PMID- 28441774 OWN - NLM STAT- MEDLINE DCOM- 20180119 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 4 DP - 2017 Apr 24 TI - Brain-Derived Neurotrophic Factor Mediated Perfluorooctane Sulfonate Induced-Neurotoxicity via Epigenetics Regulation in SK-N-SH Cells. LID - 10.3390/ijms18040893 [doi] LID - 893 AB - Perfluorooctane sulfonate (PFOS), a new kind of persistent organic pollutant, is widely distributed in the environment and exists in various organisms, where it is also a neurotoxic compound. However, the potential mechanism of its neurotoxicity is still unclear. To examine the role of epigenetics in the neurotoxicity induced by PFOS, SK-N-SH cells were treated with different concentrations of PFOS or control medium (0.1% DMSO) for 48 h. The mRNA levels of DNA methyltransferases (DNMTs) and Brain-derived neurotrophic factor (BDNF), microRNA-16, microRNA-22, and microRNA-30a-5p were detected by Quantitative PCR (QPCR). Enzyme Linked Immunosorbent Assay (ELISA) was used to measure the protein levels of BDNF, and a western blot was applied to analyze the protein levels of DNMTs. Bisulfite sequencing PCR (BSP) was used to detect the methylation status of the BDNF promoter I and IV. Results of MTT assays indicated that treatment with PFOS could lead to a significant decrease of cell viability, and the treated cells became shrunk. In addition, PFOS exposure decreased the expression of BDNF at mRNA and protein levels, increased the expression of microRNA-16, microRNA-22, microRNA-30a-5p, and decreased the expression of DNMT1 at mRNA and protein levels, but increased the expression of DNMT3b at mRNA and protein levels. Our results also demonstrate that PFOS exposure changes the methylation status of BDNF promoter I and IV. The findings of the present study suggest that methylation regulation of BDNF gene promoter and increases of BDNF-related-microRNA might underlie the mechanisms of PFOS-induced neurotoxicity. FAU - Guo, Xin-Xin AU - Guo XX AD - Department of Preventive Medicine, School of Public Health, University of South China, Hengyang 421001, China. guoxinxin1677@gmail.com. FAU - He, Qing-Zhi AU - He QZ AD - School of Pharmacy and Biology, University of South China, Hengyang 421001, China. heqingzhi666@gmail.com. AD - Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China. heqingzhi666@gmail.com. FAU - Li, Wu AU - Li W AD - Department of Preventive Medicine, School of Public Health, University of South China, Hengyang 421001, China. liwu199103@gmail.com. FAU - Long, Ding-Xin AU - Long DX AD - Department of Preventive Medicine, School of Public Health, University of South China, Hengyang 421001, China. longdx@usc.edu.cn. FAU - Pan, Xiao-Yuan AU - Pan XY AD - Department of Preventive Medicine, School of Public Health, University of South China, Hengyang 421001, China. panxiaoyuan199104@gmail.com. FAU - Chen, Cong AU - Chen C AD - Department of Preventive Medicine, School of Public Health, University of South China, Hengyang 421001, China. chencong199206@gmail.com. FAU - Zeng, Huai-Cai AU - Zeng HC AD - Department of Preventive Medicine, School of Public Health, University of South China, Hengyang 421001, China. zenghuaicai@usc.edu.cn. AD - Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang 421001, China. zenghuaicai@usc.edu.cn. LA - eng PT - Journal Article DEP - 20170424 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Alkanesulfonic Acids) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Environmental Pollutants) RN - 0 (Fluorocarbons) RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) RN - 9H2MAI21CL (perfluorooctane sulfonic acid) RN - EC 2.1.1.- (DNA-Cytosine Methylases) SB - IM MH - Alkanesulfonic Acids/*toxicity MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - DNA Methylation/drug effects MH - DNA-Cytosine Methylases/genetics/metabolism MH - Environmental Pollutants/*toxicity MH - Enzyme-Linked Immunosorbent Assay MH - Epigenesis, Genetic/*drug effects MH - Fluorocarbons/*toxicity MH - Gene Expression/drug effects MH - Humans MH - MicroRNAs/metabolism MH - Promoter Regions, Genetic MH - RNA, Messenger/metabolism MH - Real-Time Polymerase Chain Reaction PMC - PMC5412472 OTO - NOTNLM OT - BDNF OT - DNA methylation OT - DNMTs OT - PFOS OT - microRNA EDAT- 2017/04/27 06:00 MHDA- 2018/01/20 06:00 PMCR- 2017/04/01 CRDT- 2017/04/27 06:00 PHST- 2017/02/20 00:00 [received] PHST- 2017/04/17 00:00 [revised] PHST- 2017/04/19 00:00 [accepted] PHST- 2017/04/27 06:00 [entrez] PHST- 2017/04/27 06:00 [pubmed] PHST- 2018/01/20 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - ijms18040893 [pii] AID - ijms-18-00893 [pii] AID - 10.3390/ijms18040893 [doi] PST - epublish SO - Int J Mol Sci. 2017 Apr 24;18(4):893. doi: 10.3390/ijms18040893.