ArticleGlycobiology2016
Inhibition of Rab prenylation by statins induces cellular glycosphingolipid remodeling.
Article in Glycobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 37 citations in OpenAlex.
- Advances in statin adverse reactions and the potential mechanisms: A systematic review.Journal of advanced research · 2025Pooled it
- Systematic review and meta-analysis of studies assessing the relationship between statin use and risk of ovarian cancer.Cancer causes & control : CCC · 2020Pooled it
- Cholesterol Deficiency Directs Autophagy-Dependent Secretion of Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- Multi-biobank Mendelian randomization analyses identify opposing pathways in plasma low-density lipoprotein-cholesterol lowering and gallstone disease.European journal of epidemiology · 2024Article
- Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?Lipids in health and disease · 2024Article
- Entry of nanoparticles into cells and tissues: status and challenges.Beilstein journal of nanotechnology · 2024Article
- Phosphorylation of Rab29 at Ser185 regulates its localization and role in the lysosomal stress response in concert with LRRK2.Journal of cell science · 2023Article
- Epigenetic suppression of PGC1α (PPARGC1A) causes collateral sensitivity to HMGCR-inhibitors within BRAF-treatment resistant melanomas.Nature communications · 2023Article
- High-Density Lipoprotein Lipidomics in Chronic Kidney Disease.Clinical chemistry · 2023Article
- Statin therapy inhibits fatty acid synthase via dynamic protein modifications.Nature communications · 2022Article
- Article
- Review
- LXR directly regulates glycosphingolipid synthesis and affects human CD4+ T cell function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- REP1 deficiency causes systemic dysfunction of lipid metabolism and oxidative stress in choroideremia.JCI insight · 2021Article
- ATP-binding cassette transporters mediate differential biosynthesis of glycosphingolipid species.Journal of lipid research · 2021Article
- MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models.Cancers · 2020Article
- LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL.Journal of lipid research · 2020Article
- Consequences of blunting the mevalonate pathway in cancer identified by a pluri-omics approach.Cell death & disease · 2018Article
- Low level of the plasma sphingolipid, glucosylceramide, is associated with thrombotic diseases.Research and practice in thrombosis and haemostasis · 2017Article
- Protection against Shiga Toxins.Toxins · 2017Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Statins, which specifically inhibit HMG Co-A reductase, the rate-limiting step of cholesterol biosynthesis, are widely prescribed to reduce serum cholesterol and cardiac risk, but many other effects are seen. We now show an effect of these drugs to induce profound changes in the step-wise synthesis of glycosphingolipids (GSLs) in the Golgi. Glucosylceramide (GlcCer) was increased several-fold in all cell lines tested, demonstrating a widespread effect. Additionally, de novo or elevated lactotriaosylceramide (Lc3Cer; GlcNAcβ1-3Galβ1-4GlcCer) synthesis was observed in 70%. Western blot showed that GlcCer synthase (GCS) was elevated by statins, and GCS and Lc3Cer synthase (Lc3S) activities were increased; however, transcript was elevated for Lc3S only. Supplementation with the isoprenoid precursor, geranylgeranyl pyrophosphate (GGPP), a downstream product of HMG Co-A reductase, reversed statin-induced glycosyltransferase and GSL elevation. The Rab geranylgeranyl transferase inhibitor 3-PEHPC, but not specific inhibitors of farnesyl transferase, or geranylgeranyl transferase I, was sufficient to replicate statin-induced GlcCer and Lc3Cer synthesis, supporting a Rab prenylation-dependent mechanism. While total cholesterol was unaffected, the trans-Golgi network (TGN) cholesterol pool was dissipated and medial Golgi GCS partially relocated by statins. GSL-dependent vesicular retrograde transport of Verotoxin and cholera toxin to the Golgi/endoplasmic reticulum were blocked after statin or 3-PEHPC treatment, suggesting aberrant, prenylation-dependent vesicular traffic as a basis of glycosyltransferase increase and GSL remodeling. These in vitro studies indicate a previously unreported link between Rab prenylation and regulation of GCS activity and GlcCer metabolism.
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Registered trials
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