Calmodulin-dependent and -independent apoptosis in cells of a Drosophila neuronal cell line

This study was undertaken to reveal apoptotic pathways in neurons using a D rosophila neuronal cell line derived from larval central nervous system. We could induce apoptotic cell death in the cells by a Ca2+ ionophore (A23187 ), a protein kinase inhibitor (H-7), an RNA synthesis inhibitor (actinomyci n D) and a protein synthesis inhibitor (cycloheximide). All the apoptosis i nduced by each chemical required Ca2+ ions, although the origin of Ca2+ ion s were different: apoptosis induced by A23187 was dependent on extracellula r Ca2+ ions whereas those by the other three chemicals utilized intracellul ar Ca2+ ions. Furthermore, different reactions to W-7, a calmodulin inhibit or, were found: W-7 prevented the cell death by each of the three chemicals but not by A23187. Based on the results, we proposed that the apoptotic pa thways are classified into two types in individual cells. One pathway induc ed by H-7, actinomycin D or cycloheximide is calmodulin-dependent (pathway H), and another induced by A23187 is calmodulin-independent (pathway A).