肌動脈不全後の細胞死におけるCD95/Apo1/Fasの関与
I Jeremias1, C Kupatt, A Martin-Villalba
1German Cancer Research Center, Heidelberg, Germany.
Circulation
|August 23, 2000
まとめ
イシュケミア/リパーフュージョン後の心臓細胞死にはアポトーシスが含まれます. CD95系は,CD95リガンドを含む,このプロセスにおいて直接的な役割を果たし,心臓発作の回復のための治療目標として示唆しています.
科学分野:
- 心血管生物学 心血管生物学
- 細胞死メカニズム 細胞死メカニズム
- 分子心臓病学 分子心臓病学
背景:
- イシュケミアと再注射による損傷による心臓細胞死は,重要な臨床的懸念事項である.
- プログラム細胞死経路であるアポトーシスは,急性心筋梗塞後の心筋損傷に寄与する.
研究 の 目的:
- 発血後の心臓細胞死亡を媒介するCD95/Fas/Apo1受容体システムの特定の役割を調査する.
- 筋動脈不全-再注血の文脈におけるCD95リガンドおよび他の致死性リガンドの関与を調査する.
主な方法:
- 隔離されたラットとマウスの心臓のランゲンドルフ perfusion モデルを利用して ischemia-reperfusion をシミュレートしました.
- カスパーゼ依存アポトーシスとCD95リガンドおよび他の死亡リガンド (TNF-α, TRAIL) の放出/合成を評価した.
- 低酸素/低酸素化下でのCD95リガンドに対する成年ラット・プライマリ・ミオサイトの感受性を調査し,CD95欠乏マウス (lpr) と野生型の対照群の細胞死亡を比較した.
主要な成果:
- 隔離された心臓における後発血性再注血は,カスパース依存アポトシスを誘発した.
- 溶解性CD95リガンドが放出され,TNF-αとTRAILと共に,後発血性心臓によってde novoで合成されました.
- 低酸素/低酸素化は,CD95リガンドに対する肌細胞の感受性を高め,CD95欠乏した心臓は,イシュケミア-再注血後の細胞死が減少したことを示した.
結論:
- CD95/Apo1/Fas系は,心筋動脈不全後の心臓細胞死亡に直接関与しています.
- CD95シグナル伝達経路は,心臓の細胞死亡を予防する新たな治療標的となる可能性がある.
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