title: Hydrogen peroxide induces transient dephosphorylation of tau protein in cultured rat oligodendrocytes.
abstract: Oxidative stress is a major mediator of neurodegeneration. In this study, we tested the effects of oxidative stress induced by a brief exposure to hydrogen peroxide (H(2)O(2)) on the phosphorylation state of the tau protein in oligodendrocytes (OL). Primary oligodendrocyte cultures prepared from newborn rat brains were exposed to millimolar concentrations of H(2)O(2) for up to 15 min, and then incubated in normal medium for up to 12 h. The treatment caused morphological degeneration of OL characterized by the loss of cellular processes apparent approximately 3 h after H(2)O(2) exposure. The morphological degeneration was preceded by a profound dephosphorylation of tau protein revealed by immunoblot using monoclonal tau-1 antibody that recognizes the dephosphorylated epitope. The dephosphorylated form increased dramatically during H(2)O(2) exposure, peaked after 2 h of post-exposure, and returned to the baseline level within 12 h. Total tau protein levels were not changed in the course of the experiment as judged by immunoblotting with phosphorylation-insensitive tau-5 and 46-1 monoclonal antibodies. Our finding demonstrates that oxidative stress induces a rapid but transient dephosphorylation of tau protein that may underlie morphological degeneration of OL.
authors.affiliation: Department of Pathology, Loyola University Medical Center, Maywood, IL 60153-3520, USA. p-lopresti@northwestern.edu
authors.forename: P
authors.initials: P
authors.lastname: LoPresti
authors.forename: G W
authors.initials: GW
authors.lastname: Konat
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016877:Oxidants; D016875:tau Proteins; D006861:Hydrogen Peroxide