Calmodulin-dependent and -independent apoptosis in cell of a Drosophila neuronal cell line.
This study was undertaken to reveal apoptotic pathways in neurons using a Drosophila 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 (actinomycin D) and a protein synthesis inhibitor (cycloheximide). All the apoptosis induced by each chemical required Ca2+ ions, although the origin of Ca2+ ions were different: apoptosis induced by A23187 was dependent on extracellular Ca2+ ions whereas those by the other three chemicals utilized intracellular Ca2+ ions. Furthermore, different reactions to W-7, a calmodulin inhibitor, 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 pathways are classified into two types in individual cells. One pathway induced by H-7, actinomycin D or cycloheximide is calmodulin-dependent (pathway H), and another induced by A23187 is calmodulin-independent (pathway A).
Department of Pharmacology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan. tei@nms.ac.jp
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Ui-Tei
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Nagano
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Sato
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Miyata
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000166:cytology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D007476:Ionophores; D011500:Protein Synthesis Inhibitors; D013449:Sulfonamides; D003609:Dactinomycin; D000001:Calcimycin; D004533:Egtazic Acid; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D020169:Caspases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium