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Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs

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Abstract

Sphingolipids (SPs) comprise a highly diverse class of lipids that serve biological roles both as structural components of cell membranes and as mediators of cell signaling. Pharmacologic and genetic manipulation of SPs and their signaling systems have underscored their importance in most biological processes, including central nervous system development and function. Likewise, perturbations of SP accumulation or signaling have been associated with a number of disease states, such as neural tube defects, neuroinflammation, stroke, and dementia. SPs can be endogenously synthesized de novo, and their metabolism is a well-regulated process, so their value as nutraceuticals has not been scrutinized. However, there is evidence that sphingolipid-rich diets can affect lipid homeostasis, and several mycotoxins are SP analogs that are known to cause profound derangement of SP metabolism or signaling. Furthermore, plants and invertebrates have SP species that are not present in mammals. Several of these have been shown to induce biological responses in mammalian cells. These findings suggest that dietary intake of SPs or SP analogs may have significant effects on human health or disease outcome. This manuscript provides an overview of SP metabolism and signaling, their perturbations in neurological diseases, as well as potential impacts of modulating this system in the brain.

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Reprinted with permission from An Illustrated Guide to New Zealand Soil Invertebrates, http://soilbugs.massey.ac.nz. © Massey University

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References

  • Abbas, H. K., Duke, S. O., Merrill, A. H, Jr., Wang, E., & Shier, W. T. (1998). Phytotoxicity of australifungin, AAL-toxins and fumonisin B1 to Lemna pausicostata. Phytochemistry, 47(8), 1509–1514. doi:10.1016/S0031-9422(97)00781-4.

    Article  CAS  Google Scholar 

  • Abeytunga, T. U. (2015). Occurrence, structure elucidation, biosynthesis, functions and synthesis of sphingadienes. Mini-Reviews in Organic Chemistry, 12(3), 282–292.

    Article  CAS  Google Scholar 

  • Abeytunga, D. T., Glick, J. J., Gibson, N. J., Oland, L. A., Somogyi, A., Wysocki, V. H., et al. (2004). Presence of unsaturated sphingomyelins and changes in their composition during the life cycle of the moth Manduca sexta. Journal of Lipid Research, 45(7), 1221–1231. doi:10.1194/jlr.M300392-JLR200.

    Article  CAS  PubMed  Google Scholar 

  • Abeytunga, D. T., Oland, L., Somogyi, A., & Polt, R. (2008). Structural studies on the neutral glycosphingolipids of Manduca sexta. Bioorganic Chemistry, 36(2), 70–76. doi:10.1016/j.bioorg.2007.10.002.

    Article  CAS  PubMed  Google Scholar 

  • Aida, K., Kinoshita, M., Sugawara, T., Ono, J., Miyazawa, T., & Ohnishi, M. (2004). Apoptosis inducement by plant and fungus sphingoid bases in human colon cancer cells. Journal of Oleo Science, 53, 503–510.

    Article  CAS  Google Scholar 

  • Akahoshi, N., Ishizaki, Y., Yasuda, H., Murashima, Y. L., Shinba, T., Goto, K., et al. (2011). Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2. Epilepsy & Behavior, 22(4), 659–665. doi:10.1016/j.yebeh.2011.09.002.

    Article  Google Scholar 

  • Aldahmesh, M. A., Mohamed, J. Y., Alkuraya, H. S., Verma, I. C., Puri, R. D., Alaiya, A. A., et al. (2011). Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. American Journal of Human Genetics, 89(6), 745–750. doi:10.1016/j.ajhg.2011.10.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arana, L., Gangoiti, P., Ouro, A., Trueba, M., & Gomez-Munoz, A. (2010). Ceramide and ceramide 1-phosphate in health and disease. Lipids in Health and Disease, 9, 15. doi:10.1186/1476-511X-9-15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Aureli, M., Grassi, S., Prioni, S., Sonnino, S., & Prinetti, A. (2015). Lipid membrane domains in the brain. Biochimica et Biophysica Acta, 1851(8), 1006–1016. doi:10.1016/j.bbalip.2015.02.001.

    Article  CAS  PubMed  Google Scholar 

  • Aytan, N., Choi, J. K., Carreras, I., Brinkmann, V., Kowall, N. W., Jenkins, B. G., et al. (2016). Fingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer’s disease. Scientific Reports, 6, 24939. doi:10.1038/srep24939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bajjalieh, S. M., Martin, T. F., & Floor, E. (1989). Synaptic vesicle ceramide kinase. A calcium-stimulated lipid kinase that co-purifies with brain synaptic vesicles. Journal of Biological Chemistry, 264(24), 14354–14360.

    CAS  PubMed  Google Scholar 

  • Bandhuvula, P., Tam, Y. Y., Oskouian, B., & Saba, J. D. (2005). The immune modulator FTY720 inhibits sphingosine-1-phosphate lyase activity. Journal of Biological Chemistry, 280(40), 33697–33700. doi:10.1074/jbc.C500294200.

    Article  CAS  PubMed  Google Scholar 

  • Baudhuin, L. M., Jiang, Y., Zaslavsky, A., Ishii, I., Chun, J., & Xu, Y. (2004). S1P3-mediated Akt activation and cross-talk with platelet-derived growth factor receptor (PDGFR). FASEB Journal, 18(2), 341–343.

    CAS  PubMed  Google Scholar 

  • Ben-David, O., & Futerman, A. H. (2010). The role of the ceramide acyl chain length in neurodegeneration: Involvement of ceramide synthases. Neuromolecular Medicine, 12(4), 341–350. doi:10.1007/s12017-010-8114-x.

    Article  CAS  PubMed  Google Scholar 

  • Bensemhoun, J., Bombarda, I., Aknin, M., Faure, R., Vacelet, J., & Gaydou, E. M. (2008). Marine bifunctional sphingolipids from the sponge Oceanapia ramsayi. Molecules, 13(4), 772–778.

    Article  CAS  PubMed  Google Scholar 

  • Bertea, M., Rutti, M. F., Othman, A., Marti-Jaun, J., Hersberger, M., von Eckardstein, A., et al. (2010). Deoxysphingoid bases as plasma markers in diabetes mellitus. Lipids in Health and Disease, 9, 84. doi:10.1186/1476-511X-9-84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bode, H., Bourquin, F., Suriyanarayanan, S., Wei, Y., Alecu, I., Othman, A., et al. (2015). HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship. Human Molecular Genetics,. doi:10.1093/hmg/ddv611.

    Google Scholar 

  • Bohler, T., Budde, K., Neumayer, H. H., & Waiser, J. (2005). Novel mediators of FTY720 in human lymphocytes. Transplantation, 79(4), 492–495.

    Article  PubMed  CAS  Google Scholar 

  • Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., et al. (2010). Fingolimod (FTY720): Discovery and development of an oral drug to treat multiple sclerosis. [Review]. Nature Reviews Drug Discovery, 9(11), 883–897. doi:10.1038/nrd3248.

    Article  CAS  PubMed  Google Scholar 

  • Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., et al. (2002). The immune modulator FTY720 targets sphingosine 1-phosphate receptors. Journal of Biological Chemistry, 277(24), 21453–21457.

    Article  CAS  PubMed  Google Scholar 

  • Buehrer, B. M., & Bell, R. M. (1992). Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways. Journal of Biological Chemistry, 267(5), 3154–3159.

    CAS  PubMed  Google Scholar 

  • Byrdwell, W. C., & Perry, R. H. (2007). Liquid chromatography with dual parallel mass spectrometry and 31P nuclear magnetic resonance spectroscopy for analysis of sphingomyelin and dihydrosphingomyelin. II. Bovine milk sphingolipids. Journal of Chromatography A, 1146(2), 164–185. doi:10.1016/j.chroma.2007.01.108.

    Article  CAS  PubMed  Google Scholar 

  • Canals, D., & Hannun, Y. A. (2013). Novel chemotherapeutic drugs in sphingolipid cancer research. Handbook of Experimental Pharmacology, 215, 211–238. doi:10.1007/978-3-7091-1368-4_12.

    Article  CAS  PubMed  Google Scholar 

  • Chiba, K., Hoshino, Y., Suzuki, C., Masubuchi, Y., Yanagawa, Y., Ohtsuki, M., et al. (1996). FTY720, a novel immunosuppressant possessing unique mechanisms. I. Prolongation of skin allograft survival and synergistic effect in combination with cyclosporine in rats. Transplantation Proceedings, 28(2), 1056–1059.

    CAS  PubMed  Google Scholar 

  • Choi, J. W., Gardell, S. E., Herr, D. R., Rivera, R., Lee, C. W., Noguchi, K., et al. (2011). FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation. Proceedings of the National Academy of Sciences of the United States of America, 108(2), 751–756. doi:10.1073/pnas.1014154108.

    Article  CAS  PubMed  Google Scholar 

  • Christoffersen, C., Obinata, H., Kumaraswamy, S. B., Galvani, S., Ahnstrom, J., Sevvana, M., et al. (2011). Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M. Proceedings of the National Academy of Sciences of the United States of America, 108(23), 9613–9618. doi:10.1073/pnas.1103187108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chueh, S. C., Tian, L., Wang, M., Wang, M. E., Stepkowski, S. M., & Kahan, B. D. (1997). Induction of tolerance toward rat cardiac allografts by treatment with allochimeric class I MHC antigen and FTY720. Transplantation, 64(10), 1407–1414.

    Article  CAS  PubMed  Google Scholar 

  • Chumanevich, A. A., Poudyal, D., Cui, X., Davis, T., Wood, P. A., Smith, C. D., et al. (2010). Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase. Carcinogenesis, 31(10), 1787–1793. doi:10.1093/carcin/bgq158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chun, J., & Brinkmann, V. (2011). A mechanistically novel, first oral therapy for multiple sclerosis: The development of fingolimod (FTY720, Gilenya). [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Discovery Medicine, 12(64), 213–228.

    PubMed  PubMed Central  Google Scholar 

  • Chun, J., & Hartung, H. P. (2010). Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clinical Neuropharmacology, 33(2), 91–101. doi:10.1097/WNF.0b013e3181cbf825.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cingolani, F., Casasampere, M., Sanllehi, P., Casas, J., Bujons, J., & Fabrias, G. (2014). Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II. Journal of Lipid Research, 55(8), 1711–1720. doi:10.1194/jlr.M049759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cohen, J. A., & Chun, J. (2011). Mechanisms of fingolimod’s efficacy and adverse effects in multiple sclerosis. Annals of Neurology, 69(5), 759–777. doi:10.1002/ana.22426.

    Article  CAS  PubMed  Google Scholar 

  • Cowart, L. A., & Obeid, L. M. (2007). Yeast sphingolipids: Recent developments in understanding biosynthesis, regulation, and function. Biochimica et Biophysica Acta, 1771(3), 421–431. doi:10.1016/j.bbalip.2006.08.005.

    Article  CAS  PubMed  Google Scholar 

  • de la Monte, S. M., Longato, L., Tong, M., DeNucci, S., & Wands, J. R. (2009). The liver-brain axis of alcohol-mediated neurodegeneration: Role of toxic lipids. International Journal of Environmental Research and Public Health, 6(7), 2055–2075. doi:10.3390/ijerph6072055.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Luca, C., & Valacchi, G. (2010). Surface lipids as multifunctional mediators of skin responses to environmental stimuli. Mediators of Inflammation, 2010, 321494. doi:10.1155/2010/321494.

    PubMed  PubMed Central  Google Scholar 

  • Dickson, R. C. (2008). Thematic review series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast. Journal of Lipid Research, 49(5), 909–921. doi:10.1194/jlr.R800003-JLR200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dickson, M. A., Carvajal, R. D., Merrill, A. H, Jr., Gonen, M., Cane, L. M., & Schwartz, G. K. (2011). A phase I clinical trial of safingol in combination with cisplatin in advanced solid tumors. Clinical Cancer Research, 17(8), 2484–2492. doi:10.1158/1078-0432.CCR-10-2323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duan, J., & Merrill, A. H, Jr. (2015). 1-Deoxysphingolipids encountered exogenously and made de novo: Dangerous mysteries inside an enigma. Journal of Biological Chemistry, 290(25), 15380–15389. doi:10.1074/jbc.R115.658823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dukala, D. E., & Soliven, B. (2016). S1P1 deletion in oligodendroglial lineage cells: Effect on differentiation and myelination. Glia, 64(4), 570–582. doi:10.1002/glia.22949.

    Article  PubMed  Google Scholar 

  • Enosawa, S., Suzuki, S., Kakefuda, T., Li, X. K., & Amemiya, H. (1996). Induction of selective cell death targeting on mature T-lymphocytes in rats by a novel immunosuppressant, FTY720. Immunopharmacology, 34(2–3), 171–179.

    Article  CAS  PubMed  Google Scholar 

  • Fahy, E., Subramaniam, S., Brown, H. A., Glass, C. K., Merrill, A. H, Jr., Murphy, R. C., et al. (2005). A comprehensive classification system for lipids. Journal of Lipid Research, 46(5), 839–861. doi:10.1194/jlr.E400004-JLR200.

    Article  CAS  PubMed  Google Scholar 

  • Fahy, E., Subramaniam, S., Murphy, R. C., Nishijima, M., Raetz, C. R., Shimizu, T., et al. (2009). Update of the LIPID MAPS comprehensive classification system for lipids. Journal of Lipid Research, 50(Suppl), S9–S14. doi:10.1194/jlr.R800095-JLR200.

    PubMed  PubMed Central  Google Scholar 

  • Felding-Habermann, B., Igarashi, Y., Fenderson, B. A., Park, L. S., Radin, N. S., Inokuchi, J., et al. (1990). A ceramide analogue inhibits T cell proliferative response through inhibition of glycosphingolipid synthesis and enhancement of N,N-dimethylsphingosine synthesis. Biochemistry, 29(26), 6314–6322.

    Article  CAS  PubMed  Google Scholar 

  • Finley, K. D., Edeen, P. T., Cumming, R. C., Mardahl-Dumesnil, M. D., Taylor, B. J., Rodriguez, M. H., et al. (2003). blue cheese mutations define a novel, conserved gene involved in progressive neural degeneration. Journal of Neuroscience, 23(4), 1254–1264.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fleischmann, R. (2012). Novel small-molecular therapeutics for rheumatoid arthritis. Current Opinion in Rheumatology, 24(3), 335–341. doi:10.1097/BOR.0b013e32835190ef.

    Article  CAS  PubMed  Google Scholar 

  • Fujino, M., Funeshima, N., Kitazawa, Y., Kimura, H., Amemiya, H., Suzuki, S., et al. (2003). Amelioration of experimental autoimmune encephalomyelitis in Lewis rats by FTY720 treatment. Journal of Pharmacology and Experimental Therapeutics, 305(1), 70–77.

    Article  CAS  PubMed  Google Scholar 

  • Fujita, T., Inoue, K., Yamamoto, S., Ikumoto, T., Sasaki, S., Toyama, R., et al. (1994). Fungal metabolites. Part 12. Potent immunosuppressant, 14-deoxomyriocin, (2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-hydroxymethyleicos-6-enoic acid and structure-activity relationships of myriocin derivatives. Journal of Antibiotics (Tokyo), 47(2), 216–224.

    Article  CAS  Google Scholar 

  • Fukushima, N., Ishii, I., Contos, J. J., Weiner, J. A., & Chun, J. (2001). Lysophospholipid receptors. Annual Review of Pharmacology and Toxicology, 41, 507–534.

    Article  CAS  PubMed  Google Scholar 

  • Furukawa, A., Kita, K., Toyomoto, M., Fujii, S., Inoue, S., Hayashi, K., et al. (2007). Production of nerve growth factor enhanced in cultured mouse astrocytes by glycerophospholipids, sphingolipids, and their related compounds. Molecular and Cellular Biochemistry, 305(1–2), 27–34. doi:10.1007/s11010-007-9524-4.

    Article  CAS  PubMed  Google Scholar 

  • Fyrst, H., Herr, D. R., Harris, G. L., & Saba, J. D. (2004). Characterization of free endogenous C14 and C16 sphingoid bases from Drosophila melanogaster. Journal of Lipid Research, 45(1), 54–62. doi:10.1194/jlr.M300005-JLR200.

    Article  CAS  PubMed  Google Scholar 

  • Fyrst, H., Oskouian, B., Bandhuvula, P., Gong, Y. Q., Byun, H. S., Bittman, R., et al. (2009). Natural sphingadienes inhibit Akt-dependent signaling and prevent intestinal tumorigenesis. Cancer Research, 69(24), 9457–9464. doi:10.1158/0008-5472.Can-09-2341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fyrst, H., & Saba, J. D. (2010). An update on sphingosine-1-phosphate and other sphingolipid mediators. Nature Chemical Biology, 6(7), 489–497. doi:10.1038/nchembio.392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fyrst, H., Zhang, X., Herr, D. R., Byun, H. S., Bittman, R., Phan, V. H., et al. (2008). Identification and characterization by electrospray mass spectrometry of endogenous Drosophila sphingadienes. Journal of Lipid Research, 49(3), 597–606. doi:10.1194/jlr.M700414-JLR200.

    Article  CAS  PubMed  Google Scholar 

  • Garnier-Amblard, E. C., Mays, S. G., Arrendale, R. F., Baillie, M. T., Bushnev, A. S., Culver, D. G., et al. (2011). Novel synthesis and biological evaluation of enigmols as therapeutic agents for treating prostate cancer. ACS Medicinal Chemistry Letters, 2(6), 438–443. doi:10.1021/ml2000164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghasemi, R., Dargahi, L., & Ahmadiani, A. (2016). Integrated sphingosine-1 phosphate signaling in the central nervous system: From physiological equilibrium to pathological damage. Pharmacological Research, 104, 156–164. doi:10.1016/j.phrs.2015.11.006.

    Article  CAS  PubMed  Google Scholar 

  • Gibellini, F., & Smith, T. K. (2010). The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB Life, 62(6), 414–428. doi:10.1002/iub.337.

    Article  CAS  PubMed  Google Scholar 

  • Godfrey, J., Jeanguenin, L., Castro, N., Olney, J. J., Dudley, J., Pipkin, J., et al. (2015). Chronic voluntary ethanol consumption induces favorable ceramide profiles in selectively bred alcohol-preferring (P) rats. PLoS ONE, 10(9), e0139012. doi:10.1371/journal.pone.0139012.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gomez-Munoz, A., Presa, N., Gomez-Larrauri, A., Rivera, I. G., Trueba, M., & Ordonez, M. (2016). Control of inflammatory responses by ceramide, sphingosine 1-phosphate and ceramide 1-phosphate. Progress in Lipid Research, 61, 51–62. doi:10.1016/j.plipres.2015.09.002.

    Article  CAS  PubMed  Google Scholar 

  • Groves, A., Kihara, Y., & Chun, J. (2013). Fingolimod: Direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy. Journal of the Neurological Sciences, 328(1–2), 9–18. doi:10.1016/j.jns.2013.02.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gulbins, E., Walter, S., Becker, K. A., Halmer, R., Liu, Y., Reichel, M., et al. (2015). A central role for the acid sphingomyelinase/ceramide system in neurogenesis and major depression. Journal of Neurochemistry, 134(2), 183–192. doi:10.1111/jnc.13145.

    Article  CAS  PubMed  Google Scholar 

  • Han, G., Gupta, S. D., Gable, K., Niranjanakumari, S., Moitra, P., Eichler, F., et al. (2009). Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities. Proceedings of the National Academy of Sciences of the United States of America, 106(20), 8186–8191. doi:10.1073/pnas.0811269106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanson, M. A., Roth, C. B., Jo, E., Griffith, M. T., Scott, F. L., Reinhart, G., et al. (2012). Crystal structure of a lipid G protein-coupled receptor. Science, 335(6070), 851–855. doi:10.1126/science.1215904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hebbar, S., Sahoo, I., Matysik, A., Argudo Garcia, I., Osborne, K. A., Papan, C., et al. (2015). Ceramides and stress signalling intersect with autophagic defects in neurodegenerative Drosophila blue cheese (bchs) mutants. Scientific Reports, 5, 15926. doi:10.1038/srep15926.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hecht, J. H., Weiner, J. A., Post, S. R., & Chun, J. (1996). Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. Journal of Cell Biology, 135(4), 1071–1083.

    Article  CAS  PubMed  Google Scholar 

  • Herr, D. R., & Chun, J. (2007). Effects of LPA and S1P on the nervous system and implications for their involvement in disease. Current Drug Targets, 8(1), 155–167.

    Article  CAS  PubMed  Google Scholar 

  • Herr, D. R., Grillet, N., Schwander, M., Rivera, R., Muller, U., & Chun, J. (2007). Sphingosine 1-phosphate (S1P) signaling is required for maintenance of hair cells mainly via activation of S1P2. Journal of Neuroscience, 27(6), 1474–1478. doi:10.1523/JNEUROSCI.4245-06.2007.

    Article  CAS  PubMed  Google Scholar 

  • Herr, D. R., Lee, C. W., Wang, W., Ware, A., Rivera, R., & Chun, J. (2013). Sphingosine 1-phosphate receptors are essential mediators of eyelid closure during embryonic development. Journal of Biological Chemistry, 288(41), 29882–29889. doi:10.1074/jbc.M113.510099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herr, D. R., Reolo, M. J., Peh, Y. X., Wang, W., Lee, C. W., Rivera, R., et al. (2016). Sphingosine 1-phosphate receptor 2 (S1P2) attenuates reactive oxygen species formation and inhibits cell death: Implications for otoprotective therapy. Scientific Reports, 6, 24541. doi:10.1038/srep24541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heusler, K., & Pletscher, A. (2001). The controversial early history of cyclosporin. Swiss Medical Weekly, 131(21–22), 299–302. doi:2001/21/smw-09702.

  • Hoeferlin, L. A., Wijesinghe, D. S., & Chalfant, C. E. (2013). The role of ceramide-1-phosphate in biological functions. Handbook of Experimental Pharmacology, 215, 153–166. doi:10.1007/978-3-7091-1368-4_8.

    Article  CAS  PubMed  Google Scholar 

  • Hopson, K. P., Truelove, J., Chun, J., Wang, Y., & Waeber, C. (2011). S1P activates store-operated calcium entry via receptor- and non-receptor-mediated pathways in vascular smooth muscle cells. American Journal of Physiology. Cell Physiology, 300(4), C919–C926. doi:10.1152/ajpcell.00350.2010.

    Article  CAS  PubMed  Google Scholar 

  • Hornemann, T., Penno, A., Rutti, M. F., Ernst, D., Kivrak-Pfiffner, F., Rohrer, L., et al. (2009). The SPTLC3 subunit of serine palmitoyltransferase generates short chain sphingoid bases. Journal of Biological Chemistry, 284(39), 26322–26330. doi:10.1074/jbc.M109.023192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hornemann, T., Wei, Y., & von Eckardstein, A. (2007). Is the mammalian serine palmitoyltransferase a high-molecular-mass complex? Biochemical Journal, 405(1), 157–164. doi:10.1042/BJ20070025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoshino, Y., Suzuki, C., Ohtsuki, M., Masubuchi, Y., Amano, Y., & Chiba, K. (1996). FTY720, a novel immunosuppressant possessing unique mechanisms. II. Long-term graft survival induction in rat heterotopic cardiac allografts and synergistic effect in combination with cyclosporine A. Transplantation Proceedings, 28(2), 1060–1061.

    CAS  PubMed  Google Scholar 

  • Hulette, C. M., Earl, N. L., Anthony, D. C., & Crain, B. J. (1992). Adult onset Niemann-Pick disease type C presenting with dementia and absent organomegaly. Clinical Neuropathology, 11(6), 293–297.

    CAS  PubMed  Google Scholar 

  • Igarashi, Y., Kitamura, K., Toyokuni, T., Dean, B., Fenderson, B., Ogawass, T., et al. (1990). A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells. Journal of Biological Chemistry, 265(10), 5385–5389.

    CAS  PubMed  Google Scholar 

  • Ikeda, K., & Taguchi, R. (2010). Highly sensitive localization analysis of gangliosides and sulfatides including structural isomers in mouse cerebellum sections by combination of laser microdissection and hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry with theoretically expanded multiple reaction monitoring. Rapid Communications in Mass Spectrometry, 24(20), 2957–2965. doi:10.1002/rcm.4716.

    Article  CAS  PubMed  Google Scholar 

  • Imai, H., Ohnishi, M., Hotsubo, K., Kojima, M., & Ito, S. (1997). Sphingoid base composition of cerebrosides from plant leaves. Bioscience, Biotechnology, and Biochemistry, 61(2), 351–353.

    Article  CAS  Google Scholar 

  • Inamine, M., Suzui, M., Morioka, T., Kinjo, T., Kaneshiro, T., Sugishita, T., et al. (2005). Inhibitory effect of dietary monoglucosylceramide 1-O-beta-glucosyl-N-2′-hydroxyarachidoyl-4,8-sphingadienine on two different categories of colon preneoplastic lesions induced by 1,2-dimethylhydrazine in F344 rats. Cancer Science, 96(12), 876–881. doi:10.1111/j.1349-7006.2005.00127.x.

    Article  CAS  PubMed  Google Scholar 

  • Ishii, I., Friedman, B., Ye, X., Kawamura, S., McGiffert, C., Contos, J. J., et al. (2001). Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3. Journal of Biological Chemistry, 276(36), 33697–33704. Epub 32001 Jul 33696.

    Article  CAS  PubMed  Google Scholar 

  • Ishii, I., Ye, X., Friedman, B., Kawamura, S., Contos, J. J., Kingsbury, M. A., et al. (2002). Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3. Journal of Biological Chemistry, 277(28), 25152–25159. Epub 22002 May 25152.

    Article  CAS  PubMed  Google Scholar 

  • Jaillard, C., Harrison, S., Stankoff, B., Aigrot, M. S., Calver, A. R., Duddy, G., et al. (2005). Edg8/S1P5: An oligodendroglial receptor with dual function on process retraction and cell survival. Journal of Neuroscience, 25(6), 1459–1469. doi:10.1523/JNEUROSCI.4645-04.2005.

    Article  CAS  PubMed  Google Scholar 

  • Jana, A., Hogan, E. L., & Pahan, K. (2009). Ceramide and neurodegeneration: Susceptibility of neurons and oligodendrocytes to cell damage and death. Journal of the Neurological Sciences, 278(1–2), 5–15. doi:10.1016/j.jns.2008.12.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kappos, L., Antel, J., Comi, G., Montalban, X., O’Connor, P., Polman, C. H., et al. (2006). Oral fingolimod (FTY720) for relapsing multiple sclerosis [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. New England Journal of Medicine, 355(11), 1124–1140. doi:10.1056/NEJMoa052643.

    Article  CAS  PubMed  Google Scholar 

  • Kawaguchi, T., Hoshino, Y., Rahman, F., Amano, Y., Higashi, H., Kataoka, H., et al. (1996). FTY720, a novel immunosuppressant possessing unique mechanisms. III. Synergistic prolongation of canine renal allograft survival in combination with cyclosporine A. Transplantation Proceedings, 28(2), 1062–1063.

    CAS  PubMed  Google Scholar 

  • Kawamori, T., Kaneshiro, T., Okumura, M., Maalouf, S., Uflacker, A., Bielawski, J., et al. (2009). Role for sphingosine kinase 1 in colon carcinogenesis. FASEB Journal, 23(2), 405–414. doi:10.1096/fj.08-117572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawamori, T., Osta, W., Johnson, K. R., Pettus, B. J., Bielawski, J., Tanaka, T., et al. (2006). Sphingosine kinase 1 is up-regulated in colon carcinogenesis. FASEB Journal, 20(2), 386–388. doi:10.1096/fj.05-4331fje.

    CAS  PubMed  Google Scholar 

  • Keller, C. D., Rivera Gil, P., Tolle, M., van der Giet, M., Chun, J., Radeke, H. H., et al. (2007). Immunomodulator FTY720 induces myofibroblast differentiation via the lysophospholipid receptor S1P3 and Smad3 signaling. American Journal of Pathology, 170(1), 281–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keranen, A. (1976). Fatty acids and long-chain bases of gangliosides of human gastrointestinal mucosa. Chemistry and Physics of Lipids, 17(1), 14–21.

    Article  CAS  PubMed  Google Scholar 

  • Kihara, Y., Maceyka, M., Spiegel, S., & Chun, J. (2014). Lysophospholipid receptor nomenclature review: IUPHAR Review 8. British Journal of Pharmacology, 171(15), 3575–3594. doi:10.1111/bph.12678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kihara, Y., Mizuno, H., & Chun, J. (2015). Lysophospholipid receptors in drug discovery. Experimental Cell Research, 333(2), 171–177. doi:10.1016/j.yexcr.2014.11.020.

    Article  CAS  PubMed  Google Scholar 

  • Kim, G. S., Yang, L., Zhang, G., Zhao, H., Selim, M., McCullough, L. D., et al. (2015). Critical role of sphingosine-1-phosphate receptor-2 in the disruption of cerebrovascular integrity in experimental stroke. Nature Communications, 6, 7893. doi:10.1038/ncomms8893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitatani, K., Idkowiak-Baldys, J., & Hannun, Y. A. (2008). The sphingolipid salvage pathway in ceramide metabolism and signaling. Cellular Signalling, 20(6), 1010–1018. doi:10.1016/j.cellsig.2007.12.006.

    Article  CAS  PubMed  Google Scholar 

  • Kluepfel, D., Bagli, J., Baker, H., Charest, M. P., & Kudelski, A. (1972). Myriocin, a new antifungal antibiotic from Myriococcum albomyces. Journal of Antibiotics (Tokyo), 25(2), 109–115.

    Article  CAS  Google Scholar 

  • Kornhuber, J., Muller, C. P., Becker, K. A., Reichel, M., & Gulbins, E. (2014). The ceramide system as a novel antidepressant target. Trends in Pharmacological Sciences, 35(6), 293–304. doi:10.1016/j.tips.2014.04.003.

    Article  CAS  PubMed  Google Scholar 

  • Kumar, A., Pandurangan, A. K., Lu, F., Fyrst, H., Zhang, M., Byun, H. S., et al. (2012). Chemopreventive sphingadienes downregulate Wnt signaling via a PP2A/Akt/GSK3beta pathway in colon cancer. Carcinogenesis, 33(9), 1726–1735. doi:10.1093/carcin/bgs174.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunkel, G. T., Maceyka, M., Milstien, S., & Spiegel, S. (2013). Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nature Reviews Drug Discovery, 12(9), 688–702. doi:10.1038/nrd4099.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon, H. C., Lee, K. C., Cho, O. R., Jung, I. Y., Cho, S. Y., Kim, S. Y., et al. (2003). Sphingolipids from Bombycis Corpus 101A and their neurotrophic effects. Journal of Natural Products, 66(4), 466–469. doi:10.1021/np0204491.

    Article  CAS  PubMed  Google Scholar 

  • Lamour, N. F., & Chalfant, C. E. (2005). Ceramide-1-phosphate: The “missing” link in eicosanoid biosynthesis and inflammation. Molecular Interventions, 5(6), 358–367. doi:10.1124/mi.5.6.8.

    Article  CAS  PubMed  Google Scholar 

  • Lee, H., Deng, J., Kujawski, M., Yang, C., Liu, Y., Herrmann, A., et al. (2010). STAT3-induced S1PR1 expression is crucial for persistent STAT3 activation in tumors [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Nature Medicine, 16(12), 1421–1428. doi:10.1038/nm.2250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, T. C., Ou, M. C., Shinozaki, K., Malone, B., & Snyder, F. (1996). Biosynthesis of N-acetylsphingosine by platelet-activating factor: Sphingosine CoA-independent transacetylase in HL-60 cells. Journal of Biological Chemistry, 271(1), 209–217.

    Article  CAS  PubMed  Google Scholar 

  • Lee, M. J., Thangada, S., Claffey, K. P., Ancellin, N., Liu, C. H., Kluk, M., et al. (1999). Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell, 99(3), 301–312.

    Article  CAS  PubMed  Google Scholar 

  • Lee, M. J., Van Brocklyn, J. R., Thangada, S., Liu, C. H., Hand, A. R., Menzeleev, R., et al. (1998). Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science, 279(5356), 1552–1555.

    Article  CAS  PubMed  Google Scholar 

  • Levy, M., & Futerman, A. H. (2010). Mammalian ceramide synthases. IUBMB Life, 62(5), 347–356. doi:10.1002/iub.319.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, J., Zhang, C., Tao, W., & Liu, M. (2013). Systematic review and meta-analysis of the efficacy of sphingosine-1-phosphate (S1P) receptor agonist FTY720 (fingolimod) in animal models of stroke. International Journal of Neuroscience, 123(3), 163–169. doi:10.3109/00207454.2012.749255.

    Article  CAS  PubMed  Google Scholar 

  • Lynch, D. V., & Dunn, T. M. (2004). An introduction to plant sphingolipids and a review of recent advances in understanding their metabolism and function. New Phytologist, 161(3), 677–702. doi:10.1111/j.1469-8137.2004.00992.x.

    Article  CAS  Google Scholar 

  • Macauley, S. L., Sidman, R. L., Schuchman, E. H., Taksir, T., & Stewart, G. R. (2008). Neuropathology of the acid sphingomyelinase knockout mouse model of Niemann-Pick A disease including structure-function studies associated with cerebellar Purkinje cell degeneration. Experimental Neurology, 214(2), 181–192. doi:10.1016/j.expneurol.2008.07.026.

    Article  CAS  PubMed  Google Scholar 

  • MacLennan, A. J., Carney, P. R., Zhu, W. J., Chaves, A. H., Garcia, J., Grimes, J. R., et al. (2001). An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. European Journal of Neuroscience, 14(2), 203–209.

    Article  CAS  PubMed  Google Scholar 

  • Malchinkhuu, E., Sato, K., Muraki, T., Ishikawa, K., Kuwabara, A., & Okajima, F. (2003). Assessment of the role of sphingosine 1-phosphate and its receptors in high-density lipoprotein-induced stimulation of astroglial cell function. Biochemical Journal, 370(Pt 3), 817–827.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., et al. (2002). Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science, 296(5566), 346–349.

    Article  CAS  PubMed  Google Scholar 

  • Martinez, T. N., Chen, X., Bandyopadhyay, S., Merrill, A. H., & Tansey, M. G. (2012). Ceramide sphingolipid signaling mediates tumor necrosis factor (TNF)-dependent toxicity via caspase signaling in dopaminergic neurons. Molecular Neurodegeneration, 7, 45. doi:10.1186/1750-1326-7-45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Masubuchi, Y., Kawaguchi, T., Ohtsuki, M., Suzuki, C., Amano, Y., Hoshino, Y., et al. (1996). FTY720, a novel immunosuppressant, possessing unique mechanisms. IV. Prevention of graft versus host reactions in rats. Transplantation Proceedings, 28(2), 1064–1065.

    CAS  PubMed  Google Scholar 

  • Matloubian, M., Lo, C. G., Cinamon, G., Lesneski, M. J., Xu, Y., Brinkmann, V., et al. (2004). Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature, 427(6972), 355–360.

    Article  CAS  PubMed  Google Scholar 

  • Matsuoka, Y., Nagahara, Y., Ikekita, M., & Shinomiya, T. (2003). A novel immunosuppressive agent FTY720 induced Akt dephosphorylation in leukemia cells. British Journal of Pharmacology, 138(7), 1303–1312. doi:10.1038/sj.bjp.0705182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNaughton, M., Pitman, M., Pitson, S. M., Pyne, N. J., & Pyne, S. (2016). Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells. Oncotarget, 7(13), 16663–16675. doi:10.18632/oncotarget.7693.

    PubMed  PubMed Central  Google Scholar 

  • Means, C. K., Miyamoto, S., Chun, J., & Brown, J. H. (2008). S1P1 receptor localization confers selectivity for Gi-mediated cAMP and contractile responses. Journal of Biological Chemistry, 283(18), 11954–11963. doi:10.1074/jbc.M707422200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Means, C. K., Xiao, C. Y., Li, Z., Zhang, T., Omens, J. H., Ishii, I., et al. (2007). Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated Akt activation protects against in vivo myocardial ischemia-reperfusion injury. American Journal of Physiology: Heart and Circulatory Physiology, 292(6), H2944–H2951. doi:10.1152/ajpheart.01331.2006.

    CAS  PubMed  Google Scholar 

  • Merrill, A. H, Jr. (2011). Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chemical Reviews, 111(10), 6387–6422. doi:10.1021/cr2002917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Merrill, A. H, Jr., Stokes, T. H., Momin, A., Park, H., Portz, B. J., Kelly, S., et al. (2009). Sphingolipidomics: A valuable tool for understanding the roles of sphingolipids in biology and disease. Journal of Lipid Research, 50(Suppl), S97–S102. doi:10.1194/jlr.R800073-JLR200.

    PubMed  PubMed Central  Google Scholar 

  • Merrill, A. H, Jr., Sullards, M. C., Allegood, J. C., Kelly, S., & Wang, E. (2005). Sphingolipidomics: High-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods, 36(2), 207–224. doi:10.1016/j.ymeth.2005.01.009.

    Article  CAS  PubMed  Google Scholar 

  • Merrill, A. H, Jr., Wang, E., Mullins, R. E., Jamison, W. C., Nimkar, S., & Liotta, D. C. (1988). Quantitation of free sphingosine in liver by high-performance liquid chromatography. Analytical Biochemistry, 171(2), 373–381.

    Article  CAS  PubMed  Google Scholar 

  • Mielke, M. M., & Haughey, N. J. (2012). Could plasma sphingolipids be diagnostic or prognostic biomarkers for Alzheimer’s disease? Clinical Lipidology, 7(5), 525–536. doi:10.2217/clp.12.59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Missmer, S. A., Suarez, L., Felkner, M., Wang, E., Merrill, A. H, Jr., Rothman, K. J., et al. (2006). Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border. Environmental Health Perspectives, 114(2), 237–241.

    Article  PubMed  Google Scholar 

  • Mitsusada, M., Suzuki, S., Kobayashi, E., Enosawa, S., Kakefuda, T., & Miyata, M. (1997). Prevention of graft rejection and graft-versus-host reaction by a novel immunosuppressant, FTY720, in rat small bowel transplantation. Transplantation International, 10(5), 343–349.

    CAS  Google Scholar 

  • Miyake, Y., Kozutsumi, Y., Nakamura, S., Fujita, T., & Kawasaki, T. (1995). Serine palmitoyltransferase is the primary target of a sphingosine-like immunosuppressant, ISP-1/myriocin. Biochemical and Biophysical Research Communications, 211(2), 396–403.

    Article  CAS  PubMed  Google Scholar 

  • Mizugishi, K., Yamashita, T., Olivera, A., Miller, G. F., Spiegel, S., & Proia, R. L. (2005). Essential role for sphingosine kinases in neural and vascular development. Molecular and Cellular Biology, 25(24), 11113–11121. doi:10.1128/MCB.25.24.11113-11121.2005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mizushina, Y., Hanashima, L., Yamaguchi, T., Takemura, M., Sugawara, F., Saneyoshi, M., et al. (1998). A mushroom fruiting body-inducing substance inhibits activities of replicative DNA polymerases. Biochemical and Biophysical Research Communications, 249(1), 17–22. doi:10.1006/bbrc.1998.9091.

    Article  CAS  PubMed  Google Scholar 

  • Moon, E., Han, J. E., Jeon, S., Ryu, J. H., Choi, J. W., & Chun, J. (2015). Exogenous S1P exposure potentiates ischemic stroke damage that is reduced possibly by inhibiting S1P receptor signaling. Mediators of Inflammation, 2015, 492659. doi:10.1155/2015/492659.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Motta, S., Monti, M., Sesana, S., Mellesi, L., Ghidoni, R., & Caputo, R. (1994). Abnormality of water barrier function in psoriasis. Role of ceramide fractions. Archives of Dermatology, 130(4), 452–456.

    Article  CAS  PubMed  Google Scholar 

  • Mutoh, T., Rivera, R., & Chun, J. (2012). Insights into the pharmacological relevance of lysophospholipid receptors. British Journal of Pharmacology, 165(4), 829–844. doi:10.1111/j.1476-5381.2011.01622.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagle, D. G., McClatchey, W. C., & Gerwick, W. H. (1992). New glycosphingolipids from the marine sponge Halichondria panicea. Journal of Natural Products, 55(7), 1013–1017.

    Article  CAS  PubMed  Google Scholar 

  • Napoli, K. L. (2000). The FTY720 story. Therapeutic Drug Monitoring, 22(1), 47–51.

    Article  CAS  PubMed  Google Scholar 

  • Narayanaswamy, P., Shinde, S., Sulc, R., Kraut, R., Staples, G., Thiam, C. H., et al. (2014). Lipidomic “deep profiling”: An enhanced workflow to reveal new molecular species of signaling lipids. Analytical Chemistry, 86(6), 3043–3047. doi:10.1021/ac4039652.

    Article  CAS  PubMed  Google Scholar 

  • Nicholas, G. M., & Molinski, T. F. (2000). Enantiodivergent biosynthesis of the dimeric sphingolipid oceanapiside from the marine sponge Oceanapia phillipensis. Determination of remote stereochemistry. Journal of the American Chemical Society, 122(17), 4011–4019. doi:10.1021/ja994215o.

    Article  CAS  Google Scholar 

  • Noda, N., Tanaka, R., Miyahara, K., & Kawasaki, T. (1993). Isolation and characterization of a novel type of glycosphingolipid from Neanthes diversicolor. Biochimica et Biophysica Acta, 1169(1), 30–38.

    Article  CAS  PubMed  Google Scholar 

  • Nofer, J. R., van der Giet, M., Tolle, M., Wolinska, I., von Wnuck Lipinski, K., Baba, H. A., et al. (2004). HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. Journal of Clinical Investigation, 113(4), 569–581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Novotny, J., Hrabalek, A., & Vavrova, K. (2010). Synthesis and structure-activity relationships of skin ceramides. Current Medicinal Chemistry, 17(21), 2301–2324.

    Article  CAS  PubMed  Google Scholar 

  • Nyberg, L., Nilsson, A., Lundgren, P., & Duan, R. D. (1997). Localization and capacity of sphingomyelin digestion in the rat intestinal tract. Journal of Nutritional Biochemistry, 8(3), 112–118. doi:10.1016/S0955-2863(97)00010-7.

    Article  CAS  Google Scholar 

  • Obenberger, J., Seidl, Z., Pavlu, H., & Elleder, M. (1999). MRI in an unusually protracted neuronopathic variant of acid sphingomyelinase deficiency. Neuroradiology, 41(3), 182–184.

    Article  CAS  PubMed  Google Scholar 

  • O’Brien, J. S., & Sampson, E. L. (1965). Lipid composition of the normal human brain: Gray matter, white matter, and myelin. Journal of Lipid Research, 6(4), 537–544.

    PubMed  Google Scholar 

  • Ohlsson, L., Hertervig, E., Jonsson, B. A., Duan, R. D., Nyberg, L., Svernlov, R., et al. (2010). Sphingolipids in human ileostomy content after meals containing milk sphingomyelin. American Journal of Clinical Nutrition, 91(3), 672–678. doi:10.3945/ajcn.2009.28311.

    Article  CAS  PubMed  Google Scholar 

  • Okuyama, E., & Yamazaki, M. (1983). The principles of Tetragonia tetragonoides having anti-ulcerogenic activity. II. Isolation and structure of cerebrosides. Chemical and Pharmaceutical Bulletin, 31(7), 2209–2219.

    Article  CAS  PubMed  Google Scholar 

  • Olsen, I., & Jantzen, E. (2001). Sphingolipids in bacteria and fungi. Anaerobe, 7(2), 103–112. doi:10.1006/anae.2001.0376.

    Article  CAS  Google Scholar 

  • Ong, W. Y., Herr, D. R., Farooqui, T., Ling, E. A., & Farooqui, A. A. (2015). Role of sphingomyelinases in neurological disorders. Expert Opinion on Therapeutic Targets, 19(12), 1725–1742. doi:10.1517/14728222.2015.1071794.

    Article  CAS  PubMed  Google Scholar 

  • Oo, M. L., Thangada, S., Wu, M. T., Liu, C. H., Macdonald, T. L., Lynch, K. R., et al. (2007). Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor. Journal of Biological Chemistry, 282(12), 9082–9089. doi:10.1074/jbc.M610318200.

    Article  CAS  PubMed  Google Scholar 

  • Othman, A., Bianchi, R., Alecu, I., Wei, Y., Porretta-Serapiglia, C., Lombardi, R., et al. (2015). Lowering plasma 1-deoxysphingolipids improves neuropathy in diabetic rats. Diabetes, 64(3), 1035–1045. doi:10.2337/db14-1325.

    Article  CAS  PubMed  Google Scholar 

  • Panganamala, R. V., Geer, J. C., & Cornwell, D. G. (1969). Long-chain bases in the sphingolipids of atherosclerotic human aorta. Journal of Lipid Research, 10(4), 445–455.

    CAS  PubMed  Google Scholar 

  • Pappu, R., Schwab, S. R., Cornelissen, I., Pereira, J. P., Regard, J. B., Xu, Y., et al. (2007). Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science, 316(5822), 295–298.

    Article  CAS  PubMed  Google Scholar 

  • Patmanathan, S. N., Johnson, S. P., Lai, S. L., Panja Bernam, S., Lopes, V., Wei, W., et al. (2016). Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2. Scientific Reports, 6, 25650. doi:10.1038/srep25650.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Patmanathan, S. N., Yap, L. F., Murray, P. G., & Paterson, I. C. (2015). The antineoplastic properties of FTY720: Evidence for the repurposing of fingolimod. Journal of Cellular and Molecular Medicine, 19(10), 2329–2340. doi:10.1111/jcmm.12635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pebay, A., Toutant, M., Premont, J., Calvo, C. F., Venance, L., Cordier, J., et al. (2001). Sphingosine-1-phosphate induces proliferation of astrocytes: Regulation by intracellular signalling cascades. European Journal of Neuroscience, 13(12), 2067–2076.

    Article  Google Scholar 

  • Penno, A., Reilly, M. M., Houlden, H., Laura, M., Rentsch, K., Niederkofler, V., et al. (2010). Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids. Journal of Biological Chemistry, 285(15), 11178–11187. doi:10.1074/jbc.M109.092973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pruett, S. T., Bushnev, A., Hagedorn, K., Adiga, M., Haynes, C. A., Sullards, M. C., et al. (2008). Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols. Journal of Lipid Research, 49(8), 1621–1639. doi:10.1194/jlr.R800012-JLR200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pulkoski-Gross, M. J., Donaldson, J. C., & Obeid, L. M. (2015). Sphingosine-1-phosphate metabolism: A structural perspective. Critical Reviews in Biochemistry and Molecular Biology, 50(4), 298–313. doi:10.3109/10409238.2015.1039115.

    Article  CAS  PubMed  Google Scholar 

  • Pyne, S., & Pyne, N. J. (2000). Sphingosine 1-phosphate signalling in mammalian cells. Biochemical Journal, 349, 385–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pyne, S., & Pyne, N. J. (2002). Sphingosine 1-phosphate signalling and termination at lipid phosphate receptors. Biochimica et Biophysica Acta, 1582(1–3), 121–131.

    Article  CAS  PubMed  Google Scholar 

  • Quehenberger, O., Armando, A. M., Brown, A. H., Milne, S. B., Myers, D. S., Merrill, A. H., et al. (2010). Lipidomics reveals a remarkable diversity of lipids in human plasma. Journal of Lipid Research, 51(11), 3299–3305. doi:10.1194/jlr.M009449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao, T. S., Lariosa-Willingham, K. D., Lin, F. F., Palfreyman, E. L., Yu, N., Chun, J., et al. (2003). Pharmacological characterization of lysophospholipid receptor signal transduction pathways in rat cerebrocortical astrocytes. Brain Research, 990(1–2), 182–194.

    Article  CAS  PubMed  Google Scholar 

  • Renkonen, O., & Hirvisalo, E. L. (1969). Structure of plasma sphingadienine. Journal of Lipid Research, 10(6), 687–693.

    CAS  PubMed  Google Scholar 

  • Reynolds, C. P., Maurer, B. J., & Kolesnick, R. N. (2004). Ceramide synthesis and metabolism as a target for cancer therapy. Cancer Letters, 206(2), 169–180. doi:10.1016/j.canlet.2003.08.034.

    Article  CAS  PubMed  Google Scholar 

  • Riley, R. T., An, N. H., Showker, J. L., Yoo, H. S., Norred, W. P., Chamberlain, W. J., et al. (1993). Alteration of tissue and serum sphinganine to sphingosine ratio: An early biomarker of exposure to fumonisin-containing feeds in pigs. Toxicology and Applied Pharmacology, 118(1), 105–112.

    Article  CAS  PubMed  Google Scholar 

  • Row, L. C., Ho, J. C., & Chen, C. M. (2007). Cerebrosides and tocopherol trimers from the seeds of Euryale ferox. Journal of Natural Products, 70(7), 1214–1217. doi:10.1021/np070095j.

    Article  CAS  PubMed  Google Scholar 

  • Rozema, E., Binder, M., Bulusu, M., Bochkov, V., Krupitza, G., & Kopp, B. (2012a). Effects on inflammatory responses by the sphingoid base 4,8-sphingadienine. International Journal of Molecular Medicine, 30(3), 703–707. doi:10.3892/ijmm.2012.1035.

    CAS  PubMed  Google Scholar 

  • Rozema, E., Popescu, R., Sonderegger, H., Huck, C. W., Winkler, J., Krupitza, G., et al. (2012b). Characterization of glucocerebrosides and the active metabolite 4,8-sphingadienine from Arisaema amurense and Pinellia ternata by NMR and CD spectroscopy and ESI-MS/CID-MS. Journal of Agricultural and Food Chemistry, 60(29), 7204–7210. doi:10.1021/jf302085u.

    Article  CAS  PubMed  Google Scholar 

  • Russo, S. B., Tidhar, R., Futerman, A. H., & Cowart, L. A. (2013). Myristate-derived d16:0 sphingolipids constitute a cardiac sphingolipid pool with distinct synthetic routes and functional properties. Journal of Biological Chemistry, 288(19), 13397–13409. doi:10.1074/jbc.M112.428185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saba, J. D., Nara, F., Bielawska, A., Garrett, S., & Hannun, Y. A. (1997). The BST1 gene of Saccharomyces cerevisiae is the sphingosine-1-phosphate lyase. Journal of Biological Chemistry, 272(42), 26087–26090.

    Article  CAS  PubMed  Google Scholar 

  • Sadler, T. W., Merrill, A. H., Stevens, V. L., Sullards, M. C., Wang, E., & Wang, P. (2002). Prevention of fumonisin B1-induced neural tube defects by folic acid. Teratology, 66(4), 169–176. doi:10.1002/tera.10089.

    Article  CAS  PubMed  Google Scholar 

  • Saito, M., Chakraborty, G., Hegde, M., Ohsie, J., Paik, S. M., Vadasz, C., et al. (2010). Involvement of ceramide in ethanol-induced apoptotic neurodegeneration in the neonatal mouse brain. Journal of Neurochemistry, 115(1), 168–177. doi:10.1111/j.1471-4159.2010.06913.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salcedo, M., Cuevas, C., Alonso, J. L., Otero, G., Faircloth, G., Fernandez-Sousa, J. M., et al. (2007). The marine sphingolipid-derived compound ES 285 triggers an atypical cell death pathway. Apoptosis, 12(2), 395–409. doi:10.1007/s10495-006-0573-z.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez, A. M., Malagarie-Cazenave, S., Olea, N., Vara, D., Cuevas, C., & Diaz-Laviada, I. (2008). Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo synthesis of ceramide and PKCzeta activation. European Journal of Pharmacology, 584(2–3), 237–245. doi:10.1016/j.ejphar.2008.02.011.

    Article  CAS  PubMed  Google Scholar 

  • Santos-Cortez, R. L., Faridi, R., Rehman, A. U., Lee, K., Ansar, M., Wang, X., et al. (2016). Autosomal-recessive hearing impairment due to rare missense variants within S1PR2. American Journal of Human Genetics,. doi:10.1016/j.ajhg.2015.12.004.

    PubMed  PubMed Central  Google Scholar 

  • Sato, K., Ishikawa, K., Ui, M., & Okajima, F. (1999). Sphingosine 1-phosphate induces expression of early growth response-1 and fibroblast growth factor-2 through mechanism involving extracellular signal-regulated kinase in astroglial cells. Brain Research Molecular Brain Research, 74(1–2), 182–189.

    Article  CAS  PubMed  Google Scholar 

  • Schroeder, J. J., Crane, H. M., Xia, J., Liotta, D. C., & Merrill, A. H, Jr. (1994). Disruption of sphingolipid metabolism and stimulation of DNA synthesis by fumonisin B1. A molecular mechanism for carcinogenesis associated with Fusarium moniliforme. Journal of Biological Chemistry, 269(5), 3475–3481.

    CAS  PubMed  Google Scholar 

  • Schwab, S. R., & Cyster, J. G. (2007). Finding a way out: Lymphocyte egress from lymphoid organs. Nature Immunology, 8(12), 1295–1301.

    Article  CAS  PubMed  Google Scholar 

  • Schwartz, G. K., Ward, D., Saltz, L., Casper, E. S., Spiess, T., Mullen, E., et al. (1997). A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin. Clinical Cancer Research, 3(4), 537–543.

    CAS  PubMed  Google Scholar 

  • Shibuya, H., Kawashima, K., Sakagami, M., Kawanishi, H., Shimomura, M., Ohashi, K., et al. (1990). Sphingolipids and glycerolipids. I. Chemical structures and ionophoretic activities of soya-cerebrosides I and II from soybean. Chemical & Pharmaceutical Bulletin, 38(11), 2933–2938.

    Article  CAS  Google Scholar 

  • Shui, G., Stebbins, J. W., Lam, B. D., Cheong, W. F., Lam, S. M., Gregoire, F., et al. (2011). Comparative plasma lipidome between human and cynomolgus monkey: Are plasma polar lipids good biomarkers for diabetic monkeys? PLoS ONE, 6(5), e19731. doi:10.1371/journal.pone.0019731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slotte, J. P. (2016). The importance of hydrogen bonding in sphingomyelin’s membrane interactions with co-lipids. Biochimica et Biophysica Acta, 1858(2), 304–310. doi:10.1016/j.bbamem.2015.12.008.

    Article  CAS  PubMed  Google Scholar 

  • Sorensen, S. D., Nicole, O., Peavy, R. D., Montoya, L. M., Lee, C. J., Murphy, T. J., et al. (2003). Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Molecular Pharmacology, 64(5), 1199–1209. doi:10.1124/mol.64.5.1199.

    Article  CAS  PubMed  Google Scholar 

  • Spohr, T. C., Dezonne, R. S., Nones, J., Dos Santos Souza, C., Einicker-Lamas, M., Gomes, F. C., et al. (2012). Sphingosine 1-phosphate-primed astrocytes enhance differentiation of neuronal progenitor cells. Journal of Neuroscience Research, 90(10), 1892–1902. doi:10.1002/jnr.23076.

    Article  PubMed  CAS  Google Scholar 

  • Stahlberg, S., Skolova, B., Madhu, P. K., Vogel, A., Vavrova, K., & Huster, D. (2015). Probing the role of the ceramide acyl chain length and sphingosine unsaturation in model skin barrier lipid mixtures by (2)H solid-state NMR spectroscopy. Langmuir, 31(17), 4906–4915. doi:10.1021/acs.langmuir.5b00751.

    Article  CAS  PubMed  Google Scholar 

  • St-Jacques, M. (1973). Elucidation of structure and stereochemistry of myriocin. A novel antifungal antibiotic. Journal of Organic Chemistry, 38(7), 1253–1260.

    Article  CAS  PubMed  Google Scholar 

  • Stockmann-Juvala, H., & Savolainen, K. (2008). A review of the toxic effects and mechanisms of action of fumonisin B1. Human and Experimental Toxicology, 27(11), 799–809. doi:10.1177/0960327108099525.

    Article  CAS  PubMed  Google Scholar 

  • Struckhoff, A. P., Bittman, R., Burow, M. E., Clejan, S., Elliott, S., Hammond, T., et al. (2004). Novel ceramide analogs as potential chemotherapeutic agents in breast cancer. Journal of Pharmacology and Experimental Therapeutics, 309(2), 523–532. doi:10.1124/jpet.103.062760.

    Article  CAS  PubMed  Google Scholar 

  • Sugawara, T., Kinoshita, M., Ohnishi, M., Nagata, J., & Saito, M. (2003). Digestion of maize sphingolipids in rats and uptake of sphingadienine by Caco-2 cells. Journal of Nutrition, 133(9), 2777–2782.

    CAS  PubMed  Google Scholar 

  • Sugawara, T., Zaima, N., Yamamoto, A., Sakai, S., Noguchi, R., & Hirata, T. (2006). Isolation of sphingoid bases of sea cucumber cerebrosides and their cytotoxicity against human colon cancer cells. Bioscience, Biotechnology, and Biochemistry, 70(12), 2906–2912. doi:10.1271/bbb.60318.

    Article  CAS  PubMed  Google Scholar 

  • Sullards, M. C., Lynch, D. V., Merrill, A. H, Jr., & Adams, J. (2000). Structure determination of soybean and wheat glucosylceramides by tandem mass spectrometry. Journal of Mass Spectrometry, 35(3), 347–353. doi:10.1002/(SICI)1096-9888(200003)35:3<347:AID-JMS941>3.0.CO;2-3.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, S., Enosawa, S., Kakefuda, T., Shinomiya, T., Amari, M., Naoe, S., et al. (1996). A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation. Transplantation, 61(2), 200–205.

    Article  CAS  PubMed  Google Scholar 

  • Symolon, H., Bushnev, A., Peng, Q., Ramaraju, H., Mays, S. G., Allegood, J. C., et al. (2011). Enigmol: A novel sphingolipid analogue with anticancer activity against cancer cell lines and in vivo models for intestinal and prostate cancer. Molecular Cancer Therapeutics, 10(4), 648–657. doi:10.1158/1535-7163.MCT-10-0754.

    Article  CAS  PubMed  Google Scholar 

  • Symolon, H., Schmelz, E. M., Dillehay, D. L., & Merrill, A. H, Jr. (2004). Dietary soy sphingolipids suppress tumorigenesis and gene expression in 1,2-dimethylhydrazine-treated CF1 mice and ApcMin/+ mice. Journal of Nutrition, 134(5), 1157–1161.

    CAS  PubMed  Google Scholar 

  • Szepanowski, F., Derksen, A., Steiner, I., Meyer Zu Horste, G., Daldrup, T., Hartung, H. P., et al. (2016). Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling. Journal of Neuroinflammation, 13(1), 143. doi:10.1186/s12974-016-0612-9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tan, J. W., Dong, Z. J., & Liu, J. K. (2003). New cerebrosides from the basidiomycete Cortinarius tenuipes. Lipids, 38(1), 81–84.

    Article  CAS  PubMed  Google Scholar 

  • Tedesco-Silva, H., Pescovitz, M. D., Cibrik, D., Rees, M. A., Mulgaonkar, S., Kahan, B. D., et al. (2006). Randomized controlled trial of FTY720 versus MMF in de novo renal transplantation. Transplantation, 82(12), 1689–1697. doi:10.1097/01.tp.0000251718.95622.b3.

    Article  CAS  PubMed  Google Scholar 

  • Thudichum, J. L. W., Simon, J., Thudichum, J. L. W., & St. Thomas’s Hospital. Medical School Library. (1884). A treatise on the chemical constitution of the brain. London: Baillière, Tindall and Cox.

    Google Scholar 

  • t’Kindt, R., Jorge, L., Dumont, E., Couturon, P., David, F., Sandra, P., et al. (2012). Profiling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry. Analytical Chemistry, 84(1), 403–411. doi:10.1021/ac202646v.

    Article  PubMed  CAS  Google Scholar 

  • Tolle, M., Pawlak, A., Schuchardt, M., Kawamura, A., Tietge, U. J., Lorkowski, S., et al. (2008). HDL-associated lysosphingolipids inhibit NAD(P)H oxidase-dependent monocyte chemoattractant protein-1 production [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Arteriosclerosis, Thrombosis, and Vascular Biology, 28(8), 1542–1548. doi:10.1161/ATVBAHA.107.161042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tonelli, F., Lim, K. G., Loveridge, C., Long, J., Pitson, S. M., Tigyi, G., et al. (2010). FTY720 and (S)-FTY720 vinylphosphonate inhibit sphingosine kinase 1 and promote its proteasomal degradation in human pulmonary artery smooth muscle, breast cancer and androgen-independent prostate cancer cells. Cellular Signalling, 22(10), 1536–1542. doi:10.1016/j.cellsig.2010.05.022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tornquist, K., Blom, T., Shariatmadari, R., & Pasternack, M. (2004). Ceramide 1-phosphate enhances calcium entry through voltage-operated calcium channels by a protein kinase C-dependent mechanism in GH4C1 rat pituitary cells. Biochemical Journal, 380(Pt 3), 661–668. doi:10.1042/BJ20031637.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ueda, H., Takahara, S., Azuma, H., Kusaka, M., Suzuki, S., & Katsuoka, Y. (2000). Effect of a novel immunosuppressant, FTY720, on allograft survival after renal transplant in rats. European Surgical Research, 32(5), 279–283.

    Article  CAS  PubMed  Google Scholar 

  • Valsecchi, M., Chigorno, V., Nicolini, M., & Sonnino, S. (1996). Changes of free long-chain bases in neuronal cells during differentiation and aging in culture. Journal of Neurochemistry, 67(5), 1866–1871.

    Article  CAS  PubMed  Google Scholar 

  • Van Overloop, H., Denizot, Y., Baes, M., & Van Veldhoven, P. P. (2007). On the presence of C2-ceramide in mammalian tissues: Possible relationship to etherphospholipids and phosphorylation by ceramide kinase. Biological Chemistry, 388(3), 315–324. doi:10.1515/BC.2007.035.

    PubMed  Google Scholar 

  • Venkataraman, K., Riebeling, C., Bodennec, J., Riezman, H., Allegood, J. C., Sullards, M. C., et al. (2002). Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. Journal of Biological Chemistry, 277(38), 35642–35649. doi:10.1074/jbc.M205211200.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., Cheng, A., Wakade, C., & Yu, R. K. (2014). Ganglioside GD3 is required for neurogenesis and long-term maintenance of neural stem cells in the postnatal mouse brain. Journal of Neuroscience, 34(41), 13790–13800. doi:10.1523/jneurosci.2275-14.2014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, E., Norred, W. P., Bacon, C. W., Riley, R. T., & Merrill, A. H, Jr. (1991). Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusarium moniliforme. Journal of Biological Chemistry, 266(22), 14486–14490.

    CAS  PubMed  Google Scholar 

  • Wang, E., Riley, R. T., Meredith, F. I., & Merrill, A. H, Jr. (1999). Fumonisin B1 consumption by rats causes reversible, dose-dependent increases in urinary sphinganine and sphingosine. Journal of Nutrition, 129(1), 214–220.

    CAS  PubMed  Google Scholar 

  • Webb, M., Tham, C. S., Lin, F. F., Lariosa-Willingham, K., Yu, N., Hale, J., et al. (2004). Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice. Journal of Neuroimmunology, 153(1–2), 108–121.

    Article  CAS  PubMed  Google Scholar 

  • Welsch, C. A., Hagiwara, S., Goetschy, J. F., & Movva, N. R. (2003). Ubiquitin pathway proteins influence the mechanism of action of the novel immunosuppressive drug FTY720 in Saccharomyces cerevisiae. Journal of Biological Chemistry, 278(29), 26976–26982.

    Article  CAS  PubMed  Google Scholar 

  • Willis, M. A., & Cohen, J. A. (2013). Fingolimod therapy for multiple sclerosis. Seminars in Neurology, 33(1), 37–44. doi:10.1055/s-0033-1343794.

    Article  PubMed  Google Scholar 

  • Woodcock, J. M., Ma, Y., Coolen, C., Pham, D., Jones, C., Lopez, A. F., et al. (2010). Sphingosine and FTY720 directly bind pro-survival 14-3-3 proteins to regulate their function. Cellular Signalling, 22(9), 1291–1299. doi:10.1016/j.cellsig.2010.04.004.

    Article  CAS  PubMed  Google Scholar 

  • Xia, P., Gamble, J. R., Wang, L., Pitson, S. M., Moretti, P. A., Wattenberg, B. W., et al. (2000). An oncogenic role of sphingosine kinase. Current Biology, 10(23), 1527–1530.

    Article  CAS  PubMed  Google Scholar 

  • Yamagata, K., Tagami, M., Torii, Y., Takenaga, F., Tsumagari, S., Itoh, S., et al. (2003). Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes. Glia, 41(2), 199–206.

    Article  PubMed  Google Scholar 

  • Yamashita, R., Tabata, Y., Iga, E., Nakao, M., Sano, S., Kogure, K., et al. (2016). Analysis of molecular species profiles of ceramide-1-phosphate and sphingomyelin using MALDI-TOF mass spectrometry. Lipids, 51(2), 263–270. doi:10.1007/s11745-015-4082-0.

    Article  CAS  PubMed  Google Scholar 

  • Yang, A. H., Ishii, I., & Chun, J. (2002). In vivo roles of lysophospholipid receptors revealed by gene targeting studies in mice. Biochimica et Biophysica Acta, 1582(1–3), 197–203.

    Article  CAS  PubMed  Google Scholar 

  • Yang, Y., Torta, F., Arai, K., Wenk, M. R., Herr, D. R., Wong, P. T., et al. (2016). Sphingosine kinase inhibition ameliorates chronic hypoperfusion-induced white matter lesions. Neurochemistry International,. doi:10.1016/j.neuint.2016.02.012.

    Google Scholar 

  • Yatomi, Y., Ruan, F., Megidish, T., Toyokuni, T., Hakomori, S., & Igarashi, Y. (1996). N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets. Biochemistry, 35(2), 626–633. doi:10.1021/bi9515533.

    Article  CAS  PubMed  Google Scholar 

  • Yu, N., Lariosa-Willingham, K. D., Lin, F. F., Webb, M., & Rao, T. S. (2004). Characterization of lysophosphatidic acid and sphingosine-1-phosphate-mediated signal transduction in rat cortical oligodendrocytes. Glia, 45(1), 17–27. doi:10.1002/glia.10297.

    Article  PubMed  Google Scholar 

  • Yuan, S., Wu, R., Latek, D., Trzaskowski, B., & Filipek, S. (2013). Lipid receptor S1P(1) activation scheme concluded from microsecond all-atom molecular dynamics simulations. PLoS Computational Biology, 9(10), e1003261. doi:10.1371/journal.pcbi.1003261.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, K., Pompey, J. M., Hsu, F. F., Key, P., Bandhuvula, P., Saba, J. D., et al. (2007). Redirection of sphingolipid metabolism toward de novo synthesis of ethanolamine in Leishmania. EMBO Journal, 26(4), 1094–1104. doi:10.1038/sj.emboj.7601565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zitomer, N. C., Mitchell, T., Voss, K. A., Bondy, G. S., Pruett, S. T., Garnier-Amblard, E. C., et al. (2009). Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: A novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. Journal of Biological Chemistry, 284(8), 4786–4795. doi:10.1074/jbc.M808798200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore

    Mitchell K. P. Lai, Wee Siong Chew, Angad Rao & Deron R. Herr

  2. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge, Singapore

    Federico Torta

  3. Department of Biology, San Diego State University, San Diego, CA, USA

    Greg L. Harris & Deron R. Herr

  4. Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA, USA

    Jerold Chun

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D.R.H. and G.L.H. have received consulting fees or grant support from Expression Drug Designs, LLC and Bayer Healthcare. J.C. has received honoraria, consulting fees and/or grant support from: Abbott, Amira Pharmaceuticals, Biogen-Idec, Celgene, GlaxoSmithKline, Johnson and Johnson, Merck, Mitsubishi Tanabe Pharma Corporation, Novartis, Ono Pharmaceutical Co., Pfizer and Taisho Pharmaceutical Co. M.K.P.L., W.S.C., F.T., and A.R. have no financial relationships to declare.

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Lai, M.K.P., Chew, W.S., Torta, F. et al. Biological Effects of Naturally Occurring Sphingolipids, Uncommon Variants, and Their Analogs. Neuromol Med 18, 396–414 (2016). https://doi.org/10.1007/s12017-016-8424-8

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