| Literature DB >> 16815303 |
Motohiro Morioka1, Takayuki Kawano, Shigetoshi Yano, Yutaka Kai, Hiromasa Tsuiki, Yutaka Yoshinaga, Jun Matsumoto, Tatsumi Maeda, Jun-Ichiro Hamada, Hideyuki Yamamoto, Kohji Fukunaga, Jun-Ichi Kuratsu.
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.Entities:
Mesh：
Substances：
Year: 2006 PMID： 16815303 DOI： 10.1016/j.bbrc.2006.06.096
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575