title: The role of Nrf2 and MAPK pathways in PFOS-induced oxidative stress in zebrafish embryos.
abstract: Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and causes oxidative stress, apoptosis, and developmental toxicity in zebrafish embryos. In the present study, we examined nuclear factor erythroid 2-related factor 2 (Nrf2)- and mitogen-activated protein kinases (MAPKs)-mediated oxidative stress pathways in zebrafish embryos upon exposure to PFOS. Four-hour postfertilization (hpf) zebrafish embryos were exposed to 0.2, 0.4, and 1.0 mg/l PFOS until 96 hpf. PFOS enhanced production of reactive oxygen species (ROS) in a concentration-dependent manner. Activity of antioxidative enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, was significantly induced in zebrafish larvae in all PFOS-treated groups relative to the control. Exposure to 1.0 mg/l PFOS significantly increased malondialdehyde production in zebrafish larvae. The Nrf2 and heme oxygenase-1 (HO-1) gene expressions were both significantly upregulated compared with the control group. For MAPKs, we investigated gene expression profiles of extracellular signal-regulated protein kinase (ERK), c-Jun NH (2)-terminal kinase (JNK), and p38. The ERK gene expression levels were unchanged, whereas JNK and p38 gene expressions were significantly upregulated, which could be linked to PFOS-induced cell apoptosis in zebrafish larvae. In addition, we found that coexposure with sulforaphane, an Nrf2 activator, could significantly protect against PFOS-induced ROS generation, whereas inhibition of MAPKs did not exhibit significant effects on PFOS-induced HO-1 gene expression and ROS production. Furthermore, we showed that morpholino-mediated knockdown of Nrf2 reduced PFOS-induced HO-1 gene expression. These findings demonstrate that Nrf2 is protective against PFOS-induced oxidative stress in zebrafish larvae.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Xiongjie
authors.initials: X
authors.lastname: Shi
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Zhou
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism; D005466:Fluorocarbons / Q000633:toxicity*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D008315:Malondialdehyde / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D013861:Thiocyanates; D014874:Water Pollutants, Chemical; D029961:Zebrafish Proteins; C495638:nfe2l2a protein, zebrafish; D008315:Malondialdehyde; C076994:perfluorooctane sulfonic acid; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases; C016766:sulforaphane