ArticleToxicological sciences : an official journal of the Society of Toxicology2015
Role of pregnane X receptor and aryl hydrocarbon receptor in transcriptional regulation of pxr, CYP2, and CYP3 genes in developing zebrafish.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 70 citations in OpenAlex.
- Metabolic disrupting chemicals in the intestine: the need for biologically relevant models: Zebrafish: what can we learn from this small environment-sensitive fish?FEBS open bio · 2024Review
- Characterization of NR1J1 Paralog Responses of Marine Mussels: Insights from Toxins and Natural Activators.International journal of molecular sciences · 2024Article
- Differential gene expression and developmental pathologies associated with persistent organic pollutants in sentinel fish in Troutman Lake, Sivuqaq, Alaska.Environmental pollution (Barking, Essex : 1987) · 2024Article
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- Role of nuclear pregnane X receptor in Cu-induced lipid metabolism and xenobiotic responses in largemouth bass (Frontiers in endocrinology · 2022Article
- The chemical defensome of five model teleost fish.Scientific reports · 2021Article
- 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
- Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants.International journal of molecular sciences · 2021Review
- A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids UsingFrontiers in endocrinology · 2021Article
- A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
- 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
- The effect of the antidepressant venlafaxine on gene expression of biotransformation enzymes in zebrafish (Danio rerio) embryos.Environmental science and pollution research international · 2020Article
- Coupling Genome-wide Transcriptomics and Developmental Toxicity Profiles in Zebrafish to Characterize Polycyclic Aromatic Hydrocarbon (PAH) Hazard.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
- From mRNA Expression of Drug Disposition Genes to In Vivo Assessment of CYP-Mediated Biotransformation during Zebrafish Embryonic and Larval Development.International journal of molecular sciences · 2018Article
- Independent losses of a xenobiotic receptor across teleost evolution.Scientific reports · 2018Article
- A non-destructive BFCOD assay for in vivo measurement of cytochrome P450 3A (CYP3A) enzyme activity in fish embryos and larvae.Ecotoxicology (London, England) · 2017Article
- Cyp2aa9 regulates haematopoietic stem cell development in zebrafish.Scientific reports · 2016Article
- 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
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ligand-activated receptors regulate numerous genes, and mediate effects of a broad set of endogenous and exogenous chemicals in vertebrates. Understanding the roles of these transcription factors in zebrafish (Danio rerio) is important to the use of this non-mammalian model in toxicological, pharmacological, and carcinogenesis research. Response to a potential agonist for the pregnane X receptor (Pxr) [pregnenolone (PN)] was examined in developing zebrafish, to assess involvement of Pxr in regulation of selected genes, including genes in cytochrome P450 subfamilies CYP2 and CYP3. We also examined interaction of Pxr and the aryl hydrocarbon receptor (Ahr) signaling pathways. Pregnenolone caused a dose-dependent increase in mRNA levels of pxr, ahr2, CYP1A, CYP2AA1, CYP2AA12, CYP3A65, and CYP3C1, most of which peaked at 3 µM PN. The well-known Ahr agonist 3,3',4,4',5-pentachlorobiphenyl (PCB126) also upregulated expression of pxr, ahr2, CYP1A, CYP2AA12, CYP3A65, and CYP3C1 in a dose-dependent manner. Inhibition of pxr translation by morpholino antisense oligonucleotides (MO) suppressed PN-induced expression of pxr, ahr2, CYP3A65, and CYP3C1 genes. Levels of CYP2AA1 and CYP2AA12 mRNA were increased in the control-MO group exposed to PN; this was prevented by knocking down Pxr. Similarly, Ahr2-MO treatment blocked PCB126-induced mRNA expression of pxr, CYP1A, CYP2AA12, CYP3A65, and CYP3C1. The present study shows self-regulation of pxr by PN in developing zebrafish. Selected zebrafish CYP1, CYP2 (including several CYP2AAs) and CYP3 genes appear to be under the regulation of both Pxr and Ahr2.
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