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Ceramide-induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation

Record type: Article

Ceramide, the central molecule of the sphingomyelin pathway, serves as a second messenger for cellular functions ranging from proliferation and differentiation to growth arrest and apoptosis. In this study we show that c2-ceramide induces apoptosis in primary cortical neuron cultures and that this effect correlates with differential modulation of mitogen-activated protein kinase (MAPK) cascades. Phosphorylation of extracellular signal-regulated kinases (ERKs) and their upstream activators MAPK kinases (MEKs), as measured by immunoblotting is rapidly decreased by c2-ceramide. However, the MEK inhibitor PD98059 alone does not induce apoptosis and in combination with c2-ceramide it does not modify c2-ceramide-induced apoptosis. Treatment with c2-ceramide increases p38 and c-Jun N-terminal kinase (JNK) phosphorylation before and during caspase-3 activation. The p38 inhibitor SB203580 partially protects cortical neurons against c2-ceramide-induced apoptosis, implicating the p38 pathway in this process. The c2-ceramide treatment also increases levels of c-jun, c-fos and p53 mRNA in primary cortical neuron cultures, but this is independent of p38 activation. Our study further elucidates the time-courses of MAPK cascade modulation, and of c-jun, cfos
and p53 activation during c2-ceramide-induced neuronal apoptosis. It reveals that one of the activated kinases, p38, is
necessary for this apoptosis.

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Citation

Willaime, S., Vanhoutte, P., Caboche, J., Lemaigre-Dubreuil, Y., Mariani, J. and Brugg, B. (2001) Ceramide-induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation European Journal of Neuroscience, 13, (11), pp. 2037-2046. (doi:10.1046/j.0953-816x.2001.01581.x).

More information

Published date: February 2001
Keywords: c-Fos, c-Jun, JNKs/ SAPKs, MAPK, p53, primary cultures

Identifiers

Local EPrints ID: 66391
URI: http://eprints.soton.ac.uk/id/eprint/66391
ISSN: 0953-816X
PURE UUID: 9354faaf-cc89-4191-b128-4e0ae3e760d1
ORCID for S. Willaime: ORCID iD orcid.org/0000-0002-1121-6419

Catalogue record

Date deposited: 10 Jun 2009
Last modified: 19 Jul 2017 00:25

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Contributors

Author: S. Willaime ORCID iD
Author: P. Vanhoutte
Author: J. Caboche
Author: Y. Lemaigre-Dubreuil
Author: J. Mariani
Author: B. Brugg

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