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アデノシンは,ミトコンドリアのATPに敏感なカリウムチャネルの開通を誘発する: 発血の前提条件の重要なステップ?
1Institute of Molecular Cardiobiology, Johns Hopkins University, Baltimore, MD 21205, USA.
Circulation
|August 16, 2000
まとめ
アデノシンは,タンパク質キナーゼC経由で心臓保護のためのミトコンドリアのK (((ATP) チャンネルをプライムする.これは,アデノシンが,カスケードの重要な要素をリンクして,イシュミックの前提条件付けをどのように開始するかを説明する.
科学分野:
- 心血管生理学 心血管の生理学
- ミトコンドリア生物学
- 細胞シグナル伝達 細胞信号伝達
背景:
- アデノシンは,心臓損傷に対する保護現象である不血性予備状態を誘発します.
- ミトコンドリアのATP感受性カリウム (K(ATP)) チャンネルは,前置条件の重要な効果因子として関与しています.
- アデノシンとミトコンドリアのK ((ATP) 経路の正確なメカニズム的な関連は明らかにされていない.
研究 の 目的:
- アデノシンとミトコンドリアのK ((ATP) チャンネル間のメカニズム的相互作用を,不血性予備条件付けの文脈で決定する.
- ミトコンドリアのK ((ATP)) 経路に対するアデノシンの作用を媒介するタンパク質キナーゼCの役割を調査する.
主な方法:
- ミトコンドリアのK (((ATP) 経路活性については,ダイアゾキシド誘発のフラボプロテイン酸化を用いてウサギの室内ミオサイトで定量化した.
- チャンネル活性に対するアデノシンの影響は,受容体抗生物質とキナーゼ阻害剤の存在と欠如で評価されました.
- 心臓保護効果は,シミュレートされたイシュケミアモデルで評価され,介入は特定のK (((ATP)) チャンネルブロッカーによってブロックされました.
主要な成果:
- アデノシン (100μmol/L) は,ミトコンドリアのK (((ATP) チャンネル活性を増やし,開通までの遅延を減少させた.
- これらの効果は,アデノシン受容体アンタゴニスト8-(p-sulfophenyl) -theophyllineとタンパク質キナーゼC阻害剤ポリミキシンBによって廃止されました.
- アデノシンが緩和したシミュレートされたイシュケミア誘発細胞損傷は,ミトコンドリアのK (((ATP)) チャンネルブロッカー5-ヒドロキシデカノアートによってブロックされる効果ですが,HMR1098.8ではありません.
結論:
- アデノシン受容体の活性化により,ミトコンドリアのK (((ATP) チャンネルがタンパク質キナーゼC依存の方法で開きます.
- これらの発見は,アデノシンシグナル伝達と心臓保護におけるミトコンドリアのK (((ATP) チャンネル機能の間の直接的なリンクを確立しています.
- この研究は,不血性予備条件付けのカスケードにおける重要な分子イベントを明らかにしています.
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