Quinone-mediated induction of cytochrome P450 1a1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator
Journal
Journal of Toxicological Sciences
Journal Volume
41
Journal Issue
6
Pages
775-781
Date Issued
2016
Author(s)
Abiko, Y., Lin, F.-Y., Lee, H., Puga, A., Kumagai, Y.
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. © 2016, Japanese Society of Toxicology. All rights reserved.
Subjects
Aryl hydrocarbon receptor; CYP1A1; Electrophile; Quinone
SDGs
Other Subjects
1,2 naphthoquinone; 1,4 benzoquinone; 2 tert butylquinone; aromatic hydrocarbon receptor; cytochrome P450 1A1; dioxin; drug metabolite; hypoxia inducible factor 1beta; quinone derivative; 1,2-naphthoquinone; 1,4-naphthoquinone; 2-tert-butyl-4-quinone; AHR protein, human; ARNT protein, human; aromatic hydrocarbon receptor; basic helix loop helix transcription factor; benzoquinone derivative; CYP1A1 protein, human; cytochrome P450 1A1; hypoxia inducible factor 1beta; messenger RNA; naphthoquinone; quinone derivative; bioluminescence; cell assay; controlled study; electrophilicity; gas chromatography; gene activation; gene expression regulation; human; human cell; immunofluorescence; immunoprecipitation; Letter; protein expression; real time polymerase chain reaction; receptor binding; reverse transcription polymerase chain reaction; transcription initiation; transcription regulation; upregulation; Western blotting; active transport; agonists; biosynthesis; dose response; drug effects; enzyme induction; enzymology; fluorescent antibody technique; genetic transfection; genetics; Hep-G2 cell line; liver cell; metabolism; Active Transport, Cell Nucleus; Aryl Hydrocarbon Receptor Nuclear Translocator; Basic Helix-Loop-Helix Transcription Factors; Benzoquinones; Cytochrome P-450 CYP1A1; Dose-Response Relationship, Drug; Enzyme Induction; Fluorescent Antibody Technique; Hep G2 Cells; Hepatocytes; Humans; Naphthoquinones; Quinones; Receptors, Aryl Hydrocarbon; RNA, Messenger; Transfection
Type
letter