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Indirubin and Indigo Are Potent Aryl Hydrocarbon Receptor Ligands Present in Human Urine
Open accessAbstract
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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“Nevertheless, Indirubin demonstrated the strongest binding to AHR among these ligands, consistent with previous reports45,46.”
From Structural basis for the ligand-dependent activation of heterodimeric AHR-ARNT complex (2025) · cites this paper as [45]
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Metadata
- 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
- hybrid
- doi.org
- Licence
- 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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