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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-6-25
pubmed:abstractText
Mitogen-activated protein kinase kinase 7 (MKK7) induces cardiac hypertrophy by activating the c-Juns NH2-terminal kinases (JNK). It has been reported that growth arrest and DNA-damage-inducible beta (GADD45Beta) binds to MKK7 directly and blocks its catalytic activity, mediates the inhibition of JNK signaling. However, the potential role of GADD45Beta on cardiac hypertrophy has not been investigated. In this study, we found co-infection of cardiomyocytes with adenoviral vectors expressing MKK7 and GADD45B could counteract the characteristic hypertropic responses, including an increase in cell size and elevated atrial natriuretic factor (ANP) expression which induced by overexpression of MKK7. Furthermore, siRNA-mediated knockdown of GADD45B could also cause cardiomyocytes hypertrophy. GeneChip data showed that GADD45B mRNA decreased significantly in patients with hypertrophy cardiomyopathy (HCM) compared with healthy subjects. Association study indicated that haplotype (rs2024144-rs3783501) of GADD45B affected the thickness of inter-ventricular septum in patients with HCM. Dual-luciferase assay showed that C-A haplotype displayed significantly increased transcription activity compared to T-G haplotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
8
pubmed:volume
372
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
623-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18515079-Alleles, pubmed-meshheading:18515079-Animals, pubmed-meshheading:18515079-Antigens, Differentiation, pubmed-meshheading:18515079-Atrial Natriuretic Factor, pubmed-meshheading:18515079-Cardiomegaly, pubmed-meshheading:18515079-Cells, Cultured, pubmed-meshheading:18515079-Enhancer Elements, Genetic, pubmed-meshheading:18515079-Genes, Reporter, pubmed-meshheading:18515079-Haplotypes, pubmed-meshheading:18515079-Humans, pubmed-meshheading:18515079-MAP Kinase Kinase 7, pubmed-meshheading:18515079-Myocytes, Cardiac, pubmed-meshheading:18515079-Polymorphism, Genetic, pubmed-meshheading:18515079-RNA, Messenger, pubmed-meshheading:18515079-RNA, Small Interfering, pubmed-meshheading:18515079-Rats, pubmed-meshheading:18515079-Transcription, Genetic, pubmed-meshheading:18515079-Ventricular Septum
pubmed:year
2008
pubmed:articleTitle
GADD45B inhibits MKK7-induced cardiac hypertrophy and the polymorphisms of GADD45B is associated with inter-ventricular septum hypertrophy.
pubmed:affiliation
Sino-German Laboratory for Molecular Medicine, FuWai Cardiovascular Hospital and Cardiovascular Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 Beilishi Road, 100037 Beijing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't