Effects of endothelin-1 on mitochondrial function during the protection against myocardial cell apoptosis

被引:10
作者
Iwai-Kanai, E
Hasegawa, K [1 ]
Adachi, S
Fujita, M
Akao, M
Kawamura, T
Kita, T
机构
[1] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan
[2] Kyoto Univ, Grad Sch Med, Dept Pediat, Kyoto, Japan
[3] Kyoto Univ, Coll Med Technol, Kyoto 606, Japan
关键词
apoptosis; endothelin-1; cardiac myocyte mitochondrion;
D O I
10.1016/S0006-291X(03)00839-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Endothelin-1 is a potent survival factor against myocardial cell apoptosis. While apoptotic stimuli often perturb mitochondrial function by decreasing the membrane potential as well as oxygen consumption, it is unknown whether ET-1 can rescue such perturbation by apoptotic stimuli. Administration of endothelin-1 inhibited the H2O2-induced release of cytochrome c from mitochondria to the cytosol in cardiac myocytes, indicating the involvement of the mitochondria-dependent pathway in the anti-apoptotic effect of endothelin-1. We showed here by cytofluorimetric analysis that endothelin-1 prevented the H2O2-induced decrease of membrane potential. However, endothelin-1 was unable to reverse the H2O2-mediated decrease in oxygen consumption and electron transport in the mitochondria of cardiac myocytes. Endothelin-1 was unable to rescue cardiac myocytes from apoptosis when administered after the decrease in mitochondrial membrane potential. These data suggest that endothelin-1 does not target the mitochondrial respiratory chain, but rather stabilizes the mitochondrial membrane during the protection against apoptosis. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:898 / 903
页数:6
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