Morphological and Molecular Characterization of Adult Cardiomyocyte Apoptosis During Hypoxia and Reoxygenation
作者:
Peter Kang,
Armin Haunstetter,
Hiroki Aoki,
Anny Usheva,
Seigo Izumo,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2000)
卷期:
Volume 87,
issue 2
页码: 118-125
ISSN:0009-7330
年代: 2000
出版商: OVID
关键词: caspases;Bcl-2;cytochromec;adenovirus;mitochondria
数据来源: OVID
摘要:
Apoptosis has been implicated in ischemic heart disease, but its mechanism in cardiomyocytes has not been elucidated. In this study, we investigate the effects of hypoxia and reoxygenation in adult cardiomyocytes and the molecular mechanism involved in cardiomyocyte apoptosis. Morphologically, reoxygenation induced rounding up of the cells, appearance of membrane blebs that were filled with marginated mitochondria, and ultrastructural findings characteristic of apoptosis. Reoxygenation (18 hours of reoxygenation after 6 hours of hypoxia) and prolonged hypoxia (24 hours of hypoxia) resulted in a 59% and 51% decrease in cellular viability, respectively. During reoxygenation, cell death occurred predominantly via apoptosis associated with appearance of cytosolic cytochromecand activation of caspase-3 and -9. However, nonapoptotic cell death predominated during prolonged hypoxia. Both caspase inhibition and Bcl-2 overexpression during reoxygenation significantly improved cellular viability through inhibition of apoptosis but had minimal effect on hypoxia-induced cell death. Bcl-2 overexpression blocked reoxygenation-induced cytochromecrelease and activation of caspase -3 and -9, but caspase inhibition alone did not block cytochromecrelease. These results suggest that apoptosis predominates in cardiomyocytes after reoxygenation through a mitochondrion-dependent apoptotic pathway, and Bcl-2 prevents reoxygenation-induced apoptosis by inhibiting cytochromecrelease from the mitochondria and prevents activation of caspase-3 and -9.(Circ Res. 2000;87:118-125.)
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