ArticleThe Journal of pharmacology and experimental therapeutics2009
Identification of human CYP2C8 as a retinoid-related orphan nuclear receptor target gene.
Article in The Journal of pharmacology and experimental therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Pharmacokinetics, pharmacodynamics and safety of the inverse retinoic acid-related orphan receptor γ agonist AZD0284.British journal of clinical pharmacology · 2020Trial
- High retinoic acid receptor-related orphan receptor A gene expression in peripheral blood leukocytes may be related to acute myocardial infarction.The Journal of international medical research · 2021Article
- Timing in drug absorption and disposition: The past, present, and future of chronopharmacokinetics.British journal of pharmacology · 2020Review
- Ser100-Phosphorylated RORMolecular pharmacology · 2020Article
- CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver.Molecular pharmacology · 2016Article
- Inhibition of RORγt activity and Th17 differentiation by a set of novel compounds.BMC immunology · 2015Article
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- Regulation of the human hydroxysteroid sulfotransferase (SULT2A1) by RORα and RORγ and its potential relevance to human liver diseases.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα).PloS one · 2012Article
- The transcriptional regulation of the human CYP2C genes.Current drug metabolism · 2009Review
- Retinoid-related orphan receptors (RORs): critical roles in development, immunity, circadian rhythm, and cellular metabolism.Nuclear receptor signaling · 2009Review
- Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism.Nuclear receptor researchArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Retinoid-related orphan nuclear receptors (RORs) alpha and gamma (NR1F1, -3) are highly expressed in liver, adipose tissue, thymus, and brain and are involved in many physiological processes, such as circadian rhythm and immune function. Enzymes in the cytochrome P450 2C subfamily metabolize many clinically important drugs and endogenous compounds, such as the anticancer drug paclitaxel and arachidonic acid, and are highly expressed in liver. Here, we present the first evidence that RORs regulate the transcription of human CYP2C8. Overexpression of RORalpha and RORgamma in HepG2 cells significantly enhanced the activity of the CYP2C8 promoter but not that of the CYP2C9 or CYP2C19 promoters. Computer analyses, promoter deletion studies, gel shift assays, and mutational analysis identified an essential ROR-responsive element at -2045 base pairs in the CYP2C8 promoter that mediates ROR transactivation. Adenoviral overexpression of RORalpha and -gamma significantly induced endogenous CYP2C8 transcripts in both HepG2 cells and human primary hepatocytes. Knockdown of endogenous RORalpha and -gamma expression in HepG2 cells by RNA interference decreased the expression of endogenous CYP2C8 mRNA by approximately 50%. These data indicate that RORs transcriptionally up-regulate CYP2C8 in human liver and, therefore, may be important modulators of the metabolism of drugs and physiologically active endogenous compounds by this enzyme in liver and possibly extrahepatic tissues where RORs are expressed.
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Registered trials
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.