Title:Pregnane X Receptor (PXR) at the Crossroads of Human Metabolism and Disease
Volume: 14
Issue: 3
Author(s): Ioannis Koutsounas, Stamatios Theocharis, Efstratios Patsouris and Constantinos Giaginis
Affiliation:
Keywords:
Pregnane X Receptor, metabolism, bile acids, xenobiotics, drug resistance, chemotherapeutic agents, PXR, Pregane, NR, endobiotics, CYP3A, MDR1, isozymes, enzymes, hepatoprotective, Cancer
Abstract: Pregnane X Receptor (PXR), a member of the nuclear receptor (NR) superfamily, is expressed in liver and intestine, as also in
other tissues and cells. PXR is activated by a wide variety of endobiotics, dietary compounds and pharmaceuticals. This nuclear receptor
serves as a master transcriptional regulator of CYP3A isozymes, and also regulates a large number of enzymes and transporters involved
in the pharmacokinetics of both endobiotics and xenobiotics. PXR has an impact on energy homeostasis through glucose and lipid metabolism
regulation. PXR activation is also hepatoprotective against toxic bile acids. New roles for PXR have been identified in bone
homeostasis, inflammatory bowel disease, liver steatosis and fibrogenesis. PXR directly regulates the expression of multidrug resistance
protein 1 (MDR1) and other important proteins involved in drug metabolism. Drug-drug interactions can affect patients with cardiovascular
disease, tuberculosis, HIV and cancer. Especially cancer patients are at high risk of such interactions, as treated with multi-drug combinations.
PXR activation can affect the efficacy of chemotherapeutics, thus targeting PXR may represent a novel strategy for the improvement
of the pharmacokinetics of chemotherapeutic agents, thereby providing safer and more effective therapies for cancer patients.
