ArticleProceedings of the National Academy of Sciences of the United States of America2000
Control of cellular cholesterol efflux by the nuclear oxysterol receptor LXR alpha.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 368 papers.
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Who cites it
368 citing papers in PubMed, 991 citations in OpenAlex.
- Lipid droplets as redox-active organelles after spinal cord injury: lipid peroxidation, mitochondrial dysfunction, and neuroinflammation.Redox report : communications in free radical research · 2026Review
- The orientation of cholesterol's hydroxy group affects its membrane dynamics and intracellular transport.iScience · 2026Article
- Atorvastatin pre-exposure in hypercholesterolemia remedies 27HC mediated dendritic cell dysfunctions in triple-negative breast cancer.Molecular therapy. Oncology · 2026Article
- Mechanism of FXR signaling: from liver inflammation to hepatocellular carcinoma.Biochemistry and biophysics reports · 2026Review
- Kupffer cells in liver homeostasis and disease: from immune sentinels to metabolic gatekeepers.Nature reviews. Immunology · 2026Review
- Lactic Acid Bacteria with Probiotic Potential Regulating Macrophages: Mechanisms, Regulatory Features, and Clinical Applications.Probiotics and antimicrobial proteins · 2026Review
- CYP46A1-Targeted Treatment Alleviates Long-Term White Matter Injury Following Traumatic Brain Injury by Promoting Cholesterol Metabolic Clearance and Remyelination.CNS neuroscience & therapeutics · 2026Article
- Zebrafish screen of schizophrenia risk genes reveals convergent dysregulation of cholesterol metabolism.bioRxiv : the preprint server for biology · 2026Article
- Cholesterol Metabolism: An Ally in the Development and Progression of Cervical Cancer.International journal of molecular sciences · 2026Review
- Serum lipidome remodeling in viral pneumonia: from pathophysiology to therapeutics.Frontiers in immunology · 2026Review
- The IRE1α Pathway Links Endoplasmic Reticulum Stress to Atherosclerosis-Related Inflammation and Lipid Accumulation.Mediators of inflammation · 2026Article
- Cutaneous papillomaviruses infection rewires fatty-acid metabolism.Frontiers in cellular and infection microbiology · 2026Article
- 27-Hydroxycholesterol in cancer development and drug resistance.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- Inferring residue level hydrogen deuterium exchange with ReX.Communications chemistry · 2025Article
- Beyond High-density Lipoprotein-cholesterol: Unraveling the Complexity of High-density Lipoprotein Functionality.Journal of atherosclerosis and thrombosis · 2025Review
- Lipid overload meets S-palmitoylation: a metabolic signalling nexus driving cardiovascular and heart disease.Cell communication and signaling : CCS · 2025Review
- Plasma membrane accessible cholesterol is regulated by ACC1 and lipid droplets.bioRxiv : the preprint server for biology · 2025Article
- MicroRNA 223 Enhances ABCA1 Protein Stability and Supports Efflux in Cholesterol-Burdened Macrophages.Cell biochemistry and biophysics · 2025Article
- Inhibition of LXR Signaling in Human Foam Cells Impairs Macrophage-to-Endothelial Cell Cross Talk and Promotes Endothelial Cell Inflammation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Long noncoding RNAs in familial hypercholesterolemia: biomarkers, therapeutics, and AI in precision medicine.Lipids in health and disease · 2025Review
308 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
LXR alpha is a nuclear receptor that has previously been shown to regulate the metabolic conversion of cholesterol to bile acids. Here we define a role for this transcription factor in the control of cellular cholesterol efflux. We demonstrate that retroviral expression of LXR alpha in NIH 3T3 fibroblasts or RAW264.7 macrophages and/or treatment of these cells with oxysterol ligands of LXR results in 7- to 30-fold induction of the mRNA encoding the putative cholesterol/phospholipid transporter ATP-binding cassette (ABC)A1. In contrast, induction of ABCA1 mRNA in response to oxysterols is attenuated in cells that constitutively express dominant-negative forms of LXR alpha or LXR beta that lack the AF2 transcriptional activation domain. We further demonstrate that expression of LXR alpha in NIH 3T3 fibroblasts and/or treatment of these cells with oxysterols is sufficient to stimulate cholesterol efflux to extracellular apolipoprotein AI. The ability of oxysterol ligands of LXR to stimulate efflux is dramatically reduced in Tangier fibroblasts, which carry a loss of function mutation in the ABCA1 gene. Taken together, these results indicate that cellular cholesterol efflux is controlled, at least in part, at the level of transcription by a nuclear receptor-signaling pathway. They suggest a model in which activation of LXRs by oxysterols in response to cellular sterol loading leads to induction of the ABCA1 transporter and the stimulation of lipid efflux to extracellular acceptors. These findings have important implications for our understanding of mammalian cholesterol homeostasis and suggest new opportunities for pharmacological regulation of cellular lipid metabolism.
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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.