Activation of the Ah Receptor Signaling Pathway by Prostaglandins
2001; Wiley; Volume: 15; Issue: 4 Linguagem: Inglês
10.1002/jbt.16
ISSN1099-0461
AutoresShawn D. Seidel, Greg M. Winters, William J. Rogers, Michael H. Ziccardi, Violet Li, Bart Keser, Michael S. Denison,
Tópico(s)Pharmacogenetics and Drug Metabolism
ResumoAbstract The aryl hydrocarbon receptor (AhR) is a ligand‐dependent transcription factor that mediates many of the biological and toxicological actions of a diverse range of chemicals, including the environmental contaminant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD, dioxin). Although no endogenous physiological ligand for the AhR has yet been described, numerous studies support the existence of such a ligand(s). Here we have examined the ability of prostaglandins and related chemicals to activate the AhR signaling system. Using two AhR‐based bioassay systems we report that relatively high concentrations of several prostaglandins (namely, PGB 3 , PGD 3 , PGF 3α , PGG 2 , PGH 1 , and PGH 2 ) can not only stimulate AhR transformation and DNA binding in vitro, but also induce AhR‐dependent reporter gene expression in mouse hepatoma cells in culture. PGG 2 also induced AhR‐dependent reporter gene expression to a level three‐to four fold greater than that observed with a maximal inducing dose of TCDD. Sucrose gradient ligand binding analysis revealed that PGG 2 could competitively displace [ 3 H]TCDD from the AhR. Overall, our results demonstrate that selected prostaglandins are weak agonists for the AhR and they represent a structurally distinct and novel class of activator of the AhR signal transduction pathway. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:187–196, 2001
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