Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+

M. C. Marin, A. Fernandez, R. J. Bick, S. Brisbay, L. M. Buja, M. Snuggs, D. J. McConkey, A. C. Von Eschenbach, M. J. Keating, T. J. McDonnell

Research output: Contribution to journalArticle

Abstract

Bcl-2 expression is associated with the progression of prostate cancer from androgen-dependence to androgen-independence. Bcl-2 is an integral membrane protein which localizes to mitochondria, endoplasmic reticulum, and the nuclear envelope. Using spectrofluorometry and laser confocal microscopy, the ability of bcl-2 to intracellular Ca2+ was examined in the G prostate carcinoma cell line following apoptosis induction by adriamycin. Adriamycin and thapsigargin, an endoplasmic reticulum Ca2+-pump inhibitor, were effective inducers of apoptosis in control, but not bcl-2 transfected, cells. Treatment with adriamycin was accompanied by a sustained rise in cytoplasmic Ca2+ in control and bcl-2 transfected cells. An increase in intranuclear Ca2+ was observed in control cells only. Apoptosis induction by thapsigargin was associated with an increase in cytoplasmic Ca2+ in control cells that was not detected in the resistant bcl-2 transfectants. Ca2+ was excluded from nuclei isolated from bcl-2 expressing cells, but was sequestered in control nuclei, following the addition of ATP. These findings suggest that bcl-2 may regulate levels of intranuclear Ca2+ independently of cytosolic Ca2+ levels. The ability of bcl-2 to modulate, directly or indirectly, sustained increases in both cytosolic and intranuclear Ca2+ may provide a common basis for bcl-2 function in different subcellular compartments.

Original languageEnglish (US)
Pages (from-to)2259-2266
Number of pages8
JournalOncogene
Volume12
Issue number11
StatePublished - Jul 5 1996
Externally publishedYes

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Keywords

  • Apoptosis
  • Bcl-2
  • Calcium
  • Cell death

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Marin, M. C., Fernandez, A., Bick, R. J., Brisbay, S., Buja, L. M., Snuggs, M., McConkey, D. J., Von Eschenbach, A. C., Keating, M. J., & McDonnell, T. J. (1996). Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+. Oncogene, 12(11), 2259-2266.