Gα (i) とGα (o) は,活性酸素種の標的タンパク質である
M Nishida1, Y Maruyama, R Tanaka
1Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Science, University of Tokyo, Japan.
Nature
|December 2, 2000
まとめ
反応性酸素種 (ROS) は,心臓細胞内の細胞外信号調節キナーゼ (ERK) を活性化します. 過酸化水素は,Gα (i) とGα (o) のタンパク質を直接標的にして,この重要な信号伝達経路を開始します.
科学分野:
- 心血管生物学 心血管生物学
- 細胞シグナル伝達 細胞信号伝達
- 酸化ストレス研究 酸化ストレス研究
背景:
- 反応性酸素種 (ROS) は,心臓損傷と高縮を含む重要なシグナルイベントを媒介する.
- 細胞外信号調節キナーゼ (ERK) は,既知のROS反応性キナーゼですが,その初期ROS標的は未確認のままです.
- 以前の研究では,ROS誘発のERK活性化にチロシンキナーゼと小Gタンパク質が関与していた.
研究 の 目的:
- 心筋細胞におけるERK活性化に責任を負うROSの初期タンパク質標的を特定する.
- ROS媒介のERKシグナル伝達におけるGタンパク質サブユニットの役割を明らかにする.
主な方法:
- ネズミの新生児心筋細胞を用いて,過酸化水素 (H2O2) 誘発のERK活性化を研究した.
- Gタンパク質ベタガマサブユニット (Gベタガマ),フォスファディチルイノシトール-3キナーゼ,およびSrc.の関与を調査した.
- 精製されたヘトロトリメリックのGiとGoタンパク質と[35S]GTP-ガンマS結合アッセイを用いたin vitro試験を実施した.
主要な成果:
- Gベタガンマ弱化H2O2誘発ERK活性化の抑制.
- H2O2誘発のERK活性化には,フォスファディチリノシトール3キナーゼとSrcが必要で,これはGi結合受容体リガンドから独立している.
- H2O2は,精製されたGiとGoタンパク質を直接活性化し,Gα (α) のサブユニットに変化が観察され,解離に至った.
結論:
- Gアルファ (i) とGアルファ (o) タンパク質は,ERK活性化につながる経路における酸化ストレスの重要な標的である.
- この研究は,直接のGタンパク質活性化を含む心臓におけるROS信号伝達の新しいメカニズムを明らかにしています.
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