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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1996-06

AUTHORS

O Cuvillier, G Pirianov, B Kleuser, P G Vanek, O A Coso, S Gutkind, S Spiegel

ABSTRACT

Ceramide is an important regulatory participant of programmed cell death (apoptosis) induced by tumour-necrosis factor (TNF)-alpha and Fas ligand, members of the TNF superfamily. Conversely, sphingosine and sphingosine-1-phosphate, which are metabolites of ceramide, induce mitogenesis and have been implicated as second messengers in cellular proliferation induced by platelet-derived growth factor and serum. 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) pathway, 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 kinases determines the fate of the cell. More... »

PAGES

800-803

Journal

TITLE

Nature

ISSUE

6585

VOLUME

381

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/381800a0

    DOI

    http://dx.doi.org/10.1038/381800a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1002005914

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/8657285


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