Brain-Derived Neurotrophic Factor Mediated Perfluorooctane Sulfonate Induced-Neurotoxicity via Epigenetics Regulation in SK-N-SH Cells.

Xin-Xin Guo,Xiao-Yuan Pan,Wu Li,Cong Chen,Qing-Zhi He,Ding-Xin Long,Huai-Cai Zeng

doi:10.3390/ijms18040893

Xin-Xin Guo, Xiao-Yuan Pan + Show 5 more

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https://doi.org/10.3390/ijms18040893

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Abstract

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.

Highlights

Perfluorooctane sulfonate (PFOS) is one class of the representative compounds and the ultimate metabolites of perfluorinated compounds (PFCs)
These results have identified that PFOS may significantly reduce the expression of Brain-derived neurotrophic factor (BDNF) through increasing the level of microRNA-16, microRNA-22, microRNA-30a-5p, and lead to neurotoxicity in SK-N-SH cells
The present study showed that PFOS exposure could lead to the methylation status change of BDNF promoter I and IV, which may disturb the expression of BDNF

Summary

Introduction

Perfluorooctane sulfonate (PFOS) is one class of the representative compounds and the ultimate metabolites of perfluorinated compounds (PFCs). PFOS is found in carpets, textiles, leather, paper, fire-fighting foams, and food packing materials, and it is a component of pharmaceuticals and insecticides [1]. Due to their chemical and thermal stability, PFOS can exist in the environment for a long time, and is highly resistant to microbial degradation [2]. It could cause injury to the ability of memory and locomotor function and induce the neurotoxicity [5]. It was reported that the epigenetic regulation played an important role in neurodevelopment and neurobehavioral functions, including learning and memory [7]

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