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Title: | Leukemia inhibitory factor induces an antiapoptotic response in oligodendrocytes through Akt-phosphorylation and up-regulation of 14-3-3 | Authors: | SLAETS, Leen DUMONT, Debora VANDERLOCHT, Joris NOBEN, Jean-Paul Leprince, P. ROBBEN, Johan HENDRIKS, Jerome STINISSEN, Piet HELLINGS, Niels |
Issue Date: | 2008 | Publisher: | WILEY-VCH VERLAG GMBH | Source: | PROTEOMICS, 8(6). p. 1237-1247 | Abstract: | 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. | Notes: | Hasselt Univ, Biomed Res Inst, B-3590 Diepenbeek, Belgium. Transnatl Univ Limburg, Sch Life Sci, Diepenbeek, Belgium. Univ Liege, Ctr Cellular & Mol Neurobiol, Liege, Belgium.Hellings, N, Hasselt Univ, Biomed Res Inst, Agoralaan Bldg A, B-3590 Diepenbeek, Belgium.niels.hellings@uhasselt.be | Keywords: | DIGE; leukemia inhibitory factor; multiple sclerosis; oligodendrocytes;biochemical research methods; biochemistry & molecular biology | Document URI: | http://hdl.handle.net/1942/8231 | ISSN: | 1615-9853 | e-ISSN: | 1615-9861 | DOI: | 10.1002/pmic.200700641 | ISI #: | 000254483000014 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2009 |
Appears in Collections: | Research publications |
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