ArticleFrontiers in pharmacology2020
Regulation of High-Altitude Hypoxia on the Transcription of CYP450 and UGT1A1 Mediated by PXR and CAR.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Functional impact of high-altitude hypoxia on central nervous system drug transport: integrated analysis of blood-brain barrier permeability, drug transporter/enzyme expression, and pharmacokinetics.Fluids and barriers of the CNS · 2026Article
- Development and Validation of a UPLC-MS/MS Method for the Quantification of Amantadine in Rat Plasma: Application to a Pharmacokinetic Study Under High-Altitude Hypoxia and Mechanistic Insights.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Advances in laboratory diagnosis of neonatal hyperbilirubinemia and peculiarities in plateau regions: a review of evidence.Frontiers in pediatrics · 2026Review
- Chronic Hypobaric Hypoxia at High Altitudes Aggravates Chronic Obstructive Pulmonary Disease in Mice.Journal of inflammation research · 2026Article
- Effect of high-altitude hypoxia on function and cytoarchitecture of rats' liver.Scientific reports · 2025Article
- Antimicrobial resistance pattern due to oxygen gap at high altitudes.Frontiers in cellular and infection microbiology · 2025Review
- Flavonoids and Organic Acids Affect Phase II Metabolism based on the Regulation of UGT1A1 Expression and Function.Current computer-aided drug design · 2025Article
- Blood-Brain Barrier Permeability is Affected by Changes in Tight Junction Protein Expression at High-Altitude Hypoxic Conditions-this may have Implications for Brain Drug Transport.The AAPS journal · 2024Article
- Effect of High Altitude Environment on Pharmacokinetic and Pharmacodynamic of Warfarin in Rats.Current drug metabolism · 2024Article
- Induction of cytochrome P450 via upregulation of CAR and PXR: a potential mechanism for altered florfenicol metabolism by macranthoidin BFrontiers in pharmacology · 2024Article
- Altitude effect on Propofol Pharmacokinetics in Rats.Current drug metabolism · 2024Article
- Identification of key pathways, genes and immune cell infiltration in hypoxia of high-altitude acclimatizationFrontiers in genetics · 2023Article
- High-altitude Hypoxia Influences the Activities of the Drug-Metabolizing Enzyme CYP3A1 and the Pharmacokinetics of Four Cardiovascular System Drugs.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis.Frontiers in pharmacology · 2022Article
- Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil.Frontiers in physiology · 2022Article
- Hsa-miR-4277 Decelerates the Metabolism or Clearance of Sorafenib in HCC Cells and Enhances the Sensitivity of HCC Cells to Sorafenib by TargetingFrontiers in oncology · 2021Article
- Biological roles of cytochrome P450 1A1, 1A2, and 1B1 enzymes.Archives of pharmacal research · 2021Review
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Little is known about what roles the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) play in drug metabolism in high-altitude hypoxia. Likewise, the potential interaction of nuclear receptors and drug metabolism enzymes during drug metabolism of high-altitude hypoxia is not fully understood. In this work, we investigated the effects of high-altitude hypoxia on transcriptional regulation of cytochrome P450 (CYP450) and UDP-glucuronosyltransferase 1A1 (UGT1A1) genes mediated by PXR and CAR proteins. The protein and mRNA expressions of CYP450, UGT1A1, PXR, and CAR were determined by enzyme-linked immunosorbent assay and qPCR in rats and HepG2 cell lines under hypoxia. Hypoxia potently inhibited the CYP450 isoforms, UGT1A1, PXR, and CAR protein and mRNA expression. To clarify whether PXR and CAR regulate various genes involved in drug metabolism of high-altitude hypoxia, we investigated the expression of CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 using a dual-luciferase reporter assay after treatment with Ketoconazole (KCZ) and Retinoic acid (RA), or silenced PXR and CAR gene expression. In HepG2 cells, hypoxia, KCZ, and RA inhibited CYP450 isoforms and UGT1A1 expression. Activation of PXR and CAR in cells treated with 6-(4-chlorophenyl)-imidazo (2,1-b) thiazole-5-carbaldehyde (CITCO) and rifampicin (Rif) resulted in the enhancement of CYP450 isoforms, UGT1A1, PXR, and CAR. In contrast, this effect was not observed under hypoxia. Taken together, our results suggest that hypoxia inhibits CYP1A2, CYP2C9, CYP2E1, CYP3A4, and UGT1A1 expression
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