Initiation of mitochondrial-mediated apoptosis during cardiac reperfusion |
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Authors: | Lundberg Kathleen Corrigan Szweda Luke I |
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Affiliation: | Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106-4907, USA. |
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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. |
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Keywords: | Apoptosis Ischemia Reperfusion Mitochondria Heart Cytochrome c Bax |
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