Article (Scientific journals)
Leukemia inhibitory factor induces an antiapoptotic response in oligodendrocytes through Akt-phosphorylation and up-regulation of 14-3-3.
Slaets, Helena; Dumont, Debora; Vanderlocht, Joris et al.
2008In Proteomics, 8 (6), p. 1237-47
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Keywords :
Leukemia Inhibitory Factor; Multiple Sclerosis; Oligodendrocytes; DIGE
Abstract :
[en] Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes (OLG) both in vitro and in an animal model of multiple sclerosis. Here, we show that LIF protects mature rat OLG cultures selectively against the combined insult of the proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha, but it does not protect against oxidative stress nor against staurosporine induced apoptosis. We further demonstrate that LIF activates the janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and the phosphatidylinositol 3 kinase/Akt pathway in mature OLG. We show that LIF protection is independent of suppressors of cytokine signaling and Bcl-2 mRNA expression levels. To gain further insight into the protective mechanism, a quantitative proteomic approach (DIGE) was applied to identify differentially expressed proteins in LIF-treated OLG. Our results indicate that LIF induces a shift in the cellular machinery toward a prosurvival execution program, illustrated by an enhanced expression of isoforms of the antiapoptotic molecule 14-3-3. These data provide further insight into the mechanisms of LIF-mediated protection of mature OLGs.
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Biochemistry, biophysics & molecular biology
Author, co-author :
Slaets, Helena;  Hasselt University > Biomedical Research Institute
Dumont, Debora;  Hasselt University > Biomedical Research Institute
Vanderlocht, Joris;  Hasselt University > Biomedical Research Institute
Noben, Jean-Paul;  Hasselt University > Biomedical Research Institute
Leprince, Pierre ;  Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Robben, Johan;  Hasselt University > Biomedical Research Institute
Hendriks, Jerome;  Hasselt University > Biomedical Research Institute
Stinissen, Piet;  Hasselt University > Biomedical Research Institute
Hellings, Niels;  Hasselt University > Biomedical Research Institute
Language :
English
Title :
Leukemia inhibitory factor induces an antiapoptotic response in oligodendrocytes through Akt-phosphorylation and up-regulation of 14-3-3.
Publication date :
2008
Journal title :
Proteomics
ISSN :
1615-9853
eISSN :
1615-9861
Publisher :
Wiley-VCH Verlag Gmbh, Weinheim, Germany
Volume :
8
Issue :
6
Pages :
1237-47
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen [BE]
Fondation Charcot [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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