G alpha (i) 和 G alpha (o) 是活性氧物种的标蛋白
M Nishida1, Y Maruyama, R Tanaka
1Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Science, University of Tokyo, Japan.
Nature
|December 2, 2000
概括
活性氧物种 (ROS) 在心脏细胞中激活细胞外信号调节激酶 (ERK). 过氧化直接准Gαi) 和Gαo) 蛋白质,启动这一关键信号通路.
科学领域:
- 心血管生物学 心血管生物学
- 细胞信号传递 细胞信号传递
- 氧化压力研究研究 氧化压力研究
背景情况:
- 反应性氧物种 (ROS) 调解关键信号事件,包括心脏损伤和缩.
- 细胞外信号调节激酶 (ERK) 是已知的ROS响应激酶,但其最初的ROS位仍未确定.
- 之前的研究表明,氨酸激酶和小G蛋白与ROS诱导的ERK激活有关.
研究的目的:
- 在心肌细胞中确定负责ERK激活的ROS的初始蛋白标.
- 阐明G蛋白子单元在ROS介导ERK信号传递中的作用.
主要方法:
- 利用大鼠新生儿心肌细胞研究过氧化 (H2O2) 诱导的ERK激活.
- 研究了G蛋白贝塔玛子单元 (G贝塔玛),酸氨基醇-3-激酶和Src.的参与.
- 通过使用纯化的异构三分子Gi和Go蛋白和[35S]GTP-gammaS结合试验进行了体外研究.
主要成果:
- 抑制G贝塔玛减弱的H2O2诱导的ERK激活.
- H2O2诱导的ERK激活需要酸丁醇-3-酶和Src,独立于Gi-合受体连接体.
- H2O2直接激活了纯化的Gi和Go蛋白,在Gα小单元上观察到修改,导致解离.
结论:
- G alpha (i) 和 G alpha (o) 蛋白质是导致ERK激活的途径中氧化应激的关键标.
- 这项研究揭示了心脏中ROS信号传递的新机制,涉及直接激活G蛋白.
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