title: Initiation of mitochondrial-mediated apoptosis during cardiac reperfusion.
abstract: Reperfusion of myocardial tissue can result in programmed cell death. Nevertheless, relatively little information exists concerning pathways initiated in vivo that ultimately commit cardiac cells to apoptosis during ischemia/reperfusion. The goal of the present study was to determine whether mitochondrial-mediated mechanisms of apoptosis are initiated during in vivo cardiac ischemia/reperfusion. We provide evidence that the content of cytochrome c in the cytosol increases exclusively during reperfusion. Over the same time interval Bax, a pro-apoptotic protein implicated in release of cytochrome c from mitochondria, was found to disappear from cytosolic extracts. This was associated with the appearance of tightly associated Bax in the mitochondrial fraction. Cytochrome c from reperfused cytosolic extracts is present as a high molecular weight oligomer consistent with formation of the apoptosome. In addition, pro-caspase-9 was found to disappear exclusively during reperfusion. Therefore, the results of the current study indicate that the mitochondrial-mediated pathway of apoptosis is initiated as a result of in vivo cardiac ischemia/reperfusion.
authors.affiliation: Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4907, USA.
authors.forename: Kathleen Corrigan
authors.initials: KC
authors.lastname: Lundberg
authors.forename: Luke I
authors.initials: LI
authors.lastname: Szweda
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D008929:Mitochondria, Heart / Q000473:pathology; D015425:Myocardial Reperfusion; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015424:Reperfusion; D015427:Reperfusion Injury; D013997:Time Factors; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases