Ceramide biosynthesis and metabolism in trophoblast syncytialization

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 incre...

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Main Authors: Singh, A., Dharmarajan, Arunasalam, Aye, I., Keelan, J.
Format: Journal Article
Published: Elsevier Ireland Ltd 2012
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/7664
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author Singh, A.
Dharmarajan, Arunasalam
Aye, I.
Keelan, J.
author_facet Singh, A.
Dharmarajan, Arunasalam
Aye, I.
Keelan, J.
author_sort Singh, A.
building Curtin Institutional Repository
collection Online Access
description 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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spelling curtin-20.500.11937-76642017-09-13T16:02:56Z Ceramide biosynthesis and metabolism in trophoblast syncytialization Singh, A. Dharmarajan, Arunasalam Aye, I. Keelan, J. Placenta Acid sphingomyelinase Sphingolipid Cell fusion Ceramide kinase Ceramidase 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. 2012 Journal Article http://hdl.handle.net/20.500.11937/7664 10.1016/j.mce.2012.05.009 Elsevier Ireland Ltd restricted
spellingShingle Placenta
Acid sphingomyelinase
Sphingolipid
Cell fusion
Ceramide kinase
Ceramidase
Singh, A.
Dharmarajan, Arunasalam
Aye, I.
Keelan, J.
Ceramide biosynthesis and metabolism in trophoblast syncytialization
title Ceramide biosynthesis and metabolism in trophoblast syncytialization
title_full Ceramide biosynthesis and metabolism in trophoblast syncytialization
title_fullStr Ceramide biosynthesis and metabolism in trophoblast syncytialization
title_full_unstemmed Ceramide biosynthesis and metabolism in trophoblast syncytialization
title_short Ceramide biosynthesis and metabolism in trophoblast syncytialization
title_sort ceramide biosynthesis and metabolism in trophoblast syncytialization
topic Placenta
Acid sphingomyelinase
Sphingolipid
Cell fusion
Ceramide kinase
Ceramidase
url http://hdl.handle.net/20.500.11937/7664