Research Paper Volume 8, Issue 12 pp 3552—3567
Sodium fluoride (NaF) induces the splenic apoptosis via endoplasmic reticulum (ER) stress pathway in vivo and in vitro
- 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China
- 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Ya’an 625014, China
Received: November 15, 2016 Accepted: December 20, 2016 Published: December 27, 2016
https://doi.org/10.18632/aging.101150How to Cite
Abstract
At present, there are no reports on the relationship between fluoride-induced apoptosis and endoplasmic reticulum (ER) stress (ER stress) in the spleen of human and animals in vivo and in vitro. Therefore, the aim of this study was to define sodium fluoride (NaF)-induced apoptosis mediated by ER stress in the spleen of mice in vivo and in vitro. Apoptosis and expression levels of the ER stress-related proteins were detected by flow cytometry and western blot, respectively. The results showed that NaF treatment increased lymphocytes apoptosis, which was consistent with NaF-caused ER Stress. NaF-caused ER stress was characterized by up-regulating protein expression levels of glucose-regulated protein 78 (BiP) and glucose-regulated protein 94 (GRP94), and by activating unfolded protein response (UPR). The signaling pathway of ER stress-associated apoptosis was activated by up-regulating protein expression levels of cleaved cysteine aspartate specific protease-12 (cleaved caspase-12), growth arrest and DNA damage-inducible gene 153 (Gadd153/CHOP) and phosphorylation of JUN N-terminal kinase (p-JNK). Additionally, our in vitro study found that apoptotic rate was decreased with remarkable down-regulation of the cleaved caspase-12, CHOP, p-JNK after ER stress was inhibited by 4-Phenylbutyric acid (4-PBA) treatment. In conclusion, NaF-induced apoptosis may mediated by ER stress in the spleen.