Ui-Tei K, Nagano M, Sato S, Miyata Y
Department of Pharmacology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
Apoptosis. 2000 Apr;5(2):133-40. doi: 10.1023/a:1009676528805.
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).
本研究旨在利用源自幼虫中枢神经系统的果蝇神经细胞系揭示神经元中的凋亡途径。我们可以通过钙离子载体（A23187）、蛋白激酶抑制剂（H-7）、RNA合成抑制剂（放线菌素D）和蛋白质合成抑制剂（环己酰亚胺）诱导这些细胞发生凋亡性细胞死亡。每种化学物质诱导的所有凋亡都需要钙离子，尽管钙离子的来源不同：A23187诱导的凋亡依赖于细胞外钙离子，而其他三种化学物质诱导的凋亡则利用细胞内钙离子。此外，还发现了对钙调蛋白抑制剂W-7的不同反应：W-7可阻止三种化学物质中的每一种诱导的细胞死亡，但不能阻止A23187诱导的细胞死亡。基于这些结果，我们提出凋亡途径在单个细胞中可分为两种类型。由H-7、放线菌素D或环己酰亚胺诱导的一种途径是钙调蛋白依赖性的（途径H），而由A23187诱导的另一种途径是钙调蛋白非依赖性的（途径A）。
