Role of apoptosis-inducing factor in myocardial cell death by ischemia-reperfusion.
Although apoptosis contributes to myocardial cell death in the ischemia-reperfused heart, the molecular basis of apoptosis is poorly understood. Apoptosis-inducing factor (AIF) has been characterized as a caspase-independent death effector. Upon the induction of apoptosis, mitochondrial AIF is released to the cytoplasm and then enters the nucleus, in which it induces chromatin condensation and 50 kbp DNA fragmentation. In the present study, we examined the role of AIF in ischemia-reperfusion injury in isolated rat hearts. AIF was detected in the cytosolic and nuclear fractions of hearts subjected to ischemia-reperfusion, whereas it was detected only in the mitochondria of control hearts. Moreover, AIF release increased in a reperfusion time-dependent manner. Pulse field gel electrophoresis revealed that 50 kbp DNA fragments were produced by ischemia/reperfusion. In contrast, cytochrome c release and the activation of caspase-3 did not occur to a significant extent. Moreover, ischemic preconditioning attenuated the AIF release and the 50 kbp DNA fragmentation. These results suggest that AIF-dependent apoptosis is likely to attribute to myocardial cell death in the ischemia-reperfused heart and that it is related with the protective effect of ischemic preconditioning.
Kim
Gi-Tae
GT
Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, South Korea.
Chun
Yang-Sook
YS
Park
Jong-Wan
JW
Kim
Myung-Suk
MS
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor; D053148:Caspase 3; D020169:Caspases / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003574:Cytochrome c Group / Q000032:analysis; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D005420:Flavoproteins / Q000032:analysis / Q000502:physiology*; D019194:Ischemic Preconditioning; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
C494831:Aifm1 protein, rat; D051033:Apoptosis Inducing Factor; D003574:Cytochrome c Group; D005420:Flavoproteins; D008565:Membrane Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases