ドーパミンの投与により,発血後収縮機能障害の治療は,カルシウムに依存したプロアポプトシス信号伝達を迅速に誘発する
Christof Stamm1, Ingeborg Friehs, Douglas B Cowan
1Department of Cardiac Surgery, Children's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
Circulation
|October 2, 2002
まとめ
ドーパミン治療は,イシュケミアの後の心臓の収縮性を改善したが,カルシウム依存経路とミトコンドリア損傷を通じた心筋細胞アポトシスを著しく増加させた. これは,心不全後の心臓ケアにおける重要なトレードオフを強調しています.
科学分野:
- 心臓病学 心臓病学
- 細胞生物学 細胞生物学
- バイオケミストリー バイオケミストリー
背景:
- 発血不全とアドレネルジック刺激は,心筋細胞アポトシスを誘発する可能性があります.
- ドーパミンは,一般的なカテキオラミンであり,カルシウムシグナル伝達を通じて,収縮機能不全のポストイシュメアにおけるアポトーシスを増加させる可能性があります.
研究 の 目的:
- ドーパミンが心筋細胞アポトーシスを増加させるかどうかを,後発血性収縮機能不全のモデルで調査する.
- ドーパミン誘発アポトーシスにおけるカルシウム依存シグナリングカスケードの役割を明らかにする.
主な方法:
- 隔離されたウサギの心臓は,イシュケミア-再輸血を受けた.
- 心臓はドーパミン,ドーパミンはMGATPase阻害剤 (BDM),またはカルシウム感受性イノトロップ (ORG 30029) を投与した.
- アポトーシスは,TUNEL,PARP分裂,カスパース活性化,およびBax/Bcl-2発現を用いて評価され,細胞内カルシウムは測定された.
主要な成果:
- ischemia-reperfusionは機能障害を引き起こしたが,有意なネクロースやアポトーシスではない.
- ドーパミンは収縮性を改善したが,心筋細胞のアポプトシスを著しく増加させた (32.5±9対5.5±1.6/1000核).
- ドーパミンは細胞内カルシウムを上昇させ,カスパース (-3, -9) を活性化させ,バックスを増加させ,Bcl-2を減少させた. BDMとORG 30029は,これらの効果を異なる方法で調節した.
結論:
- 収縮性機能障害に対するドーパミン治療は,プロアポプトシス信号を活性化します.
- この活性化は,カルシウムに依存するプロセスとミトコンドリアの損傷によって媒介される可能性が高い.
- ドーパミンのプロアポプトティック効果は,収縮性に対する有益な効果とは異なる.
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