title: PFOS Disturbs BDNF-ERK-CREB Signalling in Association with Increased MicroRNA-22 in SH-SY5Y Cells.
abstract: Perfluorooctane sulfonate (PFOS), a ubiquitous environmental pollutant, is neurotoxic to mammalian species. However, the underlying mechanism of its neurotoxicity was unclear. We hypothesized that PFOS suppresses BDNF expression to produce its neurotoxic effects by inhibiting the ERK-CREB pathway. SH-SY5Y human neuroblastoma cells were exposed to various concentrations of PFOS to examine the role of the BDNF-ERK-CREB signalling pathway in PFOS-induced apoptosis and cytotoxicity. Furthermore, to ascertain the mechanism by which PFOS reduces BDNF signalling, we examined the expression levels of miR-16 and miR-22, which potentially regulate BDNF mRNA translation at the posttranscriptional level. Results indicated that PFOS significantly decreased cell viability and induced apoptosis in SH-SY5Y cells. In addition, BDNF and pERK protein levels decreased after PFOS treatment; however, pCREB protein levels were significantly elevated in PFOS treated groups. TrkB protein expression increased in the 10 μM and 50 μM PFOS groups and significantly decreased in the 100 μM PFOS group. Our results demonstrated that PFOS exposure decreased miR-16 expression and increased miR-22 expression, which may represent a possible mechanism by which PFOS decreases BDNF protein levels. PFOS may inhibit BDNF-ERK-CREB signalling by increasing miR-22 levels, which may, in part, explain the mechanism of PFOS neurotoxicity.
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Li
authors.affiliation: Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Qing-zhi
authors.initials: QZ
authors.lastname: He
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Cheng-qiu
authors.initials: CQ
authors.lastname: Wu
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Xiao-yuan
authors.initials: XY
authors.lastname: Pan
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Xiao-yun
authors.initials: XY
authors.lastname: Shan
authors.affiliation: Department of Preventive Medicine, School of Public Health, University of South China, 28 Western Changsheng Road, Hengyang 421001, China ; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, 28 Western Changsheng Road, Hengyang 421001, China.
authors.forename: Huai-cai
authors.initials: HC
authors.lastname: Zeng
mesh_terms: D017738:Alkanesulfonic Acids / Q000378:metabolism / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000096:biosynthesis*; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity; D005466:Fluorocarbons / Q000378:metabolism / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D017738:Alkanesulfonic Acids; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004785:Environmental Pollutants; D005466:Fluorocarbons; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; C076994:perfluorooctane sulfonic acid; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1