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

Nature volume 381, pages 800–803 (1996)Cite this article

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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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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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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