Research on signal transduction of ischemic neuronal death

缺血性神经元死亡的信号转导研究

• 批准号: 13470283
• 负责人: SAITO Nobuhito
• 金额: $ 7.87万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470283/
• 关键词: cerebral ischemia; MAP kinase; signal transduction; 免疫抑制剤

MEK is in the course of MAP kinase cascade and bears the signal transduction of growth factors and protects cells from various insults. However, it is reported recently that inhibition of MEK activity may protect neurons from excitotoxic insults. In this study, we aimed to clarify weather MEK mediates death signal or not.Constitutively active MEK1 was adenoviral transdused in primary cultured neurons. Four days after MEK1 adenovirus infection, neuronal death was evaluated by LDH measurement of the supernatant. MEK1 induced neuronal death dose-dependently. A MEK inhibitor, U0126, prevented the death. Thus, MEK1 was considered to mediate death signal in the cultured neurons.To examine the effect of MEK inhibitor in vivo, focal cerebral ischemia by middle cerebral artery occlusion was induced in rats after administration of U0126 or vehicles. In our experiment, U0126 did not have protective effect against cerebral ischemia. Further investigation is indicated to clarify the difference.

MEK正在MAP激酶级联反应过程中，并带有生长因子的信号转导，并保护细胞免受各种侮辱。但是，据报道，抑制MEK活性可能会保护神经元免受兴奋性毒性损伤。在这项研究中，我们旨在阐明天气MEK是否介导了死亡信号。 MEK1腺病毒感染四天后，通过LDH测量上清液评估了神经元死亡。 MEK1依赖于神经元死亡剂量。 MEK抑制剂U0126阻止了死亡。因此，MEK1被认为可以介导培养的神经元中的死亡信号。为了检查MEK抑制剂在体内的作用，在给药后，在U0126或车辆后，在大鼠中诱导了脑动脉闭塞的局灶性脑缺血。在我们的实验中，U0126对脑缺血没有保护作用。进一步调查被指出以阐明差异。

项目成果

Mochizuki T, Asai A, Saito N, Tanaka S, Katagiri H, Asano T, Nakane M, Tamura A, Kuchino Y, Kitanaka C, Kirino T.: "Akt protein kinase inhibits non-apoptotic programmed cell death induced by ceramide."J.Biol.Chem.. 277. 2790-2797 (2002)

Mochizuki T、Asai A、Saito N、Tanaka S、Katagiri H、Asano T、Nakane M、Tamura A、Kuchino Y、Kitanaka C、Kirino T.：“Akt 蛋白激酶抑制神经酰胺诱导的非凋亡性程序性细胞死亡。”

Sugawara Ki K, Kurihara H, Negishi M, Saito N, et al.: "Nestin as a marker for proliferative endothelium in gliomas"Lab Invest. 82・3. 345-351 (2002)

Sukawara Ki K、Kurihara H、Negishi M、Saito N 等：“Nestin 作为神经胶质瘤中增殖性内皮细胞的标记”Lab Invest. 82·3（2002）。

T Tosaka M, Hashiba Y, Saito N, et al.: "Contractile responses to reactive oxygen species in the canine basilar artery in vitro : selective inhibitory effect of MCI-186, a new hydroxyl radical scavenger."Acta Neurochir. 144. 1305-1310 (2002)

T Tosaka M、Hashiba Y、Saito N 等人：“体外犬基底动脉对活性氧的收缩反应：MCI-186（一种新型羟自由基清除剂）的选择性抑制作用。”Acta Neurochir。

Asai A, Tanahashi N, Qiu JH, Saito N, et al.: "Selective Proteasomal Dysfunction in the Hippocampal CA1 Region After Transient Forebrain Ischemia"J.Cereb.Blood Flow Metab.. 22. 705-710 (2002)

Asai A、Tanahashi N、Qiu JH、Saito N 等：“短暂前脑缺血后海马 CA1 区的选择性蛋白酶体功能障碍”J.Cereb.Blood Flow Metab.. 22. 705-710 (2002)

Sugawara K, Kurihara H, Negishi M, Saito N, Nakazato Y, Sasaki T, Takeuchi T.: "Nestin as a Marker for Proliferative Endothelium in Gliomas"Lab.Invest.. 82. 345-351 (2002)

Sukawara K、Kurihara H、Negishi M、Saito N、Nakazato Y、Sasaki T、Takeuchi T.：“巢蛋白作为神经胶质瘤增殖内皮细胞的标志物”Lab.Invest.. 82. 345-351 (2002)