Activation of the Ah receptor by tryptophan and tryptophan metabolites

Sharon Heath-Pagliuso, William J. Rogers, Kathryn Tullis, Shawn D. Seidel, Peter H. Cenijn, Abraham Brouwer, Michael S. Denison

Research output: Contribution to journalArticle

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Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of a variety of hydrophobic natural and synthetic chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin). A variety of indole-containing chemicals, such as indole-3-carbinol, indolo[3,2-b]carbazole, and UV photoproducts of tryptophan (TRP), have previously been identified as ligands for AhR. Here we have examined the ability of endogenous metabolites of tryptophan (TRP) to bind to and activate AhR in vitro and in cells in culture. Although hydroxylated TRP metabolites were inactive, two metabolites, namely tryptamine (TA) and indole acetic acid (IAA), were shown to be AhR agonists. Not only do TA and IAA bind competitively to AhR, but they also can stimulate AhR transformation and DNA binding and induce expression of an AhR-dependent reporter gene in cells. In addition to being an AhR ligand, TA is also a competitive substrate for cytochrome P4501A1, a well-characterized AhR- and TCDD-inducible gene product. Although these compounds are relatively weak ligands, compared to TCDD, they represent some of the first endogenous hydrophilic AhR agonists identified to date.

Original languageEnglish (US)
Pages (from-to)11508-11515
Number of pages8
JournalBiochemistry
Volume37
Issue number33
DOIs
StatePublished - Aug 18 1998

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Aryl Hydrocarbon Receptors
Metabolites
Tryptophan
Chemical activation
Ligands
Genes
tryptophyltryptophan
Dioxins
Cytochromes
Reporter Genes
Toxicology
Transcription Factors
Cell Culture Techniques
Impurities

ASJC Scopus subject areas

  • Biochemistry

Cite this

Heath-Pagliuso, S., Rogers, W. J., Tullis, K., Seidel, S. D., Cenijn, P. H., Brouwer, A., & Denison, M. S. (1998). Activation of the Ah receptor by tryptophan and tryptophan metabolites. Biochemistry, 37(33), 11508-11515. https://doi.org/10.1021/bi980087p

Activation of the Ah receptor by tryptophan and tryptophan metabolites. / Heath-Pagliuso, Sharon; Rogers, William J.; Tullis, Kathryn; Seidel, Shawn D.; Cenijn, Peter H.; Brouwer, Abraham; Denison, Michael S.

In: Biochemistry, Vol. 37, No. 33, 18.08.1998, p. 11508-11515.

Research output: Contribution to journalArticle

Heath-Pagliuso, S, Rogers, WJ, Tullis, K, Seidel, SD, Cenijn, PH, Brouwer, A & Denison, MS 1998, 'Activation of the Ah receptor by tryptophan and tryptophan metabolites', Biochemistry, vol. 37, no. 33, pp. 11508-11515. https://doi.org/10.1021/bi980087p
Heath-Pagliuso S, Rogers WJ, Tullis K, Seidel SD, Cenijn PH, Brouwer A et al. Activation of the Ah receptor by tryptophan and tryptophan metabolites. Biochemistry. 1998 Aug 18;37(33):11508-11515. https://doi.org/10.1021/bi980087p
Heath-Pagliuso, Sharon ; Rogers, William J. ; Tullis, Kathryn ; Seidel, Shawn D. ; Cenijn, Peter H. ; Brouwer, Abraham ; Denison, Michael S. / Activation of the Ah receptor by tryptophan and tryptophan metabolites. In: Biochemistry. 1998 ; Vol. 37, No. 33. pp. 11508-11515.
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