title: Aryl hydrocarbon receptor modulates NADPH oxidase activity via direct transcriptional regulation of p40phox expression.
abstract: A member of the NADPH oxidase subunits, p40(phox) plays an important role in the regulation of NADPH oxidase activity and the subsequent production of reactive oxygen species (ROS). In this study, we show that mouse p40(phox) is a novel transcriptional target of the aryl hydrocarbon receptor (AhR), known as a dioxin receptor or xenobiotic receptor, in the liver. Treatment of mice with 3-methylcholanthrene (3MC) increased p40(phox) gene expression in the liver, but this induction of p40(phox) gene expression was diminished by the deletion of the AhR gene in the liver. Consistent with the in vivo results, the expression of the p40(phox) gene was increased in 3MC-treated Hepa1c1c7 cells in an AhR-dependent manner. In addition, promoter analysis established p40(phox) as a transcriptional target of AhR. Studies using the RNA-interference technique revealed that p40(phox) is involved in the increase of NADPH oxidase activity and the subsequent ROS production in AhR-activated Hepa1c1c7 cells. Consequently, the results obtained here may provide a novel molecular mechanism for ROS production after exposure to dioxins.
authors.affiliation: Department of Health Science, School of Pharmacy, Nihon University, Funabashi, Chiba, Japan.
authors.forename: Taira
authors.initials: T
authors.lastname: Wada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sunaga
authors.forename: Reiko
authors.initials: R
authors.lastname: Ohkawara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimba
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; C085072:neutrophil cytosol factor 40K; D019255:NADPH Oxidases