QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bittinger, M. A. Articles by Bradfield, C. A. Search for Related Content PubMed PubMed Citation Articles by Bittinger, M. A. Articles by Bradfield, C. A.

ACCELERATED COMMUNICATION

Aspartate Aminotransferase Generates Proagonists of the Aryl Hydrocarbon Receptor

McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin

The aryl hydrocarbon receptor (AHR) binds planar aromatic compounds and up-regulates the transcription of a battery of xenobiotic-metabolizing enzymes. To identify proteins involved in the biosynthesis of endogenous AHR ligands, we screened extracts of various mouse tissues for AHR signaling activity. We found heart extract to activate AHR and identified the active component to be the enzyme aspartate aminotransferase (EC 2.6.1.1). We demonstrate that this transaminase can activate AHR signaling by converting L-tryptophan to indole-3-pyruvate. In turn, indole-3-pyruvate spontaneously reacts in aqueous solution to form a large number of compounds that act as agonists of AHR. Tyrosine and the serotonin-precursor 5-hydroxytryptophan also activate AHR signaling in combination with aspartate aminotransferase, suggesting that 4-hydroxyphenylpyruvate and 5-hydroxyindolepyruvate also act as proagonists of AHR. This study demonstrates that the known tryptophan metabolic-intermediate indole-3-pyruvate is a proagonist of AHR that reacts in aqueous solution to form a variety of AHR agonists.

Address correspondence to: Christopher A. Bradfield, Ph.D., McArdle Laboratory for Cancer Research, 1400 University Avenue, Madison, WI 53706. E-mail: bradfield{at}oncology.wisc.edu

This article has been cited by other articles:

				I. Teneng, V. Stribinskis, and K. S. Ramos Context-specific regulation of LINE-1 Genes Cells, October 1, 2007; 12(10): 1101 - 1110. [Abstract] [Full Text] [PDF]

				B. J. McMillan and C. A. Bradfield The Aryl Hydrocarbon Receptor sans Xenobiotics: Endogenous Function in Genetic Model Systems Mol. Pharmacol., September 1, 2007; 72(3): 487 - 498. [Abstract] [Full Text] [PDF]

				A. B. Okey An Aryl Hydrocarbon Receptor Odyssey to the Shores of Toxicology: The Deichmann Lecture, International Congress of Toxicology-XI Toxicol. Sci., July 1, 2007; 98(1): 5 - 38. [Abstract] [Full Text] [PDF]

				C. G. Woods, J. P. Vanden Heuvel, and I. Rusyn Genomic Profiling in Nuclear Receptor-Mediated Toxicity Toxicol Pathol, June 1, 2007; 35(4): 474 - 494. [Abstract] [Full Text] [PDF]

				W. Hu, C. Sorrentino, M. S. Denison, K. Kolaja, and M. R. Fielden Induction of Cyp1a1 Is a Nonspecific Biomarker of Aryl Hydrocarbon Receptor Activation: Results of Large Scale Screening of Pharmaceuticals and Toxicants in Vivo and in Vitro Mol. Pharmacol., June 1, 2007; 71(6): 1475 - 1486. [Abstract] [Full Text] [PDF]

				S. Diani-Moore, E. Labitzke, R. Brown, A. Garvin, L. Wong, and A. B. Rifkind Sunlight Generates Multiple Tryptophan Photoproducts Eliciting High Efficacy CYP1A Induction in Chick Hepatocytes and In Vivo Toxicol. Sci., March 1, 2006; 90(1): 96 - 110. [Abstract] [Full Text] [PDF]

				S. Mulero-Navarro, E. Pozo-Guisado, P. A. Perez-Mancera, A. Alvarez-Barrientos, I. Catalina-Fernandez, E. Hernandez-Nieto, J. Saenz-Santamaria, N. Martinez, J. M. Rojas, I. Sanchez-Garcia, et al. Immortalized Mouse Mammary Fibroblasts Lacking Dioxin Receptor Have Impaired Tumorigenicity in a Subcutaneous Mouse Xenograft Model J. Biol. Chem., August 5, 2005; 280(31): 28731 - 28741. [Abstract] [Full Text] [PDF]