In this study, we investigate the roles of two apoptotic
endonucleases, CAD and
DNase gamma, in neuronal apoptosis. High expression of CAD, but not
DNase gamma, is detected in proliferating N1E-115
neuroblastoma cells, and apoptotic DNA fragmentation induced by
staurosporine under proliferating conditions is abolished by the expression of a
caspase-resistant form of ICAD. After the induction of neuronal differentiation, CAD disappearance and the induction of
DNase gamma occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation that occurs under differentiating conditions is suppressed by the downregulation of
DNase gamma caused by its
antisense RNA. The induction of
DNase gamma is also observed during neuronal differentiation of PC12 cells, and apoptotic DNA fragmentation induced by
NGF deprivation is inhibited by the antisense-mediated downregulation of
DNase gamma. These observations suggest that DNA fragmentation in neuronal apoptosis is catalyzed by either CAD or
DNase gamma depending on the differentiation state. Furthermore,
DNase gamma is suggested to be involved in naturally occurring apoptosis in developing nervous systems.