通讯机构：
Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang, China
期刊：
International Journal of Molecular Sciences,2017年18(4):893- ISSN：1422-0067
通讯作者：
Zeng, Huai-Cai
作者机构：
[Li, Wu; Pan, Xiao-Yuan; Chen, Cong; Guo, Xin-Xin; Zeng, Huai-Cai; Long, Ding-Xin] Univ South China, Sch Publ Hlth, Dept Prevent Med, Hengyang 421001, Peoples R China.;[He, Qing-Zhi] Univ South China, Sch Pharm & Biol, Hengyang 421001, Peoples R China.;[He, Qing-Zhi; Zeng, Huai-Cai] Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
通讯机构：
[Zeng, Huai-Cai] U;[Zeng, Huai-Cai] H;Univ South China, Sch Publ Hlth, Dept Prevent Med, Hengyang 421001, Peoples R China.;Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Peoples R China.
关键词：
PFOS;BDNF;DNMTs;microRNA;DNA methylation
摘要：
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.
摘要：
Carbamates and pyrethroids are widely used pesticides. However, their joint toxicity at low doses with long-term exposure remains unknown. Therefore, we investigated the subchronic joint hepatotoxicity of the two representative pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in rats. The male Wistar rats were orally treated with three different doses of PR, PE and their mixtures for 90 consecutive days. Liver weight, serum clinical chemistry parameters and histopathological changes were measured to access the hepatotoxicity. In addition, oxidative stress markers in liver were measured using biochemical assays. The results showed that PR reduced liver weight and lead to prominent liver histological changes. Moreover, PR dose-dependently induced lipid peroxidation and reduced superoxide dismutase activity. In contrast, PE induced a relatively mild hepatotoxicity. Intriguingly, the mixture of PR and PE did not reduce liver weight or increase serum aspartate transaminase activity. In addition, the mixture did not reduce the antioxidant enzyme activity as PR did. Thus, these results showed that PR induced prominent hepatotoxicity with subchronic exposure, and there is a potential antagonistic interaction between PR and PE on the oxidative damage in liver of rats. (C) 2017 Elsevier B.V. All rights reserved.
