ROS‐dependent caspase‐9 activation in hypoxic cell death

FEBS Letters

Kim, Jee-Youn¹  Park, Jae-Hoon¹ 

[1] Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130-701, South Korea

关键词: Hypoxia;    Caspase-9;    Cytochrome c;    Reactive oxygen species;    Apoptosis;    Mitochondrion;    AIF;    apoptosis-inducing factor;    Apaf-1;    apoptotic protease activating factor-1;    BA;    bonkrekic acid;    CsA;    cyclosporin A;    DCFH-DA;    dichlorodihydrofluorescein diacetate;    MMP;    mitochondrial membrane potential;    NAC;    N-acetylcysteine;    PT;    permeability transition;    PTP;    permeability transition pore;    ROS;    reactive oxygen species;   

DOI  :  10.1016/S0014-5793(03)00795-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Mitochondria are known to play a fundamental role in apoptosis by releasing apoptogenic molecules such as cytochrome c into the cytoplasm, thereby sequentially activating initiator caspase-9. However, the mechanisms of cytochrome c release or caspase-9 activation in response to hypoxia are unclear. In this report, we show that caspase-9 is activated by reactive oxygen species (ROS) without involvement of cytochrome c release in hypoxic injury. In addition, activated caspase-9 induces permeability transition (PT)-independent cytochrome c release, suggesting that caspase-9 may disrupt mitochondrial diffusion limit of cytochrome c and serve to amplify further release of cytochrome c.

【 授权许可】

Unknown