ArticleAquatic toxicology (Amsterdam, Netherlands)2013
Functional characterization of a full length pregnane X receptor, expression in vivo, and identification of PXR alleles, in zebrafish (Danio rerio).
Article in Aquatic toxicology (Amsterdam, Netherlands), 2013. 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, 59 citations in OpenAlex.
- Review
- Role of nuclear pregnane X receptor in Cu-induced lipid metabolism and xenobiotic responses in largemouth bass (Frontiers in endocrinology · 2022Article
- Resistance to Cyp3a induction by polychlorinated biphenyls, including non-dioxin-like PCB153, in gills of killifish (Fundulus heteroclitus) from New Bedford Harbor.Environmental toxicology and pharmacology · 2021Article
- Expression and Function of ABC Proteins in Fish Intestine.Frontiers in physiology · 2021Review
- A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids UsingFrontiers in endocrinology · 2021Article
- Vitamin K in Vertebrates' Reproduction: Further Puzzling Pieces of Evidence from Teleost Fish Species.Biomolecules · 2020Review
- The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos.Environmental science and pollution research international · 2020Article
- Evolutionary Plasticity in Detoxification Gene Modules: The Preservation and Loss of the Pregnane X Receptor in Chondrichthyes Lineages.International journal of molecular sciences · 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
- Endocrine disruption and differential gene expression in sentinel fish on St. Lawrence Island, Alaska: Health implications for indigenous residents.Environmental pollution (Barking, Essex : 1987) · 2018Article
- Development of a common carp (Cyprinus carpio) pregnane X receptor (cPXR) transactivation reporter assay and its activation by azole fungicides and pharmaceutical chemicals.Toxicology in vitro : an international journal published in association with BIBRA · 2017Article
- BFCOD activity in fish cell lines and zebrafish embryos and its modulation by chemical ligands of human aryl hydrocarbon and nuclear receptors.Environmental science and pollution research international · 2015Article
- Zebrafish vitamin K epoxide reductases: expression in vivo, along extracellular matrix mineralization and under phylloquinone and warfarin in vitro exposure.Fish physiology and biochemistry · 2015Article
- Metformin exposure at environmentally relevant concentrations causes potential endocrine disruption in adult male fish.Environmental toxicology and chemistry · 2015Article
- Regulation of pregnane-X-receptor, CYP3A and P-glycoprotein genes in the PCB-resistant killifish (Fundulus heteroclitus) population from New Bedford Harbor.Aquatic toxicology (Amsterdam, Netherlands) · 2015Article
- Role of pregnane X receptor and aryl hydrocarbon receptor in transcriptional regulation of pxr, CYP2, and CYP3 genes in developing zebrafish.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- Marine invertebrate xenobiotic-activated nuclear receptors: their application as sensor elements in high-throughput bioassays for marine bioactive compounds.Marine drugs · 2014Review
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
The pregnane X receptor (PXR) (nuclear receptor NR1I2) is a ligand activated transcription factor, mediating responses to diverse xenobiotic and endogenous chemicals. The properties of PXR in fish are not fully understood. Here we report on cloning and characterization of full-length PXR of zebrafish, Danio rerio, and pxr expression in vivo. Initial efforts gave a cDNA encoding a 430 amino acid protein identified as zebrafish pxr by phylogenetic and synteny analysis. The sequence of the cloned Pxr DNA binding domain (DBD) was highly conserved, with 74% identity to human PXR-DBD, while the ligand-binding domain (LBD) of the cloned sequence was only 44% identical to human PXR-LBD. Sequence variation among clones in the initial effort prompted sequencing of multiple clones from a single fish. There were two prominent variants, one sequence with S183, Y218 and H383 and the other with I183, C218 and N383, which we designate as alleles pxr*1 (nr1i2*1) and pxr*2 (nr1i2*2), respectively. In COS-7 cells co-transfected with a PXR-responsive reporter gene, the full-length Pxr*1 (the more common variant) was activated by known PXR agonists clotrimazole and pregnenolone 16α-carbonitrile but to a lesser extent than the full-length human PXR. Activation of full-length Pxr*1 was only 10% of that with the Pxr*1 LBD. Quantitative real time PCR analysis showed prominent expression of pxr in liver and eye, as well as brain and intestine of adult zebrafish. The pxr was expressed in heart and kidney at levels similar to that in intestine. The expression of pxr in liver was weakly induced by ligands for mammalian PXR or constitutive androstane receptor (NR1I3). The results establish a foundation for PXR studies in this vertebrate model. PXR allelic variation and the differences between the full-length PXR and the LBD in reporter assays have implications for assessing the action of PXR ligands in zebrafish.
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