Role of extracellular calcium and calcium stores in the intracellular calcium rise induced by diethylstilboestrol in C6 rat glioma cells

Abstract

The aneuploidy-inducing carcinogenic oestrogen diethylstilboestrol (DES) causes an elevation of the cytoplasmic Ca 2+ concentration of C6 rat glioma cells. It is known that the intracellular calcium concentration is a critical factor in mitosis. DES induces mitotic disturbances resulting in aneuploidy; the mechanisms of these events are still largely unknown. It is therefore important to identify the calcium source for the DES-mediated calcium rise. Experiments with isolated rat liver mitochondria showed no release of calcium after DES treatment. However, DES releases calcium from the same stores as the tumour promotor thapsigargin, which are the inositol 1,4,5-triphosphate- and GTP-sensitive Ca 2+ stores. In contrast to DES, thapsigargin also induces a calcium influx into the cell. Administration of DES following thapsigargin treatment strongly reduced the thapsigargin-mediated calcium entry. Furthermore, DES inhibits the decay of the ionomycin-induced calcium signal, suggesting an interference of DES with the extrusion of calcium from the cell. In conclusion, thapsigargin and DES both cause release of calcium from the endoplasmic reticulum. However, for each compound the prolongation of the calcium signal is based on different mechanisms.