Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-16
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
287
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1495-500
pubmed:dateRevised
2007-11-15
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
pubmed:year
2004
pubmed:articleTitle
Activation of Rho/Rho kinase signaling pathway by reactive oxygen species in rat aorta.
pubmed:affiliation
Dept. of Physiology, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-3000, USA. ljin@mcg.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't