CH223191 IS A LIGAND-SPECIFIC ANTAGONIST OF THE AH RECEPTOR
The Ah receptor (AhR) is a ligand-dependent nuclear receptor that regulates gene expression in a wide variety of species and tissues. While the best-characterized high affinity AhR ligands include halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD, dioxin) and polycyclic aromatic hydrocarbons (PAHs), the AhR can bind and be activated by a structurally diverse range of chemicals. While differences in the binding of ligands within the AhR ligand binding domain (LBD) could account for some of the observed diversity of AhR ligand structure, strong support for the hypothesis is lacking. Utilizing a combination of AhR ligand and DNA binding and gene expression assays we have identified a novel antagonist (CH223191) that can specifically inhibit the ability of HAHs, but not PAHs or PAH-like chemicals, to bind to and/or stimulate AhR DNA binding or AhR-dependent gene expression. These results not only demonstrate that HAHs and PAHs (and PAH-like chemicals) differentially interact within the AhR LBD, but that CH223191 is an HAH-specific antagonist.
Bin Zhao Danica DeGroot Guochun He Ai Hayashi Michael S.Denison
Department of Environmental Toxicology,University of California,Davis,California,USA Research Center Department of Environmental Toxicology,University of California,Davis,California,USA
国际会议
北京
英文
1-6
2009-08-24（万方平台首次上网日期，不代表论文的发表时间）