PT  - JOURNAL ARTICLE
AU  - Taira Wada
AU  - Hiroshi Sunaga
AU  - Reiko Ohkawara
AU  - Shigeki Shimba
TI  - Aryl Hydrocarbon Receptor Modulates NADPH Oxidase Activity via Direct Transcriptional Regulation of p40<sup>phox</sup> Expression
AID  - 10.1124/mol.112.083303
DP  - 2013 May 01
TA  - Molecular Pharmacology
PG  - 1133--1140
VI  - 83
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/83/5/1133.short
4100  - http://molpharm.aspetjournals.org/content/83/5/1133.full
SO  - Mol Pharmacol2013 May 01; 83
AB  - A member of the NADPH oxidase subunits, p40phox 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 p40phox 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 p40phox gene expression in the liver, but this induction of p40phox gene expression was diminished by the deletion of the AhR gene in the liver. Consistent with the in vivo results, the expression of the p40phox gene was increased in 3MC-treated Hepa1c1c7 cells in an AhR-dependent manner. In addition, promoter analysis established p40phox as a transcriptional target of AhR. Studies using the RNA-interference technique revealed that p40phox 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.