ArticleThe Journal of biological chemistry2010
Interaction between oxidative stress sensor Nrf2 and xenobiotic-activated aryl hydrocarbon receptor in the regulation of the human phase II detoxifying UDP-glucuronosyltransferase 1A10.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 123 citations in OpenAlex.
- Decoding the Multi-Component Synergy of Fu Ling Yin Zi for Anti-Oxidative Stress Applications: Formulation Optimization, Molecular Docking, Cell-Based Validation, and 3D-Printed Dysphagia-Friendly Diets.Foods (Basel, Switzerland) · 2026Article
- The impact of oxidative stress and the NRF2-KEAP1-ARE signaling pathway on anticancer drug resistance.Oncology research · 2025Review
- Mapping the functional network of human cancer through machine learning and pan-cancer proteogenomics.Nature cancer · 2025Article
- Targeting aryl hydrocarbon receptor functionally restores tolerogenic dendritic cells derived from patients with multiple sclerosis.The Journal of clinical investigation · 2024Article
- Identification of novel FRedox biology · 2024Article
- Article
- High-Throughput Transcriptomics of Water Extracts Detects Reductions in Biological Activity with Water Treatment Processes.Environmental science & technology · 2024Article
- Environmentally persistent free radicals: Methods for combustion generation, whole-body inhalation and assessing cardiopulmonary consequences.Environmental pollution (Barking, Essex : 1987) · 2023Article
- Development, scrutiny, and modulation of transient reporter gene assays of the xenobiotic metabolism pathway in zebrafish hepatocytes.Cell biology and toxicology · 2023Article
- Redox Proteomic Profile of Tirapazamine-Resistant Murine Hepatoma Cells.International journal of molecular sciences · 2023Article
- Tensile strain and altered synovial tissue metabolism in human knee osteoarthritis.Scientific reports · 2022Article
- Gene Expression Analysis of Adapted Insect Cells during Influenza VLP Production Using RNA-Sequencing.Viruses · 2022Article
- The Aryl Hydrocarbon Receptor in the Pathogenesis of Environmentally-Induced Squamous Cell Carcinomas of the Skin.Frontiers in oncology · 2022Review
- UDP-glucuronosyltransferases mediate coffee-associated reduction of liver fibrosis in bile duct ligated humanized transgenicHepatobiliary surgery and nutrition · 2021Article
- Review
- Genome-wide CRISPR screen identifies LGALS2 as an oxidative stress-responsive gene with an inhibitory function on colon tumor growth.Oncogene · 2021Article
- Article
- Cytochrome P4501B1 in bone marrow is co-expressed with key markers of mesenchymal stem cells. BMS2 cell line models PAH disruption of bone marrow niche development functions.Toxicology and applied pharmacology · 2020Article
- Ozone-Induced Aryl Hydrocarbon Receptor Activation Controls Lung Inflammation via Interleukin-22 Modulation.Frontiers in immunology · 2020Article
- Investigation of Molecular Details of Keap1-Nrf2 Inhibitors Using Molecular Dynamics and Umbrella Sampling Techniques.Molecules (Basel, Switzerland) · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The defense against oxidative stress is a critical feature that prevents cellular and DNA damage. UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of xenobiotics, mutagens, and reactive metabolites and thus act as indirect antioxidants. Aim of this study was to elucidate the regulation of UGTs expressed in the mucosa of the gastrointestinal tract by xenobiotics and the main mediator of antioxidant defense, Nrf2 (nuclear factor erythroid 2-related factor 2). Xenobiotic (XRE) and antioxidant (ARE) response elements were detected in the promoters of UGT1A8, UGT1A9, and UGT1A10. Reporter gene experiments demonstrated XRE-mediated induction by dioxin in addition to tert-butylhydroquinone (ARE)-mediated induction of UGT1A8 and UGT1A10, which are expressed in extrahepatic tissue in humans in vivo. The responsible XRE and ARE motifs were identified by mutagenesis. Small interfering RNA knockdown, electrophoretic mobility shifts, and supershifts identified a functional interaction of Nrf2 and the aryl hydrocarbon receptor (AhR). Induction of UGT1A8 and UGT1A10 requires Nrf2 and AhR. It proceeds by utilizing XRE- as well as ARE-binding motifs. In summary, we demonstrate the coordinated AhR- and Nrf2-dependent transcriptional regulation of human UGT1As. Cellular protection by glucuronidation is thus inducible by xenobiotics via AhR and by oxidative metabolites via Nrf2 linking glucuronidation to cellular protection and defense against oxidative stress.
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