Linked Life Data

10750584

Source:http://linkedlifedata.com/resource/pubmed/id/10750584

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12A
pubmed:dateCreated
2000-4-19
pubmed:abstractText
The transition of nonfailing to failing cardiac hypertrophy cannot be prevented by current drug regimens. This investigation examined whether possible drug targets have remained unexplored because they do not result in acute improvement of heart function. Of major importance, in this respect, is an inadequate performance of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2). In the present approach, binding sequences within the proximal promoter of SERCA2 are described which may be useful in the development of drugs (i.e., transcriptional modulators) that interfere selectively with the transcription of genes of the cardiomyocyte. The proximal promoter region of the SERCA2 genes has a thyroid response element, 9 potential Sp1-binding sites (5'-GGGCGG-3', 5'-CCGCCC-3' and 5'-GGGAGG-3'), and an E-box motif (5'-CACATG-3'), which may function as glucose response elements. This region also has 2 putative fatty-acid response elements (5'-GGGGGA-3'). It is proposed that the beneficial effects of the camitine palmitoyltransferase-1 inhibitor etomoxir arise from a shift in fuel metabolism involving glucose response elements and/or peroxisomal proliferator-activated receptors. Although the relative contribution of these DNA regulatory elements remains to be defined, it appears that they provide the driving force that prevents the decrease in transcriptional activity of the SERCA2 gene in the hypertrophic heart. It is further concluded that etomoxir represents a member of a novel class of transcriptional modulators that improve function of hypertrophied hearts with unimpeded blood flow by modulating gene expression of the cardiomyocyte.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0002-9149
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31H-37H
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Transcriptional modulators targeted at fuel metabolism of hypertrophied heart.
pubmed:affiliation
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't