Serum deprivation increases ceramide levels and induces apoptosis in undifferentiated HN9.10e cells. |
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Authors: | Laura Colombaioni Laura M Frago Isabel Varela-Nieto Rossana Pesi Mercedes Garcia-Gil |
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Institution: | Institute of Neurophysiology of CNR, Pisa, Italy. |
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Abstract: | Sphingolipid metabolites have been involved in the regulation of proliferation, differentiation and apoptosis. While cellular mechanisms of these processes have been extensively analysed in the post-mitotic neurons, little is known about proliferating neuronal precursors. We have taken as a model of neuroblasts the embryonic hippocampal cell line HN9.10e. Apoptosis was induced by serum deprivation and by treatment with N-acetylsphingosine (C2-Cer), a membrane-permeant analogue of the second messenger ceramide. Following C2-Cer addition, cytochrome c was released from mitochondria, Ca(2+)](i) and caspase-3-like activity increased. Both cytochrome c release and rise of Ca(2+)](i) occurred before caspase-3 activation and nuclear condensation. The intracellular levels of ceramide peaked at 1h following the serum deprivation. These results indicate that the serum deprivation induces a rise in the intracellular ceramide level, and that increased ceramide concentration leads to calcium dysregulation and release of cytochrome c followed by caspase-3 activation. We show that cytochrome c is released without a loss of mitochondrial transmembrane potential. |
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