Effects of melatonin on wortmannin-induced tau hyperphosphorylation.
OBJECTIVE
To explore the underlying mechanism of tau hyperphosphorylation in an Alzheimeros-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, 32P-labeling and the detection of malondialdehyde level and superoxide 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 obvious lipid peroxidation, reduction of cell viability, cell process retraction, and plasma vacuolation, but with no obvious cell apoptosis. We also found that preincubation of the cells with melatonin or vitamin E attenuated differentially wortmannin-induced oxidative stress as well as GSK-3 overactivation and tau hyperphosphorylation.


CONCLUSIONS
Wortmannin is an effective tool for reproducing Alzheimer-like tau hyperphosphorylation cell model and melatonin/vitamin E can effectively protect the cells from wortmannin-induced impairments.
Deng
Yan-qiu
YQ
Department of Pathophysiology, Institute of Neuroscience, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Xu
Guo-gang
GG
Duan
Ping
P
Zhang
Qi
Q
Wang
Jian-zhi
JZ
D000730:Androstadienes / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D000077191:Wortmannin; D016875:tau Proteins / Q000378:metabolism*
D000730:Androstadienes; D016875:tau Proteins; D014810:Vitamin E; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D008550:Melatonin; D000077191:Wortmannin