Characterization of the Ah receptor
Abstract
The Ah receptor is a soluble protein that binds xenobiotic compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, with high affinity. Following ligand binding, the Ah receptor-ligand complex translocates into the nucleus. The ultimate biological response is the induction of genes, such as CYP1A1. In the work presented in this thesis, some of the biochemical properties of the Ah receptor and Ah receptor-ligand interactions were examined. The Ah receptor half-life was determined during unoccupied conditions and during ligand occupation. The half-life of the unoccupied Ah receptor was determined to be 4.5 hours in Hepa 1 cells. During occupation with ligand, both the half-life and the cytosolic concentrations of the Ah receptor decreased. This appeared to be ligand dependent, but did not appear to require nuclear translocation. The interaction of the Ah receptor with a newly synthesized radioligand, 4$\sp\prime$- ($\sp{125}$I) flavone, was examined. Although the Ah receptor binds 4$\sp\prime$- ($\sp{125}$l) flavone with relatively low affinity, this ligand was found to effectively act as an Ah receptor agonist. However, nuclear uptake of 4$\sp\prime$- ($\sp{125}$I) flavone differed from that of 2- ($\sp{125}$I) 7,8-dibromodibenzo-p-dioxin. Finally, the presence of the Ah receptor in rainbow trout derived cells was determined. The molecular weight of rainbow trout Ah receptor was much greater than rodent Ah receptor. It is apparent that the mechanisms of Ah receptor mediation proceed similarly in both rainbow trout and rodent systems.
Degree
Ph.D.
Advisors
Perdew, Purdue University.
Subject Area
Molecular biology|Food science|Nutrition
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