RRC ID 51940
Author Abiko Y, Lin FY, Lee H, Puga A, Kumagai Y.
Title Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator.
Journal J Toxicol Sci
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.
Volume 41(6)
Pages 775-781
Published 2016-1-1
DOI 10.2131/jts.41.775
PMID 27853106
MeSH Active Transport, Cell Nucleus Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism* Basic Helix-Loop-Helix Transcription Factors / agonists* Basic Helix-Loop-Helix Transcription Factors / metabolism Benzoquinones / toxicity Cytochrome P-450 CYP1A1 / biosynthesis* Cytochrome P-450 CYP1A1 / genetics Dose-Response Relationship, Drug Enzyme Induction Fluorescent Antibody Technique Hep G2 Cells Hepatocytes / drug effects* Hepatocytes / enzymology Humans Naphthoquinones / toxicity Quinones / toxicity* RNA, Messenger / biosynthesis* RNA, Messenger / genetics Receptors, Aryl Hydrocarbon / agonists* Receptors, Aryl Hydrocarbon / metabolism Transfection
IF 1.737
Times Cited 7
Resource
Human and Animal Cells Hep G2(RCB1648)