CYTOLYSIS MEDIATED BY IONOPHORES AND PORE-FORMING AGENTS - ROLE OF INTRACELLULAR CALCIUM IN APOPTOSIS

Apoptosis is a term used to describe certain forms of physiological ce ll death that occur during embryogenesis, differentiation, and normal cell turnover. Previous reports concerning the effects of calcium iono phores on rodent thymocytes and the pore-forming proteins perforin and staphylococcal alpha-toxin on murine tumor cells led to the suggestio n that simply raising intracellular calcium causes apoptotic cell deat h. This hypothesis was tested using two ionophores, A23187 and valinom ycin, and two pore-forming agents, melittin and staphylococcal alpha-t oxin, on four murine tumor cell lines. Although treatment with these a gents could raise intracellular calcium, and in some instances cause D NA fragmentation, only valinomycin caused apoptosis. In contrast to pr evious reports, our results suggest that raising intracellular calcium and inducing internucleosomal DNA fragmentation is not sufficient to elicit apoptotic cell death in all cell types.