ROS-dependent caspase-9 activation in hypoxic cell death.
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.
Kim
Jee-Youn
JY
Department of Pathology, College of Medicine, Kyung Hee University, Seoul 130-701, South Korea.
Park
Jae-Hoon
JH
D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D015687:Cell Hypoxia; D002460:Cell Line; D002463:Cell Membrane Permeability; D045304:Cytochromes c / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007425:Intracellular Membranes; D008407:Mast Cells / Q000166:cytology; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D045304:Cytochromes c; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases