MENADIONE-INDUCED TAU-DEPHOSPHORYLATION IN CULTURED HUMAN NEUROBLASTOMA-CELLS

Oxidative stress has been implicated in the mechanism of aging and neu rodegenerative disorders such as Alzheimer's disease (AD). Menadione c auses oxidative stress by generating reactive oxygen species through i ts redox cycling and these free radicals are detoxified subsequently a t the expense of intracellular thiol homeostasis. In non-neuronal cell s, the cytoskeleton is a prime target of menadione-induced thiol oxida tion. 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 consequen ce of such oxidative insult in these neuronal cells was tau dephosphor ylation. This dephosphorylation resulted in disappearance of phosphory lated 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-depend ent immunoprobes Tau-1 and PHF-1 with the aid of alkaline phosphatase demonstrated that 53-kDa tan was derived from dephosphorylation of 57- kDa tau. Despite its effect on thiol oxidation, menadione treatment di d not lead to cytoskeletal changes reminiscent of the neurofibrillary tangles of AD. The data thus indicate that tau dephosphorylation const itutes a major feature of the menadione-induced oxidative injury in th ese neuronal cells.