暫定的なミトコンドリアの浸透性,過渡期の孔開きは,予備条件による保護を媒介する
Derek Hausenloy1, Abigail Wynne, Michael Duchen
1The Hatter Institute and Centre for Cardiology, University College London, UK.
Circulation
|April 7, 2004
まとめ
mitochondrial permeability transition pore (mPTP) の一時的な開口と反応性酸素種 (ROS) は,プリコンディショニングと解離からの心臓保護の鍵です. mPTPまたはROSを阻害すると,これらの保護効果は廃止されます.
科学分野:
- 心血管科学の研究について
- ミトコンドリア生理学 ミトコンドリア生理学
- セルラー・シグナリング
背景:
- mitochondrial permeability transition pore (mPTP) の一時的な開口は, mitochondrial のカルシウムレベルと反応性酸素種 (ROS) のシグナル伝達に影響する.
- この一時的なmPTP開口は,心筋前置条件とミトコンドリア解離で観察された保護効果を媒介すると仮定されています.
研究 の 目的:
- 暫定的なmPTP開口とROSが,心筋前置条件とミトコンドリア解離の保護効果を媒介する役割を調査する.
主な方法:
- 隔離された浸透されたラットの心臓は,イシュケミア/再注射損傷を受けた.
- 心臓発作リスクと体積の比率は,介入後に評価された.
- 薬理学的薬剤は,プリコンディショニングプロトコル中にmPTP開口 (サイクロスポリンA,サングリフェリンA) またはROS (N-メルカプトプロピオニルグリシン) を阻害するために使用されました.
- ダイアゾキシド,CCPA,および2,4-ディニトロフェノールは,薬理学的条件付けおよびミトコンドリア解離のために使用されました.
主要な成果:
- プリコンディショニング中のmPTP開封の阻害は,不全性プリコンディショニング (IPC),ダイアゾキシド,CCPA,および2,4-ジニトロフェノールの保護効果を廃止しました.
- ROSの抑制は,IPC,ディアゾキシド,および2,4-ジニトロフェノールの保護効果を無効にしたが,CCPAはそうではなかった.
- ダイアゾキシドが誘発したCsA感受性,一時的なmPTP開口は,大人のラットミオサイトで発生した.
結論:
- IPC,ダイアゾキシド,およびミトコンドリア解離の保護効果は,一時的なmPTP開封に依存しています.
- ROSシグナリングは,IPC,ダイアゾキシド,ミトコンドリア解離によって媒介される保護機構にも重要である.
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