The University of Southampton
University of Southampton Institutional Repository

C-Jun N-terminal kinases/c-Jun and p38 pathways cooperate in ceramide-induced neuronal apoptosis

Record type: Article

Understanding the regulation of the apoptotic program
in neurons by intracellular pathways is currently a subject
of great interest. Recent results suggest that c-Jun N-terminal
kinases (JNK), mitogen-activated protein kinases
and the transcription factor c-Jun are important regulators of
this cell death program in post-mitotic neurons following
survival-factor withdrawal. Our study demonstrates that ceramide levels increase upon survival-factor withdrawal in primary cultured cortical neurons. Furthermore, survival-factor
withdrawal or addition of exogenous c2-ceramide induces
JNK pathway activation in these cells. Western blot analyses
of JNK and c-Jun using phospho-specific antibodies reveal
that JNK and subsequent c-Jun phosphorylation occur hours
before the initiation of apoptosis, reflected morphologically
by neurite retraction and fragmentation, cell-body shrinkage
and chromatin fragmentation. Immunocytochemistry using
the same antibodies shows that phospho-JNK are localized
in the neurites of control neurons and translocate to the
nucleus where phospho-c-Jun concurrently appears upon
ceramide-induced apoptosis. To determine if ceramide-induced
c-Jun activation is responsible for the induction of the
apoptotic program, we performed transient transfections of a
dominant negative form of c-Jun, truncated in its transactivation
region. Our results show that DNc-Jun partially protects
cortical neurons from ceramide-induced apoptosis.
Treatment of dominant negative c-Jun-expressing neurons
with the pharmacological inhibitor of p38 kinase, SB203580,
completely blocked neuronal death. Thus our data show that
p38 and JNK/c-Jun pathways cooperate to induce neuronal
apoptosis.

PDF Willaime-Morawek_NSC_2003.pdf - Other
Download (539kB)

Citation

Willaime-Morawek, S., Brami-Cherrier, K., Mariani, J., Caboche, J. and Brugg, B. (2003) C-Jun N-terminal kinases/c-Jun and p38 pathways cooperate in ceramide-induced neuronal apoptosis Neuroscience, 119, (2), pp. 387-397. (doi:10.1016/S0306-4522(02)00996-X).

More information

Published date: 27 June 2003
Keywords: primary cultures, SAPK, serum withdrawal, neuronal death

Identifiers

Local EPrints ID: 66392
URI: http://eprints.soton.ac.uk/id/eprint/66392
ISSN: 0306-4522
PURE UUID: f63c24b4-3006-444f-a645-097b854805da
ORCID for S. Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

Catalogue record

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

Export record

Altmetrics

Contributors

Author: K. Brami-Cherrier
Author: J. Mariani
Author: J. Caboche
Author: B. Brugg

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×