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rdf:type |
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lifeskim:mentions |
umls-concept:C0003483,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0026844,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C1366765,
umls-concept:C1516334,
umls-concept:C1527240,
umls-concept:C1658578,
umls-concept:C1879547,
umls-concept:C1883254
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pubmed:issue |
6
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pubmed:dateCreated |
2008-3-5
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pubmed:abstractText |
The increased potential for growth of vascular smooth muscle cells (VSMCs) is a key abnormality in the development of atherosclerosis and postangioplasty restenosis. Platelet-derived growth factor (PDGF)-BB is a potent mitogen for VSMCs that plays an important role in the intimal accumulation of VSMCs. This study examined the effect of JM91, a newly synthesized indoledione derivative, on the proliferation of PDGF-BB-stimulated rat aortic VSMCs. The antiproliferative effect of JM91 on rat aortic VSMCs was examined by cell counting and [(3)H]thymidine incorporation assay. The pre-incubation of JM91 (0.5-3.0 microM) significantly inhibited the proliferation and DNA synthesis of 25 ng/mL PDGF-BB-stimulated rat aortic VSMCs in a concentration-dependent manner. JM91 inhibited the PDGF-BB-stimulated phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt kinase, while had no effect on PLCgamma1 and PDGF-Rbeta activation. In addition, treatment with JM91 (0.5-3.0 microM) induced cell-cycle arrest in the G(1) phase, which was associated with the down-regulation of cyclins and CDKs. These findings suggest that the inhibitory effects of JM91 against proliferation, DNA synthesis and cell cycle progression of PDGF-BB-stimulated rat aortic VSMCs are mediated by the suppression of the ERK1/2 and PI3K/Akt signaling pathways. Furthermore, JM91 may be a potential antiproliferative agent for the treatment of atherosclerosis and angioplasty restenosis.
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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/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
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/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolones,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1873-2968
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
75
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1331-40
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18191105-Animals,
pubmed-meshheading:18191105-Aorta,
pubmed-meshheading:18191105-Cell Cycle,
pubmed-meshheading:18191105-Cell Cycle Proteins,
pubmed-meshheading:18191105-Cell Proliferation,
pubmed-meshheading:18191105-Cells, Cultured,
pubmed-meshheading:18191105-DNA,
pubmed-meshheading:18191105-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:18191105-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:18191105-Myocytes, Smooth Muscle,
pubmed-meshheading:18191105-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:18191105-Phosphorylation,
pubmed-meshheading:18191105-Platelet-Derived Growth Factor,
pubmed-meshheading:18191105-Protein Kinase Inhibitors,
pubmed-meshheading:18191105-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:18191105-Quinolones,
pubmed-meshheading:18191105-Quinones,
pubmed-meshheading:18191105-Rats,
pubmed-meshheading:18191105-Retinoblastoma Protein
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pubmed:year |
2008
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pubmed:articleTitle |
JM91, a newly synthesized indoledione derivative, inhibits rat aortic vascular smooth muscle cells proliferation and cell cycle progression through inhibition of ERK1/2 and Akt activations.
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pubmed:affiliation |
College of Pharmacy, CBITRC, Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Republic of Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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