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冈田酸所致微管相关蛋白tau Ser396位点过度磷酸化抑制细胞凋亡

Inhibition of Apoptosis by Hyperphosphorylation of Microtubule-associated Protein Tau at Set396 Site Induced by Okadaic Acid

目的 探讨磷酸酯酶活性降低致tau过度磷酸化与细胞凋亡的关系.方法 稳定表达人tau eDNA的鼠成神经瘤细胞(N2a/tau)分3组.对照组不处理;十字孢碱(staurosporine,STP,凋亡诱导剂)处理6 h为STP组;用磷酸酯酶PP-2A的抑制剂冈田酸(okadaic acid,OA)处理4 h,再用STP处理6 h为OA+STP组.流式细胞仪检测凋亡率,免疫印迹检测Ser396位点磷酸化tau(Ser396 p-tau)和总tau的表达,免疫荧光双标检测Ser396 p-tau的阳性产物与活化的半胱氨酸蛋白酶(Cleaved Caspase-3)阳性产物的共定位关系.结果 ①凋亡率:对照组为(4.37±1.47)%,STP组为(19.84±3.25)%,OA+STP组为(12.12±2.46)%;②免疫印迹:OA+STP组Ser396 p-tau的表达明显高于另两组,总tau表达组间无差异;③免疫荧光双标:进一步印证免疫印迹结果,且3组均显示活化的Caspase-3和Ser396 p-tau阳性产物大多不共定位于相同细胞.结论 PP-2A活性降低所致tau Ser396位点的过度磷酸化可抑制细胞凋亡,结合前期的实验进一步明确特殊位点过度磷酸化的tau可抑制细胞进入快速的凋亡程序.

作 者:
沈建英 徐桂香 左斌 甘辉 肖娟娟 张敏海 汪薇曦 李宏莲  
作者单位:
华中科技大学同济医学院基础医学院解剖学系组织胚胎学教研室,武汉,430030 
刊 名:
华中科技大学学报(医学版)  ISTIC PKU
英文刊名:
ACTA MEDICINAE UNIVERSITATIS SCIENCE OF TECHNOLOGIAE HUAZHONG 
年,卷(期):
2009 38(3) 
分类号:
R749.1 
关键词:
阿尔茨海默病 知识脉络  tau蛋白 知识脉络  磷酸酯酶PP-2A 知识脉络  细胞凋亡 知识脉络 
机标分类号:
R74 R97 
机标关键词:
冈田酸微管相关蛋白tau过度磷酸化位点抑制细胞凋亡Okadaic Acid免疫荧光双标免疫印迹检测STPCaspase-3磷酸酯酶活性降低处理稳定表达鼠成神经瘤细胞流式细胞仪检测半胱氨酸蛋白酶staurosporine阳性共定位 
基金项目:
国家自然科学基金,教育部博士点基金新教师基金 
DOI:
10.3870/j.issn.1672-0741.2009.03.001 
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