Aryl hydrocarbon receptor ligands

Pandini, A., Denison, M.S., Song, Y., Soshilov, A.A. and Bonati, L. (2007) Structural and functional characterization of the aryl hydrocarbon receptor ligand binding domain by homology modeling and mutational analysis. Biochemistry, 46, 696-708. 

Adachi J, Mori Y, Matsui S, Takigami H, Fu-jino J, Kitagawa H, Miller CAI, Kato T, Saeki K, Matsuda T (2001) Indirubin and indigo are potent aryl hydrocarbon receptor ligands in human urine. J Biol Chem 276, 31475-31478. 

Kawanishi, M., Sakamoto, M., Ito, A., Kishi, K. and Yagi, T. (2003) Construction of reporter yeasts for mouse aryl hydrocarbon receptor ligand activity. Mutation Research, 540, 99-105. 

Hestermann, E.V., J.J. Stegeman and M.E. Hahn. Relative contributions of affinity and intrinsic efficacy to aryl hydrocarbon receptor ligand potency. Toxicol. Appl. Pharmacol. 168 160-172, 2000. 

Metz, R. P. and Ritter, J. K. (1998) Transcriptional activation of the UDP-glucuronosyltransferase 1A7 gene in rat liver by aryl hydrocarbon receptor ligands and oltipraz. J. Biol. Chem. 273, 5607-5614. 

Soshilov A, Denison MS (2011) Ligand displaces heat shock protein 90 from overlapping binding sites within the aryl hydrocarbon receptor ligand-binding domain. J Biol Chem 286 35275-35282... 

In U937 cells and human macrophages aryl hydrocarbon receptor, with its partner cofactor aryl hydrocarbon receptor nuclear translocator, was expressed and CYPlAl mRNA expression was induced in the presence of aryl hydrocarbon receptor ligand 3-methylcholanthrene (Komura et al. 2001). 

Indolo[3,2-fi]carbazole (4) has also been the focus of many recent studies, since the discovery in the 1980s that 4 and several derivatives thereof are powerful aryl hydrocarbon receptor (AHR) ligands. The remaining three isomers have been more... 

The most recent synthetic efforts in this area have focused on the preparation of mono- and diformyl-substituted indolo[3,2-l)]carbazoles 202 and 203, which are potent aryl hydrocarbon receptor (AHR) ligands (cf. Section V,C). 

Carver, L. and Bradfield, C., Ligand-dependent interaction of the aryl hydrocarbon receptor with a novel immunophilin homolog in vivo, J. Biol. Chem., 272, 11452, 1997. 

Camacho, I., et. al., Treatment of mice with 2,3,7,8-tetrachlorodibenzo-p-dioxin leads to aryl hydrocarbon receptor-dependent nuclear translocation of NF-kappa B and expression of Fas ligand in thymic stromal cells and consequent T cell apoptosis, J. Immunol., 175, 90, 2005. 

P450 Inducers Acting via Transcription Factors 330 Aryl Hydrocarbon Receptor 330 General Ligand Features Leading to NR Activation 332 References 333... 

Ciolino, H.P., Daschner, P.J., and Yeh, G.C., Dietary flavonoids quercetin and kaempferol are ligands of aryl hydrocarbon receptor that affect CYPlAl differentially, Biochem. J., 340, 715, 1999. 

Hahn ME, Westler WM, Sicinski RR, De-Luca HF (2002) A ligand for the aryl hydrocarbon receptor isolated from lung. 

Table 2 Nuclear receptors (NR) for enzyme inducers. Enzyme inducers are now known to act as ligands to nuclear receptors, leading to gene activation and increased synthesis of the enzyme. Affinity of inducers to die receptors is now known to be responsible for the differential induction potential and can explain die observed species-differences in induction. The receptors tabulated are aryl hydrocarbon receptors (AhR), constituitively androstane receptor (CAR), pregnane X receptor (PXR), and glucocorticoid receptor (GR). The isoforms in bold type are the major isoform regulated by the corresponding receptors.

Many of the toxic and biological effects induced by polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and PCBs such as carcinogenesis, reproductive disturbances and immunotoxic effects are believed to be mediated via the hepatic cytosolic aryl hydrocarbon receptor (Ah receptor) [254,255]. Based on in vitro and in vivo studies, the toxicity of individual organochlorines have been determined relative to 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD) and expressed as toxic equivalency factors (TEFs) [254, 256]. In addition to PCDD/F, structurally related PCBs and PCNs bind to the Ah receptor. After binding to the Ah-receptor, the receptor-ligand complex is transferred into the nucleus where it binds to specific DNA sequences and causes transcription of structural genes, which in turn causes synthesis of various cytochrome P4501A1-dependent enzymes such as ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH). TEFs for PCNs have been estimated from enzyme-induction assays of EROD and AHH [10, 257] and Luciferase assays in rat cells [12] cf. Table 4. 

Perhaps the environmental chemical most studied with regard to effects on the immune system has been 2,3,7,8-tetrachlorodibenzo-p-dioxin, which is also known as TCDD or dioxin . While it appears that dioxin may affect multiple cell types, it is apparent that the B cell is an especially sensitive target. The mechanism of action for the immunotoxic effects of dioxin remains poorly understood. It is well established that many of the actions of dioxin, including inhibition of the primary antibody response, are mediated by a specific cytosolic receptor, termed the aryl hydrocarbon receptor (AhR). AhR exhibits a profile of activity similar to steroid receptors in that the ligand-activated receptor undergoes a nuclear... 

Ciolino HP, Daschner PJ, Yeh GC. 1999. Dietary flavonols quercetin and kaemp-ferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Biochem. J. 340 715-22... 

Singh S, Hord N, Perdew GH. 1996. Characterization of the activated form of the aryl hydrocarbon receptor in the nucleus of Hela cells in the absence of exogenous ligand. Arch. Biochem. Biophys. 329 47-55... 

Miller CA 3rd. 1999. A human aryl hydrocarbon receptor signaling pathway constructed in yeast displays additive responses to ligand mixtures. Toxicol. Appl. Pharmacol. 160 297-303... 

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