Elevated extracellular calcium can prevent apoptosis via the calcium-sensing receptor

Biochem Biophys Res Commun. 1998 Aug 19;249(2):325-31. doi: 10.1006/bbrc.1998.9124.

Abstract

The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (Ca2+o) and transduces signals involved in serum calcium regulation. Expression of CaR protein in tissues with functions unrelated to systemic calcium homeostasis, including the brain, suggests that extracellular calcium (Ca2+o) may act as a first messenger to regulate diverse cellular functions. To test this hypothesis, we examined the effect of increasing Ca2+o on apoptosis induced by Sindbis Virus in AT-3 prostate carcinoma cells. We found a steep increase in cell survival with between 5 and 7 mM added Ca2+o (EC50 = 6.1 mM). Magnesium, a less potent agonist of the calcium sensing receptor, was also protective (EC50 = 23.4 mM). Northern and immunocytochemical analyses confirmed the presence of the CaR message and protein in AT-3 prostate carcinoma cells. Enforced expression of CaR protein by stable transfection in human embryonic kidney (HEK)-293 cells, which normally don't express the receptor, resulted in resistance to SV-induced apoptosis in the presence of elevated Ca2+o. In addition to preventing SV-induced death, elevated Ca2+o also abrogated apoptosis induced by c-Myc overexpression/serum deprivation in rat 1A fibroblasts, and these fibroblasts were shown to express CaR message and protein. Altogether, these observations suggest that Ca2+o can act with the CaR to prevent apoptosis and define a novel mechanism by which calcium ions can regulate cell survival.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Blotting, Northern
  • Calcium / administration & dosage
  • Calcium / pharmacology*
  • Cell Line
  • Embryo, Mammalian
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Kidney
  • Male
  • Prostatic Neoplasms
  • Rats
  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Sindbis Virus / physiology
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Receptors, Calcium-Sensing
  • Receptors, Cell Surface
  • extracellular calcium cation-sensing receptor, rat
  • Calcium