Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-31
pubmed:abstractText
Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However, little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells, EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore, we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricular myocytes in vitro. In adult rat ventricular myocytes (ARVM), beta-adrenergic receptor (betaAR) stimulation and H(2)O(2) (24 h) each increased EMMPRIN expression as assessed by immunoblotting. Pretreatment with a catalase/superoxide dismutase mimetic or adenoviral-mediated expression of catalase or a dominant-negative c-jun N-terminal kinase-1 (JNK) mutant inhibited the betaAR- and H(2)O(2)-stimulated increases in EMMPRIN expression suggesting that EMMPRIN expression is regulated via a reactive oxygen species-dependent JNK pathway. To determine whether EMMPRIN expression regulates matrix metalloproteinase (MMP) activity, EMMPRIN activity was inhibited by adenoviral expression of an inhibitory mutant of EMMPRIN. Expression of mutant EMMPRIN inhibited the betaAR-stimulated increases in MMP2 expression and zymographic MMP activity. Thus, in cardiac myocytes betaAR stimulation induces the expression of EMMPRIN via the ROS-dependent activation of JNK. The resulting increase in EMMPRIN activity stimulates MMP expression and activity. These findings suggest that in the myocardium the regulated expression of EMMPRIN is a determinant of MMP activity and may thus play a role in myocardial remodeling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1095-8584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
210-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes.
pubmed:affiliation
Myocardial Biology Unit, Boston University School of Medicine, 650 Albany Street, X740, Boston, MA 02118, USA. dasiwik@bu.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't