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rdf:type |
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lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0030012,
umls-concept:C0030054,
umls-concept:C0205332,
umls-concept:C1314939,
umls-concept:C1514762,
umls-concept:C1517499,
umls-concept:C1522492,
umls-concept:C1704259,
umls-concept:C1705987
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-30
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pubmed:abstractText |
The role of apurinic/apyrimidinic endonuclease-1/redox factor-1 (Ref-1) in vascular smooth muscle cells has yet to be clearly elucidated. Therefore, we attempted to determine the roles of Ref-1 in the migration induced by platelet-derived growth factor (PDGF)-BB and in its signaling in rat aortic smooth muscle cells (RASMCs). Cellular migration, superoxide (O(2)(-*)) production, Rac-1 activity, and neointima formation were determined in cells transfected with adenoviruses encoding for Ref-1 (AdRef-1) and small interference RNA of Ref-1. Overexpression of Ref-1 induced by treatment with RASMCs coupled with AdRef-1 inhibited the migration induced by PDGF-BB. PDGF-BB also increased the phosphorylation of the PDGFbeta receptor, spleen tyrosine kinase (Syk), mitogen-activated protein kinase, and heat shock protein 27, but these increases were significantly inhibited by AdRef-1 treatment. PDGF-BB increased O(2)(-*) production and Rac-1 activity, and these were diminished in cells transfected with AdRef-1. In contrast, RASMC migration, phosphorylation of Syk and O(2)(-*) production in response to PDGF-BB were increased by the knock down of Ref-1 with small interference RNA. The phosphorylation of PDGFbeta receptor in response to PDGF-BB was inhibited completely by the Syk inhibitor and was partly attenuated by a NADPH oxidase inhibitor. PDGF-BB increased the sprout outgrowth of the aortic ring ex vivo, which was inhibited in the AdRef-1-infected RASMCs as compared with the controls. Balloon injury-induced neointimal formation was significantly attenuated by the gene transfer of AdRef-1. These results indicate that Ref-1 inhibits the PDGF-mediated migration signal via the inhibition of reactive oxygen species-mediated Syk activity in RASMCs.
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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/APEX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-(Apurinic or Apyrimidinic...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Rac1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1524-4571
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pubmed:author |
pubmed-author:BaeYoung MinYM,
pubmed-author:ChoiWahn SooWS,
pubmed-author:IraniKaikobadK,
pubmed-author:JeonByeong HwaBH,
pubmed-author:KimBokyungB,
pubmed-author:KimHyo ShinHS,
pubmed-author:LeeChang-KwonCK,
pubmed-author:LeeHwan MyungHM,
pubmed-author:LeeSang KiSK,
pubmed-author:ParkSeung HwaSH,
pubmed-author:ParkTae-KyuTK,
pubmed-author:WonKyung-JongKJ
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pubmed:issnType |
Electronic
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pubmed:day |
30
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
219-27, 5p following 227
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:19038866-Adenoviridae,
pubmed-meshheading:19038866-Animals,
pubmed-meshheading:19038866-Aorta,
pubmed-meshheading:19038866-Carotid Artery Injuries,
pubmed-meshheading:19038866-Cell Movement,
pubmed-meshheading:19038866-Cell Proliferation,
pubmed-meshheading:19038866-Cells, Cultured,
pubmed-meshheading:19038866-DNA-(Apurinic or Apyrimidinic Site) Lyase,
pubmed-meshheading:19038866-Disease Models, Animal,
pubmed-meshheading:19038866-Enzyme Inhibitors,
pubmed-meshheading:19038866-Gene Knockdown Techniques,
pubmed-meshheading:19038866-Genetic Vectors,
pubmed-meshheading:19038866-Humans,
pubmed-meshheading:19038866-Hyperplasia,
pubmed-meshheading:19038866-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:19038866-Male,
pubmed-meshheading:19038866-Muscle, Smooth, Vascular,
pubmed-meshheading:19038866-NADPH Oxidase,
pubmed-meshheading:19038866-Neovascularization, Physiologic,
pubmed-meshheading:19038866-Phosphorylation,
pubmed-meshheading:19038866-Platelet-Derived Growth Factor,
pubmed-meshheading:19038866-Protein-Tyrosine Kinases,
pubmed-meshheading:19038866-Rats,
pubmed-meshheading:19038866-Rats, Sprague-Dawley,
pubmed-meshheading:19038866-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:19038866-Signal Transduction,
pubmed-meshheading:19038866-Superoxides,
pubmed-meshheading:19038866-Transduction, Genetic,
pubmed-meshheading:19038866-Transfection,
pubmed-meshheading:19038866-Tunica Intima,
pubmed-meshheading:19038866-rac1 GTP-Binding Protein
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pubmed:year |
2009
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pubmed:articleTitle |
Gene transfer of redox factor-1 inhibits neointimal formation: involvement of platelet-derived growth factor-beta receptor signaling via the inhibition of the reactive oxygen species-mediated Syk pathway.
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pubmed:affiliation |
Institute of Medical Sciences, School of Medicine, Konkuk University, Chungju, South Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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