Caspase-9-dependent nuclear translocation of cytochrome c in hypoxic injury.
OBJECTIVE
Hypoxia signals the release of cytochrome c from mitochondria as well as sequential activation of caspase-9 and caspase-3 in the pathway to apoptosis. In this report, we describe novel mechanisms governing the nuclear translocation of cytochrome c during hypoxia-induced apoptosis in neuroepithelioma, SK-N-MC cells.


METHODS
This work focuses on an investigation of the mechanism of cytochrome c translocation by means of immunocytochemistry, cell fractionation, Western blot and caspase assay.


RESULTS
Using immunocytochemistry and subcellular fractionation, we found that caspase-9 activation precedes cytochrome c release and translocation. Inhibition of caspase-9 activity blocked these responses to hypoxia. Previous studies suggest a key role for c-Jun N-terminal kinase (JNK) in apoptosis regulation and accordingly we found that JNK activation was essential for caspase-9 activation and nuclear translocation of cytochrome c.


CONCLUSIONS
In this report, we describe novel mechanisms of caspase-9-dependent nuclear translocation of cytochrome c in hypoxic injury.
Department of Pathology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Jee-Youn
JY
Kim
Yong-Jun
YJ
Kim
Kum-Ok
KO
Seok
Sun
S
Lee
Jae-Hoon
JH
Park
D017209:Apoptosis / Q000502:physiology; D001693:Biological Transport, Active; D053453:Caspase 9 / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; C506433:CASP9 protein, human; D053453:Caspase 9