Exposure to perfluorooctane sulfonate or fenofibrate causes PPAR-alpha dependent transcriptional responses in chicken embryo hepatocytes.
Perfluorooctane sulfonate (PFOS) is a globally distributed environmental contaminant that is detected in the serum and liver of numerous mammalian and avian species. PFOS acts as a peroxisome proliferator in rodents, which occurs subsequent to activation of the nuclear receptor peroxisome proliferator activated receptor-alpha (PPAR-alpha). Activated PPAR-alpha up-regulates PPAR-alpha target genes, most of which are involved in lipid metabolism. Although several studies have investigated the effects of PFOS exposure on mammalian gene expression, there are few studies in avian species. To determine if PFOS is capable of activating avian PPAR-alpha, we exposed chicken embryo primary hepatocyte cultures (N=3 independent cell cultures) to PFOS or fenofibrate, a mammalian PPAR-alpha agonist, and examined the expression of PPAR-alpha and PPAR-alpha target genes using quantitative real-time PCR. The target genes examined were peroxisomal acyl-CoA oxidase (ACOX), liver fatty acid binding protein (L-FABP), enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase bifunctional enzyme (BIEN), peroxisomal 3-ketoacyl thiolase (PKT), and malic enzyme (ME). All five target genes were induced in response to PFOS exposure and all of the target genes, except L-FABP, were induced in response to fenofibrate. PPAR-alpha mRNA expression was not altered by PFOS or fenofibrate. This study provides the first evidence that PFOS can induce PPAR-alpha-dependent transcriptional responses in an avian species and provides the first characterization of fenofibrate induced transcriptional responses in chicken embryo hepatocyte cultures.
Cwinn
Matthew A
MA
Department of Biology and Centre for Advanced Research in Environmental Genomics, University of Ottawa, Ottawa, ON, Canada K1N 6N5.
Jones
Stephanie P
SP
Kennedy
Sean W
SW
D017738:Alkanesulfonic Acids / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000494:pharmacology* / Q000633:toxicity; D011345:Fenofibrate / Q000494:pharmacology*; D005466:Fluorocarbons / Q000494:pharmacology* / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; C449302:GW 6471; D010080:Oxazoles; D047493:PPAR alpha; D012333:RNA, Messenger; D014443:Tyrosine; C076994:perfluorooctane sulfonic acid; D011345:Fenofibrate