Environmental contaminants modulate the transcriptional activity of polar bear (Ursus maritimus) and human peroxisome proliferator-activated receptor alpha (PPARA)

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DOI

  • Heli Routti, Norwegian Polar Res Inst, Fram Ctr
  • ,
  • Mari K. Berg, Norwegian Polar Institute, FRAM Centre, University of Bergen, Norge
  • Roger Lille-Langøy, University of Bergen, Norge
  • Lene Øygarden, University of Bergen, Norwegian Polar Institute, FRAM Centre, Norge
  • Mikael Harju, Norwegian Institute for Air research (NILU), FRAM Centre
  • ,
  • Rune Dietz
  • Christian Sonne
  • Anders Goksøyr, University of Bergen, Danmark

Peroxisome proliferator-activated receptor alfa (PPARA/NR1C1) is a ligand activated nuclear receptor that is a key regulator of lipid metabolism in tissues with high fatty acid catabolism such as the liver. Here, we cloned PPARA from polar bear liver tissue and studied in vitro transactivation of polar bear and human PPARA by environmental contaminants using a luciferase reporter assay. Six hinge and ligand-binding domain amino acids have been substituted in polar bear PPARA compared to human PPARA. Perfluorocarboxylic acids (PFCA) and perfluorosulfonic acids induced the transcriptional activity of both human and polar bear PPARA. The most abundant PFCA in polar bear tissue, perfluorononanoate, increased polar bear PPARA-mediated luciferase activity to a level comparable to that of the potent PPARA agonist WY-14643 (~8-fold, 25 μM). Several brominated flame retardants were weak agonists of human and polar bear PPARA. While single exposures to polychlorinated biphenyls did not, or only slightly, increase the transcriptional activity of PPARA, a technical mixture of PCBs (Aroclor 1254) strongly induced the transcriptional activity of human (~8-fold) and polar bear PPARA (~22-fold). Polar bear PPARA was both quantitatively and qualitatively more susceptible than human PPARA to transactivation by less lipophilic compounds.

OriginalsprogEngelsk
Artikelnummer6918
TidsskriftScientific Reports
Vol/bind9
Nummer1
Antal sider14
ISSN2045-2322
DOI
StatusUdgivet - maj 2019

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