ArticleMolecular pharmacology2015
Induction of CYP26A1 by metabolites of retinoic acid: evidence that CYP26A1 is an important enzyme in the elimination of active retinoids.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 73 citations in OpenAlex.
- The antileukemic activity of decitabine upon PML/RARA-negative AML blasts is supported by all-trans retinoic acid: in vitro and in vivo evidence for cooperation.Blood cancer journal · 2022Trial
- Retinoic Acid Signalling Regulates Zebrafish Tooth Germ Repair Following Injury.Cell proliferation · 2026Article
- All-trans retinoic acid modulates proliferation and apoptosis of secondary hair follicle-dermal papilla cells in cashmere goats via the TGF-Frontiers in veterinary science · 2026Article
- AllJournal of the Royal Society, Interface · 2025Article
- Ethanol causes rapid decreases in the hepatic retinoid levels shaping the early steps of alcohol-associated liver disease.Alcohol, clinical & experimental research · 2025Article
- The interplay between retinoic acid binding proteins and retinoic acid degrading enzymes in modulating retinoic acid concentrations.Current topics in developmental biology · 2025Review
- Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials.Journal of functional biomaterials · 2023Review
- The Promise of Retinoids in the Treatment of Cancer: Neither Burnt Out Nor Fading Away.Cancers · 2023Review
- Effects of all-trans and 9-cis retinoic acid on differentiating human neural stem cells in vitro.Toxicology · 2023Article
- Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers.Frontiers in cell and developmental biology · 2023Review
- Temporal changes in the systemic concentrations of retinoids in pregnant and postpartum women.PloS one · 2023Article
- Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits.Journal of applied toxicology : JAT · 2022Article
- Retinoid metabolism: new insights.Journal of molecular endocrinology · 2022Review
- Application ofMolecular therapy. Methods & clinical development · 2022Article
- Isotretinoin and its Metabolites Alter mRNA of Multiple Enzyme and Transporter Genes In Vitro, but Downregulation of Organic Anion Transporting Polypeptide Does Not Translate to the Clinic.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Pesticides Inhibit Retinoic Acid Catabolism in PLHC-1 and ZFL Fish Hepatic Cell Lines.Chemical research in toxicology · 2022Article
- Review
- Retinoids in the Pathogenesis and Treatment of Liver Diseases.Nutrients · 2022Review
- Mechanisms of Feedback Regulation of Vitamin A Metabolism.Nutrients · 2022Review
- Anterior patterning genes induced by Zic1 are sensitive to retinoic acid and its metabolite, 4-oxo-RA.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
All-trans-retinoic acid (atRA), the active metabolite of vitamin A, induces gene transcription via binding to nuclear retinoic acid receptors (RARs). The primary hydroxylated metabolites formed from atRA by CYP26A1, and the subsequent metabolite 4-oxo-atRA, bind to RARs and potentially have biologic activity. Hence, CYP26A1, the main atRA hydroxylase, may function either to deplete bioactive retinoids or to form active metabolites. This study aimed to determine the role of CYP26A1 in modulating RAR activation via formation and elimination of active retinoids. After treatment of HepG2 cells with atRA, (4S)-OH-atRA, (4R)-OH-atRA, 4-oxo-atRA, and 18-OH-atRA, mRNAs of CYP26A1 and RARβ were increased 300- to 3000-fold, with 4-oxo-atRA and atRA being the most potent inducers. However, >60% of the 4-OH-atRA enantiomers were converted to 4-oxo-atRA in the first 12 hours of treatment, suggesting that the activity of the 4-OH-atRA was due to 4-oxo-atRA. In human hepatocytes, atRA, 4-OH-atRA, and 4-oxo-atRA induced CYP26A1 and 4-oxo-atRA formation was observed from 4-OH-atRA. In HepG2 cells, 4-oxo-atRA formation was observed even in the absence of CYP26A1 activity and this formation was not inhibited by ketoconazole. In human liver microsomes, 4-oxo-atRA formation was supported by NAD(+), suggesting that 4-oxo-atRA formation is mediated by a microsomal alcohol dehydrogenase. Although 4-oxo-atRA was not formed by CYP26A1, it was depleted by CYP26A1 (Km = 63 nM and intrinsic clearance = 90 μl/min per pmol). Similarly, CYP26A1 depleted 18-OH-atRA and the 4-OH-atRA enantiomers. These data support the role of CYP26A1 to clear bioactive retinoids, and suggest that the enzyme forming active 4-oxo-atRA may be important in modulating retinoid action.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.