Effects of endothelin-1 on mitochondrial function during the protection against myocardial cell apoptosis.
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 H(2)O(2)-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 H(2)O(2)-induced decrease of membrane potential. However, endothelin-1 was unable to reverse the H(2)O(2)-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.
Iwai-Kanai
Eri
E
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Hasegawa
Koji
K
Adachi
Souichi
S
Fujita
Masatoshi
M
Akao
Masaharu
M
Kawamura
Teruhisa
T
Kita
Toru
T
D000818:Animals; D017209:Apoptosis; D002316:Cardiotonic Agents / Q000494:pharmacology; D004579:Electron Transport / Q000187:drug effects; D019332:Endothelin-1 / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects
D002316:Cardiotonic Agents; D019332:Endothelin-1; D006861:Hydrogen Peroxide