ArticleMolecular pharmacology2013
Pregnane X receptor mediates dyslipidemia induced by the HIV protease inhibitor amprenavir in mice.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 33 citations in OpenAlex.
- A Universal Plasticizer Alkylsulfonic Phenyl Ester Activates Pregnane X Receptor to Increase Intestinal Cholesterol Uptake.International journal of molecular sciences · 2026Article
- A cholesterol-responsive hepatic tRNA-derived small RNA regulates cholesterol homeostasis and atherosclerosis development.Nature communications · 2025Article
- Cannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.Frontiers in endocrinology · 2024Article
- Adverse outcome pathway for pregnane X receptor-induced hypercholesterolemia.Archives of toxicology · 2023Review
- HIV Protein Tat Induces Macrophage Dysfunction and Atherosclerosis Development in Low-Density Lipoprotein Receptor-Deficient Mice.Cardiovascular drugs and therapy · 2022Article
- Article
- Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice.Environmental health perspectives · 2021Article
- Regulation of PXR Function by Coactivator and Corepressor Proteins: Ligand Binding Is Just the Beginning.Cells · 2021Review
- Article
- Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action.Biochemical pharmacology · 2021Review
- Article
- PXR-mediated idiosyncratic drug-induced liver injury: mechanistic insights and targeting approaches.Expert opinion on drug metabolism & toxicology · 2020Review
- Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice.Journal of lipid research · 2020Article
- The Other Obesity Epidemic-Of Drugs and Bugs.Frontiers in endocrinology · 2020Review
- Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis.Journal of hepatology · 2019Article
- Drug discovery technologies to identify and characterize modulators of the pregnane X receptor and the constitutive androstane receptor.Drug discovery today · 2019Review
- Macrophage nuclear receptors: Emerging key players in infectious diseases.PLoS pathogens · 2019Review
- Epigenetic impact of endocrine disrupting chemicals on lipid homeostasis and atherosclerosis: a pregnane X receptor-centric view.Environmental epigenetics · 2017Article
- Review
- Novel functions of PXR in cardiometabolic disease.Biochimica et biophysica acta · 2016Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
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 within the ligand-binding pocket of PXR that constitute points of interaction with amprenavir. Amprenavir efficiently activated PXR and induced PXR target gene expression in vitro and in vivo. Short-term exposure to amprenavir significantly increased plasma total cholesterol and atherogenic low-density lipoprotein cholesterol levels in wild-type mice, but not in PXR-deficient mice. Amprenavir-mediated PXR activation stimulated the expression of several key intestinal genes involved in lipid homeostasis. These findings provide critical mechanistic insight for understanding the impact of PIs on cardiovascular disease and demonstrate a potential role of PXR in mediating the adverse effects of HIV PIs in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.