Source:http://linkedlifedata.com/resource/pubmed/id/21624955
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2011-5-31
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| pubmed:abstractText |
Atherosclerosis is readily observed in regions of blood vessels where disturbed blood flow (d-flow) is known to occur. A positive correlation between protein kinase C ? (PKC?) activation and d-flow has been reported, but the exact role of d-flow-mediated PKC? activation in atherosclerosis remains unclear. We tested the hypothesis that PKC? activation by d-flow induces endothelial cell (EC) apoptosis by regulating p53. We found that d-flow-mediated peroxynitrite (ONOO(-)) increased PKC? activation, which subsequently induced p53 SUMOylation, p53-Bcl-2 binding, and EC apoptosis. Both d-flow and ONOO(-) increased the association of PKC? with protein inhibitor of activated STATy (PIASy) via the Siz/PIAS-RING domain (amino acids 301-410) of PIASy, and overexpression of this domain of PIASy disrupted the PKC?-PIASy interaction and PKC?-mediated p53 SUMOylation. En face confocal microscopy revealed increases in nonnuclear p53 expression, nitrotyrosine staining, and apoptosis in aortic EC located in d-flow areas in wild-type mice, but these effects were significantly decreased in p53(-/-) mice. We propose a novel mechanism for p53 SUMOylation mediated by the PKC?-PIASy interaction during d-flow-mediated EC apoptosis, which has potential relevance to early events of atherosclerosis.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
1540-8140
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| pubmed:author |
pubmed-author:AbeJun-ichiJ,
pubmed-author:BerkBradford CBC,
pubmed-author:ChangEugeneE,
pubmed-author:FujiwaraKeigiK,
pubmed-author:HeoKyung-SunKS,
pubmed-author:KingMichael RMR,
pubmed-author:LeNhat-TuNT,
pubmed-author:LeeHakjooH,
pubmed-author:McClainCarolynC,
pubmed-author:NigroPatriziaP,
pubmed-author:Reinhart-KingCynthia ACA,
pubmed-author:TamlynThomasT,
pubmed-author:WooChang-HoonCH
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
30
|
| pubmed:volume |
193
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
867-84
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| pubmed:meshHeading |
pubmed-meshheading:21624955-Animals,
pubmed-meshheading:21624955-Apoptosis,
pubmed-meshheading:21624955-Cells, Cultured,
pubmed-meshheading:21624955-Endothelial Cells,
pubmed-meshheading:21624955-Humans,
pubmed-meshheading:21624955-Mice,
pubmed-meshheading:21624955-Mice, Inbred C57BL,
pubmed-meshheading:21624955-Mice, Knockout,
pubmed-meshheading:21624955-Protein Kinase C,
pubmed-meshheading:21624955-Regional Blood Flow,
pubmed-meshheading:21624955-SUMO-1 Protein,
pubmed-meshheading:21624955-Sumoylation,
pubmed-meshheading:21624955-Tumor Suppressor Protein p53
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| pubmed:year |
2011
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| pubmed:articleTitle |
PKC? mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation.
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| pubmed:affiliation |
Aab Cardiovascular Research Institute, University of Rochester, Rochester, NY 14642, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|