Source:http://linkedlifedata.com/resource/pubmed/id/12589822
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2003-2-18
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pubmed:abstractText |
The French paradox has been attributed to the antioxidant properties of flavonoids present in the red wine. Quercetin, a bioflanoid present in the human diet, is known to inhibit angiotensin II-induced hypertrophy and serum-induced smooth muscle cell proliferation. However, it is not known whether quercetin exerts similar cardioprotective effects in cells treated with TNF-alpha. In this study, we investigated whether quercetin exerts the multiple suppressive effects on cytokine TNF-alpha-induced human aortic smooth muscle cells (HASMC). Treatment of quercetin showed potent inhibitory effects on the DNA synthesis of cultured HASMC in the presence of TNF-alpha. These inhibitory effects were associated with reduced extracellular signal-regulated kinase (ERK)1/2 activity and G1 cell-cycle arrest. Treatment of quercetin, which induced a cell-cycle block in G1-phase, induced down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 expression, whereas up-regulation of p27 or p53 by quercetin was not observed. Because anti-atherogenic effects need not be limited to antiproliferation, we decided to examine whether quercetin exerted inhibitory effects on matrix metalloproteinase-9 (MMP-9) activity in TNF-alpha-induced HASMC. Quercetin inhibited TNF-alpha-induced MMP-9 secretion on HASMC in a dose-dependent manner. This inhibition was characterized by down-regulation of MMP-9, which was transcriptionally regulated at NF-kappaB site and activation protein-1 (AP-1) site in the MMP-9 promoter. These findings indicate the efficacy of quercetin in inhibiting cell proliferation, G1- to S-phase cell-cycle progress, and MMP-9 expression through the transcription factors NF-kappaB and AP-1 on TNF-alpha-induced HASMC.
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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/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Quercetin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
301
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1069-78
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12589822-Cell Cycle,
pubmed-meshheading:12589822-Cell Division,
pubmed-meshheading:12589822-Cells, Cultured,
pubmed-meshheading:12589822-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:12589822-Cyclin-Dependent Kinases,
pubmed-meshheading:12589822-Cyclins,
pubmed-meshheading:12589822-Humans,
pubmed-meshheading:12589822-Matrix Metalloproteinase 9,
pubmed-meshheading:12589822-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:12589822-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:12589822-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12589822-Muscle, Smooth, Vascular,
pubmed-meshheading:12589822-NF-kappa B,
pubmed-meshheading:12589822-Promoter Regions, Genetic,
pubmed-meshheading:12589822-Quercetin,
pubmed-meshheading:12589822-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cell-cycle regulation, and matrix metalloproteinase-9.
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pubmed:affiliation |
National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Kyungju, 780-714, Kyungbuk, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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