ArticleJournal of lipid research2019
Regulation of ABCA1-mediated cholesterol efflux by sphingosine-1-phosphate signaling in macrophages.
Article in Journal of lipid research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
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- NLRP3 mediates lipid-driven macrophage proliferation in established atherosclerosis.Basic research in cardiology · 2025Article
- Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism.Nature communications · 2025Article
- Review
- Sphingolipid metabolites involved in the pathogenesis of atherosclerosis: perspectives on sphingolipids in atherosclerosis.Cellular & molecular biology letters · 2025Review
- Differential organ responses to fumonisins in rabbits: kidney, liver, and spleen membrane fatty acid composition, oxidation markers, and histopathology.Frontiers in veterinary science · 2025Article
- Regulatory role of S1P and its receptors in sepsis-induced liver injury.Frontiers in immunology · 2025Review
- LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.Aging · 2024Article
- ANGPTL3 is a novel HDL component that regulates HDL function.Journal of translational medicine · 2024Article
- Fatty acid elongation by ELOVL6 hampers remyelination by promoting inflammatory foam cell formation during demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome.Frontiers in endocrinology · 2023Article
- Microglia and Brain Macrophages as Drivers of Glioma Progression.International journal of molecular sciences · 2022Review
- Proteomic-Based Approach Reveals the Involvement of Apolipoprotein A-I in Related Phenotypes of Autism Spectrum Disorder in the BTBR Mouse Model.International journal of molecular sciences · 2022Article
- Sphingosine-1-Phosphate (S1P) Lyase Inhibition Aggravates Atherosclerosis and Induces Plaque Rupture inInternational journal of molecular sciences · 2022Article
- Hypercholesterolemia-Induced HDL Dysfunction Can Be Reversed: The Impact of Diet and Statin Treatment in a Preclinical Animal Model.International journal of molecular sciences · 2022Article
- Metabolic-related gene pairs signature analysis identifies ABCA1 expression levels on tumor-associated macrophages as a prognostic biomarker in primary IDHFrontiers in immunology · 2022Article
- Sphingolipids in metabolic disease: The good, the bad, and the unknown.Cell metabolism · 2021Review
- Current Understanding of the Immunomodulatory Activities of High-Density Lipoproteins.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingolipid and cholesterol metabolism are closely associated at the structural, biochemical, and functional levels. Although HDL-associated sphingosine-1-phosphate (S1P) contributes to several HDL functions, and S1P signaling regulates glucose and lipid metabolism, no study has addressed the involvement of S1P in cholesterol efflux. Here, we show that sphingosine kinase (Sphk) activity was induced by the LXR agonist 22(R)-hydroxycholesterol and required for the stimulation of ABCA1-mediated cholesterol efflux to apolipoprotein A-I. In support, pharmacological Sphk inhibition and Sphk2 but not Sphk1 deficiency abrogated efflux. The involved mechanism included stimulation of both transcriptional and functional ABCA1 regulatory pathways and depended for the latter on the S1P receptor 3 (S1P3). Accordingly, S1P3-deficient macrophages were resistant to 22(R)-hydroxycholesterol-stimulated cholesterol efflux. The inability of excess exogenous S1P to further increase efflux was consistent with tonic S1P3 signaling by a pool of constitutively generated Sphk-derived S1P dynamically regulating cholesterol efflux. In summary, we have established S1P as a previously unrecognized intermediate in LXR-stimulated ABCA1-mediated cholesterol efflux and identified S1P/S1P3 signaling as a positive-feedback regulator of cholesterol efflux. This constitutes a novel regulatory mechanism of cholesterol efflux by sphingolipids.
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