Sodium fluoride induces apoptosis in mouse splenocytes by activating ROS-dependent NF-κB signaling

Huidan Deng; Ping Kuang; Hengmin Cui; Qin Luo; Huan Liu; Yujiao Lu; Jing Fang; Zhicai Zuo; Junliang Deng; Yinglun Li; Xun Wang; Ling Zhao

doi:10.18632/oncotarget.22826

Sodium fluoride induces apoptosis in mouse splenocytes by activating ROS-dependent NF-κB signaling

Oncotarget. 2017 Dec 1;8(70):114428-114441. doi: 10.18632/oncotarget.22826. eCollection 2017 Dec 29.

Authors

Huidan Deng^#¹, Ping Kuang^#¹, Hengmin Cui^{1

2}, Qin Luo¹, Huan Liu¹, Yujiao Lu¹, Jing Fang^{1

2}, Zhicai Zuo^{1

2}, Junliang Deng^{1

2}, Yinglun Li^{1

2}, Xun Wang^{1

2}, Ling Zhao^{1

2}

Affiliations

¹ College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.
² Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu 611130, China.

^# Contributed equally.

Abstract

In this study, we investigated the roles of reactive oxygen species (ROS) and nuclear factor-κB (NF-κB) signaling in sodium fluoride-induced DNA damage and apoptosis in mouse splenocytes. Intragastric administration of 12, 24 or 48 mg/kg sodium fluoride resulted in a time- and dose-dependent increase in DNA fragmentation and apoptosis in mouse splenocytes on days 21 and 42. High ROS levels correlated with increased levels of phosphorylated IκB kinase and NF-κB p65 and decreased levels of inhibitory kappa B protein in splenocytes from mice treated with sodium fluoride. Moreover, splenocytes from sodium fluoride-treated mice showed high expression of pro-apoptotic proteins, including Bim, Bax, Bak, caspase-3 and poly ADP-ribose polymerase, and low expression of the anti-apoptotic proteins BcL-2 and BcL-xL. These results show that sodium fluoride induces apoptosis in mouse splenocytes by enhancing ROS-dependent NF-κB signaling.

Keywords: DNA damage; Gerotarget; NF-κB pathway; ROS; apoptosis; sodium fluoride.