DOI: 10.1046/j.0953-816x.2001.01581.x. Ceramide‐induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation

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

10.1046/j.0953-816x.2001.01581.x

Crossref journal-article

Wiley

European Journal of Neuroscience (311)

Abstract

AbstractCeramide, 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, c‐fos and p53 activation during c2‐ceramide‐induced neuronal apoptosis. It reveals that one of the activated kinases, p38, is necessary for this apoptosis.

Bibliography

Willaime, S., Vanhoutte, P., Caboche, J., LemaigreâDubreuil, Y., Mariani, J., & Brugg, B. (2001). Ceramideâinduced 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), 2037â2046. Portico.

Authors 6

Sandrine Willaime (first)
Peter Vanhoutte (additional)
Jocelyne Caboche (additional)
Yolande Lemaigre‐Dubreuil (additional)
Jean Mariani (additional)
Bernard Brugg (additional)

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Dates

Type	When
Created	22 years, 5 months ago (March 6, 2003, 9:36 a.m.)
Deposited	1 year, 10 months ago (Oct. 3, 2023, 11:43 a.m.)
Indexed	1 month, 3 weeks ago (July 7, 2025, 1:25 a.m.)
Issued	24 years, 2 months ago (June 1, 2001)
Published	24 years, 2 months ago (June 1, 2001)
Published Online	23 years, 8 months ago (Dec. 20, 2001)
Published Print	24 years, 2 months ago (June 1, 2001)

Funders 0

None

BibTeX

@article{Willaime_2001, title={Ceramide‐induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation}, volume={13}, ISSN={1460-9568}, url={http://dx.doi.org/10.1046/j.0953-816x.2001.01581.x}, DOI={10.1046/j.0953-816x.2001.01581.x}, number={11}, journal={European Journal of Neuroscience}, publisher={Wiley}, author={Willaime, Sandrine and Vanhoutte, Peter and Caboche, Jocelyne and Lemaigre‐Dubreuil, Yolande and Mariani, Jean and Brugg, Bernard}, year={2001}, month=jun, pages={2037–2046} }

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