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Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate

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Abstract

CERAMIDE is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-α and Fas ligand, members of the TNF superfamily1–6. Conversely, sphingosine and sphingosine-1-phosphate, which are metabolites of ceramide, induce mitogenesis7 and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor and serum8,9. Here we report that sphingosine-1-phosphate prevents the appearance of the key features of apoptosis, namely intranucleosomal DNA fragmentation and morphological changes, which result from increased concentrations of ceramide. Furthermore, inhibition of ceramide-mediated apoptosis by activation of protein kinase C results from stimulation of sphingosine kinase and the concomitant increase in intracellular sphingosine-1-phosphate. Finally sphingosine-1-phosphate not only stimulates the extracellular signal-regulated kinase (ERK) pathway10, it counteracts the ceramide-induced activation of stress-activated protein kinase (SAPK/JNK). Thus, the balance between the intracellular levels of ceramide and sphingosine-1-phosphate and their regulatory effects on different family members of mitogen-activated protein kineses determines the fate of the cell.

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References

  1. Hannun, Y. A. J. biol. Chem. 269, 3125–3128 (1994).

    CAS  PubMed  Google Scholar 

  2. Kolesnick, R. & Golde, D. W. Cell 77, 325–328 (1994).

    Article  CAS  Google Scholar 

  3. Heller, R. A. & Krönke, M. J. Cell Biol. 126, 5–9 (1994).

    Article  CAS  Google Scholar 

  4. Obeid, L. M., Linardic, C. M., Karolak, L. A. & Hannun, Y. A. Science 259, 1769–1771 (1993).

    Article  ADS  CAS  Google Scholar 

  5. Cifone, M. G. et al. J. exp. Med. 177, 1547–1552 (1994).

    Article  Google Scholar 

  6. Gulbins, E. et al. Immunity 2, 1–20 (1995).

    Article  Google Scholar 

  7. Spiegel, S. & Milstien, S. J. Membr. Biol. 146, 225–237 (1995).

    Article  CAS  Google Scholar 

  8. Olivera, A. & Spiegel, S. Nature 365, 557–560 (1993).

    Article  ADS  CAS  Google Scholar 

  9. Coroneos, E., Martinez, M., McKenna, S. & Kester, M. J. biol. Chem. 270, 23305–23309 (1995).

    Article  CAS  Google Scholar 

  10. Wu, J., Spiegel, S. & Sturgill, T. W. J. biol. Chem. 270, 11484–11488 (1995).

    Article  CAS  Google Scholar 

  11. Jarvis, W. D. et al. J. biol. Chem. 269, 31685–31692 (1994).

    CAS  PubMed  Google Scholar 

  12. Jayadev, S. et al. J. biol. Chem. 270, 2047–2052 (1995).

    Article  CAS  Google Scholar 

  13. Cifone, M. G. et al. EMBO J. 14, 5859–5868 (1995).

    Article  CAS  Google Scholar 

  14. Gill, B. M., Nishikata, H., Chan, G., Delovitch, T. L. & Ochi, A. Immun. Rev. 142, 113–125 (1994).

    Article  CAS  Google Scholar 

  15. Tepper, C. G. et al. Proc. natn. Acad. Sci. U.S.A. 92, 8443–8447 (1995).

    Article  ADS  CAS  Google Scholar 

  16. Haimovitz-Friedman, A. et al. J. exp. Med. 180, 525–535 (1994).

    Article  CAS  Google Scholar 

  17. Jarvis, W. D., Turner, A. J., Povirk, L. F., Traylor, R. S. & Grant, S. Cancer Res. 54, 1707–1714 (1994).

    CAS  PubMed  Google Scholar 

  18. Bornfeldt, K. E. et al. J. Cell Biol. 130, 193–206 (1995).

    Article  CAS  Google Scholar 

  19. Derijard, B. et al. Cell 76, 1025–1037 (1994).

    Article  CAS  Google Scholar 

  20. Kyriakis, J. M. et al. Nature 369, 156–160 (1994).

    Article  ADS  CAS  Google Scholar 

  21. Westwick, J. K., Bielawska, A. E., Dbaibo, G., Hannun, Y. A. & Brenner, D. A. J. biol. Chem. 270, 22689–22692 (1995).

    Article  CAS  Google Scholar 

  22. Verheij, M. et al. Nature 380, 75–79 (1996).

    Article  ADS  CAS  Google Scholar 

  23. Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J. & Saltiel, A. R. Proc. natn. Acad. Sci. U.S.A. 92, 7686–7689 (1995).

    Article  ADS  CAS  Google Scholar 

  24. Crespo, P. et al. J. biol. Chem. 269, 21103–21109 (1994).

    CAS  PubMed  Google Scholar 

  25. Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J. & Greenberg, M. E. Science 270, 1326–1331 (1995).

    Article  ADS  CAS  Google Scholar 

  26. Zhang, H. et al. J. Cell Biol. 114, 155–167 (1991).

    Article  CAS  Google Scholar 

  27. Duke, R. C. & Cohen, J. J. in Current Protocols in Immunology (suppl. 3) (eds Coligan, J. E., Kruisbeek, A. M., Margulies, D. H., Shevach, E. M. & Strober, W.) 3.17.1–3.17.16 (Green/Wiley, New York, 1992).

    Google Scholar 

  28. Olivera, A., Rosenthal, J. & Spiegel, S. Analyt. Biochem. 223, 306–312 (1995).

    Article  Google Scholar 

  29. Yatomi, T. et al. Analyt. Biochem. 230, 315–320 (1995).

    Article  CAS  Google Scholar 

  30. Coso, O. A. et al. J. biol. Chem. 270, 5620–5624 (1995).

    Article  CAS  Google Scholar 

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Author notes

  1. Philip G. Vanek: Trevigen Inc., Gaithersburg, Maryland 20877, USA

  2. Omar A. Coso and J. Silvio Gutkind: Laboratory of Cellular Development and Oncology, NIDR, NIH, Bethesda, Maryland 20892, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, Washington DC, 20007, USA

    Olivier Cuvillier, Grisha Pirianov, Burkhard Kleuser, Philip G. Vanek, Omar A. Coso, J. Silvio Gutkind & Sarah Spiegel

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  1. Olivier Cuvillier
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  2. Grisha Pirianov
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  3. Burkhard Kleuser
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  4. Philip G. Vanek
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  5. Omar A. Coso
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  6. J. Silvio Gutkind
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  7. Sarah Spiegel
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Cuvillier, O., Pirianov, G., Kleuser, B. et al. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature 381, 800–803 (1996). https://doi.org/10.1038/381800a0

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