Pregnane X receptor mediates dyslipidemia induced by the HIV protease inhibitor amprenavir in mice.

ABSTRACT: Human immunodeficiency virus (HIV) protease inhibitors (PIs) have been used successfully in extending the life span of people infected with HIV. The use of PIs has also been associated with dyslipidemia and an increased risk of cardiovascular disease, but the underlying mechanisms remain elusive. Several PIs have been implicated in activating the nuclear receptor pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism in the liver and intestine. Recent studies indicate that PXR may also play an important role in the regulation of lipid homeostasis. In the present study, we identified amprenavir, a widely used HIV PI, as a potent PXR-selective agonist. Computational docking studies combined with site-direct mutagenesis identified several key residues w

SUBMITTER: Helsley RN 

PROVIDER: S-EPMC3657097 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature