ArticleMolecular endocrinology (Baltimore, Md.)2011
Transcriptional regulation of the human P450 oxidoreductase gene: hormonal regulation and influence of promoter polymorphisms.
Article in Molecular endocrinology (Baltimore, Md.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Cytochrome P450 oxidoreductase genetic polymorphisms A503V and rs2868177 do not significantly affect warfarin stable dosage in Han-Chinese patients with mechanical heart valve replacement.European journal of clinical pharmacology · 2013Trial
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Deciphering cytochrome P450 reductase role in MASLD: molecular mechanisms and pathophysiological implications.Nature reviews. Gastroenterology & hepatology · 2026Review
- Article
- Diagnostic challenges and management advances in cytochrome P450 oxidoreductase deficiency, a rare form of congenital adrenal hyperplasia, with 46, XX karyotype.Frontiers in endocrinology · 2023Review
- Steroidogenic electron-transfer factors and their diseases.Annals of pediatric endocrinology & metabolism · 2021Article
- Inhibition of phase-1 biotransformation and cytostatic effects of diphenyleneiodonium on hepatoblastoma cell line HepG2 and a CYP3A4-overexpressing HepG2 cell clone.Clinical hemorheology and microcirculation · 2021Article
- The Role of the FMN-Domain of Human Cytochrome P450 Oxidoreductase in Its Promiscuous Interactions With Structurally Diverse Redox Partners.Frontiers in pharmacology · 2020Article
- NADPH-cytochrome P450 reductase expression and enzymatic activity in primary-like human hepatocytes and HepG2 cells for in vitro biotransformation studies.Clinical hemorheology and microcirculation · 2019Article
- The P450 oxidoreductase (POR) rs2868177 and cytochrome P450 (CYP) 2B6*6 polymorphisms contribute to the interindividual variability in human CYP2B6 activity.European journal of clinical pharmacology · 2016Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- CyTRANSFINDER: a Cytoscape 3.3 plugin for three-component (TF, gene, miRNA) signal transduction pathway construction.BMC bioinformatics · 2016Article
- NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family.Archives of biochemistry and biophysics · 2012Review
- Identification of six novel P450 oxidoreductase missense variants in Ashkenazi and Moroccan Jewish populations.Pharmacogenomics · 2012Article
- Intensification of doxorubicin-related oxidative stress in the heart by hypothyroidism is not related to the expression of cytochrome P450 NADPH-reductase and inducible nitric oxide synthase, as well as activity of xanthine oxidase.Oxidative medicine and cellular longevity · 2012Article
- Nicotine induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production.Toxicology and applied pharmacology · 2011Article
- Identification of cytochrome P450 oxidoreductase gene variants that are significantly associated with the interindividual variations in warfarin maintenance dose.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Consequences of POR mutations and polymorphisms.Molecular and cellular endocrinology · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
P450 oxidoreductase (POR) is the flavoprotein that acts as the obligatory electron donor to all microsomal P450 enzymes, including those involved in hepatic drug metabolism as well as three steroidogenic P450 enzymes. The untranslated first exon of human POR was located recently, permitting analysis of human POR transcription. Expression of deletional mutants containing up to 3193 bp of the human POR promoter in human adrenal NCI-H295A and liver Hep-G2 cells located the proximal promoter at -325/-1 bp from the untranslated exon. Common human POR polymorphisms at -208 and -173 had little influence on transcription, but the polymorphism at -152 reduced transcription significantly in both cell lines. EMSA and supershift assays identified binding of Smad3/Smad4 between -249 and -261 and binding of thyroid hormone receptor-β (TRβ) at -240/-245. Chromatin immunoprecipitation showed that Smad3, Smad4, TRα, TRβ, and estrogen receptor-α were bound between -374 and -149. Cotransfection of vectors for these transcription factors and POR promoter-reporter constructs into both cell types followed by hormonal treatment showed that T(3) exerts major tropic effects via TRβ, with TRα, estrogen receptor-α, Smad3, and Smad4 exerting lesser, modulatory effects. T(3) also increased POR mRNA in both cell lines. Thyroid hormone also is essential for rat liver POR expression but acts via different transcription factor complexes. These are the first data on human POR gene transcription, establishing roles for TRβ and Smad3/4 in its expression and indicating that the common polymorphism at -152 may play a role in genetic variation in steroid biosynthesis and drug metabolism.
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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.