Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes.

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Serval ID
serval:BIB_EBA9B8610022
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes.
Journal
Cardiovascular Research
Author(s)
Planavila A., Rodríguez-Calvo R., Jové M., Michalik L., Wahli W., Laguna J.C., Vázquez-Carrera M.
ISSN
0008-6363[print], 0008-6363[linking]
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
65
Number
4
Pages
832-841
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
OBJECTIVE: Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is the predominant PPAR subtype in cardiac cells and plays a prominent role in the regulation of cardiac lipid metabolism. However, the role of PPARbeta/delta activators in cardiac hypertrophy is not yet known. METHODS AND RESULTS: In cultured neonatal rat cardiomyocytes, the selective PPARbeta/delta activator L-165041 (10 micromol/L) inhibited phenylephrine (PE)-induced protein synthesis ([(3)H]leucine uptake), induction of the fetal-type gene atrial natriuretic factor (ANF) and cardiac myocyte size. Induction of cardiac hypertrophy by PE stimulation also led to a reduction in the transcript levels of both muscle-type carnitine palmitoyltransferase (50%, P<0.05) and pyruvatedehydrogenase kinase 4 (30%, P<0.05), and these changes were reversed in the presence of the PPARbeta/delta agonist L-165041. Stimulation of neonatal rat cardiomyocytes with PE and embryonic rat heart-derived H9c2 cells with lipopolysaccharide (LPS) enhanced the expression of the nuclear factor (NF)-kappaB-target gene monocyte chemoattractant protein 1 (MCP-1). The induction of MCP-1 was reduced in the presence of L-165041, suggesting that this compound prevented NF-kappaB activation. Electrophoretic mobility shift assay (EMSA) revealed that L-165041 significantly decreased LPS-stimulated NF-kappaB binding activity in H9c2 myotubes. Finally, coimmunoprecipitation studies showed that L-165041 strongly enhanced the physical interaction between PPARbeta/delta and the p65 subunit of NF-kappaB, suggesting that increased association between these two proteins is the mechanism responsible for antagonizing NF-kappaB activation by PPARbeta/delta activators. CONCLUSION: These results suggest that PPARbeta/delta activation inhibits PE-induced cardiac hypertrophy and LPS-induced NF-kappaB activation.
Keywords
Acetic Acids/pharmacology, Animals, Animals, Newborn, Cardiomegaly/metabolism, Cardiomegaly/pathology, Cells, Cultured, Chemokine CCL2/metabolism, Gene Expression Regulation/drug effects, Ligands, Lipid Metabolism, Lipopolysaccharides/pharmacology, Myocytes, Cardiac/drug effects, Myocytes, Cardiac/pathology, NF-kappa B/metabolism, PPAR delta/agonists, PPAR delta/physiology, PPAR-beta/agonists, PPAR-beta/physiology, Phenols/pharmacology, Phenoxyacetates, Phenylephrine/pharmacology, Rats, Rats, Sprague-Dawley
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:44
Last modification date
25/09/2019 6:11
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