Perfluorooctane sulfonate (PFOS) impairs the proliferation of C17.2 neural stem cells via the downregulation of GSK-3ß/ß-catenin signaling.
J Appl Toxicol
; 36(12): 1591-1598, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27018151
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-3ß (pSer9-GSK-3ß), leading to the activation of GSK-3ß and resultant downregulation of cellular ß-catenin. Furthermore, blockage of GSK-3ß with lithium chloride significantly attenuated both the PFOS-induced downregulation of GSK-3ß/ß-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-3ß/ß-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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Alcanossulfônicos
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Poluentes Ambientais
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Beta Catenina
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Células-Tronco Neurais
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Fluorocarbonos
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Glicogênio Sintase Quinase 3 beta
Limite:
Animals
Idioma:
En
Revista:
J Appl Toxicol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China