Source:http://linkedlifedata.com/resource/pubmed/id/15993097
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2005-7-4
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pubmed:abstractText |
This study was undertaken to investigate whether a physiologically compatible concentration of 7-ketocholesterol had any effect on human vascular smooth muscle cells (HVSMCs). We found that 7-ketocholesterol changed the viability of human aorta smooth muscle cells (HAoSMC) not by cytotoxicity but by activation of tumor necrosis factor-alpha receptor (TNFR)-mediated death. Whereas TNF-alpha did not affect the viability in the presence of 7alpha-hydroxycholesterol or cholesterol, the cytokine induced HAoSMC death in the presence of 7-ketocholesterol as detected by morphology, viability, and fragmentation of chromosomal DNA. The HAoSMC death was inhibited by a neutralizing anti-TNF receptor 1 (TNFR1) antibody and by the caspase inhibitors of z-VAD and z-DEVD. Activations of caspase-8 and -3 were detected from dying HAoSMCs. 7-Ketocholesterol inhibited translocation of the nuclear factor kappaB (NF-kappaB) subunits of p65 and p50 from the cytosol into the nucleus, increase of NF-kappaB activity, and expression of caspase-8 homolog Fas ligand interleukin-1-converting enzyme inhibitory protein by TNF-alpha. We also found that X-chromosome-linked inhibitor of apoptosis protein was degraded in dying HAoSMC. The present study proposes that 7-ketocholesterol would contribute to the disappearance of HVSMC in the atherosclerotic lesions by enhancing receptor-mediated death. This is the first report demonstrating induction of TNF-alpha-mediated death by oxysterol in cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
333
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
1093-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15993097-Aorta,
pubmed-meshheading:15993097-Apoptosis,
pubmed-meshheading:15993097-Cells, Cultured,
pubmed-meshheading:15993097-Dose-Response Relationship, Drug,
pubmed-meshheading:15993097-Humans,
pubmed-meshheading:15993097-Ketocholesterols,
pubmed-meshheading:15993097-Muscle, Smooth, Vascular,
pubmed-meshheading:15993097-Myocytes, Smooth Muscle,
pubmed-meshheading:15993097-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
TNF-alpha activates death pathway in human aorta smooth muscle cell in the presence of 7-ketocholesterol.
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pubmed:affiliation |
Laboratory of Lipid Metabolism, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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