Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia

Motohiro Morioka, Takayuki Kawano, Shigetoshi Yano, Yutaka Kai, Hiromasa Tsuiki, Yutaka Yoshinaga, Jun Matsumoto, Tatsumi Maeda, Jun ichiro Hamada, Hideyuki Yamamoto, Kohji Fukunaga, Jun ichi Kuratsu

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)273-278
Number of pages6
JournalBiochemical and biophysical research communications
Volume347
Issue number1
DOIs
Publication statusPublished - 2006 Aug 18

Keywords

  • Hippocampus
  • Ischemia
  • Phosphorylation
  • Tau factor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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