title: Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) by perfluoroalkyl acids (PFAAs): further investigation of C4-C12 compounds.
abstract: Perfluorinated alkyl acids (PFAAs) are manufactured surfactants found globally in the environment and in tissues of humans and wildlife. Several PFAAs adversely affect rodents and activation of PPARα is thought to be their mode of action. Our previous study demonstrated that some PFAAs activate mouse and human PPARα in transiently transfected COS-1 cells. Here, we test more PFAAs for PPARα activation in the same system. Cells were transfected with either mouse or human PPARα-luciferase reporter plasmid, exposed the next day to either vehicle, PPARα agonist (WY14643), perfluoropentanoic acid (C5), perfluoroheptanoic acid (C7), perfluorooctanoic acid (C8), perfluoroundecanoic acid (C11), or perfluorododecanoic acid (C12) at concentrations from 0.5μM to 100μM, and luminescence was measured after 24h. C8 induced the highest activity for human PPARα, followed by C7, C5, and C11. C12 had little activity. C8 induced the highest activity for mouse PPARα, followed by C11, C7, C12 and C5. The two studies together found increasing activity of PPARα with increasing chain length of the PFAA up to perfluorononanoic acid (C9) and lower activity with longer chain PFAAs with both mouse and human PPARα.
authors: Developmental Toxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC 27711, United States. Electronic address: wolf.cynthiaj@epa.gov.
authors: Cynthia J
authors: CJ
authors: Wolf
authors: Biostatistics & Bioinformatics Branch, Research Core Unit, NHEERL, ORD, U.S. EPA Research Triangle Park, NC 27711, United States.
authors: Judith E
authors: JE
authors: Schmid
authors: Developmental Toxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC 27711, United States.
authors: Christopher
authors: C
authors: Lau
authors: Developmental Toxicology Branch, Toxicity Assessment Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC 27711, United States.
authors: Barbara D
authors: BD
authors: Abbott
mesh_terms: D000818:Animals; D019556:COS Cells; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000737:chemistry* / Q000633:toxicity*; D005466:Fluorocarbons / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D016014:Linear Models; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D013045:Species Specificity; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D004785:Environmental Pollutants; D005466:Fluorocarbons; D047493:PPAR alpha