Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430060, P.R. China.
Oncol Rep. 2021 Feb;45(2):595-605. doi: 10.3892/or.2020.7884. Epub 2020 Dec 8.
Rho family GTPase 3 (RND3) is involved in multiple physiological activities involving the Rho kinase‑dependent 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 Rnd3‑knockout 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 NF‑κB P65. Notably, Rnd3 blocked the anti‑apoptotic action of NF‑κB P65 in vitro by downregulating P65. Therefore, RND3‑NF‑κB 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 RND3‑NF‑κB P65 signaling pathway in the central nervous system.
Rho 家族 GTP 酶 3（RND3）参与涉及 Rho 激酶依赖性信号通路的多种生理活动。本研究揭示了 RND3 在调节大脑细胞凋亡中的新作用。通过免疫荧光和 TUNEL 检测，发现 Rnd3 基因敲除小鼠大脑细胞凋亡率降低。此外，通过 RNA 干扰和过表达实验中的免疫印迹和流式细胞术分析，确定了 RND3 在促进 PC12 细胞凋亡中的作用。此外，本研究通过免疫沉淀分析表明 Rnd3 和 P65 蛋白相互作用，并且 Rnd3 通过与 NF-κB P65 结合来调节细胞凋亡。值得注意的是，Rnd3 通过下调 P65 在体外阻断了 NF-κB P65 的抗凋亡作用。因此，RND3-NF-κB P65 代表了调节大脑细胞凋亡的中枢神经系统中一种新的信号通路。本研究通过调节中枢神经系统中的 RND3-NF-κB P65 信号通路来调节细胞凋亡，为治疗神经退行性疾病提供了一种新的方法。
