PI3K／Akt途径在Aβ诱导细胞凋亡过程中的作用  

Role of PI3K/Akt signaling pathway in P12 cells apoptosis induced by β-amyloid peptide

作　　者：孙治坤[1,2] 潘静[1] 杨红旗[1] 梁梁[1] 丁健青[1] 陈生弟[1,2] 

机构地区：[1]海交通大学医学院附属瑞金医院神经内科,上海200025 [2]上海生科院健康科学研究所,上海200025

出　　处：《中国病理生理杂志》2009年第1期84-88,共5页Chinese Journal of Pathophysiology

基　　金：国家重点基础研究发展计划资助项目(No.2006cb500706);上海市重大基础研究项目(No.07DJ14005);上海市医学领军人才计划(No.LJ06003)

摘　　要：目的:探讨凝聚态β-淀粉样蛋白25-35片段(Aβ25-35)诱导细胞凋亡过程中PI3K/Akt转导通路的作用。方法:MTT法检测Aβ25-35作用不同时间后PC12细胞活力的变化;Annexin V-PI双染检测Aβ25-35作用不同时间后PC12细胞的凋亡情况;Western blotting检测Aβ25-35作用不同时间后p-AktSer473、p-GSK-3βSer9的水平变化。结果:20μmol/LAβ25-35作用不同时间(30 min、1 h、3 h、6 h、12 h、24 h、48 h)后,MTT结果显示细胞活力均明显下降(P<0.05);Annexin V-PI结果显示,Aβ25-35作用后均可引起细胞凋亡(P<0.05);Western blotting结果表明,Aβ25-35作用于细胞后,p-AktSer473和p-GSK-3βSer9的表达均出现迅速的下调(P<0.05),在作用3 h时两者的表达出现迅速的上升,在作用6 h时又出现表达的下调,两者在该时间段的变化趋势相符。p-AktSer473在Aβ25-35作用于细胞12 h后出现逐渐回升趋势,但在48 h时仍没有达到正常水平;而p-GSK-3βSer9的表达在Aβ25-35作用于细胞12 h后出现迅速的升高(P<0.05),而后逐渐恢复到正常水平。结论:PI3K/Akt信号通路可能参与了Aβ诱导的细胞损伤,本研究为AD的发病机制及选择合适的药物作用时点提供了新思路。AIM： To investigate the role of PI3K/Akt signaling pathway on cell apoptosis induced by β- amyloid peptide in PC12 cells. METHODS ： The viability of PC12 cells and the levels of p - Akt^Ser473 and p - GSK - 3β^Ser9 were detected by MTT and Western blotting, respectively. Cell apoptosis was determined by Annexin V -PI staining. RESULTS： Aβ25-35 treatment decreased the viability of PC12 cells in a time - depended manner （P 〈 0. 05）. Annexin V - PI staining demonstrated that Aβ25-35 induced PC12 cells apoptosis in a time - depended manner （P 〈 0. 05 ）. Western blotting showed that Aβ25-35 induced an immediately decreased expression of p - Akt^Ser473 and p - GSK - 3β^Ser9 at 30 min （P 〈0. 05）, but increased at 3 h and decreased again at 6 h. However, after 12 h of peptide treatment, the p - GSK - 3β^Ser9 increased while the p - Akts^Ser473 remained decrease. CONCLUSION： PI3K/Akt signaling pathway is involved in cell apoptosis induced by β- amyloid peptide, which provides a new clue for the study of pathogenesis and management of AD.

关 键 词：淀粉样Β蛋白 细胞凋亡 PI3K/AKT信号通路 阿尔茨海默病 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R749.16[医药卫生—基础医学]