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    Ceramide biosynthesis and metabolism in trophoblast syncytialization

    Access Status
    Fulltext not available
    Authors
    Singh, A.
    Dharmarajan, Arunasalam
    Aye, I.
    Keelan, J.
    Date
    2012
    Type
    Journal Article
    
    Metadata
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    Citation
    Singh, A. and Dharmarajan, A. and Aye, I. and Keelan, J. 2012. Ceramide biosynthesis and metabolism in trophoblast syncytialization. Molecular and Cellular Endocrinology. 362 (1-2): pp. 48-59.
    Source Title
    Molecular and Cellular Endocrinology
    DOI
    10.1016/j.mce.2012.05.009
    ISSN
    0303-7207
    URI
    http://hdl.handle.net/20.500.11937/7664
    Collection
    • Curtin Research Publications
    Abstract

    Sphingolipid mediators such as ceramide are pleiotropic regulators of cellular growth, differentiation and apoptosis. We investigated the role of ceramide biosynthesis, metabolism and actions in term human cytotrophoblasts syncytialized over 7 days in culture. Intracellular C16 ceramide levels increased modestly after 3 days in culture, then declined. Ceramidase was present at particularly high levels in syncytialized trophoblasts; inhibition of ceramidase reduced the degree of cell fusion. Exposure to short chain C8 ceramide or aSMase enhanced secretion of the differentiation marker hCG without affecting fusion or cell viability. In contrast, pharmacological inhibition of ceramidase reduced the extent of fusion. Inhibition of the ceramide-responsive JNK and PP2A pathways did not abolish the effects of ceramide, and JNK phosphorylation was unresponsive to ceramide; however, ceramide significantly inhibited phosphorylation of Akt. This study suggests that changes in ceramide biosynthesis and metabolism play a differential role in the biochemical and morphological features of trophoblast differentiation.

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