Menadione-induced tau dephosphorylation in cultured human neuroblastoma cells.
Oxidative stress has been implicated in the mechanism of aging and neurodegenerative disorders such as Alzheimer's disease (AD). Menadione causes oxidative stress by generating reactive oxygen species through its redox cycling and these free radicals are detoxified subsequently at the expense of intracellular thiol homeostasis. In non-neuronal cells, the cytoskeleton is a prime target of menadione-induced thiol oxidation. We used cultured human neuroblastoma MSN cells in this study to determine how tau proteins in neuronal cells are affected by menadione exposure. Menadione caused a dose-dependent thiol oxidation in these cells just like their non-neuronal counterparts. A prominent consequence of such oxidative insult in these neuronal cells was tau dephosphorylation. This dephosphorylation resulted in disappearance of phosphorylated 57-kDa tau with a concomitant emergence of 53-kDa tau whose full-length nature is indicated by its reactivity with antibodies Alz 50, Tau-1 and Tau-46. Immunochemical analyses using phosphorylation-dependent immunoprobes Tau-1 and PHF-1 with the aid of alkaline phosphatase demonstrated that 53-kDa tau was derived from dephosphorylation of 57-kDa tau. Despite its effect on thiol oxidation, menadione treatment did not lead to cytoskeletal changes reminiscent of the neurofibrillary tangles of AD. The data thus indicate that tau dephosphorylation constitutes a major feature of the menadione-induced oxidative injury in these neuronal cells.
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Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Odawara
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Yen
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D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D009447:Neuroblastoma / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014812:Vitamin K / Q000494:pharmacology*; D016875:tau Proteins / Q000187:drug effects*
D006490:Hemostatics; D016875:tau Proteins; D014812:Vitamin K