Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-2-18
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1069-78
pubmed:dateRevised
2009-11-19
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
pubmed:year
2003
pubmed:articleTitle
Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cell-cycle regulation, and matrix metalloproteinase-9.
pubmed:affiliation
National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Kyungju, 780-714, Kyungbuk, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't