TY - JOUR
T1 - Some amphiphilic cations block the mitochondrial apoptosis-induced channel, MAC
AU - Martinez-Caballero, Sonia
AU - Dejean, Laurent M.
AU - Kinnally, Kathleen W.
N1 - Funding Information:
This research was supported by NIH Grant GM57249, NSF Grants MCB-0235834 and INT003797to K.W.K. Opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the N.S.F. or N.I.H. We thank Cynthia Hughes and Olgica Chopra for their excellent technical assistance and Evgeny Pavlov (University of Calgary, Canada) and Serg Grigoriev for their suggestions.
PY - 2004/6/18
Y1 - 2004/6/18
N2 - 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 IC50 of 39 μM. In contrast, the IC50 for propranolol and trifluoperazine are 52 and 0.9 μM, 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.
AB - 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 IC50 of 39 μM. In contrast, the IC50 for propranolol and trifluoperazine are 52 and 0.9 μM, 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.
KW - Apoptosis
KW - Bax
KW - Cytochrome c
KW - Ion channel
KW - MAC, mitochondrial apoptosis-induced channel
KW - Mitochondrial apoptosis-induced channel
KW - PTP, permeability transition pore
KW - Patch clamp
KW - Pharmacology
KW - Tim, translocase of the inner membrane
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U2 - 10.1016/j.febslet.2004.05.006
DO - 10.1016/j.febslet.2004.05.006
M3 - Article
C2 - 15196916
AN - SCOPUS:2942620728
SN - 0014-5793
VL - 568
SP - 35
EP - 38
JO - FEBS Letters
JF - FEBS Letters
IS - 1-3
ER -