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Título: | Serum deprivation increases ceramide levels and induces apoptosis in undifferentiated HN9.10e cells |
Autor: | Colombaioni, Laura; Frago, Laura M.; Varela-Nieto, Isabel CSIC ORCID ; Pesi, Rossana; García-Gil, Mercedes | Fecha de publicación: | 2002 | Editor: | Elsevier | Citación: | Neurochemistry International 40(4): 327-336 (2002) | Resumen: | 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, [Ca2+]i and caspase-3-like activity increased. Both cytochrome c release and rise of [Ca2+]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. © 2002 Elsevier Science Ltd. All rights reserved. | URI: | http://hdl.handle.net/10261/80081 | DOI: | 10.1016/S0197-0186(01)00090-0 | Identificadores: | doi: 10.1016/S0197-0186(01)00090-0 issn: 0197-0186 e-issn: 1872-9754 |
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