Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator

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 curren...

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Bibliographic Details
Published in:Journal of toxicological sciences 2016/12/01, Vol.41(6), pp.775-781
Main Authors: Abiko, Yumi, Lin, Fang-Yu, Lee, Hsinyu, Puga, Alvaro, Kumagai, Yoshito
Format: Article
Language:English
Subjects:
Activation analysis
Active Transport, Cell Nucleus
Aromatic compounds
Aromatic hydrocarbons
Aryl hydrocarbon receptor
Aryl Hydrocarbon Receptor Nuclear Translocator - metabolism
Basic Helix-Loop-Helix Transcription Factors - agonists
Basic Helix-Loop-Helix Transcription Factors - metabolism
Benzoquinone
Benzoquinones - toxicity
Bioluminescence
CYP1A1
Cytochrome
Cytochrome P-450 CYP1A1 - biosynthesis
Cytochrome P-450 CYP1A1 - genetics
Cytochrome P450
Dose-Response Relationship, Drug
Electrophile
Enzyme Induction
Fluorescent Antibody Technique
Hep G2 Cells
Hepatocytes - drug effects
Hepatocytes - enzymology
Humans
Hydrocarbons
Immunofluorescence
Metabolites
mRNA
Naphthalene
Naphthoquinones - toxicity
Nuclei
Quinone
Quinones
Quinones - toxicity
Receptors, Aryl Hydrocarbon - agonists
Receptors, Aryl Hydrocarbon - metabolism
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Toxicology
Transfection
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Summary: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.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.41.775