title: Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator.
abstract: While it has long been believed that benzenes and naphthalenes are unable to activate the aryl hydrocarbon receptor (AhR) because they are poor ligands, we recently reported that these quinoid metabolites upregulated cytochrome P450 1A1 (CYP1A1) in Hepa1c1c7 cells (Abiko et al., 2015). In the current study, AhR activation, measured with a bioluminescence-based cell free assay, was induced by 1,2-naphthoquinone (1,2-NQ), a metabolite of naphthalene. Consistent with this, 1,4-benzoquinone (1,4-BQ), tert-butyl-1,4-BQ, and 1,4-NQ, as well as 1,2-NQ, all electrophilic mono- and bi-cyclic quinones, upregulated CYP1A1 mRNA and protein in HepG2 cells, whereas their parent aromatic hydrocarbons had little effect. Furthermore, immunofluorescence analysis confirmed that these quinones enhanced translocation of AhR to the nucleus.
authors.affiliation: Faculty of Medicine, University of Tsukuba.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Abiko
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Lin
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.forename: Alvaro
authors.initials: A
authors.lastname: Puga
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Kumagai
mesh_terms: D021581:Active Transport, Cell Nucleus; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists* / Q000378:metabolism; D016227:Benzoquinones / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005455:Fluorescent Antibody Technique; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D009285:Naphthoquinones / Q000633:toxicity; D011809:Quinones / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000378:metabolism; D014162:Transfection
chemical_list: D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D016227:Benzoquinones; D019363:Cytochrome P-450 CYP1A1; D009285:Naphthoquinones; D011809:Quinones; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C497396:ARNT protein, human; C040756:1,2-naphthoquinone; C569463:CYP1A1 protein, human; C051290:2-tert-butyl-4-quinone; C035342:1,4-naphthoquinone