Linked Life Data

19850048

Source:http://linkedlifedata.com/resource/pubmed/id/19850048

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-1-28
pubmed:abstractText
MTK1 (MEKK4) is a mitogen-activated protein kinase kinase kinase that regulates the activity of its downstream mitogen-activated kinases, p38, and c-Jun N-terminal kinase (JNK). However, the physiological function of MTK1 in the heart remains to be determined. Here, we attempted to elucidate the function of MTK1 in the heart using in vitro and in vivo models. MTK1 was activated in the hearts of mice subjected to pressure overload-induced heart failure. Overexpression of a constitutively active mutant of MTK1 (MTK1DeltaN) induced apoptosis in isolated neonatal rat cardiomyocytes, whereas a kinase domain-deleted form of MTK1 attenuated H(2)O(2)-induced apoptosis. Specific inhibitors of p38 or JNK effectively protected cardiomyocytes from MTK1DeltaN-induced cell death. In mice, cardiac-specific overexpression of MTK1DeltaN resulted in early mortality compared with the lifespan of littermate controls. Echocardiographic analysis revealed increases in end-diastolic and end-systolic left ventricular internal dimensions and a decrease in fractional shortening in MTK1DeltaN transgenic mice. In addition, the mice showed characteristic phenotypes of heart failure such as an increase in lung weight. The number of TUNEL-positive myocytes and the level of cleaved caspase 3 protein were both increased in MTK1DeltaN transgenic mice. Thus, MTK1 plays an important role in the regulation of cell death and is also involved in the pathogenesis of heart failure.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1095-8584
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
302-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure.
pubmed:affiliation
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't