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血管の滑らかな筋肉細胞のヘム酸化酵素は,ガニリルサイクラスを刺激する一酸化炭素を生成する
N Christodoulides1, W Durante, M H Kroll
1Houston (Tex) Veterans Affairs Medical Center 77030, USA.
Circulation
|May 1, 1995
まとめ
血管の滑らかな筋肉細胞 (SMCs) は,ヘム酸素酶 (HO) 活動を通じて一酸化炭素 (CO) を生成します. このCOは,SMCと血小板のcGMP生成を刺激し,新しいシグナル伝達経路を示しています.
科学分野:
- 血管生物学 血管生物学
- セルラー・シグナリング
- バイオケミストリー バイオケミストリー
背景:
- 一酸化炭素 (CO) と一酸化窒素 (NO) は,溶性ガニリルサイクラスを活性化し,細胞内cGMPを増加させます.
- ヘム酸化酵素 (HO) は,ヘムを代謝する酵素である.
研究 の 目的:
- 血管の滑らかな筋肉細胞 (SMC) によるCOの内生的な生成を調査する.
- SMC内のCO生成におけるヘム酸素酶 (HO) の役割を決定する.
- SMCから派生したCOがcGMPレベルに与える影響を評価する.
主な方法:
- ネズミの培養大動脈SMC (RASMCs) が使用されました.
- ヘムオキシゲナーゼ-1 (HO-1) とヘムオキシゲナーゼ-2 (HO-2) の発現を評価した.
- RASMCはHO-1誘発剤 (ヘミン,ナトリウムアルセニート) で治療された.
- RASMCおよび併立血小板のcGMP濃度が測定されました.
- ヘム酸素酶阻害剤 (亜鉛プロトポルフィリンIX) が使用されました.
主要な成果:
- RASMCは,HO-1とHO-2の両方を表現した.
- HO-1誘導は,RASMCsと血小板のcGMPを増加させた.
- RASMCによって誘発されたCO生成は血小板cGMPを上昇させた.
- NO合成酵素の活動は,観察されたcGMP増加には関与しませんでした.
- ヘムオキシゲナーゼの抑制により,cGMPの上昇が逆転した.
結論:
- 血管系SMCは,構成的および誘導性ヘム酸素酵素活性の両方を有する.
- SMCは,SMCと血小板内のガニリルサイクラスを刺激するCOを生成します.
- これは,血管細胞における新たな内生性CO媒介シグナル伝達経路を浮き彫りにしています.
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