Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cells, Cultured
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Cerebral Cortex / cytology
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Embryo, Mammalian
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Enzyme Inhibitors / toxicity*
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Gene Expression Regulation / drug effects
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Glycogen Synthase Kinase 3 / metabolism*
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Glycogen Synthase Kinase 3 beta
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Immunohistochemistry / methods
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Nerve Degeneration / chemically induced*
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Nerve Degeneration / enzymology
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Neurons / drug effects*
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Neurons / enzymology
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Okadaic Acid / toxicity*
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Oncogene Proteins / metabolism
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins c-akt
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Rats
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Time Factors
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tau Proteins / metabolism
Substances
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Enzyme Inhibitors
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Oncogene Proteins
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tau Proteins
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Okadaic Acid
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Akt3 protein, mouse
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Gsk3b protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Glycogen Synthase Kinase 3