Abstract
Although there is evidence that changes in cellular ionic concentrations are important early events in apoptosis, the regulation of ion fluxes across the plasma membrane during this process is poorly understood. We report here that Bcl-2 overexpression results in up-regulation of capacitative Ca2+ entry (CCE) and that SKF-96365, an inhibitor of CCE, is a potent inducer of apoptosis. Cells that overexpress Bcl-2 are resistant to SKF-96365-mediated apoptosis and to its inhibition of CCE. Enhanced CCE can be reversed with ouabain, suggesting that Bcl-2-associated plasma membrane hyperpolarization plays a role in up-regulating CCE and may partially explain the antiapoptotic effect of Bcl-2.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Apoptosis / drug effects
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Apoptosis / physiology*
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Calcium / metabolism*
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Calcium / physiology
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Calcium Channel Blockers / pharmacology*
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Calcium Channels / physiology
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Dose-Response Relationship, Drug
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Drug Resistance
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Electric Conductivity
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Electric Impedance
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Endoplasmic Reticulum / drug effects
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Endoplasmic Reticulum / metabolism
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Enzyme Inhibitors / pharmacology
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HL-60 Cells / drug effects
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HL-60 Cells / metabolism
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HL-60 Cells / physiology
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Humans
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Imidazoles / pharmacology*
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Jurkat Cells / drug effects
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Jurkat Cells / metabolism
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Jurkat Cells / physiology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Ouabain / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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Thapsigargin / pharmacology
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Transfection
Substances
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Calcium Channel Blockers
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Calcium Channels
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Enzyme Inhibitors
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Imidazoles
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Proto-Oncogene Proteins c-bcl-2
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Ouabain
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Thapsigargin
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1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
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Calcium