Differential DNases are selectively used in neuronal apoptosis depending on the differentiation state

Abstract

In this study, we investigate the roles of two apoptotic endonucleases, CAD and DNase γ, in neuronal apoptosis. High expression of CAD, but not DNase γ, 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 γ occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation that occurs under differentiating conditions is suppressed by the downregulation of DNase γ caused by its antisense RNA. The induction of DNase γ 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 γ. These observations suggest that DNA fragmentation in neuronal apoptosis is catalyzed by either CAD or DNase γ depending on the differentiation state. Furthermore, DNase γ is suggested to be involved in naturally occurring apoptosis in developing nervous systems. © 2004 Nature Publishing Group All rights reserved.