ミトコンドリアのチオレドキシン還元酵素は,早期の発血後の心筋膜の保護に不可欠です
Jan Horstkotte1, Tamara Perisic, Manuela Schneider
1Medizinische Klinik und Poliklinik I, Munich Heart Alliance, Klinikum Grosshadern of the Ludwig Maximilians-University, Munich, Germany.
Circulation
|December 7, 2011
まとめ
ミトコンドリアのチオレドキシン還元酵素-2 (Txnrd2) は,イシュケミアと再注射後の損傷から心臓を保護します. Txnrd2の喪失は心臓の損傷を悪化させるが,抗酸化物質と毛穴遮断剤は助けとなる.
科学分野:
- 心臓病学 心臓病学
- ミトコンドリア生物学
- オキシダティブ・ストレスは,
背景:
- 過剰な反応性酸素種 (ROS) は,心筋不全/再輸血中に組織損傷を引き起こす.
- ミトコンドリアのROSは,有害なミトコンドリアの透過性の移行ポールを誘発する可能性があります.
- ミトコンドリアのチオレドキシン還元酵素-2 (Txnrd2) を含むチオレドキシンは,心臓の抗酸化防御に不可欠です.
研究 の 目的:
- ミトコンドリアのチオレドキシン還元酵素 (Txnrd2) が心筋動脈不全/再注射損傷に対する保護的役割を調査する.
- 心臓の保護におけるTxnrd2の機能の基礎となるメカニズムを理解する.
主な方法:
- マウスにおけるTxnrd2欠乏症の調査は,α-MHC制限のCre媒介デリレーションを用いて行われました.
- 保護剤としてN-アセチルシステイン (ROS scavenger) とサイクロスポリンA (ポアブロック) を利用した.
- 低酸素/低酸素化の条件下で,心筋細胞を含む様々な細胞タイプにおけるTxnrd2の機能を調べました.
主要な成果:
- Txnrd2欠乏症は,マウスの乳房収縮機能不全と心臓筋細胞死亡を悪化させた.
- ミトコンドリアの整合性と機能は,Txnrd2欠乏した心臓では損なわれていましたが,N-アセチルシステインまたはサイクロスポリンAで改善されました.
- 異なる細胞モデルにおけるTxnrd2のデリレーションは,N-アセチルシステインが投与された場合を除き,低酸素/リオキシゲネーション中に細胞死亡を増加させた.
結論:
- Txnrd2は,チオルを再生することによって,発血後の再注血に重要な役割を果たします.
- Txnrd2は,ミトコンドリアのROSを減らすことにより,ミトコンドリアの透過性移行の孔を開くのを防ぐことができます.
- この発見は,Txnrd2を,心筋不全/再注射損傷の潜在的な治療標的として強調しています.
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