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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2006-2-22
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pubmed:abstractText |
Activation of the terminal complement cascade involving C5 to C9 proteins has a beneficial role for oligodendrocytes (OLG) in experimental allergic encephalomyelitis, an animal model of multiple sclerosis, by protecting them from apoptotic cell death. We have previously shown that sublytic C5b-9 complexes, through posttranslational regulation of Bad, inhibit the mitochondrial pathway of apoptosis induced by serum deprivation. In the present study, we examined the possible involvement of the caspase-8 and Fas pathway in OLG apoptosis and the role of C5b-9 in this process. In a serum-free defined medium, OLG undergo apoptosis and differentiation concomitantly. Under this condition, we found that caspase-8 processing was increased in association with Bid cleavage and markedly reduced expression of cellular FLIP long isoform protein. The caspase-8 inhibitor Z-IETD-FMK inhibited cell death associated with differentiation in a dose-dependent manner. Exposure to C5b-9 induced an inhibition of caspase-8 activation, Bid cleavage, and a significant increase in expression of cellular FLIP long isoform. These C5b-9 effects were reversed by PI3K inhibitor LY294002. C5b-9 also down-regulated the expression of FasL and the Fas-induced apoptosis. These data suggest that C5b-9 through PI3K signaling can rescue OLG from Fas-mediated apoptosis by regulating caspase-8 processing.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/Bid protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 and FADD-Like Apoptosis...,
http://linkedlifedata.com/resource/pubmed/chemical/CASP8 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CFLAR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Complement Membrane Attack Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Death Domain Receptor Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf6 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
176
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3173-80
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16493077-Animals,
pubmed-meshheading:16493077-Animals, Newborn,
pubmed-meshheading:16493077-Apoptosis,
pubmed-meshheading:16493077-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:16493077-CASP8 and FADD-Like Apoptosis Regulating Protein,
pubmed-meshheading:16493077-Caspase 8,
pubmed-meshheading:16493077-Caspases,
pubmed-meshheading:16493077-Cells, Cultured,
pubmed-meshheading:16493077-Complement Membrane Attack Complex,
pubmed-meshheading:16493077-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:16493077-Down-Regulation,
pubmed-meshheading:16493077-Fas Ligand Protein,
pubmed-meshheading:16493077-Humans,
pubmed-meshheading:16493077-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16493077-Membrane Glycoproteins,
pubmed-meshheading:16493077-Oligodendroglia,
pubmed-meshheading:16493077-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16493077-Protein Processing, Post-Translational,
pubmed-meshheading:16493077-Rats,
pubmed-meshheading:16493077-Rats, Sprague-Dawley,
pubmed-meshheading:16493077-Tumor Necrosis Factor Receptor-Associated Peptides and...,
pubmed-meshheading:16493077-Tumor Necrosis Factors,
pubmed-meshheading:16493077-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
C5b-9 terminal complex protects oligodendrocytes from apoptotic cell death by inhibiting caspase-8 processing and up-regulating FLIP.
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pubmed:affiliation |
Department of Neurology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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