Some amphiphilic cations block the mitochondrial apoptosis-induced channel, MAC.
The mitochondrial apoptosis-induced channel (MAC) forms in the outer membrane of mitochondria early in apoptosis and this activity is altered by physiological levels of cytochrome c. While cyclosporine A and lidocaine have no effect, dibucaine induces a fast blockade of MAC with an IC(50) of 39 microM. In contrast, the IC(50) for propranolol and trifluoperazine are 52 and 0.9 microM, respectively, and these drugs likely destabilize the open state of MAC. These agents, and others not yet identified, should be valuable tools in the study of apoptosis. Profiling MAC's pharmacology may generate novel therapeutic regimes for disease.
Martinez-Caballero
Sonia
S
Department of Basic Sciences, College of Dentistry, New York University, 345 East 24th Street, New York, NY 10010, USA.
Dejean
Laurent M
LM
Kinnally
Kathleen W
KW
D017209:Apoptosis; D002412:Cations; D002460:Cell Line; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008928:Mitochondria / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D002412:Cations; D007473:Ion Channels