Stimulation of protein tyrosine phophorylation participates in delayd neuronal death in ischemic hippocampus

刺激蛋白质酪氨酸磷酸化参与缺血海马延迟性神经元死亡

• 批准号: 06670715
• 负责人: HANDA Nobuo
• 金额: $ 0.38万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670715/
• 关键词: tyrosine phosphorylation; cerebral ischemia; kainic acid; pp60c-src; radicicol

Glutamate triggers neuronal degeneration following ischemia/reperfusion in the brain. However, the details of intracellular signal transduction that propagate cell death remain unknown. The present work investigated whether protein tyrosine phophorylation mediates neuronal death in the ischemic brain. Transient forebrain ischemia for 5-10 min in Mobgolian gerbils or intoxication of glutamate analogue (kainic acid, 12 mg/kg) in Sprague-dawley rats caused neuronal death selectively in the hippocampus 2-4 days or 1 day later, respectively. Under these conditions, 160,115,105,92,85 kDa proteins showed a significant increase in tyrosyl residue phosphorylation selectively in the hippocampus 3-12 h after ischemia or 4-8 h after kainic acid-induced seizures. Tyrosine kinase, including pp60c-src, were activated without a change of tyrosine phophatases. Administration of radicicol, a selective inhibitor of tyrosine kinases, attenuated stimulation of tyrosine phophorylation and hippocampal degeneration after ischemia or kainic acid injection. the results suggest that protein tyrosine phosphorylation might propagate delayd neuronal death in the amture hippocampus through glutamate overload after ischemia/reperfusion.

谷氨酸在脑缺血/再灌流后触发神经元退化。然而，传播细胞死亡的细胞内信号转导的细节仍不清楚。本研究调查了蛋白酪氨酸磷酸化是否介导了缺血脑内神经元的死亡。沙土鼠短暂性前脑缺血5~10min和SD大鼠谷氨酸类似物(海人酸，12 mg/kg)中毒分别在2~4天和1天后选择性地引起海马神经元死亡。在此条件下，160、115、105、92、85 kDa蛋白在脑缺血3~12h或海人藻酸致痫后4~8h海马区酪氨酸残基选择性磷酸化显著增加。酪氨酸激酶，包括pp60c-src，在不改变酪氨酸磷酸酶的情况下激活。给予酪氨酸激酶的选择性抑制剂--自由基酚，可减轻缺血或注射海人藻酸后对酪氨酸磷酸化和海马区变性的刺激。结果提示，蛋白酪氨酸磷酸化可能通过谷氨酸超载促进缺血/再灌流后海马区迟发性神经元死亡。

项目成果

Toshiho Ohtsuki, Masayasu Matsumoto, Kazuo Kitagawa, Takuma Mabuchi, Kohji Matsushita, Keisuke Kuwabara, Masafumi Tagaya, Satoshi Ogawa, Hirolazu Ueda, Nobuo Handa, Takehiko Yanagihara: "Stimulation of protein tyrosine phophorylation participates in delay

Toshiho Ohtsuki、Masayasu Matsumoto、Kazuo Kitakawa、Takuma Mabuchi、Kohji Matsushita、Keisuke Kuwabara、Masafumi Tagaya、Satoshi Okawa、Hirolazu Ueda、Nobuo Handa、Takehiko Yanagihara：“蛋白质酪氨酸磷酸化的刺激参与延迟

T. Ohtsuki,M. Matsumoto,N. Handa他: "Stimulation of protein tyrosine phosphorylation participates in delayed neuronal death in ischemic hippocampus" American Journal of Physiology. (印刷中).

T. Ohtsuki、M. Matsumoto、N. Handa 等人：“蛋白质酪氨酸磷酸化的刺激参与缺血性海马的延迟性神经元死亡”美国生理学杂志（正在出版）。

T.ohtsuki,M.Matsumoto,N.Handa 他: "Stimulation of protein tyrosine phosphorylation participates in delayed nevronal death in lschemic hippocompus" American Journal of physiology. (印刷中).

T. ohtsuki、M. Matsumoto、N. Handa 等人：“蛋白质酪氨酸磷酸化的刺激参与缺血性海马的延迟性神经元死亡”美国生理学杂志（正在出版）。