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New aspects of pregnane X receptor function and regulation
Hyršová, Lucie ; Trejtnar, František (advisor) ; Skálová, Lenka (referee) ; Vondráček, Jan (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Lucie Hyršová, MSc. First Supervisor: doc. PharmDr. František Trejtnar, CSc. Consultant: prof. PharmDr. Petr Pávek, PhD. Title of Dissertation Thesis: New aspects of pregnane X receptor function and regulation The pregnane X receptor belongs to the superfamily of nuclear receptors; it is a ligand dependent transcription factor regulating expression of its target genes. During last two decades, PXR was extensively studied as a xenosensor, i.e. the receptor, which is able to bind xenobiotics including many drugs and to regulate their metabolism by induction of the most important metabolizing enzymes of both phase I. and phase II. Induction, i.e. transcriptional stimulation of expression of the most important cytochrome P450 enzymes, by PXR ligands was described in details at many levels. Within this dissertation thesis, I am dealing with aspects of regulation via PXR, which extend the common understanding of PXR as a receptor whose exclusive function is to up-regulate drug metabolizing enzymes mediated by its agonists. Within the first, project I studied regulation of OCT1 transporter in hepatic cell models, I shown that PXR did not induce, but it rather suppressed the expression of this...
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