Perfluorooctane sulfonate (PFOS) impairs the proliferation of C17.2 neural stem cells via the downregulation of GSK‐3β/β‐catenin signaling. Issue 12 (28th March 2016)

• Record Type: Journal Article
• Authors: Dong, Xuan; Yang, Jianbin; Nie, Xiaoke; Xiao, Jing; Jiang, Shengyang
• Is Part Of: Journal of applied toxicology. Volume 36:Issue 12(2016)
• Page Start: 1591
• Page End: 1598
• Publication Date: 2016-03-28
• Subjects: perfluorooctane sulfonate (PFOS) -- Wnt/β‐catenin signaling -- neural stem cells (NSCs) -- proliferation -- neurotoxicology; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3320
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: The neurotoxic effects of perfluorooctane sulfonate (PFOS) have attracted significant research attention in recent years. In the present study, we investigated the impact of PFOS exposure on the physiology of neural stem cells (NSCs) in vitro . We showed that PFOS exposure markedly attenuated the proliferation of C17.2 neural stem cells in both dose‐ and time‐dependent manners. Additionally, we found that PFOS decreased Ser9 phosphorylation of glycogen synthase kinase‐3β (pSer9‐GSK‐3β), leading to the activation of GSK‐3β and resultant downregulation of cellular β‐catenin. Furthermore, blockage of GSK‐3β with lithium chloride significantly attenuated both the PFOS‐induced downregulation of GSK‐3β/β‐catenin and the proliferative impairment of C17.2 cells. Notably, the expression of various downstream targets was altered accordingly, such as c‐myc, cyclin D1 and survivin. In conclusion, the present study demonstrated that PFOS decreased the proliferation of C17.2 cells via the negative modulation of the GSK‐3β/β‐catenin pathway. We present the potential mechanisms underlying the PFOS‐induced toxic effects on NSCs to provide novel insights into the neurotoxic mechanism of PFOS. Copyright © 2016 John Wiley & Sons, Ltd. Abstract : PFOS has been recently documented to cause significant adverse effects on nervous system. We herein reported that PFOS exposure led to the downregulation of GSK‐3β/β‐catenin in C17.2 neural stem cells at a dose range of 25‐200 nM, which is correlated with impaired proliferation of C17.2 cells. Our findings may help gain a better insight into the molecular mechanisms underlying PFOS‐induced neurological deficits.