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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Sodium fluoride induces apoptosis in mouse splenocytes by activating ROS-dependent NF-κB signaling
Huidan Deng1, Ping Kuang1, Hengmin Cui1,2
1College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China.
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.
Insights
Sodium fluoride exposure causes DNA damage and cell death in mouse immune cells. This occurs through increased reactive oxygen species (ROS) and nuclear factor-kappa B (NF-κB) signaling pathways.
Area of Science:
- Immunotoxicology
- Cellular and Molecular Toxicology
Background:
- Sodium fluoride (NaF) is an environmental contaminant with known toxic effects.
- The mechanisms underlying NaF-induced cellular damage, particularly in immune cells, require further elucidation.
Purpose of the Study:
- To investigate the roles of reactive oxygen species (ROS) and nuclear factor-kappa B (NF-κB) signaling in sodium fluoride-induced DNA damage and apoptosis in mouse splenocytes.
Main Methods:
- Mice were administered varying doses of sodium fluoride (12, 24, or 48 mg/kg) via intragastric gavage.
- Splenocytes were analyzed for DNA fragmentation, apoptosis, ROS levels, and expression of key proteins in the NF-κB pathway and apoptosis-related proteins at 21 and 42 days post-treatment.
Main Results:
- Sodium fluoride exposure led to a time- and dose-dependent increase in DNA fragmentation and apoptosis in mouse splenocytes.
- Elevated ROS levels were observed, correlating with increased phosphorylated IκB kinase and NF-κB p65, and decreased inhibitory kappa B protein.
- NaF-treated splenocytes exhibited increased expression of pro-apoptotic proteins (Bim, Bax, Bak, caspase-3, PARP) and decreased expression of anti-apoptotic proteins (Bcl-2, Bcl-xL).
Conclusions:
- Sodium fluoride induces apoptosis in mouse splenocytes.
- This apoptosis is mediated by enhanced ROS production and subsequent activation of the NF-κB signaling pathway.
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