Source:http://linkedlifedata.com/resource/pubmed/id/15371261
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2004-9-16
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pubmed:abstractText |
Evidence indicates that both the Rho/Rho kinase signaling pathway and reactive oxygen species (ROS) such as superoxide and H(2)O(2) are involved in the pathogenesis of hypertension. This study aimed to determine whether ROS-induced vascular contraction is mediated through activation of Rho/Rho kinase. Rat aortic rings (endothelium denuded) were isolated and placed in organ chambers for measurement of isometric force development. ROS were generated by a xanthine (X)-xanthine oxidase (XO) mixture. The antioxidants tempol (3 mM) and catalase (1,200 U/ml) or the XO inhibitor allopurinol (400 microM) significantly reduced X/XO-induced contraction. A Rho kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl-N-4-pyridil)cyclohexanecarboxamide dihydrochloride (Y-27632), decreased the contraction in a concentration-dependent manner; however, the Ca(2+)-independent protein kinase C inhibitor rottlerin did not have an effect on X/XO-induced contraction. Phosphorylation of the myosin light chain phosphatase target subunit (MYPT1) was increased by ROS, and preincubation with Y-27632 blocked this increased phosphorylation. Western blotting for cytosolic and membrane-bound fractions of Rho showed that Rho was increased in the membrane fraction by ROS, suggesting activation of Rho. These observations demonstrate that ROS-induced Ca(2+) sensitization is through activation of Rho and a subsequent increase in Rho kinase activity but not Ca(2+)-independent PKC.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin-Light-Chain Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/rho GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0363-6135
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
287
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H1495-500
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15371261-Amides,
pubmed-meshheading:15371261-Animals,
pubmed-meshheading:15371261-Aorta,
pubmed-meshheading:15371261-Enzyme Inhibitors,
pubmed-meshheading:15371261-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15371261-Male,
pubmed-meshheading:15371261-Muscle, Smooth, Vascular,
pubmed-meshheading:15371261-Muscle Contraction,
pubmed-meshheading:15371261-Myosin-Light-Chain Phosphatase,
pubmed-meshheading:15371261-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15371261-Pyridines,
pubmed-meshheading:15371261-Rats,
pubmed-meshheading:15371261-Rats, Sprague-Dawley,
pubmed-meshheading:15371261-Reactive Oxygen Species,
pubmed-meshheading:15371261-Signal Transduction,
pubmed-meshheading:15371261-rho GTP-Binding Proteins,
pubmed-meshheading:15371261-rho-Associated Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta.
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pubmed:affiliation |
Dept. of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3000, USA. ljin@mcg.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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