title: Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons.
abstract: The molecular mechanism of inflammation and carcinogenesis induced by exposure of polycyclic aromatic hydrocarbons (PAHs) is not clearly understood. Our study was undertaken due to the strong pro-carcinogenic potential and reactivity of PAH-metabolites, as well as the susceptibility of polyunsaturated fatty acids to oxidation. The aim of this study was to evaluate the pro- or anti-inflammatory impact of n-3 docosahexaenoic acid on human primary umbilical vein endothelial cells (HUVEC) exposed to polycyclic aromatic hydrocarbons. We analysed the influence of docosahexaenoic acid (DHA) and/or PAHs supplementation on the fatty acid profile of cell membranes, on cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) protein expression as well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and cytochrome P450 CYP1A1 gene expression. We observed that COX-2 and AHR protein expression was increased while GSTM1 expression was decreased in cells exposed to DHA and PAHs. Docosahexaenoic acid down-regulated CYP1A1 and up-regulated the AHR and PTGS2 genes. Our findings suggested that DHA contributes significantly to alleviate the harmful effects caused by PAHs in endothelial cells. Moreover, these results suggest that a diet rich in n-3 fatty acids is helpful to reduce the harmful effects of PAHs exposure on human living in heavily polluted areas.
authors.affiliation: Department of Radioligands, Faculty of Pharmacy, Jagiellonian University, Medical College, Kraków, Poland. Electronic address: jargasinska@cm-uj.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gdula-Argasińska
authors.affiliation: Department of Infectious Diseases, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Czepiel
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Totoń-Żurańska
authors.affiliation: Department of Hematology, University Hospital, Kraków, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Jurczyszyn
authors.affiliation: Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: William
authors.initials: W
authors.lastname: Perucki
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland; Center for Medical Genomics-OMICRON, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wołkow
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*
chemical_list: D051546:Cyclooxygenase 2; D019363:Cytochrome P-450 CYP1A1; D004281:Docosahexaenoic Acids; D005982:Glutathione Transferase; D011084:Polycyclic Aromatic Hydrocarbons
keywords: COX-2; CYP1A1; DHA; HUVEC; Polycyclic aromatic hydrocarbons; RT-qPCR