Linked Life Data

11866664

Source:http://linkedlifedata.com/resource/pubmed/id/11866664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-2-27
pubmed:abstractText
Inhibitors of carnitine palmitoyl-transferase I (CPT I), the key enzyme for the transport of long-chain acyl-coenzyme A (acyl-CoA) compounds into mitochondria, have been developed as agents for treating diabetes mellitus Type 2. Findings that the CPT I inhibitor, etomoxir, has effects on overloaded heart muscle, which are associated with an improved function, were unexpected and can be attributed to selective changes in the dysregulated gene expression of hypertrophied cardiomyocytes. Also, the first clinical trial with etomoxir in patients with heart failure showed that etomoxir improved the clinical status and several parameters of heart function. In view of the action of etomoxir on gene expression, putative molecular mechanisms involved in an increased expression of SERCA2, the Ca(2+) pump of sarcoplasmic reticulum (SR) and alpha-myosin heavy chain (MHC) of failing overloaded heart muscle are described. The first 225 bp of human, rabbit, rat and mouse SERCA2 promoter sequence have high identity. Various cis-regularory elements are also given for the promoter of the rat cardiac alpha-MHC gene. It is hypothesised that etomoxir increases glucose-phosphate intermediates resulting in activation of signalling pathway(s) mediated by phosphatases. Regarding the possible direct action of etomoxir on peroxisome proliferator activated receptor alpha (PPAR-alpha) activation, it could upregulate the expression of various enzymes that participate in beta-oxidation, thereby modulating some effects of CPT 1 inhibition. Any development of alternative drugs requires a better understanding of the signal pathways involved in the altered gene expression. In particular, signals need to be identified which are altered in overloaded hearts and can selectively be re-activated by etomoxir.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1354-3784
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-56
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:11866664-Animals, pubmed-meshheading:11866664-Calcium-Transporting ATPases, pubmed-meshheading:11866664-Carnitine O-Palmitoyltransferase, pubmed-meshheading:11866664-Enzyme Inhibitors, pubmed-meshheading:11866664-Epoxy Compounds, pubmed-meshheading:11866664-Gene Expression Regulation, Enzymologic, pubmed-meshheading:11866664-Heart Failure, pubmed-meshheading:11866664-Humans, pubmed-meshheading:11866664-Mice, pubmed-meshheading:11866664-Molecular Sequence Data, pubmed-meshheading:11866664-Myocytes, Cardiac, pubmed-meshheading:11866664-Myosin Heavy Chains, pubmed-meshheading:11866664-Rabbits, pubmed-meshheading:11866664-Rats, pubmed-meshheading:11866664-Sarcoplasmic Reticulum, pubmed-meshheading:11866664-Sarcoplasmic Reticulum Calcium-Transporting ATPases, pubmed-meshheading:11866664-Sequence Homology, Amino Acid, pubmed-meshheading:11866664-Transcriptional Activation
pubmed:year
2002
pubmed:articleTitle
Therapeutic potential of CPT I inhibitors: cardiac gene transcription as a target.
pubmed:affiliation
Laboratorio de Biología Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado Postal 70-159, México D.F. 04510. angelz@laguna.fmedic.unam.mx
pubmed:publicationType
Journal Article, Review