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dc.contributor.authorOlufsen, Marianne Opsahl
dc.contributor.authorCangialosi, Maria Vittoria
dc.contributor.authorArukwe, Augustine
dc.identifier.citationPLoS ONE 2014, 9(7)nb_NO
dc.description.abstractThe relative importance of environmental hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to perfluorooctane sulfonamide (PFOSA) and chemically induced hypoxia on membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to PFOSA at 0, 25 and 50 mM singly or in combination with either cobalt chloride (CoCl2: 0 and 150 mM) or deferroxamine (DFO: 0 and 100 mM) for 24 and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two chemicals have been commonly used in animal experiments for this purpose and have been shown to increase hypoxia-inducible factor 1-alpha (HIF-1a) and vascular endothelial growth factor (VEGF) levels. Fatty acid (FA) profiles were determined by GC-MS, while gene expression patterns were determined by quantitative PCR. Hypoxic condition was confirmed with time-related increases of HIF-1a mRNA levels in CoCl2 and DFO exposed cells. In general, significant alterations of genes involved in lipid homeostasis were predominantly observed after 48 h exposure. Gene expression analysis showed that biological responses related to peroxisome proliferation (peroxisome proliferatoractivated receptors (PPARs) and acyl coenzyme A (ACOX)) and FA desaturation (D5- and D6-desaturases: FAD5 and FAD6, respectively) and elongation (FAE) were elevated slightly by single exposure (i.e. either PFOSA, CoCl2 or DFO exposure alone), and these responses were potentiated in combined exposure conditions. Principal component analysis (PCA) showed a clustering of peroxisome proliferation responses at transcript levels and FA desaturation against membrane FAs levels whose changes were explained by PFOSA and chemically induced hypoxia exposures. Overall, our data show that most of the observed responses were stronger in combined stressor exposure conditions, compared to individual stressor exposure. In general, our data show that hypoxia may, singly or in combination with PFOSA produce deleterious health, physiological and developmental consequences through the alteration of membrane lipid profile in organisms.nb_NO
dc.publisherPublic Library of Sciencenb_NO
dc.rightsNavngivelse 3.0 Norge*
dc.titleModulation of membrane lipid composition and homeostasis in salmon hepatocytes exposed to hypoxia and perfluorooctane sulfonamide, given singly or in combinationnb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalPLoS ONEnb_NO
dc.description.localcode© 2014 Olufsen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.nb_NO

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