机构地区：[1]四川大学生物治疗国家重点实验室精神医学研究室,成都610041 [2]华西医院心理卫生中心

出　　处：《中华医学遗传学杂志》2014年第6期693-697,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81071089）

摘　　要：目的探讨抗精神病药物利培酮对蛋白激酶B（protein kinase B，Akt）-糖原合成酶激酶3p（glycogen synthase kinase 3β，GSK3β）信号通路的影响以及磷脂酰肌醇-3-羟激酶（phosphoinositide 3-kinase，PI3K）在多巴胺D2受体基因（dopaminereceptorD2，DRD2）表达和Akt-GSK3β信号通路中的作用。方法正常培养人胶质瘤细胞（U251），以未经任何处理的细胞为对照，应用Western印迹检测利培酮以及P13K抑制剂LY294002对U251细胞中Akt（Thr308和Ser473）和GSK3β（Ser9）磷酸化蛋白表达水平的影响，应用实时PCR检测利培酮以及PI3K抑制剂LY294002对U251细胞中DRD2表达的影响。结果利培酮能够增加U251细胞中Akt和GSK3β磷酸化蛋白的表达水平（P〈0．05），但DRD2表达水平无明显变化。利培酮介导的Akt和GSK313磷酸化蛋白的表达升高可以被LY294002抑制（P〈0．01，P％0．05），且LY294002可抑制DRD2的表达（P〈0．05）。结论利培酮能激活U251细胞中Akt-GSK3β信号通路，P13K是Akt-aSK3β信号通路和DRD2表达共同的调节位点。Objective To investigate the effect of risperidone, an antipsychotic drug, on the Akt- GSK3β pathway and the role of PI3K in dopamine D2 receptor （DRD2） expression and Akt-GSK3β signal pathway. Methods Human glioma cells （U251） were cultured in vitro. Cells without any treatment as control, Western blotting was used for measuring the expression of Akt （Thr308 and Ser473） and GSK3β （Ser9） protein phosphorylation by risperidone and LY294002 in U251 cell, and reabtime PCR was used for detecting the expression of DRD2 mRNA. Results Risperidone has significantly enhanced the expression of phosphorylated Akt and phosphorylated GSK3β （P 〈 0. 05）, but did not alter the mRNA expression of DRD2. LY294002 could reduce the phosphorylation of Akt and GSK313 （P〈 0. 01, P〈0. 05）, and also decrease the DRD2 mRNA （P〈0. 05）. Conclusion Risperidone can activate the Akt-GSK3β signaling pathway in the U251 cells, and PI3K is a common regulatory site in Akt-GSK3β signaling and D2 receptor gene expression.

关 键 词：利培酮 蛋白激酶B 糖原合成酶激酶3B 多巴胺D2受体 磷脂酰肌醇-3-羟激酶 

分 类 号：R394[医药卫生—医学遗传学]