Linked Life Data

12114317

Source:http://linkedlifedata.com/resource/pubmed/id/12114317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-7-12
pubmed:abstractText
The steroid hormone 1alpha,25-dihydroxyvitamin D3 [1alpha, 25-(OH)2D3] promotes vascular smooth muscle cell (VSMC) growth and calcification, but the precise mechanism by which 1alpha, 25-(OH)2D3 regulates VSMC migration is unknown. In rat aortic SMCs, we found that 1alpha, 25-(OH)2D3 (0.1 to 100 nmol/L) induced a dose-dependent increase in VSMC migration. This response required the activation of phosphatidylinositol 3-kinase (PI3 kinase) because 1alpha, 25-(OH)2D3-induced migration was completely abolished by the PI3 kinase inhibitors, LY294002 (10 micromol/L) or wortmannin (30 nmol/L). Furthermore, the RNA polymerase inhibitor, 5,6-dichlorobenzimidazole riboside (50 micromol/L), did not affect 1alpha, 25-(OH)2D3-induced VSMC migration, suggesting that gene transcription is not involved in this rapid response. Using analogs of 1alpha, 25-(OH)2D3, which have been characterized for their abilities to induce either transcriptional or nontranscriptional responses of 1alpha, 25-(OH)2D3, we found that 1alpha,25-dihydroxylumisterol, which is a potent agonist of the rapid, nongenomic responses, was equipotent with 1alpha, 25-(OH)2D3 in inducing PI3 kinase activity and VSMC migration. Moreover, 1beta, 25-(OH)2D3, which specifically antagonizes the nongenomic actions of 1alpha, 25-(OH)2D3, abolished 1alpha, 25-(OH)2D3-induced PI3 kinase activity and VSMC migration, whereas the inhibitor of the genomic actions of vitamin D, (23S)-25-dehydro-1alpha-OH-D3-26,23-lactone, did not affect these responses. These results indicate that 1alpha, 25-(OH)2D3 induces VSMC migration independent of gene transcription via PI3 kinase pathway, and suggest a possible mechanism by which 1alpha, 25-(OH)2D3 may contribute to neointima formation in atherosclerosis and vascular remodeling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-24
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12114317-Animals, pubmed-meshheading:12114317-Blotting, Western, pubmed-meshheading:12114317-Calcitriol, pubmed-meshheading:12114317-Cell Adhesion, pubmed-meshheading:12114317-Cell Movement, pubmed-meshheading:12114317-Cells, Cultured, pubmed-meshheading:12114317-Dichlororibofuranosylbenzimidazole, pubmed-meshheading:12114317-Dose-Response Relationship, Drug, pubmed-meshheading:12114317-Enzyme Activation, pubmed-meshheading:12114317-Enzyme Inhibitors, pubmed-meshheading:12114317-Ergosterol, pubmed-meshheading:12114317-Muscle, Smooth, Vascular, pubmed-meshheading:12114317-Osteopontin, pubmed-meshheading:12114317-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12114317-RNA Polymerase II, pubmed-meshheading:12114317-Rats, pubmed-meshheading:12114317-Rats, Sprague-Dawley, pubmed-meshheading:12114317-Sialoglycoproteins
pubmed:year
2002
pubmed:articleTitle
1alpha,25-dihydroxyvitamin D3 induces vascular smooth muscle cell migration via activation of phosphatidylinositol 3-kinase.
pubmed:affiliation
Vascular Medicine Research, Brigham and Women's Hospital and Harvard Medical School, Cambridge, Mass 02139, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't