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

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), 2037-2046. (doi:10.1046/j.0953-816x.2001.01581.x).


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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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1046/j.0953-816x.2001.01581.x
ISSNs: 0953-816X (print)
Related URLs:
Keywords: c-Fos, c-Jun, JNKs/ SAPKs, MAPK, p53, primary cultures
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QH Natural history > QH301 Biology
Divisions : University Structure - Pre August 2011 > School of Medicine > Clinical Neurosciences
ePrint ID: 66391
Accepted Date and Publication Date:
February 2001Published
Date Deposited: 10 Jun 2009
Last Modified: 31 Mar 2016 12:52
URI: http://eprints.soton.ac.uk/id/eprint/66391

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