Inactivation of GSK-3beta in okadaic acid-induced neurodegeneration: relevance to Alzheimer's disease.
Hyperphosphorylation of tau is a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD). Okadaic acid is used as a research model of AD to increase the tau phosphorylation and neuronal death. Using Western blotting, we found that the amounts of activated PKB[pS-473] and inactivated GSK-3beta[pS-9] were increased in proportion to the progress of okadaic acid induced tau phosphorylation. Immunocytochemistry showed that PKB[pS-473] and GSK-3beta[pS-9] immunoreactivity increased in dystrophic neurites and cell bodies in degenerating neurons after okadaic acid treatment. Double staining with phosphospecific tau antibodies showed that PKB[pS-473] and GSK-3beta[pS-9] were colocalized with phosphospecific tau in response to okadaic acid. Taken together, our data suggest that inhibition of protein phosphatase results in the hyperphosphorylation of tau without GSK-3beta overactivation.
Yoon
Seung Yong
SY
Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, 388-1 PoongNap-Dong, SongPa-Gu, Seoul 138-736, Korea.
Choi
Jung Eun
JE
Huh
Jae-Wan
JW
Hwang
Onyou
O
Nam Hong
Hea
H
Kim
Donghou
D
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry / Q000379:methods; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000201:enzymology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D019319:Okadaic Acid / Q000633:toxicity*; D015513:Oncogene Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D013997:Time Factors; D016875:tau Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D015513:Oncogene Proteins; D016875:tau Proteins; D019319:Okadaic Acid; C491753:Akt3 protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3