Perfluorooctane sulfonate (PFOS) impairs the proliferation of C17.2 neural stem cells via the downregulation of GSK-3β/β-catenin signaling
Perfluorooctane sulfonate (PFOS) impairs the proliferation of C17.2 neural stem cells via the downregulation of GSK-3β/β-catenin signaling
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全氟辛烷磺酸 (PFOS) 通过下调 GSK-3 β/β-连环蛋白信号传导损害 C17.2 神经干细胞的增殖
DOI：
10.1002/jat.3320
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发表时间：
2016-12-01
影响因子：
3.3
通讯作者：
Jiang, Shengyang
中科院分区：
文献类型：
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作者：
Dong, Xuan;Yang, Jianbin;Jiang, Shengyang
全氟辛烷磺酸（PFOS）的神经毒性效应近年来引起了广泛的研究关注。在本研究中，我们研究了全氟辛烷磺酸暴露对体外神经干细胞（NSCs）生理的影响。我们发现，全氟辛烷磺酸暴露显着衰减C17.2神经干细胞的增殖，剂量和时间依赖性的方式。此外，我们发现PFOS降低了糖原合成酶激酶-3（pSer 9-GSK-3）的Ser 9磷酸化，导致GSK-3的激活和细胞-连环蛋白的下调。此外，用氯化锂阻断GSK-3显著减弱了全氟辛烷磺酸诱导的GSK-3/β-catenin下调和C17.2细胞的增殖损伤。值得注意的是，各种下游靶点的表达相应地改变，如c-myc，细胞周期蛋白D1和生存素。总之，本研究表明，全氟辛烷磺酸通过对GSK-3/-catenin通路的负调节来降低C17.2细胞的增殖。我们提出了潜在的机制PFOS诱导的神经干细胞的毒性作用，提供新的见解PFOS的神经毒性机制。版权所有（c）2016 John Wiley & Sons，Ltd.全氟辛烷磺酸最近被证明会对神经系统造成重大不良影响。我们在本文中报告了全氟辛烷磺酸暴露导致C17.2神经干细胞中GSK-3/-catenin在25- 200 nM剂量范围内下调，这与C17.2细胞增殖受损相关。我们的研究结果可能有助于更好地了解PFOS诱导的神经功能缺损的分子机制。
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-3 (pSer9-GSK-3), leading to the activation of GSK-3 and resultant downregulation of cellular -catenin. Furthermore, blockage of GSK-3 with lithium chloride significantly attenuated both the PFOS-induced downregulation of GSK-3/-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-3/-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 (c) 2016 John Wiley & Sons, Ltd.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-3/-catenin in C17.2 neural stem cells at a dose range of 25-200nM, 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.