Linked Life Data

12646195

Source:http://linkedlifedata.com/resource/pubmed/id/12646195

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-3-20
pubmed:abstractText
Rapamycin inhibits vascular smooth muscle cell (VSMC) proliferation and rapamycin-eluting stents represent a novel therapeutic strategy for preventing postangioplasty restenosis. The precise molecular mechanism, for rapamycin-mediated inhibition of VSMC cell cycle progression and DNA replication remain to be elucidated. Minichromosome maintenance proteins (MCM) are essential regulators of DNA replication and the objective of this study was to examine the effect of rapamycin on their expression in rat aortic VSMC. Rapamycin substantially inhibited mitogen-induced MCM6 and MCM7 mRNA and protein expression in a dose-dependent fashion. Transient transfection experiments revealed that rapamycin inhibited MCM6 and MCM7 promoter activity, implicating a transcriptional mechanism. MCM6 and MCM7 transcriptional activation is regulated by E2F and activity of a luciferase reporter plasmid driven by four E2F elements was also significantly inhibited by rapamycin. The inhibitory effect of rapamycin on MCM6 and MCM7 was reversed by overexpression of E2F, indicating that their downregulation by rapamycin involves an E2F-dependent mechanism. These observations suggest that rapamycin inhibits MCM6 and MCM7 expression by blocking their E2F-dependent transactivation which may contribute importantly to the inhibition of VSMC DNA synthesis by rapamycin.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
303
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
251-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12646195-Animals, pubmed-meshheading:12646195-Antibiotics, Antineoplastic, pubmed-meshheading:12646195-Blotting, Northern, pubmed-meshheading:12646195-Blotting, Western, pubmed-meshheading:12646195-Cell Cycle Proteins, pubmed-meshheading:12646195-Cell Division, pubmed-meshheading:12646195-Cells, Cultured, pubmed-meshheading:12646195-DNA, pubmed-meshheading:12646195-DNA-Binding Proteins, pubmed-meshheading:12646195-Down-Regulation, pubmed-meshheading:12646195-E2F Transcription Factors, pubmed-meshheading:12646195-Endothelium, Vascular, pubmed-meshheading:12646195-Muscle, Smooth, pubmed-meshheading:12646195-Nuclear Proteins, pubmed-meshheading:12646195-Phosphorylation, pubmed-meshheading:12646195-Promoter Regions, Genetic, pubmed-meshheading:12646195-RNA, pubmed-meshheading:12646195-RNA, Messenger, pubmed-meshheading:12646195-Rats, pubmed-meshheading:12646195-Rats, Sprague-Dawley, pubmed-meshheading:12646195-Serine, pubmed-meshheading:12646195-Sirolimus, pubmed-meshheading:12646195-Transcription Factors, pubmed-meshheading:12646195-Transcriptional Activation, pubmed-meshheading:12646195-Transfection
pubmed:year
2003
pubmed:articleTitle
Rapamycin inhibits E2F-dependent expression of minichromosome maintenance proteins in vascular smooth muscle cells.
pubmed:affiliation
Division of Endocrinology, Diabetes and Hypertension and the Gonda (Goldschmied) Diabetes Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't