Dong Xuan, Yang Jianbin, Nie Xiaoke, Xiao Jing, Jiang Shengyang
Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China.
Department of Disease Prevention, the Second People's Hospital of Nan Tong, Nantong, 226019, China.
J Appl Toxicol. 2016 Dec;36(12):1591-1598. doi: 10.1002/jat.3320. Epub 2016 Mar 28.
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.
近年来，全氟辛烷磺酸（PFOS）的神经毒性作用引起了大量研究关注。在本研究中，我们调查了体外暴露于PFOS对神经干细胞（NSCs）生理功能的影响。我们发现，PFOS暴露以剂量和时间依赖性方式显著减弱了C17.2神经干细胞的增殖。此外，我们发现PFOS降低了糖原合酶激酶-3β（pSer9-GSK-3β）的Ser9磷酸化水平，导致GSK-3β激活，进而引起细胞β-连环蛋白表达下调。此外，用氯化锂阻断GSK-3β可显著减弱PFOS诱导的GSK-3β/β-连环蛋白下调以及C17.2细胞的增殖受损。值得注意的是，各种下游靶点的表达也相应改变，如c-myc、细胞周期蛋白D1和生存素。总之，本研究表明PFOS通过对GSK-3β/β-连环蛋白通路的负调控降低了C17.2细胞的增殖。我们提出了PFOS对NSCs产生毒性作用的潜在机制，为PFOS的神经毒性机制提供了新的见解。版权所有© 2016约翰威立父子有限公司。
