Study on some proteins controling cell death in oxidative stress-induced neuronal cell death.

氧化应激诱导的神经细胞死亡中一些控制细胞死亡的蛋白质的研究。

• 批准号: 22590091
• 负责人: HIGUCHI Yoshihiro
• 金额: $ 2.91万
• 依托单位: Suzuka University of Medical Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590091/
• 关键词: グルタミン酸; 細胞死; アポトーシス; プロテオミクス; シグナル伝達; ストレス; タンパク質; 脳神経疾患; GRP-78; Galectin-1; プロテオミクス解析; 老化; プロテインキナーゼC; シグナル伝津

We have reported that glutamate exerts cytotoxic action through inhibition of cystine uptake, which leads to a marked decrease in cellular glutathione (GSH) levels exposing the cells to oxidative stresses leading to cell death. This cell death seemed to be apoptosis accompanying with 1-2Mbp giant DNA fragmentation led to internucleosomal DNA fragmentation. We expand on recent studies of intracellular proteins by examining the cell death regulating proteins or factors by using two-dimensional differential in-gel electrophoresis (2D-DIGE) in the intracellular peptides from cell extracts of C6 rat glioma cells. We identified a protein kinase C-δas one of protein kinases involved in the glutamate-induced cell death, and furthermore, identified 3 peptides derived from 10 proteins with LC-MS/MS in theglutamate-treated cells. Three peptides such as 78-kDa glucose-regulated protein (GRP78), annexin -A5and galectin-1 were increased in glutamate -treated glioma cells.

我们已经报道谷氨酸通过抑制胱氨酸摄取发挥细胞毒性作用，导致细胞谷胱甘肽（GSH）水平显著降低，使细胞暴露于氧化应激导致细胞死亡。这种细胞死亡似乎是伴随1-2Mbp巨大DNA断裂导致核小体间DNA断裂的细胞凋亡。我们通过对C6大鼠胶质瘤细胞提取物的细胞内肽进行二维凝胶电泳（2D-DIGE）检测细胞死亡调节蛋白或因子，扩展了最近对细胞内蛋白的研究。我们鉴定了一种蛋白激酶C-δ是参与谷氨酸诱导的细胞死亡的蛋白激酶之一，此外，在谷氨酸处理的细胞中，用LC-MS/MS鉴定了从10种蛋白中提取的3种肽。在谷氨酸处理的胶质瘤细胞中，78-kDa葡萄糖调节蛋白（GRP78）、膜联蛋白- a5和半乳糖凝集素-1等三种肽增加。

项目成果

Proteomic identification of oxidatively damaged proteins in excitotoxin-induced hippocampal injury

兴奋毒素诱导的海马损伤中氧化损伤蛋白的蛋白质组学鉴定

• 发表时间: 2012
• 作者: Furukawa;A. Shimada;A. and Higuchi
• 通讯作者: A. and Higuchi

TiO2 particles induces apoptosis associated with chromosomal DNA fragmentation and without ROS production in L1210 leukemia cells

TiO2 颗粒诱导 L1210 白血病细胞中与染色体 DNA 断裂相关的细胞凋亡，且不产生 ROS

• 作者: Higuchi,;Y.; Takaki;K; Furukawa;A. and Shimizu;N.
• 通讯作者: N.

Reactive oxygen species-independent chromosomal giant DNA fragmentation associated with caspase-mediated apoptosis in ultraviolet-irradiated cells

紫外线照射细胞中活性氧独立的染色体巨DNA断裂与半胱天冬酶介导的细胞凋亡相关

• 发表时间: 2011
• 作者: Higuchi;Y.;Hashii;M.;Tanii;H.;Koriyama;Y.
• 通讯作者: Y.

Effect of zonisamide on apoptosis-related factors formedduring iron-induced epileptogenesis in rat brain.

唑尼沙胺对铁诱导大鼠脑癫痫发生过程中形成的凋亡相关因子的影响。

• 发表时间: 2012
• 作者: Higuchi;Y.;Furukawa;A.;Oowada;S.;Komatsu;M. and Hiramatsu;M.
• 通讯作者: M.

内側側頭葉てんかん患者の海馬硬化組織における酸化損傷タンパク質の検出と同定

内侧颞叶癫痫患者海马硬化组织氧化损伤蛋白的检测与鉴定

• 发表时间: 2012
• 作者: 前田武彦;他;古川絢子,柿田明美,千葉陽一,武井史郎,石井さなえ,河村則子,細川昌則,樋口善博,高橋均,島田厚良
• 通讯作者: 古川絢子,柿田明美,千葉陽一,武井史郎,石井さなえ,河村則子,細川昌則,樋口善博,高橋均,島田厚良