ArticleToxicology and applied pharmacology2015
Environmental contaminants activate human and polar bear (Ursus maritimus) pregnane X receptors (PXR, NR1I2) differently.
Article in Toxicology and applied pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- E-waste: mechanisms of toxicity and safety testing.FEBS open bio · 2024Review
- Characterization of NR1J1 Paralog Responses of Marine Mussels: Insights from Toxins and Natural Activators.International journal of molecular sciences · 2024Article
- Article
- Integrative omics-analysis of lipid metabolism regulation by peroxisome proliferator-activated receptor a and b agonists in male Atlantic cod.Frontiers in physiology · 2023Article
- Xenobiotic metabolism and its physiological consequences in high-Antarctic Notothenioid fishes.Polar biology · 2022Article
- Virtual screening web servers: designing chemical probes and drug candidates in the cyberspace.Briefings in bioinformatics · 2021Review
- Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food.EFSA journal. European Food Safety Authority · 2021Article
- CRISPR-Cas9-Mutated Pregnane X Receptor (pxr) Retains Pregnenolone-induced Expression of cyp3a65 in Zebrafish (Danio rerio) Larvae.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Xenobiotic Receptors and Their Mates in Atopic Dermatitis.International journal of molecular sciences · 2019Review
- Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages.International journal of molecular sciences · 2019Article
- Environmental contaminants modulate the transcriptional activity of polar bear (Ursus maritimus) and human peroxisome proliferator-activated receptor alpha (PPARA).Scientific reports · 2019Article
- Sequence Variations in pxr (nr1i2) From Zebrafish (Danio rerio) Strains Affect Nuclear Receptor Function.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response.The Journal of investigative dermatology · 2018Article
- Multiple-stressor effects in an apex predator: combined influence of pollutants and sea ice decline on lipid metabolism in polar bears.Scientific reports · 2017Article
- Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view.Environmental epigenetics · 2017Article
- Predictive models for identifying the binding activity of structurally diverse chemicals to human pregnane X receptor.Environmental science and pollution research international · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundMany persistent organic pollutants (POPs) accumulate readily in polar bears because of their position as apex predators in Arctic food webs. The pregnane X receptor (PXR, formally NR1I2, here proposed to be named promiscuous xenobiotic receptor) is a xenobiotic sensor that is directly involved in metabolizing pathways of a wide range of environmental contaminants.
objectivesIn the present study, we comparably assess the ability of 51 selected pharmaceuticals, pesticides and emerging contaminants to activate PXRs from polar bears and humans using an in vitro luciferase reporter gene assay.
resultsWe found that polar bear PXR is activated by a wide range of our test compounds (68%) but has a slightly more narrow ligand specificity than human PXR that was activated by 86% of the 51 test compounds. The majority of the agonists identified (70%) produces a stronger induction of the reporter gene via human PXR than via polar bear PXR, however with some notable and environmentally relevant exceptions.
conclusionsDue to the observed differences in activation of polar bear and human PXRs, exposure of each species to environmental agents is likely to induce biotransformation differently in the two species. Bioinformatics analyses and structural modeling studies suggest that amino acids that are not part of the ligand-binding domain and do not interact with the ligand can modulate receptor activation.
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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.