title: Activation of peroxisome proliferator-activated receptor α ameliorates perfluorododecanoic acid-induced production of reactive oxygen species in rat liver.
abstract: Perfluorododecanoic acid (PFDoA) is a ubiquitous environmental pollutant known to cause hepatocellular hypertrophy; however, the mechanisms of hepatotoxicity remain poorly understood. In this study, male rats were exposed to 0, 0.05, 0.2 and 0.5 mg/kg/day of PFDoA for 110 days. After two-dimensional differential gel electrophoresis and MALDI-TOF/TOF analysis, 73 differentially expressed proteins involved in lipid metabolism, inflammation, stress response and other functions were successfully identified. Among them, six significantly changed proteins (CTE1, MTE1, HADHA, ECH1, ALDH2 and CPS1) were found to be regulated by peroxisome proliferator-activated receptor alpha (PPARα). The anti-oxidant enzyme activity assays of superoxide dismutase and glutathione peroxidase and the content of thiobarbituric acid-reactive substances in the liver implied that PFDoA caused oxidative stress. The mRNA levels of PPARα in rat primary hepatocytes were knocked down by lentivirus-mediated RNAi. Furthermore, targeted protein levels of CTE1 and MTE1 were down-regulated, while those of HADHA, ALDH2 and CPS1 were up-regulated. After PFDoA exposure, however, the targeted protein levels of CTE1 and ALDH2 increased compared with those of the knockdown untreated group. The reactive oxygen species (ROS) content in rat hepatocytes assayed by flow cytometry significantly increased in the PPARα knockdown groups, consistent with the PPARα antagonist GW6471- and agonist WY14643-treated groups. These results strongly suggested that PPARα played an important role in suppressing ROS content in hepatocytes following PFDoA exposure.
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Ruina
authors.initials: R
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, 210029, People's Republic of China.
authors.forename: Xuejiang
authors.initials: X
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Marine Environmental Science/Environmental Science Research Center, Xiamen University, Xiamen, 361005, People's Republic of China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China. daijy@ioz.ac.cn.|State Key Laboratory of Marine Environmental Science/Environmental Science Research Center, Xiamen University, Xiamen, 361005, People's Republic of China. daijy@ioz.ac.cn.
authors.forename: Jiayin
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005434:Flow Cytometry; D005466:Fluorocarbons; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007850:Lauric Acids / Q000032:analysis / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D005466:Fluorocarbons; D007850:Lauric Acids; D047493:PPAR alpha; D017382:Reactive Oxygen Species; C522391:perfluorododecanoic acid
keywords: Lentivirus; Perfluorododecanoic acid (PFDoA); Peroxisome proliferator-activated receptor alpha (PPARα); RNAi; Reactive oxygen species (ROS)