K (((ATP) 経路の遺伝子発現は,ウロコルチンによって誘発され,その心臓保護効果を媒介する

K M Lawrence¹, A Chanalaris, T Scarabelli

¹Medical Molecular Biology Unit, Institute of Child Health, University College London, London, England.

Circulation

|September 18, 2002

まとめ

心臓保護剤であるウロコルチンは,心臓細胞のキル6.1カリウムチャネル発現を高めます. この特定のチャネル活動は,ウロコルチンの作用において極めて重要です.

科学分野:

心臓病学心臓病学
分子生物学は分子生物学である.
薬理学薬理学とは

背景:

ウロコルチンは新しい心臓保護剤です.
心臓のミオサイトを ischemia/reperfusion 損傷から保護する.
ウロコルチンは,再注射時に投与した場合に有効です.

研究の目的:

ウロコルチンの心臓保護効果の基礎となる分子メカニズムを調査する.
ウロコルチンによって誘発される特定の遺伝子発現の変化を特定するために.
ウロコルチンの保護作用における特定された標的の役割を決定する.

主な方法:

心臓のミオサイトにおける遺伝子チップ技術を用いたグローバル遺伝子発現分析.
ウロコルチンによる治療.
孤立した心臓細胞と無傷の心臓における心臓保護効果の評価.
K (((ATP)) 経路の薬理学的阻害 (一般的およびミトコンドリア特異的).
Kir 6.1 チャンネルサブユニットの阻害.

主要な成果:

ウロコルチンは特に,Kir 6.1心臓のカリウムチャネルサブユニットの増強表現を誘導します.
ウロコルチンによる心臓保護は,K ((ATP) チャンネルブロッカーによって阻害されます.
Cardiotrophin-1の心臓保護効果は,これらの阻害剤によって影響を受けません.
Kir 6.1の阻害は,イシュケミアの後の心臓細胞死を高めます.

結論:

この研究は,心臓保護剤による変化したK (((ATP) チャンネルサブユニット発現の最初の事例を報告しています.
K (((ATP) チャンネル開口は,ウロコルチンの心臓保護効果に不可欠です.
キル6.1は,ウロコルチン誘発の心臓保護の重要な媒介である.

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