Chronic hypoxia induces apoptosis in cardiac myocytes: a possible role for Bcl-2-like proteins.
The effect of prolonged hypoxia as well as the molecular mechanisms on cardiac cell death is not well established. A possible role of Bcl-2 and Bax in hypoxia-induced apoptosis in different cell types has been proposed. Here we demonstrate the effect of hypoxia on the induction of apoptosis and the expression of Bcl-2-like proteins in vivo and in vitro. Hearts from rats exposed to chronic hypoxia (n = 4) showed an increased rate of apoptosis compared to normoxic hearts (n = 4). The induction of apoptosis in hypoxic hearts correlated with a significant decrease of Bcl-2 protein level, whereas Bax protein expression was increased. Exposure of isolated neonatal rat cardiac myocytes to hypoxia also resulted in a significant increase in apoptosis. However, Bcl-2 and Bax protein levels essentially remained unchanged. Our results may suggest a different molecular mechanism of hypoxia-induced apoptosis in vivo and in vitro.
Jung
F
F
Molecular Cardiology, University of Frankfurt, Frankfurt, Germany.
Weiland
U
U
Johns
R A
RA
Ihling
C
C
Dimmeler
S
S
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein