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参与MAP激酶级联反应，承担生长因子的信号转导，保护细胞免受各种损伤。然而，最近报道，抑制MEK活性可能保护神经元免受兴奋性毒性损伤。本研究旨在阐明MEK是否介导死亡信号。在MEK1腺病毒感染后4天，通过上清液的LDH测量来评估神经元死亡。MEK 1剂量依赖性地诱导神经元死亡。一种MEK抑制剂U0126阻止了死亡。为了检测MEK抑制剂在体内的作用，在大鼠中给予U0126或赋形剂后，通过大脑中动脉闭塞诱导局灶性脑缺血。在本实验中，U0126对脑缺血无保护作用。进一步的调查表明，以澄清的差异。

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。

Mochizuki T, Asai A, Saito N, et al.: "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 等人：“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”J.Biol.Chem。

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)