The role of phosphorylation reaction of tau factor in ischemic neuronal cell death

tau因子磷酸化反应在缺血性神经细胞死亡中的作用

• 批准号: 13671445
• 负责人: MORIOKA Motohiro
• 金额: $ 2.24万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671445/
• 关键词: HIPPOCAMPUS; ISCHEMIA; TAR FACTOR; PHOSPHORYLATION; NEURONAL CELL DEATH; 燐酸化反応

Tau factor is cytoskeletal protein, which regulated by phosphorylation reaction. Recently, hyperphosphorylated tau factor is known to be involved in the mechanism of Alzheimer Disease. We examined the phosphorylation state of tau factor in the hippocampus after transient forebrain ischemia. The hyperphosphorylation of serin199/202 was transiently found in CA1 subfield, while the phosphorylation of serin396 did not change. Furthermore, we prepared 199/202-dephosphorylated form-tau factor by the site directed mutagenesis combined with TAT protein. Intraventricle injection of this dephosphorylated form-tau prevented ischemic neuronal cell death, while normal form-tau did not. It is concluded that the hyperphosphorylation of serin199/202 play an important role for neuronal cell death after transient ischemia.

Tau因子是细胞骨架蛋白，受磷酸化反应调节。最近，已知过度磷酸化的 tau 因子参与阿尔茨海默病的机制。我们检查了短暂前脑缺血后海马 tau 因子的磷酸化状态。在CA1亚区中短暂发现serin199/202的过度磷酸化，而serin396的磷酸化没有改变。此外，我们通过定点诱变结合TAT蛋白制备了199/202去磷酸化的tau因子。脑室内注射这种去磷酸化的 tau 蛋白可以预防缺血性神经元细胞死亡，而正常的 tau 蛋白则不能。结论是serin199/202的过度磷酸化在短暂性缺血后神经元细胞死亡中发挥重要作用。

项目成果

Motohiro Morioka: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochemical and Biophysical Research Communications. 286. 802-806 (2000)

Motohiro Morioka：“静脉注射 FK506 未能抑制海马神经钙蛋白”《生物化学与生物物理研究通讯》。

T. Kawano, K. Fukunaga, M. Morioka, S. Yano, T. Todaka, Y. Kai, J. Hamada, E. Miyamoto, Y. Ushio: "Decreased Akt activity is associated with activation of Forkhead transcription factor following transient forebrain ischemia in gerbil hippocampus"J. Cereb.

T. Kawano、K. Fukunaga、M. Morioka、S. Yano、T. Todaka、Y. Kai、J. Hamada、E. Miyamoto、Y. Ushio：“Akt 活性降低与瞬态后 Forkhead 转录因子的激活有关

M.Morioka, S.Yano, J.Hamada, et al.: "Intravenously injected FK506 failed to inhibit hippocampal calcineurin"Biochemical. and Biophyshical Research Communications.. 286. 802-806 (2001)

M.Morioka、S.Yano、J.Hamada 等人：“静脉注射 FK506 未能抑制海马神经钙蛋白”生物化学。

Takayuki Kawano: "Neuroprotective effect of sodium orthocanadate on delayed neuronal death after transient forebrain ischemia in gerbil hippocampus"J Cerb. Blood Flow Metab. 21. 1268-1280 (2001)

Takayuki Kawano：“原加拿大酸钠对沙鼠海马短暂前脑缺血后迟发性神经元死亡的神经保护作用”J Cerb。

T.Kawano, M.Morioka et al.: "Decreased Akt activity is associated with activation of Forkhead transcription factor following transient forebrain ischemia in gerbil hippocampus"Journal of Cerebral Blood Flow and Metabolism. 22. 926-934 (2002)

T.Kawano、M.Morioka 等人：“沙鼠海马短暂前脑缺血后，Akt 活性降低与 Forkhead 转录因子的激活有关”《脑血流与代谢杂志》。