Involvement of MAPK cascades in ischemic tolerance in neurons

MAPK 级联参与神经元缺血耐受

• 批准号: 11470288
• 负责人: NOZAKI Kazuhiko
• 金额: $ 9.34万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470288/
• 关键词: Cerebral ischemia; Ischemic tolerance; MAPK; gerbil; Delayed neuronal death; C-Jun NH_2-terminal kinase; p38 mitogen-activated protein kinase; Extracellular signal-regulated kinase; transient global ischemia; ischemic tolerance; hippo campus; g

Molecular mechanisms of ischemic neuronal death and ischemic tolerance in brain remain to be elucidated. We studied in this project how mitogen-activated protein kinases (MAPKs) cascades would be involved in cerebral ischemia using immunoblotting and immunohistochemistry in rodent models. In gerbil hippocampus, ERK, JNK and p38 were strongly activated (that is, phosphorylated) with specific temporal and spatial patterns after transient forebrain ischemia, and a specific inhibitor for p38 attenuated ischemic neuronal death in CA1 of the hippocampus. MAPK cascades were also activated in rat striatum after mitochondrial impairment by 3-nitropropionic acid and in mouse hippocampus after transient forebrain ischemia. Mild ischemia, which induced ischemic tolerance in gerbil hippocampus, also activated MAPK cascades and an inhibitor of p38 reduced ischemic tolerance. These data suggested that p38 might play a significant role in neuronal death and survival after cerebral ischemia and that control of MAPK cascades would modify clinical outocomes of stroke patients.

脑缺血性神经元死亡和脑缺血耐受的分子机制仍有待阐明。在这个项目中，我们研究了有丝分裂原活化蛋白激酶（MAPKs）级联反应将参与脑缺血在啮齿动物模型中使用免疫印迹和免疫组化。在沙土鼠海马，ERK，JNK和p38被强烈激活（即磷酸化）与特定的时间和空间模式短暂前脑缺血后，和p38的特异性抑制剂衰减海马CA 1区缺血性神经元死亡。MAPK级联反应也激活大鼠纹状体线粒体损伤后3-硝基丙酸和小鼠海马短暂前脑缺血后。在沙鼠海马中诱导缺血耐受的轻度缺血也激活MAPK级联，并且p38抑制剂降低缺血耐受。这些数据表明，p38可能在脑缺血后神经元死亡和存活中起重要作用，并且MAPK级联反应的控制将改变中风患者的临床结局。

项目成果

野崎和彦: "脳虚血の分子生物学"脳神経外科. (印刷中).

Kazuhiko Nozaki：“脑缺血的分子生物学”，神经外科（正在出版）。

Nozaki,K: "Nitogen-activated protein kinases and cerinal is chemia"Molecular Neurobiology. (in press).

Nozaki,K：“氮激活蛋白激酶和细胞化学”分子神经生物学。

Nozaki K: "Molecular biology in cerebral ischemia."Neurological Surgery. (in press).

野崎 K：“脑缺血的分子生物学。”神经外科。

Sugino,T: "3-Nitropropionic acid induces ischemic tolerance in gerbil hippocampus in vivo"Neuriosci Lett. 259. 9-12 (1999)

Sugino，T：“3-硝基丙酸在体内诱导沙鼠海马的缺血耐受性”Neuriosci Lett。

Sugino T: "3-Nitropropionic acid induces ischemic tolerance in gerbil hippocampus in vivo"Neurosci lett. 259. 9-12 (1999)

Sugino T：“3-硝基丙酸在体内诱导沙鼠海马的缺血耐受性”Neurosci lett。