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

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• 作者：Motohiro Morioka ; Takayuki Kawano ; Shigetoshi Yano ; Yutaka Kai ; Hiromasa Tsuiki ; Yutaka Yoshinaga ; Jun Matsumoto ; Tatsumi Maeda ; Jun-ichiro Hamada ; Hideyuki Yamamoto et al.
• 关键词：Ischemia ; Hippocampus ; Tau factor ; Phosphorylation
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2006
• 出版时间：18 August 2006
• 年：2006
• 卷：347
• 期：1
• 页码：273-278
• 全文大小：272 K

文摘

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.