title: Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia.
abstract: We examined the phosphorylation state of tau factor in hippocampal delayed neuronal death (DND) after transient forebrain ischemia. A transient phosphorylation increase at serine 199/202 but not serine 396 of tau factor after transient ischemia was clearly observed. Intraventricular injections of olomoucine and U-0126 (CDK5 and MAP kinase inhibitors, respectively) inhibited hyperphosphorylation. In contrast, wortmannin (PI3 kinase inhibitor) increased phosphorylation at serine 199/202 and corresponded with an increase in GSK3 phosphorylation. Our findings suggest that CDK5, MAP kinase, and GSK3 phosphorylate these sites after ischemia. We prepared recombinant normal human tau (N-Tau40) with TAT-HA protein and dephosphorylated-form human Tau-40 (D-tau40) in which 199/202 serines were changed to alanine by site-directed mutagenesis. Intraventricularly injected D-tau40 protected somewhat against DND while N-Tau40 did not. These data suggest that hyperphosphorylation at serine 199/202 of tau factor is induced by MAP kinase, CDK5, and GSK3, and contributes to ischemic neuronal injury.
authors.affiliation: Department of Neurosurgery, Kumamoto University School of Medicine, Japan. morioka@kaiju.medic.kumamoto-u.ac.jp
authors.forename: Motohiro
authors.initials: M
authors.lastname: Morioka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawano
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Yano
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kai
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tsuiki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshinaga
authors.forename: Jun
authors.initials: J
authors.lastname: Matsumoto
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Maeda
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Hamada
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kuratsu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D002545:Brain Ischemia / Q000378:metabolism*; D005849:Gerbillinae; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D011485:Protein Binding; D015427:Reperfusion Injury / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000378:metabolism
chemical_list: D012694:Serine