Abstract
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.
MeSH terms
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Animals
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Apoptosis
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Cell Membrane Permeability
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Cells, Cultured
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Erythrocytes / cytology
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Fluoresceins / metabolism
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Hemolysis
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Humans
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Hydrogen-Ion Concentration
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Ion Channels / physiology*
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Lipid Bilayers
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Liposomes
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Membrane Potentials
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Neurons / cytology
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Patch-Clamp Techniques
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Proto-Oncogene Proteins / pharmacology
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Sheep
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Sympathetic Nervous System / cytology
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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Fluoresceins
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Ion Channels
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Lipid Bilayers
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Liposomes
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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6-carboxyfluorescein