Effect of glucocorticosteroid treatment on intracellular calcium homeostasis in mouse lymphoma cells

Mol Endocrinol. 1993 May;7(5):686-93. doi: 10.1210/mend.7.5.8316252.


There is growing evidence for the involvement of Ca2+ in the programmed cell death (apoptosis) of lymphocytes, but the nature of glucocorticoid-induced Ca2+ fluxes and their role in the cell death pathway are poorly understood. In the study reported here, we assessed the effect of glucocorticoid treatment on intracellular Ca2+ homeostasis in W7MG1 mouse lymphoma cells. Levels of cytosolic Ca2+ were measured using the intracellular Ca2+ indicator fura2 AM, and total cellular Ca2+ was measured by atomic absorbance spectroscopy. The level of Ca2+ within internal stores, including the endoplasmic reticulum (ER), was estimated by measuring the increase in cytosolic Ca2+ induced by either ionomycin, an ionophore that mobilizes Ca2+ from a variety of internal stores, and by thapsigargin, a specific inhibitor of the ER-associated Ca(2+)-ATPase that mobilizes Ca2+ from the ER. Glucocorticoid treatment induced a significant decrease in ionomycin- and thapsigargin-mobilizable Ca2+ stores that was accompanied by an initial decrease in total cellular Ca2+, followed by a modest increase in both total cellular Ca2+ and cytosolic Ca2+. The glucocorticoid-induced depletion of internal Ca2+ stores was receptor mediated and occurred after a delay corresponding to the time required for glucocorticoid receptor complexes to regulate gene transcription. Mobilization of ER-associated Ca2+ stores by thapsigargin treatment induced DNA fragmentation and cell death similar to that observed after glucocorticoid treatment. These findings suggest that a mobilization of Ca2+ from internal stores may be a critical step in the apoptotic pathway of mouse lymphoma cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Calcium / metabolism*
  • Cytosol / metabolism
  • DNA / metabolism
  • Dexamethasone / pharmacology*
  • Fluorescent Dyes
  • Fura-2
  • Homeostasis / drug effects*
  • Ionomycin / pharmacology
  • Kinetics
  • Lymphoma / metabolism*
  • Mice
  • Terpenes / pharmacology
  • Thapsigargin
  • Tumor Cells, Cultured


  • Fluorescent Dyes
  • Terpenes
  • Ionomycin
  • Thapsigargin
  • Dexamethasone
  • DNA
  • Calcium
  • Fura-2