ArticleToxicological sciences : an official journal of the Society of Toxicology2014
Flame retardant BDE-47 effectively activates nuclear receptor CAR in human primary hepatocytes.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Developing adverse outcome pathways underlying CAR activation-induced liver injuries using HepG2 spheroid model.Archives of toxicology · 2026Article
- Halogenated flame retardant exposure was associated with pediatric gut microbiome profiles in a Canadian cohort.Gut microbes reports · 2026Article
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Polybrominated diphenyl ether flame retardants inhibit growth factor-induced activation of EGFR by binding to its extracellular domain.Archives of toxicology · 2025Article
- Liver matrin-3 protects mice against hepatic steatosis and stress response via constitutive androstane receptor.Molecular metabolism · 2024Article
- Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.EFSA journal. European Food Safety Authority · 2024Article
- Human toxicity of polybrominated diphenyl ethers (PBDEs) and their derivatives: A comprehensive review.Current research in food science · 2024Review
- Toxic Effects and Mechanisms of Polybrominated Diphenyl Ethers.International journal of molecular sciences · 2023Review
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Understanding the physiological functions of the host xenobiotic-sensing nuclear receptors PXR and CAR on the gut microbiome using genetically modified mice.Acta pharmaceutica Sinica. B · 2022Article
- Review
- Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes.The Journal of biological chemistry · 2020Article
- Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure.Toxicologic pathology · 2020Article
- The gut microbiome: an orchestrator of xenobiotic metabolism.Acta pharmaceutica Sinica. B · 2020Review
- Transcriptomic profiling of PBDE-exposed HepaRG cells unveils critical lncRNA- PCG pairs involved in intermediary metabolism.PloS one · 2020Article
- Human constitutive androstane receptor agonist DL5016: A novel sensitizer for cyclophosphamide-based chemotherapies.European journal of medicinal chemistry · 2019Article
- Validation of in vitro methods for human cytochrome P450 enzyme induction: Outcome of a multi-laboratory study.Toxicology in vitro : an international journal published in association with BIBRA · 2019Article
- Polybrominated Diphenyl Ethers and Gut Microbiome Modulate Metabolic Syndrome-Related Aqueous Metabolites in Mice.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Pharmacological Activation of PXR and CAR Downregulates Distinct Bile Acid-Metabolizing Intestinal Bacteria and Alters Bile Acid Homeostasis.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Additional pathways of sterol metabolism: Evidence from analysis of Cyp27a1-/- mouse brain and plasma.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Polybrominated diphenyl ether BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) is a thyroid hormone disruptor in mice; hepatic induction of various metabolic enzymes and transporters has been suggested as the mechanism for this disruption. Utilizing Car (-/-) and Pxr (-/-) mice as well as human primary hepatocytes, here we have demonstrated that BDE-47 activated both mouse and human nuclear receptor constitutive activated/androstane receptor (CAR). In mouse livers, CAR, not PXR, was responsible for Cyp2b10 mRNA induction by BDE-47. In human primary hepatocytes, BDE-47 was able to induce translocation of YFP-tagged human CAR from the cytoplasm to the nucleus andCYP2B6 and CYP3A4 mRNAs expressions. BDE-47 activated human CAR in a manner akin to the human CAR ligand CITCO (6-(4-Chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime) in luciferase-reporter assays using Huh-7 cells. In contrast, mouse CAR was not potently activated by BDE-47 in the same reporter assays. Furthermore, human pregnane X receptor (PXR) was effectively activated by BDE-47 while mouse PXR was weakly activated in luciferase-reporter assays. Our results indicate that BDE-47 induces CYP genes through activation of human CAR in addition to the previously identified pathway through human PXR.
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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.