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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-10-6
pubmed:abstractText
CARP, a cardiac doxorubicin (adriamycin)-responsive protein, has been identified as a nuclear protein whose expression is downregulated in response to doxorubicin. In the present study, we tested the hypothesis that CARP serves as a reliable genetic marker of cardiac hypertrophy in vivo and in vitro. CARP expression was markedly increased in 3 distinct models of cardiac hypertrophy in rats: constriction of abdominal aorta, spontaneously hypertensive rats, and Dahl salt-sensitive rats. In addition, we found that CARP mRNA levels correlate very strongly with the brain natriuretic peptide mRNA levels in Dahl rats. Transient transfection assays into primary cultures of neonatal rat cardiac myocytes indicate that transcription from the CARP and brain natriuretic peptide promoters is stimulated by overexpression of p38 and Rac1, components of the stress-activated mitogen-activated protein kinase pathways. Mutation analysis and electrophoretic mobility shift assays indicated that the M-CAT element can serve as a binding site for nuclear factors, and this element is important for the induction of CARP promoter activity by p38 and Rac1. Thus, our data suggest that M-CAT element is responsible for the regulation of the CARP gene in response to the activation of stress-responsive mitogen-activated protein kinase pathways. Moreover, given that activation of these pathways is associated with cardiac hypertrophy, we propose that CARP represents a novel genetic marker of cardiac hypertrophy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0194-911X
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-53
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10904011-Animals, pubmed-meshheading:10904011-Ankyrin Repeat, pubmed-meshheading:10904011-Cardiomegaly, pubmed-meshheading:10904011-Gene Expression Regulation, pubmed-meshheading:10904011-Male, pubmed-meshheading:10904011-Mitogen-Activated Protein Kinases, pubmed-meshheading:10904011-Muscle Proteins, pubmed-meshheading:10904011-Natriuretic Peptide, Brain, pubmed-meshheading:10904011-Nuclear Proteins, pubmed-meshheading:10904011-Promoter Regions, Genetic, pubmed-meshheading:10904011-RNA, Messenger, pubmed-meshheading:10904011-Rats, pubmed-meshheading:10904011-Rats, Inbred SHR, pubmed-meshheading:10904011-Rats, Inbred WKY, pubmed-meshheading:10904011-Repressor Proteins, pubmed-meshheading:10904011-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:10904011-rac1 GTP-Binding Protein
pubmed:year
2000
pubmed:articleTitle
Cardiac ankyrin repeat protein is a novel marker of cardiac hypertrophy: role of M-CAT element within the promoter.
pubmed:affiliation
Second Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't