Linked Life Data

21433064

Source:http://linkedlifedata.com/resource/pubmed/id/21433064

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2011-6-9
pubmed:abstractText
The Rho-kinase (ROCK) plays an important role in the pathogenesis of heart injury. Recent cellular and molecular biology studies indicated a pivotal role of the RhoA/ROCK cascade in many aspects of cardiovascular function such as heart failure, cardiac hypertrophy, and ventricular remodeling following myocardial infarction. However, the signal transduction of RhoA/ROCK and its down-stream signaling pathways remains elusive, and the mechanism of ROCK-mediated isoproterenol (ISO)-induced heart failure is still not thoroughly understood. In the present study, we investigated the effect of the ROCK inhibitor, fasudil hydrochloride hydrate, on ISO-induced heart failure and the potential relationship of RhoA/ROCK to the extracellular signal-regulated kinases (ERK) and the c-jun NH 2-terminal kinase (JNK) pathways. Male Sprague-Dawley (SD) rats, maintained on a normal diet, were randomly divided into four groups given control, ISO alone, ISO with low-dose fasudil, or ISO with high-dose fasudil treatments. Fasudil effectively inhibited ISO-induced heart failure, as evaluated by biometric, hemodynamic, and histological examinations. Consistently, ISO-induced ROCK-1 mRNA expression and myosin phosphatase target subunit-1 (MYPT-1) phosphorylation were markedly suppressed by fasudil. In addition, fasudil significantly decreased ISO-induced JNK activation, ERK translocation to the nucleus and subsequent c-fos, c-jun expression and upregulated c-FLIP(L) expression. Taken together, these results indicate that the RhoA/ROCK pathway is essential for ISO induced heart failure, which can be effectively suppressed by fasudil.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1920-9
pubmed:meshHeading
pubmed-meshheading:21433064-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:21433064-Animals, pubmed-meshheading:21433064-CASP8 and FADD-Like Apoptosis Regulating Protein, pubmed-meshheading:21433064-Enzyme Activation, pubmed-meshheading:21433064-Gene Expression, pubmed-meshheading:21433064-Heart, pubmed-meshheading:21433064-Heart Failure, pubmed-meshheading:21433064-Hemodynamics, pubmed-meshheading:21433064-Isoproterenol, pubmed-meshheading:21433064-MAP Kinase Signaling System, pubmed-meshheading:21433064-Male, pubmed-meshheading:21433064-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:21433064-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:21433064-Mitogen-Activated Protein Kinase 8, pubmed-meshheading:21433064-Myocardium, pubmed-meshheading:21433064-Organ Size, pubmed-meshheading:21433064-Rats, pubmed-meshheading:21433064-Rats, Sprague-Dawley, pubmed-meshheading:21433064-rho-Associated Kinases
pubmed:year
2011
pubmed:articleTitle
Fasudil hydrochloride hydrate, a Rho-kinase inhibitor, suppresses isoproterenol-induced heart failure in rats via JNK and ERK1/2 pathways.
pubmed:affiliation
Department of Pharmacology, School of Basic Medicine, Heibei Medical University, Shijiazhuang 050091, Hebei, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't