アルドステロンは,血管の滑らかな筋肉細胞におけるアンジオテンシンII誘発信号伝達を強化する
Istvan Mazak1, Anette Fiebeler, Dominik N Muller
1Medical Faculty of the Charité, Franz Volhard Clinic, HELIOS Klinikum-Berlin and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Circulation
|May 26, 2004
まとめ
アルドステロンは,血管細胞におけるAng II誘発信号伝達を強化する. ミネラロコルチコイド受容体阻害はこれらの効果を阻害し,アンジオテンシンII誘発の損傷に対するインビオ効果を説明する.
科学分野:
- 心血管生物学 心血管生物学
- 腎臓生理学 腎臓生理学
- 細胞シグナル伝達 細胞信号伝達
背景:
- ミネラロコルチコイド受容体 (MR) 阻害は,アンジオテンシンII (Ang II) 誘発の臓器損傷を軽減する.
- この文脈におけるAng IIとアルドステロン (Ald) の相互作用は十分に理解されていません.
研究 の 目的:
- 血管の滑らかな筋肉細胞 (VSMC) 信号伝達に対するAng IIとAldの結合効果を調査する.
- Ang IIとAldのシグナル伝達における反応性酸素種 (ROS),MR,および表皮成長因子受容体 (EGFR) の役割を明らかにする.
主な方法:
- ウェスタン・ブロッティングとコンフォカル顕微鏡を用いて,VSMCにおける細胞外信号調節キナーゼ (ERK) とc-Jun N-末端キナーゼ (JNK) のリン酸化を評価した.
- オキシジングラジカルスキャベンジャー,EGFRアンタゴニスト (AG1478),MRブロッカー (スピロノラクトン) を使用しています.
主要な成果:
- Ang IIとAldは独立してERK1/2とJNKのリン酸化を誘導し,その組み合わせは強化効果を示した.
- ROS,MR,EGFRは,Ang IIとAld.によって活性化されたシグナル伝達経路に関与していた.
- スピロノラクトンは,Ang II誘発のROS生成,EGFRトランザクティベーション,ERK1/2リン酸化を廃止しました.
結論:
- アルドステロンは,VSMCにおけるAng II誘発ERK1/2およびJNKリン酸化を強化する.
- ROS,MR,EGFRは,Ang IIとAldの早期シグナル伝達の重要なメディエーターである.
- これらの発見は,Ang II誘発の末端臓器損傷に対するMR阻害の有効性について,in vitro機構学的洞察を提供します.
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