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dc.contributor.authorRoutti, Heli Anna Irmeli
dc.contributor.authorBerg, Mari Katrine
dc.contributor.authorLille-Langøy, Roger
dc.contributor.authorØygarden, Lene Eidsvik
dc.contributor.authorHarju, Mikael
dc.contributor.authorDietz, Rune
dc.contributor.authorSonne, Christian
dc.contributor.authorGoksøyr, Anders
dc.date.accessioned2019-08-22T12:46:00Z
dc.date.available2019-08-22T12:46:00Z
dc.date.issued2019-05-06
dc.PublishedRoutti HAI, Berg MK, Lille-Langøy R, Øygarden LE, Harju M, Dietz R, Sonne C, Goksøyr A. Environmental contaminants modulate the transcriptional activity of polar bear (Ursus maritimus) and human peroxisome proliferator-activated receptor alpha (PPARA). Scientific Reports. 2019;9:6918eng
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://hdl.handle.net/1956/20708
dc.description.abstractPeroxisome 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.en_US
dc.language.isoengeng
dc.publisherSpringer Natureen_US
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0eng
dc.titleEnvironmental contaminants modulate the transcriptional activity of polar bear (Ursus maritimus) and human peroxisome proliferator-activated receptor alpha (PPARA)en_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2019-06-20T11:57:12Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.identifier.doihttps://doi.org/10.1038/s41598-019-43337-w
dc.identifier.cristin1706473
dc.source.journalScientific Reports


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