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Indirubin and Indigo Are Potent Aryl Hydrocarbon Receptor Ligands Present in Human Urine

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Adachi, Jun, Mori, Yoshitomo, Matsui, Saburo, Takigami, Hidetaka, Fujino, Junko, Kitagawa, Hiroko, Miller, Charles A., Kato, Takaaki, Saeki, Kenichi, Matsuda, Tomonari·2001·Journal of Biological Chemistry

DOI 10.1074/jbc.c100238200

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Abstract

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates genes involved in xenobiotic metabolism, cellular proliferation, and differentiation. Numerous xenobiotic and biological compounds are known to interact with AhR, but it remains an orphan receptor, because its physiological ligand is unknown. We identified AhR ligands in human urine using a yeast AhR signaling assay and then characterized their properties. Two ligands, indirubin and indigo, were both present at average concentrations of approximately 0.2 nm in the urine of normal donors. Indirubin was also detected in fetal bovine serum and contributed half of the total AhR ligand activity. The activities of indirubin and indigo were comparable with or more potent than that of the archetypal ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin, in yeast AhR activation assays. We suggest that the endogenous levels and potencies of indirubin and indigo are such that they activate AhR-mediated signaling mechanisms in vivo.

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Authors: Adachi, J., Mori, Y., Matsui, S., Takigami, H., Fujino, J., Kitagawa, H., Miller, C. A., Kato, T., Saeki, K., & Matsuda, T.
Affiliations: Kyoto University (JP)
Tulane University (US)
Nagoya City University (JP)
Corresponding author: Matsuda, Tomonari
ORCID: Adachi, Jun
Mori, Yoshitomo
Miller, Charles A.
Kato, Takaaki
Matsuda, Tomonari
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2001-08
Volume: 276
Issue: 34
Pages: 31475-31478
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.c100238200
OpenAlex: W1989060543
Cited by: 407
References: 22
Citations by year: 2026: 4 · 2025: 11 · 2024: 9 · 2023: 14 · 2022: 21 · 2021: 15 · 2020: 12 · 2019: 16 · 2018: 19 · 2017: 9 · 2016: 18 · 2015: 14 · 2014: 13 · 2013: 20 · 2012: 16
FWCI: 15.22
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7016 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Institute of Environmental Health Sciences (ES09055, R29ES009055)
Topics: Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords: aryl hydrocarbon receptor, indirubin, indigo, AhR ligands, human urine, endogenous ligands, 2,3,7,8-tetrachlorodibenzo-p-dioxin, xenobiotic metabolism, transcription factor signaling
MeSH terms: Polychlorinated Dibenzodioxins, Humans, Indigo Carmine, Indoles, Ligands, Male, Saccharomyces cerevisiae, Signal Transduction, Genes, Reporter, Receptors, Aryl Hydrocarbon

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Indirubin and Indigo Are Potent Aryl Hydrocarbon Receptor Ligands Present in Human Urine

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