ArticleProceedings of the National Academy of Sciences of the United States of America2004
Sphingosine-dependent apoptosis: a unified concept based on multiple mechanisms operating in concert.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Pro-Apoptotic Effects of Anandamide in Human Gastric Cancer Cells Are Mediated by AKT and ERK Signaling Pathways.International journal of molecular sciences · 2025Article
- Trifunctional Sphinganine: A New Tool to Dissect Sphingolipid Function.ACS chemical biology · 2024Article
- Article
- Desipramine induces eryptosis in human erythrocytes, an effect blunted by nitric oxide donor sodium nitroprusside and N-acetyl-L-cysteine but enhanced by Calcium depletion.Cell cycle (Georgetown, Tex.) · 2023Article
- "Flash & Click": Multifunctionalized Lipid Derivatives as Tools To Study Viral Infections.Journal of the American Chemical Society · 2022Review
- Manifold Roles of Ceramide Metabolism in Non-Alcoholic Fatty Liver Disease and Liver Cancer.Advances in experimental medicine and biology · 2022Article
- FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment.Current medicinal chemistry · 2020Review
- In Human and Mouse Spino-Cerebellar Tissue, Ataxin-2 Expansion Affects Ceramide-Sphingomyelin Metabolism.International journal of molecular sciences · 2019Article
- The Role of Distinctive Sphingolipids in the Inflammatory and Apoptotic Effects of Electronegative LDL on Monocytes.Biomolecules · 2019Article
- Sphingolipids as Emerging Mediators in Retina Degeneration.Frontiers in cellular neuroscience · 2019Review
- The emerging role of FTY720 (Fingolimod) in cancer treatment.Oncotarget · 2016Review
- Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response.Oncotarget · 2016Article
- Article
- Sphingolipid metabolites in inflammatory disease.Nature · 2014Review
- The pleiotropic roles of sphingolipid signaling in autophagy.Cell death & disease · 2014Review
- Ceramide signaling in mammalian epidermis.Biochimica et biophysica acta · 2014Review
- FTY720 inhibits tumor growth and enhances the tumor-suppressive effect of topotecan in neuroblastoma by interfering with the sphingolipid signaling pathway.Pediatric blood & cancer · 2013Article
- Sphingolipids in cardiovascular and cerebrovascular systems: Pathological implications and potential therapeutic targets.World journal of cardiology · 2013Article
- Sphingosine and FTY720 are potent inhibitors of the transient receptor potential melastatin 7 (TRPM7) channels.British journal of pharmacology · 2013Article
- Sphingosine kinase and sphingosine 1-phosphate in the heart: a decade of progress.Biochimica et biophysica acta · 2013Review
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Exposure of 3T3/A31 cells to serum-free medium, one type of apoptotic stimulus, causes a rapid increase in the sphingosine (Sph) level, which initiates a series of processes: (i) activation of caspase 3 through an enhanced "cascade" of caspases, (ii) release of the C-terminal-half kinase domain of PKCdelta (PKCdelta KD) by caspase 3, and (iii) activation of Sph-dependent kinase 1 (SDK1), which was previously identified as PKCdelta KD. The activation of caspase 3 and release of PKCdelta KD are inhibited strongly by the incubation of cells with the ceramidase inhibitor D-erythro-2-tetradecanoylamino-1-phenyl-1-propanol and, to a much lesser extent, by L-cycloserine, an inhibitor of de novo ceramide synthesis. Exogenous addition of Sph or N,N-dimethyl-Sph to U937 cells causes caspase 3 activation and release of PKCdelta KD (SDK1), leading to apoptosis. The Sph-induced apoptotic process associated with activation of caspase 3 and release of PKCdelta KD (SDK1) may promote the proapoptotic effect of BAD or BAX through an increase of phosphorylated 14-3-3. In addition, Sph induces apoptosis through a separate process: the blocking of "survival signal" through the Akt kinase pathway induced by alpha3beta1-mediated cell adhesion to laminin 10/11 in extracellular matrix. We hereby propose a unified concept of Sph-dependent apoptosis based on these multiple mechanisms operating in concert.
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