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Hyperphosphorylation at serine 199/202 of tau factor in the gerbil hippocampus after transient forebrain ischemia |
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| Authors: | Morioka Motohiro Kawano Takayuki Yano Shigetoshi Kai Yutaka Tsuiki Hiromasa Yoshinaga Yutaka Matsumoto Jun Maeda Tatsumi Hamada Jun-Ichiro Yamamoto Hideyuki Fukunaga Kohji Kuratsu Jun-Ichi |
| Affiliation: | a Department of Neurosurgery, Kumamoto University School of Medicine, Japan b Department of Pharmacology, Kumamoto University School of Medicine, Japan c Department of Neurosurgery, Kanazawa University Graduate School of Medical Science, Japan d Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan |
| 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. |
| Keywords: | Ischemia Hippocampus Tau factor Phosphorylation |
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