Genetic deletion of Rnd3 suppresses apoptosis through NF­κB signaling in the brain.

ABSTRACT

Rho family GTPase 3 (RND3) is involved in multiple physiological activities involving the Rho kinase­dependent signaling pathway. The present study revealed a novel role of RND3 in the regulation of apoptosis in the brain. Using immunofluorescence and TUNEL assays, a decreased rate of brain apoptosis was observed in Rnd3­knockout mice. In addition, the function of RND3 in promoting apoptosis was determined in PC12 cells by immunoblotting assays and flow cytometry analysis in RNA interference and overexpression experiments. Furthermore, the present study demonstrated that Rnd3 and P65 protein interacted using immunoprecipitation analysis, and Rnd3 regulated apoptosis via its association with NF­κB P65. Notably, Rnd3 blocked the anti­apoptotic action of NF­κB P65 in vitro by downregulating P65. Therefore, RND3­NF­κB P65 represents a novel signaling pathway in the regulation of brain apoptosis. The present study suggested an alternative approach for the treatment of neurodegenerative diseases through regulation of apoptosis via the RND3­NF­κB P65 signaling pathway in the central nervous system.