Study of the Prenane X Receptor in the Non-Mammalian Vertebrate Species Danio rerio : Polychlorinated Biphenyl Activation and Cytochrome P450 Regulation
O'Meara, Conor M.
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The pregnane X receptor (PXR) is a nuclear receptor transcription factor that regulates transcription of genes for proteins involved in xenobiotic and endogenous chemical disposition and metabolism, including phase I/II enzymes, along with ABC transporters. A cluster of cytochrome P450 (CYP) genes involved in phase I activity is regulated by mammalian PXR. Mammalian CYP gene families 1-3 (CYP1-CYP3) are primarily involved in the metabolism of drugs and xenobiotics such as polychlorinated biphenyls (PCBs), which are a group of ubiquitously distributed and persistent toxicants. Little is known about PXR in non-mammalian vertebrate species. Therefore, zebrafish embryos were exposed to 2 PCB congeners (126,153), and transcript levels of a select CYP gene (3A65) was measured via RT-qPCR in order to study PXR in non-mammalian vertebrates. PCB153 was found to have no effect on the expression of PXR and its target genes in zebrafish, while PCB126 was found to activate a different nuclear receptor transcription factor (AhR). A computational analysis of the promoter region of CYP20A1, an ‘orphan’ gene, was conducted to observe PXR’s putative role in regulation, and to get a functional clue on the ‘orphan’ gene. Results suggest PXR does not regulate CYP20A1, while putative function of CYP20A1 was found to include neurogenesis, cell migration, and immunity. This study lays the groundwork for future research on PXR and its potential ligands along with possible target genes it may regulate, as well as CYP20A1 functionality.