Source:http://linkedlifedata.com/resource/pubmed/id/17916362
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2007-10-29
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pubmed:abstractText |
Yeast Sir2 plays critical roles in gene silencing, stress resistance and longevity. Mammalian Sirt1 NAD(+)-dependent protein deacetylase, the closest homolog of Sir2, regulates cell cycle, cellular senescence, apoptosis and metabolism, by functional interactions with a number of biological molecules such as p53. To investigate a role of Sirt1 in endothelial dysfunction and premature senescence, we examined the effects of Sirt1 inhibition in human umbilical vein endothelial cells (HUVEC). Sirt1 inhibition by sirtinol, which is a 2-hydroxy-1-napthaldehyde derivative, or siRNA for Sirt1-induced premature senescence-like phenotype, as judged by increased senescence-associated beta-galactosidase (SA-beta-gal) activity, sustained growth arrest and enlarged and flattened cell morphology at 10 days after the treatment. Sixty-four percent of sirtinol (60 mumol/L)-treated HUVEC was SA-beta-gal-positive, whereas only 17% of vehicle-treated cells were positive. Sirt1 inhibition by sirtinol or Sirt1 siRNA increased PAI-1 expression and decreased both protein expression and activity of eNOS. Treatment with sirtinol or Sirt1 siRNA increased acetylation of p53, while p53 expression was unaltered. Impaired epidermal growth factor-induced activation of mitogen-activated protein kinases was associated with Sirt1 inhibition-induced senescence-like growth arrest. Conversely, overexpression of Sirt1 prevented hydrogen peroxide-induced SA-beta-gal activity, morphological changes and deranged expression of PAI-1 and eNOS. These results showed that Sirt1 inhibition increased p53 acetylation and induced premature senescence-like phenotype in parallel with increased PAI-1 and decreased eNOS expression. Our data suggest that Sirt1 may exert protective effects against endothelial dysfunction by preventing stress-induced premature senescence and deranged expression of PAI-1 and eNOS.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SIRT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Sirtuin 1,
http://linkedlifedata.com/resource/pubmed/chemical/Sirtuins,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-2828
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
571-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17916362-Cell Aging,
pubmed-meshheading:17916362-Cell Division,
pubmed-meshheading:17916362-Cells, Cultured,
pubmed-meshheading:17916362-Endothelium, Vascular,
pubmed-meshheading:17916362-Humans,
pubmed-meshheading:17916362-Nitric Oxide Synthase,
pubmed-meshheading:17916362-Phenotype,
pubmed-meshheading:17916362-RNA, Small Interfering,
pubmed-meshheading:17916362-Recombinant Proteins,
pubmed-meshheading:17916362-Sirtuin 1,
pubmed-meshheading:17916362-Sirtuins,
pubmed-meshheading:17916362-Transfection,
pubmed-meshheading:17916362-Umbilical Veins,
pubmed-meshheading:17916362-beta-Galactosidase
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pubmed:year |
2007
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pubmed:articleTitle |
Sirt1 modulates premature senescence-like phenotype in human endothelial cells.
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pubmed:affiliation |
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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