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Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator
- Source :
- The Journal of Toxicological Sciences. 41:775-781
- Publication Year :
- 2016
- Publisher :
- Japanese Society of Toxicology, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Aryl hydrocarbon receptor nuclear translocator
Metabolite
Active Transport, Cell Nucleus
Fluorescent Antibody Technique
Transfection
Toxicology
03 medical and health sciences
chemistry.chemical_compound
Downregulation and upregulation
Basic Helix-Loop-Helix Transcription Factors
Benzoquinones
Cytochrome P-450 CYP1A1
Humans
Cytochrome P450, family 1, member A1
RNA, Messenger
Naphthalene
Dose-Response Relationship, Drug
biology
Chemistry
Aryl Hydrocarbon Receptor Nuclear Translocator
Quinones
Cytochrome P450
Hep G2 Cells
respiratory system
Aryl hydrocarbon receptor
Quinone
030104 developmental biology
Receptors, Aryl Hydrocarbon
Biochemistry
Enzyme Induction
Hepatocytes
biology.protein
Naphthoquinones
Subjects
Details
- ISSN :
- 18803989 and 03881350
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- The Journal of Toxicological Sciences
- Accession number :
- edsair.doi.dedup.....9ccd4c9c45c1b04dd0d1c1f7136ba022