Roles of cytoplasmic Ca2+ and intracellular Ca2+ stores in induction and suppression of apoptosis in S49 cells

Am J Physiol. 1997 Apr;272(4 Pt 1):C1241-9. doi: 10.1152/ajpcell.1997.272.4.C1241.


The Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid, depleted intracellular Ca2+ stores, induced large increases in intracellular Ca2+ concentration, and caused apoptosis in S49 cells. Removal of extracellular Ca2+ augmented apoptosis due to thapsigargin, indicating that depletion of Ca2+ from intracellular stores is responsible for apoptosis with this agent. Overexpression of the apoptosis suppressor, Bcl-2, inhibited apoptosis due to thapsigargin but did not affect thapsigargin-induced Ca2+ signaling. Dexamethasone induced apoptosis, diminished the size of the endoplasmic reticulum Ca2+ pool, and caused a small elevation of intracellular Ca2+. However, this elevation was not due to Ca2+ influx because the increase was similar in the presence or absence of Ca2+ in the medium. Furthermore, in contrast to the results with thapsigargin, apoptosis due to dexamethasone was unchanged in a Ca2+-free medium. These results indicate that depletion of Ca2+ stores initiates a pathway leading to apoptosis. Elevations in cytoplasmic Ca2+ appears to play a lesser role than previously thought in the actions of Bcl-2 and glucocorticoids.

MeSH terms

  • Apoptosis / physiology*
  • Calcium / metabolism*
  • Calcium / physiology*
  • Cell Line, Transformed / drug effects
  • Cytoplasm / metabolism*
  • Dexamethasone / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Glucocorticoids / pharmacology
  • Indoles / pharmacology
  • Intracellular Membranes / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction
  • Thapsigargin / pharmacology


  • Enzyme Inhibitors
  • Glucocorticoids
  • Indoles
  • Proto-Oncogene Proteins c-bcl-2
  • Thapsigargin
  • Dexamethasone
  • Calcium
  • cyclopiazonic acid