NADPH酸化酵素は,ヒトの血管の滑らかな筋肉細胞におけるトロンビンによる組織因子依存の表面凝固活性を媒介する
Olaf Herkert1, Isabel Diebold, Ralf P Brandes
1Institut für Kardiovaskuläre Physiologie, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Circulation
|May 1, 2002
まとめ
トロンビンは,NADPH酸化酵素と活性酸素種 (ROS) を通して,血管細胞内の組織因子 (TF) を上調する. この経路は,p38 MAP キナーゼとPI 3-キナーゼ/Aktを含むもので,血管損傷後の凝固を永続させます.
科学分野:
- 血管生物学 血管生物学
- 凝固カスケード (凝固カスケード)
- 細胞シグナル伝達 細胞信号伝達
背景:
- 組織因子 (TF) は凝固を開始し,トロンビンは血管の滑らかな筋肉細胞 (VSMCs) でその発現を拡大します.
- このポジティブなフィードバックループは,血管損傷の部位における長期のプロコアグラント活性と血栓形成性に貢献します.
- このサイクルを支える正確なシグナル伝達機構,特に反応性酸素種 (ROS) の役割は,まだ完全に理解されていません.
研究 の 目的:
- VSMCにおけるROSの主な源であるNADPH酸化酵素が,トロンビン誘発のTF発現を媒介する役割を調査する.
- TFのこのリドックス感受性アップレギュレーションに関与するシグナル伝達経路を解明する.
主な方法:
- 培養されたヒトのVSMCは,トロンビンで治療された.
- TF mRNA発現と表面プロコアグラント活性が評価されました.
- 抗酸化物質,NADPH酸化酵素阻害剤 (ディフェニレンヨドニウム,p22phox antisense,RacT17N),および経路阻害剤 (p38 MAP キナーゼ,PI 3-キナーゼ) の効果が評価されました.
- タンパク質のリン酸化 (Akt) を分析した.
主要な成果:
- トロンビンは,VSMCにおけるTF mRNAとプロコアグラント活性を著しく増加させた.
- これらの反応は,抗酸化物質とNADPH酸化酵素阻害剤によって著しく減少した.
- また,p38 MAP キナーゼとPI 3 キナーゼの抑制により,トロンビン誘発のTF mRNA発現が弱まりました.
- トロンビンは,酸化還元素に敏感でNADPH酸化酵素に依存した方法でAktのリン酸化を刺激した.
結論:
- NADPH酸化酵素は,VSMCにおけるトロンビンによるTF mRNAのリドックス感受性誘導とプロコアグラント活性に不可欠である.
- このプロセスは,p38 MAP キナーゼとPI 3-キナーゼ/Akt経路の活性化によって媒介されます.
- NADPH酸化酵素は,損傷した血管内の血栓生成サイクルを維持する重要な要因である可能性があります.
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