Cited by 412Toxic Organic Pollutants ImpactPharmacogenetics and Drug MetabolismGenomics, phytochemicals, and oxidative stress

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 +2 more·2001·Journal of Biological Chemistry

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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Crossref · 10.1074/jbc.c100238200

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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
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2001-08
Volume
276
Issue
34
Pages
31475-31478
ISSN
0021-9258 (ISSN-L)
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
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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