Linked Life Data

18612190

Source:http://linkedlifedata.com/resource/pubmed/id/18612190

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-7-9
pubmed:abstractText
Prostaglandin F(2alpha) (PGF(2alpha)) stimulates hypertrophic growth of neonatal rat cardiac myocytes, a feature of which includes downregulation of the Ca(2+)-ATPase (SERCA2), a major Ca(2+) transport protein in SR. The molecular mechanisms by which PGF(2alpha) inhibits SERCA2 gene expression remain unknown. We determined the cis-regulatory elements responsible for the regulation of the SERCA2 gene expression in cultured neonatal rat cardiac myocytes exposed to PGF(2alpha). The role of Egr-1 was evaluated by transient transfection of its expression vector and antisense oligonucleotide. Signaling pathways were determined by using the pharmacological inhibitors or cDNA expression plasmids coding for dominant negative forms of Ras and Rac. PGF(2alpha) reduced the SERCA2 mRNA levels in a time- and dose-dependent manner in cultured rat cardiac myocytes. Transient transfection analyses showed that PGF(2alpha) -responsive elements are located between -284 and -72 of the SERCA2 promoter, which contains G+C-rich sequences homologous to Sp1, Egr-1 and AP2-binding sites. PGF(2alpha) significantly increased Egr-1 expression, and overexpression of Egr-1 largely reduced the transcription of the SERCA2 gene. Egr-1 antisense oligonucleotides blocked the PGF(2alpha) -mediated decrease in SERCA2 mRNA expression. Furthermore, inhibitors for either genistein-sensitive tyrosine kinase or p38 MAPK, and dominant negative forms of either Ras or Rac, prevented PGF(2alpha) -induced repression of SERCA2 mRNA levels. These results suggest that Egr-1, as well as Ras, Rac, and p38 MAPK, plays a crucial role in the repression of SERCA2 gene expression during PGF(2alpha) -induced cardiac hypertrophy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1349-2365
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-42
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Prostaglandin F2alpha inhibits SERCA2 gene transcription through an induction of Egr-1 in cultured neonatal rat cardiac myocytes.
pubmed:affiliation
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't