PT  - JOURNAL ARTICLE
AU  - Taira Wada
AU  - Hiroshi Sunaga
AU  - Reiko Ohkawara
AU  - Shigeki Shimba
TI  - AhR Modulates NADPH Oxidase Activity Via Direct Transcriptional Regulation of p40<sup>phox</sup> Expression
AID  - 10.1124/mol.112.083303
DP  - 2013 Mar 11
TA  - Molecular Pharmacology
PG  - mol.112.083303
4099  - http://molpharm.aspetjournals.org/content/early/2013/03/11/mol.112.083303.short
4100  - http://molpharm.aspetjournals.org/content/early/2013/03/11/mol.112.083303.full
AB  - p40phox , a member of the NADPH oxidase subunits, 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-methylcholantren (3MC) increased p40phox gene expression in the liver. However, this induction of p40phox gene expression was diminished by the deletion of the AhR gene in the liver. Consist 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 RNAi technique revealed that p40phox is essential for the increase of NADPH oxidase activity and the subsequent ROS production in AhR-activated Hepa1c1c7 cells. Consequently, these results indicate that AhR is involved in the oxidative stress network associated with NADPH oxidase via the regulation of p40phox expression.