Inhibition of Bax channel-forming activity by Bcl-2.
Proteins of the Bcl-2 family are intracellular membrane-associated proteins that regulate programmed cell death (apoptosis) either positively or negatively by as yet unknown mechanisms. Bax, a pro-apoptotic member of the Bcl-2 family, was shown to form channels in lipid membranes. Bax triggered the release of liposome-encapsulated carboxyfluorescein at both neutral and acidic pH. At physiological pH, release could be blocked by Bcl-2. Bcl-2, in contrast, triggered carboxyfluorescein release at acidic pH only. In planar lipid bilayers, Bax formed pH- and voltage-dependent ion-conducting channels. Thus, the pro-apoptotic effects of Bax may be elicited through an intrinsic pore-forming activity that can be antagonized by Bcl-2.
Antonsson
B
B
Geneva Biomedical Research Institute, Glaxo Wellcome R&D S. A., 1288 Plan les Ouates, Geneva, Switzerland. beau6063@ggr.co.uk
Conti
F
F
Ciavatta
A
A
Montessuit
S
S
Lewis
S
S
Martinou
I
I
Bernasconi
L
L
Bernard
A
A
Mermod
J J
JJ
Mazzei
G
G
Maundrell
K
K
Gambale
F
F
Sadoul
R
R
Martinou
J C
JC
D000818:Animals; D017209:Apoptosis; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004912:Erythrocytes / Q000166:cytology; D005452:Fluoresceins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology*; D008051:Lipid Bilayers; D008081:Liposomes; D008564:Membrane Potentials; D009474:Neurons / Q000166:cytology; D018408:Patch-Clamp Techniques; D011518:Proto-Oncogene Proteins / Q000494:pharmacology / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D012756:Sheep; D013564:Sympathetic Nervous System / Q000166:cytology; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D005452:Fluoresceins; D007473:Ion Channels; D008051:Lipid Bilayers; D008081:Liposomes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C024098:6-carboxyfluorescein