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rdf:type |
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lifeskim:mentions |
umls-concept:C0003483,
umls-concept:C0017718,
umls-concept:C0018270,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0044602,
umls-concept:C0598312,
umls-concept:C1135918,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C2349975
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pubmed:issue |
2
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pubmed:dateCreated |
2001-7-26
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pubmed:abstractText |
Vascular smooth muscle cells play a key role in the development of atherosclerosis. Culture of vascular smooth muscle A10 cells with high glucose for 4 weeks enhanced platelet-derived growth factor (PDGF)-induced BrdU incorporation. Since a long period of high glucose incubation was required for the effect, and it was inhibited by co-incubation with azaserine, the role of hexosamine biosynthesis in the development of atherosclerosis in diabetes was studied in A10 cells. Addition of glucosamine to the culture media enhanced PDGF-stimulated BrdU incorporation, and PDGF-induced tyrosine phosphorylation of the PDGF beta-receptor was increased by glucosamine treatment. Of the subsequent intracellular signaling pathways, PDGF-induced PDGF beta-receptor association with PLC gamma was not affected, whereas tyrosine phosphorylation of Shc, subsequent association of Shc with Grb2, and MAP kinase activation were relatively decreased. In contrast, PDGF-induced PDGF beta-receptor association with the p85 regulatory subunit of PI3-kinase and PI3-kinase activation were increased by 20% (P<0.01) and 36% (P<0.01), respectively. The intracellular signaling molecules responsible for the glucosamine effect were further examined using pharmacological inhibitors. Pretreatment with PLC inhibitor (U73122) had negligible effects, and MEK1 inhibitor (PD98059) showed only a slight inhibitory effect on the PDGF-induced BrdU incorporation. In contrast, pretreatment with PI3-kinase inhibitor (LY294002) significantly inhibited glucosamine enhancement of PDGF-induced BrdU incorporation. These findings suggest that glucosamine is involved in the development of atherosclerosis by enhancing PDGF-induced mitogenesis specifically via the PI3-kinase pathway.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Azaserine,
http://linkedlifedata.com/resource/pubmed/chemical/Bromodeoxyuridine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Glucosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Grb2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Shc Signaling Adaptor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Shc1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9150
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pubmed:author |
pubmed-author:IshiharaHH,
pubmed-author:IshikoKK,
pubmed-author:KishidaMM,
pubmed-author:KobayashiMM,
pubmed-author:NakamuraNN,
pubmed-author:SasaokaTT,
pubmed-author:SatoAA,
pubmed-author:TakataMM,
pubmed-author:TemaruRR,
pubmed-author:UrakazeMM,
pubmed-author:UsuiII,
pubmed-author:WadaTT,
pubmed-author:YamazakiKK
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pubmed:issnType |
Print
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pubmed:volume |
157
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
341-52
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11472733-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:11472733-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:11472733-Animals,
pubmed-meshheading:11472733-Aorta,
pubmed-meshheading:11472733-Azaserine,
pubmed-meshheading:11472733-Bromodeoxyuridine,
pubmed-meshheading:11472733-Cells, Cultured,
pubmed-meshheading:11472733-DNA,
pubmed-meshheading:11472733-Dose-Response Relationship, Drug,
pubmed-meshheading:11472733-Drug Synergism,
pubmed-meshheading:11472733-Enzyme Inhibitors,
pubmed-meshheading:11472733-GRB2 Adaptor Protein,
pubmed-meshheading:11472733-Glucosamine,
pubmed-meshheading:11472733-Glucose,
pubmed-meshheading:11472733-Isoenzymes,
pubmed-meshheading:11472733-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11472733-Muscle, Smooth, Vascular,
pubmed-meshheading:11472733-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:11472733-Phospholipase C gamma,
pubmed-meshheading:11472733-Phosphorylation,
pubmed-meshheading:11472733-Platelet-Derived Growth Factor,
pubmed-meshheading:11472733-Proteins,
pubmed-meshheading:11472733-Rats,
pubmed-meshheading:11472733-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:11472733-Shc Signaling Adaptor Proteins,
pubmed-meshheading:11472733-Type C Phospholipases,
pubmed-meshheading:11472733-Tyrosine
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pubmed:year |
2001
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pubmed:articleTitle |
Glucosamine enhances platelet-derived growth factor-induced DNA synthesis via phosphatidylinositol 3-kinase pathway in rat aortic smooth muscle cells.
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pubmed:affiliation |
First Department of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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