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.

缺血性神经元死亡和脑缺血性耐受性的分子机制仍有待阐明。我们在该项目中研究了有丝分裂原激活的蛋白激酶（MAPKS）如何在啮齿动物模型中使用免疫印迹和免疫组织化学参与脑缺血。在海马海马，ERK，JNK和p38中，在短暂的前脑缺血后具有特定的时间和空间模式，强烈激活（即，磷酸化），p38减毒的特异性抑制剂在海马的Ca1中减毒性缺血性神经元死亡。三硝基离子酸线粒体损伤后，MAPK级联反应在大鼠纹状体中也被激活，在短暂的前脑缺血后，小鼠海马中也激活了小鼠海马。温和的缺血，诱导海马州海马的缺血性耐受性，也激活了MAPK级联反应和p38的抑制剂，降低了缺血性耐受性。这些数据表明，p38可能在脑缺血后的神经元死亡和生存中起重要作用，并且对MAPK级联反应的控制将改变中风患者的临床外聚体。

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。

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。

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: "Activation of motogen-activated protein kinases in gerbil hippocompus with ischemic tolerance induced by 3NP"Neurosci Lett. 278. 101-104 (2000)

Sugino,T：“沙鼠海马中运动原激活蛋白激酶的激活与 3NP 诱导的缺血耐受性”Neurosci Lett。