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A ligand for the aryl hydrocarbon receptor isolated from lung.

Authors :
Jiasheng Song
Clagett-Dame, Margaret
Peterson, Richard E.
Hahn, Mark E.
Westler, William M.
Sicinski, Rafal R.
DeLuca, Hector F.
Source :
Proceedings of the National Academy of Sciences of the United States of America. 11/12/2002, Vol. 99 Issue 23, p14694. 6p. 1 Diagram, 1 Chart, 6 Graphs.
Publication Year :
2002

Abstract

The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is best known because it mediates the actions of polycyclic and halogenated aromatic hydrocarbon environmental toxicants such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. We report here the successful identification of an endogenous ligand for this receptor; ≈20 µg was isolated in pure form from 35 kg of porcine lung. Its structure was deduced as 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester from extensive physical measurements and quantum mechanical calculations. In a reporter gene assay, this ligand activates the AHR with a potency five times greater than that of β-naphthoflavone, a prototypical synthetic AHR ligand. 2-(l′H-indole-3′-carbonyl)thiazole-4-carboxylic acid methyl ester competes with 2,3,7,8[³H]tetrachlorodibenzo-p-dioxin for binding to human, murine, and fish AHRs, thus showing that AHR activation is caused by direct receptor binding, and that recognition of this endogenous ligand is conserved from early vertebrates (fish) to humans. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
99
Issue :
23
Database :
Academic Search Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
8683194
Full Text :
https://doi.org/10.1073/pnas.232562899