蝙蝠葛碱拮抗缓激肽引起的钙稳态改变及细胞骨架蛋白的异常磷酸化(英文)  

Dauricine Prevents Bradykinin-induced Alteration of Calcium Homeostasis and tau Hyperphosphorylation in N2a Cells

作　　者：王瓅 王小川[1] 李宏莲[1] 王丹玲[1] 周新文[1] 王建枝[1] 

机构地区：[1]华中科技大学同济医学院病理生理系,武汉430030

出　　处：《生物化学与生物物理进展》2005年第7期612-617,共6页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30430270,30328007)~~

摘　　要：为研究蝙蝠葛碱(dauricine,Dau)拮抗缓激肽(bradykinin,BK)诱导的Alzheimer样钙稳态失衡及细胞骨架蛋白异常磷酸化的作用,采用双波长荧光分光光度计测定细胞内钙离子浓度([Ca2+]i),用MTT法检测细胞代谢水平,用免疫组织化学方法观察tau蛋白表达和磷酸化.结果表明,Dau(3滋mol/L,6滋mol/L)可抑制BK诱导的[Ca2+]i升高,保护BK引起的神经元代谢降低,拮抗BK引起的tau蛋白异常磷酸化和聚集.结果提示:Dau可拮抗BK诱导的Alzheimer样钙稳态失衡及细胞骨架蛋白异常磷酸化的作用.To study the prevention of dauricine (Dan) on bradykinin (BK) induced alteration of intracellular calcium homeostasis and tau phosphorylation, fluorescence spectrophotometer with dual excitation was utilized to measure the intracellular calcium concentration ([Ca(2+)]), MTT to detect cell viability and immuncytochernistry to examine tau phosphorylation. The results showed (1) cells treated with BK 1 mu mol/L induced a transit increase in [Ca(2+)](i) in all the cell lines detected, among them, the sustained increase of [Ca(2+)](i) level was only seen in PS1 Delta 9/APPswe cell at 2 h and 24 h after the treatment. Dan (3 mu mol/L or 6 mu mol/L) prevented BK-induced transit and sustained elevation and fluctuation of [Ca(2+)](i); (2) BK treatment decreased the cell metabolism detected at 2 It in PS1 Delta 9/APPswe and Dau antagonized the effect; (3) BK induces Alzheimer-like tau hyperphosphorylation at tau-1 epitope and Dan partially antagonized this effect. In conclusion, Dan inhibits BK-induced disturbance in intracellular calcium homeostasis and tau hyperphosphorylation at tau-1 sites.

关 键 词：蝙蝠葛碱 缓激肽 细胞内钙离子浓度 TAU蛋白 磷酸化 鼠成神经瘤细胞 

分 类 号：R745.7[医药卫生—神经病学与精神病学] Q513[医药卫生—临床医学]