ArticleInternational journal of molecular sciences2021
The Glucosylceramide Synthase Inhibitor PDMP Causes Lysosomal Lipid Accumulation and mTOR Inactivation.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Glucosylceramide synthase is required for C6-ceramide nanoliposome-induced organelle stress and cell death.bioRxiv : the preprint server for biology · 2026Article
- Roles of Ceramide Glucosyltransferase in Controlling Cerebral Microvascular Endothelial Integrity and Angiogenesis Post-Ischemia/Reperfusion.Translational stroke research · 2026Article
- Endolysosomal Impact of Elevated Ceramide Levels Revealed by Optical and Ultrastructural Nanoprobing.ACS nano · 2026Article
- Downregulation of AKT-mediated p27IBRO neuroscience reports · 2025Article
- Bifunctional Probes Reveal the Rules of Intracellular Ether Lipid Transport.Angewandte Chemie (International ed. in English) · 2025Article
- The SGLT2 Inhibitor Dapagliflozin Disrupts the Cell Cycle at High Concentrations Without Altering Glycosphingolipid (De Novo)Biosynthesis.International journal of molecular sciences · 2025Article
- In Vivo Accumulation of Regulatory T Cells Using Eliglustat-Loaded Cryogels.Advanced healthcare materials · 2025Article
- Discovery of compound 1105486 as a selective inhibitor of B4GALT1: potential for pancreatic cancer therapy.Frontiers in chemistry · 2025Article
- Biochemical Pathways Delivering Distinct Glycosphingolipid Patterns in MDA-MB-231 and MCF-7 Breast Cancer Cells.Current issues in molecular biology · 2024Review
- Glucosylceramide in bunyavirus particles is essential for virus binding to host cells.Cellular and molecular life sciences : CMLS · 2024Article
- Providing open imaging data at scale: An EMBL-EBI perspective.Histochemistry and cell biology · 2023Article
- Salvianolic acid B suppresses hepatic fibrosis by inhibiting ceramide glucosyltransferase in hepatic stellate cells.Acta pharmacologica Sinica · 2023Article
- Role of UDP-glucose ceramide glucosyltransferase in venous malformation.Frontiers in cell and developmental biology · 2023Article
- Sphingolipid subtypes differentially control proinsulin processing and systemic glucose homeostasis.Nature cell biology · 2023Article
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Type 2 diabetes disrupts circadian orchestration of lipid metabolism and membrane fluidity in human pancreatic islets.PLoS biology · 2022Article
- Blockade of Glycosphingolipid Synthesis Inhibits Cell Cycle and Spheroid Growth of Colon Cancer Cells In Vitro and Experimental Colon Cancer Incidence In Vivo.International journal of molecular sciences · 2021Article
- Ceramide Metabolism Enzymes-Therapeutic Targets against Cancer.Medicina (Kaunas, Lithuania) · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
For many years, the biology of glycosphingolipids was elucidated with the help of glucosylceramide synthase (GCS) inhibitors such as 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP). Additionally, PDMP gained interest because of its chemosensitizing effects. Several studies have successfully combined PDMP and anti-cancer drugs in the context of cancer therapy. However, the mechanism of action of PDMP is not fully understood and seems to go beyond glycolipid inhibition. Here, we used a functionalized sphingosine analogue (pacSph) to investigate the acute effects of PDMP on cellular sphingolipid distribution and found that PDMP, but not other GCS inhibitors, such as ND-DNJ (also called Miglustat), induced sphingolipid accumulation in lysosomes. This effect could be connected to defective export from lysosome, as monitored by the prolonged lysosomal staining of sphingolipids as well as by a delay in the metabolic conversion of the pacSph precursor. Additionally, other lipids such as lysobisphosphatidic acid (LBPA) and cholesterol were enriched in lysosomes upon PDMP treatment in a time-dependent manner. We could further correlate early LBPA enrichment with dissociation of the mechanistic target of rapamycin (mTOR) from lysosomes followed by nuclear translocation of its downtream target, transcription factor EB (TFEB). Altogether, we report here a timeline of lysosomal lipid accumulation events and mTOR inactivation arising from PDMP treatment.
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