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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2007-9-10
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pubmed:abstractText |
Hepatocytes in fatty livers are hypersensitive to apoptosis and undergo escalated apoptotic activity via death receptor-mediated pathways, particularly that of Fas-FasL, causing hepatic injury that can eventually proceed to cirrhosis and end-stage liver disease. Here we report that the hepatocyte growth factor receptor, Met, plays an important part in preventing Fas-mediated apoptosis of hepatocytes by sequestering Fas. We also show that Fas antagonism by Met is abrogated in human fatty liver disease (FLD). Through structure-function studies, we found that a YLGA amino-acid motif located near the extracellular N terminus of the Met alpha-subunit is necessary and sufficient to specifically bind the extracellular portion of Fas and to act as a potent FasL antagonist and inhibitor of Fas trimerization. Using mouse models of FLD, we show that synthetic YLGA peptide tempers hepatocyte apoptosis and liver damage and therefore has therapeutic potential.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/MET protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-met,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Growth Factor
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:DeFrancesMarie CMC,
pubmed-author:EakerAmanda EAE,
pubmed-author:GuoLidaL,
pubmed-author:JohnsonCarla JCJ,
pubmed-author:MaJihongJ,
pubmed-author:MichalopoulosGeorge KGK,
pubmed-author:StoopsJohnJ,
pubmed-author:StromStephenS,
pubmed-author:WangXueX,
pubmed-author:ZarnegarRezaR,
pubmed-author:ZhuZhenqiZ,
pubmed-author:ZouChunbinC
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1078-85
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17704785-Amino Acid Sequence,
pubmed-meshheading:17704785-Antigens, CD95,
pubmed-meshheading:17704785-Apoptosis,
pubmed-meshheading:17704785-Carcinoma, Hepatocellular,
pubmed-meshheading:17704785-Cell Line, Tumor,
pubmed-meshheading:17704785-Collagen,
pubmed-meshheading:17704785-Fatty Liver,
pubmed-meshheading:17704785-Hepatocytes,
pubmed-meshheading:17704785-Humans,
pubmed-meshheading:17704785-Immunohistochemistry,
pubmed-meshheading:17704785-Jurkat Cells,
pubmed-meshheading:17704785-Kinetics,
pubmed-meshheading:17704785-Liver Neoplasms,
pubmed-meshheading:17704785-Molecular Sequence Data,
pubmed-meshheading:17704785-Peptide Fragments,
pubmed-meshheading:17704785-Protein Subunits,
pubmed-meshheading:17704785-Proto-Oncogene Proteins,
pubmed-meshheading:17704785-Proto-Oncogene Proteins c-met,
pubmed-meshheading:17704785-Receptors, Growth Factor
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pubmed:year |
2007
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pubmed:articleTitle |
Lack of Fas antagonism by Met in human fatty liver disease.
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pubmed:affiliation |
Department of Pathology, School of Medicine, University of Pittsburgh, S411A Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, Pennsylvania 15261, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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