Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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 and Ling Zhao

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Oncotarget. 2017; 8:114428-114441. https://doi.org/10.18632/oncotarget.22826

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Abstract

Huidan Deng1,*, Ping Kuang1,*, Hengmin Cui1,2, Qin Luo1, Huan Liu1, Yujiao Lu1, Jing Fang1,2, Zhicai Zuo1,2, Junliang Deng1,2, Yinglun Li1,2, Xun Wang1,2 and Ling Zhao1,2

1College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China

2Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu 611130, China

*These authors contributed equally to this work

Correspondence to:

Hengmin Cui, email: cui580420@sicau.edu.cn

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

Received: October 17, 2017     Accepted: November 09, 2017     Published: December 01, 2017

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.


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