Calcium chelators induce apoptosis--evidence that raised intracellular ionised calcium is not essential for apoptosis.

A moderate sustained rise in intracellular ionised calcium has been observed to be associated with apoptosis occurring in many experimental systems. The application of extracellular and intracellular chelators of calcium has been reported to produce a decrease in apoptosis, while the addition of calcium ionophores often increases apoptosis. These findings, together with the observation of calcium-induced internucleosomal DNA cleavage in isolated nuclei, have suggested that DNA cleavage (and apoptosis) is a calcium-dependent process. However, a number of studies have shown that apoptosis is not always associated with a rise in the level of intracellular ionised calcium. In the present study, calcium chelators were found to induce apoptosis in cultured cells, concomitant with a decrease in both intracellular ionised calcium and total cell calcium content. Decreased intracellular ionised magnesium was also induced by extracellular chelators. These findings provide further evidence that a raised intracellular ionised calcium is not universally present during the induction of apoptosis. It is proposed that loss of calcium homeostasis, rather than a sustained rise in cytosolic calcium, is a determining factor in cell death by apoptosis.

Spontaneous apoptosis in NS-1 myeloma cultures: effects of cell density, conditioned medium and acid pH.

Apoptosis is a form of cell death which plays an important role in many biological processes including the regulation of B and T lymphocyte functions. We report here the spontaneous development of extensive apoptosis in cultures of the NS-1 mouse myeloma cell line following overgrowth. The apoptosis was identified by both its ultrastructural features and its DNA fragmentation pattern. High cell density and conditioned medium, but not acid pH, were found to be major inducers of apoptosis in this experimental system.