Effects of melatonin on wortmannin-induced tau hyperphosphorylation  

作　　者：Yan-qiuDENG Guo-gangXU PingDUAN QiZHANG Jian-zhiWANG 

机构地区：[1]DepartmentofPathophysiology,InstituteofNeuroscience,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan430030,China

出　　处：《Acta Pharmacologica Sinica》2005年第5期519-526,共8页中国药理学报（英文版）

基　　金：Project supported in part by grants from the National Natural Science Foundation of China(№ 30170221,30430270, 30328007,and 30400068)

摘　　要：Aim:To explore the underlying mechanism of tau hyperphosphorylation in an Alzheimer's-affected brain and the possible arresting strategies.Methods:MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide),crystal violet assay, phase-contrast,dead end colorimetric apoptosis detection system(TUNEL)and electron microscopy were used to detect cell viability,morphology and apoptosis. Western blot,^(32)P-labeling and the detection of malondialdehyde level and super- oxide dismutase activity were used respectively for the phosphorylation level of tau,the activity of glycogen synthase kinase(GSK-3),and oxidative stress measurement.Results:Exposure of the cells to wortmannin resulted in an obvi- ous lipid peroxidation,reduction of cell viability,cell process retraction,and plasma vacuolation,but with no obvious cell apoptosis.We also found that preincuba- tion of the cells with melatonin or vitamin E attenuated differentially wortmannin- induced oxidative stress as well as GSK-3 overactivation and tau hyperphosphoryla- tion.Conclusion:Wortmannin is an effective tool for reproducing Alzheimer-like tau hyperphosphorylation cell model and melatonin/vitamin E can effectively pro- tect the cells from wortmannin-induced impairments.Aim:To explore the underlying mechanism of tau hyperphosphorylation in an Alzheimer's-affected brain and the possible arresting strategies.Methods:MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide),crystal violet assay, phase-contrast,dead end colorimetric apoptosis detection system(TUNEL)and electron microscopy were used to detect cell viability,morphology and apoptosis. Western blot,^(32)P-labeling and the detection of malondialdehyde level and super- oxide dismutase activity were used respectively for the phosphorylation level of tau,the activity of glycogen synthase kinase(GSK-3),and oxidative stress measurement.Results:Exposure of the cells to wortmannin resulted in an obvi- ous lipid peroxidation,reduction of cell viability,cell process retraction,and plasma vacuolation,but with no obvious cell apoptosis.We also found that preincuba- tion of the cells with melatonin or vitamin E attenuated differentially wortmannin- induced oxidative stress as well as GSK-3 overactivation and tau hyperphosphoryla- tion.Conclusion:Wortmannin is an effective tool for reproducing Alzheimer-like tau hyperphosphorylation cell model and melatonin/vitamin E can effectively pro- tect the cells from wortmannin-induced impairments.

关 键 词：Alzheimer disease WORTMANNIN mela-tonin tau protein 

分 类 号：R971[医药卫生—药品]