title: Perfluorooctane sulfonate (PFOS) impairs the proliferation of C17.2 neural stem cells via the downregulation of GSK-3β/β-catenin signaling.
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.
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Disease Prevention, the Second People's Hospital of Nan Tong, Nantong, 226019, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China. xiaoj_1980@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Occupational Medicine and Environmental Toxicology, School of Public Health, Nantong University, Nantong, 226019, China. Jiang_shengyang@163.com.
authors.forename: Shengyang
authors.initials: S
authors.lastname: Jiang
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005466:Fluorocarbons / Q000633:toxicity*; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D017738:Alkanesulfonic Acids; C495267:CTNNB1 protein, mouse; D004785:Environmental Pollutants; D005466:Fluorocarbons; D051176:beta Catenin; C076994:perfluorooctane sulfonic acid; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Wnt/β-catenin signaling; neural stem cells (NSCs); neurotoxicology; perfluorooctane sulfonate (PFOS); proliferation