Bcl-2 overexpression results in enhanced capacitative calcium entry and resistance to SKF-96365-induced apoptosis.
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.
Williams
S S
SS
Department of Radiation Oncology, Stanford University School of Medicine, California 94305-5302, USA.
French
J N
JN
Gilbert
M
M
Rangaswami
A A
AA
Walleczek
J
J
Knox
S J
SJ
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004553:Electric Conductivity; D017097:Electric Impedance; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007093:Imidazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D010042:Ouabain; D019284:Thapsigargin; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium