Research for the mechanism of ischemic tolerance in neuronal cells

神经细胞缺血耐受机制研究

• 批准号: 13671446
• 负责人: YANO Shigetoshi
• 金额: $ 2.5万
• 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-13671446/
• 关键词: ISCHEMIC TOLERANCE; Akt; CREB; PHOSPHORYLATION; HIPPOCAMPUS; リン酸化反応; 燐酸化反応

To investigate the mechanism of ischemic tolerance, we first focused on the activity of Akt that was reported as a key enzyme of anti-apoptotic signaling. Sublethal ischemia gradually and persistently activated Akt in hippocampal CA1 region. Intra-cerebral ventricular infusion of wortmannin prior to preconditioning blocked both the increase in Akt activation and the neuroprotective action of preconditioning. Next we examined the activation of CREB that was one of the candidates for the target of Akt signaling. Phosphorylation and binding activity of CREB after sublethal ischemia was observed transiently. Inhibition of CREB-DNA binding by infusion of CRE-decoy into the cerebral ventricle resulted in failure of induction of ischemic tolerance. These results suggested that Akt signaling and CREB activation contributed to neuroprotective ischemic tolerance in CA1 pyramidal neurons. As these effects could not explain the entire mechanism of ischemic tolerance, we are going to keep on investigating other key molecules.

为了研究缺血耐受的机制，我们首先关注了Akt的活性，Akt被报道为抗凋亡信号传导的关键酶。亚致死性脑缺血逐渐持续激活海马CA 1区Akt。预处理前脑室注射渥曼青霉素可阻断Akt活化的增加和预处理的神经保护作用。接下来，我们检查了CREB的激活，CREB是Akt信号传导的靶点之一。亚致死性缺血后CREB的磷酸化和结合活性被短暂观察到。通过将CREB-decoy注入脑室抑制CREB-DNA结合导致诱导缺血耐受失败。这些结果表明，Akt信号和CREB激活参与了CA 1锥体神经元的神经保护性缺血耐受。由于这些作用不能解释缺血耐受的全部机制，我们将继续研究其他关键分子。

项目成果

Naoki Shinojima: "Myofibroblastoma in the suprasellar region. Case report"Journal of Neurosurgery. 97. 1203-1207 (2002)

Naoki Shinojima：“鞍上区肌纤维母细胞瘤。病例报告”神经外科杂志。

Kazunari Koga: "Expression of Angiopoietin-2 in human glioma cells and its role for angiogenesis"Cancer Research. 61. 6248-6254 (2001)

Kazunari Koga：“Angiopoietin-2 在人神经胶质瘤细胞中的表达及其对血管生成的作用”癌症研究。

Tatemi Todaka: "Successful clipping of a distal posterior inferior cerebellar artery aneurysm located on the anterior surface of the medulla oblongata--case report"Neurol Med Chir (Tokyo). 42. 158-161 (2002)

Tatemi Todaka：“成功夹闭位于延髓前表面的小脑后下动脉远端动脉瘤——病例报告”Neurol Med Chir（东京）。

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。

K. Koga, T. Todaka, M. Morioka, J. Hamada, Y. Kai, S. Yano, A. Okamura, N. Takakura, T. Suda, Y. Ushio: "Expression of Angiopoietin-2 in human glioma cells and its role for angiogenesis"Cancer Res. 61. 6248-6254 (2001)

K. Koga、T. Todaka、M. Morioka、J. Hamada、Y. Kai、S. Yano、A. Okamura、N. Takakura、T. Suda、Y. Ushio：“Angiopoietin-2 在人胶质瘤细胞中的表达