ArticleThe Journal of cell biology2000
Sphingomyelin hydrolysis to ceramide during the execution phase of apoptosis results from phospholipid scrambling and alters cell-surface morphology.
Article in The Journal of cell biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 196 citations in OpenAlex.
- Exercise training improves mitochondrial respiration and is associated with an altered intramuscular phospholipid signature in women with obesity.Diabetologia · 2021Trial
- Hypertensive stretch regulates endothelial cell inflammation and apoptosis through ceramide metabolism.American journal of physiology. Cell physiology · 2026Article
- Neutral sphingomyelinase inhibition promotes local and network degeneration in vitro and in vivo.Cell communication and signaling : CCS · 2023Article
- Extracellular RNA in melanoma: Advances, challenges, and opportunities.Frontiers in cell and developmental biology · 2023Review
- Potential Drug Targets for Ceramide Metabolism in Cardiovascular Disease.Journal of cardiovascular development and disease · 2022Review
- Vascular Smooth Muscle Cell Neutral Sphingomyelinase 2 in the Release of Exosomes and Vascular Calcification.International journal of molecular sciences · 2022Review
- Ceramide from sphingomyelin hydrolysis induces neuronal differentiation, whereas de novo ceramide synthesis and sphingomyelin hydrolysis initiate apoptosis after NGF withdrawal in PC12 Cells.Cell communication and signaling : CCS · 2022Article
- Lipids as Regulators of Cellular Senescence.Frontiers in physiology · 2022Review
- Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases.International journal of molecular sciences · 2021Review
- Sphingomyelinase-Mediated Multitimescale Clustering of Ganglioside GM1 in Heterogeneous Lipid Membranes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Article
- The Emerging Role of Extracellular Vesicles in the Glioma Microenvironment: Biogenesis and Clinical Relevance.Cancers · 2020Review
- Antineoplastic Agents Targeting Sphingolipid Pathways.Frontiers in oncology · 2020Review
- High FA2H and UGT8 transcript levels predict hydroxylated hexosylceramide accumulation in lung adenocarcinoma.Journal of lipid research · 2019Article
- Changes in Membrane Ceramide Pools in Rat Soleus Muscle in Response to Short-Term Disuse.International journal of molecular sciences · 2019Article
- Astrocytic ceramide as possible indicator of neuroinflammation.Journal of neuroinflammation · 2019Article
- Receptor-interacting Ser/Thr kinase 1 (RIPK1) and myosin IIA-dependent ceramidosomes form membrane pores that mediate blebbing and necroptosis.The Journal of biological chemistry · 2019Article
- Review
- Role of sphingolipids in the biogenesis and biological activity of extracellular vesicles.Journal of lipid research · 2018Review
- γ-Tocotrienol induces apoptosis in pancreatic cancer cells by upregulation of ceramide synthesis and modulation of sphingolipid transport.BMC cancer · 2018Article
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6 authors at 2 institutions in 2 countries.
Funding
Abstract
Apoptosis is generally accompanied by a late phase of ceramide (Cer) production, the significance of which is unknown. This study describes a previously unrecognized link between Cer accumulation and phosphatidylserine (PS) exposure at the cell surface, a characteristic of the execution phase of apoptosis resulting from a loss of plasma membrane phospholipid asymmetry. Using a fluorescent sphingomyelin (SM) analogue, N-(N-[6-[(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]caproyl]-sphingosylphosphorylcholine (C(6)-NBD-SM), we show that Cer is derived from SM, initially located in the outer leaflet of the plasma membrane, which gains access to a cytosolic SMase by flipping to the inner leaflet in a process of lipid scrambling paralleling PS externalization. Lipid scrambling is both necessary and sufficient for SM conversion: Ca(2+) ionophore induces both PS exposure and SM hydrolysis, whereas scrambling-deficient Raji cells do not show PS exposure or Cer formation. Cer is not required for mitochondrial or nuclear apoptotic features since these are still observed in Raji cells. SM hydrolysis facilitates cholesterol efflux to methyl-beta-cyclodextrin, which is indicative of a loss of tight SM-cholesterol interaction in the plasma membrane. We provide evidence that these biophysical alterations in the lipid bilayer are essential for apoptotic membrane blebbing/vesiculation at the cell surface: Raji cells show aberrant apoptotic morphology, whereas replenishment of hydrolyzed SM by C(6)- NBD-SM inhibits blebbing in Jurkat cells. Thus, SM hydrolysis, during the execution phase of apoptosis, results from a loss of phospholipid asymmetry and contributes to structural changes at the plasma membrane.
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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.