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The role of PERK and IRE1 signaling pathways in excessive fluoride mediated impairment of lymphocytes in rats' spleen in vivo and in vitro

Published on May 1, 2019in Chemosphere5.108
· DOI :10.1016/j.chemosphere.2019.02.031
Wei Wei2
Estimated H-index: 2
(HMU: Harbin Medical University),
Shujuan Pang2
Estimated H-index: 2
(CCDC: Chinese Center for Disease Control and Prevention)
+ 4 AuthorsDianjun Sun5
Estimated H-index: 5
(HMU: Harbin Medical University)
Abstract
Abstract Fluoride is capable of inducing immunotoxicity, but its molecular mechanisms remain elusive. This study aimed to explore the roles of Protein kinase receptor-like ER kinase (PERK) and inositol requiring enzyme 1 (IRE1) signaling pathways in excessive fluoride-induced immunotoxicity, focusing on the regulatory roles of these two pathways in cell division and apoptosis. Firstly, we assessed the changes in cell division and apoptosis in rats exposed to 0, 50, or 100 mg/L fluoride, and detected the expression of PERK and IRE1 signaling-related proteins in spleen. Additionally, to validate the role of these two pathways, we evaluated the changes in cell division and apoptosis of primary lymphocytes from rat's spleen to 4 mM fluoride after knockdown of PERK and IRE1 in vitro. In vivo results confirmed that fluoride inhibited cell division, promoted the apoptosis and resulted in histological and ultrastructural abnormalities of rat spleen. In addition, fluoride induced activation of the PERK and IRE1 signalings and the associated apoptosis. Moreover, the in vitro results further verified the findings in vivo that fluoride activated these two signalings in B lymphocytes. Importantly, after knockdown of PERK and IRE1 in lymphocytes, the cell division ability was restored, and apoptosis decreased in fluoride-treated lymphocytes; the results correlated well with the expression of PERK and IRE1 signaling-related proteins, thus confirming the pivotal role of these pathways in immunosuppression by excessive fluoride. This study indicates that the mechanisms underlying the deleterious effects of fluoride on immune system are related to activation of the PERK and IRE1 signaling pathways.
  • References (47)
  • Citations (1)
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References47
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Abstract In reviewing the literature, the cellular mechanism of fluoride F-induced osteoblast OB cells apoptosis is diverse and perplexing, but detailed regulatory pathway, targets and role of extracellular Ca2+ remains still unclear. Hence, in the present study, we investigated the effects of F (9 mg/L F ion) and different Ca2+ (0.5, 1, 2, 4, 8 mmol/L) levels treatment on the proliferation rate of osteoblast cells, intracellular free Ca2+ ([Ca2+]i) and endoplasmic reticulum (ER) stress apoptosi...
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// Hongrui Guo 1, * , Ping Kuang 1, * , Qin Luo 1, * , Hengmin Cui 1, 2 , Huidan Deng 1 , Huan Liu 1 , Yujiao Lu 1 , Jing Fang 1, 2 , Zhicai Zuo 1, 2 , Junliang Deng 1, 2 , Yinglun Li 1, 2 , Xun Wang 1, 2 and Ling Zhao 1, 2 1 College of Veterinary Medicine, Sichuan Agricultural University, Ya’an 625014, China 2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Ya’an 625014, China * These authors have contributed equally to this work ...
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Abstract Fluoride has been considered as a risk factor of cardiovascular disease due to its endothelial toxicology. However, the mechanism underlying the endothelial toxicity of fluoride has not been clearly illustrated. MiR-200c-3p was strongly linked with endothelial function and its level is increased in serum of fluorosis patients, but it is unclear the role of miR-200c-3p in the fluoride induced endothelial dysfunction. In this study, we confirmed that fluoride exposure induced the apoptosi...
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