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缺血的条件付けは,抗死遺伝子Bcl-2を上調することで,アポトーシスを減少させます
N Maulik1, R M Engelman, J A Rousou
1Department of Surgery, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA. nmaulik@panda.uchc.edu
Circulation
|November 24, 1999
まとめ
缺血的予備条件は,NF-kappaBを活性化し,活性酸素種を含むBCL-2を上調することで心臓を保護します. このプロセスは,心筋細胞のアポトーシスと心筋梗塞を減少させます.
科学分野:
- 心血管科学の研究について
- 分子心臓病学 分子心臓病学
- セルラー・シグナリング
背景:
- 発血性再流傷は,心筋細胞のアポトーシスとBcl-2遺伝子のダウンレギュレーションを引き起こします.
- 缺血予備条件付け (PC) は,チロシンキナーゼ,p38 MAP キナーゼ,NF-カッパBシグナル伝達を通じてアポプトーシスを減少させます.
- 反応性酸素種 (ROS) は,NF-kappaBの感受性とBcl-2の抗酸化作用のために関与しています.
研究 の 目的:
- 発血前条件化の保護信号経路における活性酸素種とNF-kappaBの役割を調査する.
- ROSとNF-kappaBがPCによる心筋細胞アポトーシスおよび心筋梗塞の減少を媒介するかどうかを判断する.
主な方法:
- 孤立したネズミの心臓は,ヒドロキシルラジカルスキャベンジャー (DMTU) またはNF-kappaB阻害剤 (SN50) を含め,または含めずに,イシュケミア/再輸を受けた.
- プリコンディショニングは,持続的なグローバル・イシュケミアと再注射の前に,繰り返された短期のイシュケミア/再注射エピソードを含む.
- クレアチンキナーゼの放出,マロナルデヒド,心臓発作の大きさ,アポトーシス,DNAの断片化,NF-kappaBの活性化,Bcl-2の発現を評価した.
主要な成果:
- PCは,心筋梗塞と心筋細胞アポトシスを有意に減少させました.
- PCの心臓保護効果はDMTUとSN50.0によって廃止されました.
- PCはBcl-2を上位調節し,その効果はDMTUとSN50.0によって部分的に阻害された.
- イシュケミア/再注射とPCの両方がNF-kappaBを活性化させ,PC心臓におけるより高い活性化をもたらした.
結論:
- 反応性酸素種は,NF-kappaB.B.を含むPC媒介信号伝導に不可欠です.
- PCによるNF-kappaBの活性化は,単純なイシュケミア/リパーフュージョンよりも高く,アポトーシスの減少と相関しています.
- 抗酸化物質遺伝子Bcl-2のアップレギュレーションは,PCによって達成される心筋細胞アポトーシスの減少と逆に関連しています.
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