Activation of PPARß/δ protects cardiac myocytes from oxidative stress-induced apoptosis by suppressing generation of reactive oxygen/nitrogen species and expression of matrix metalloproteinases.
Pharmacol Res
; 95-96: 102-10, 2015.
Article
em En
| MEDLINE
| ID: mdl-25828396
ABSTRACT
Heart failure still remains one of the leading causes of morbidity and mortality worldwide. A major contributing factor is reactive oxygen/nitrogen species (RONS) overproduction which is associated with cardiac remodeling partly through cardiomyocyte apoptosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear receptor superfamily and have been implicated in cardioprotection. However, the molecular mechanisms are largely unexplored. In this study we sought to investigate the potential beneficial effects evoked by activation of PPARß/δ under the setting of oxidative stress induced by H2O2 in adult rat cardiac myocytes. The selective PPARß/δ agonist GW0742 inhibited the H2O2-induced apoptosis and increased cell viability. In addition, generation of RONS was attenuated in cardiac myocytes in the presence of PPARß/δ agonist. These effects were abolished in the presence of the PPARß/δ antagonist indicating that the effect was through PPARß/δ receptor activation. Treatment with PPARß/δ agonist was also associated with attenuation of caspase-3 and PARP cleavage, upregulation of anti-apoptotic Bcl-2 and concomitant downregulation of pro-apoptotic Bax. In addition, activation of PPARß/δ inhibited the oxidative-stress-induced MMP-2 and MMP-9 mRNA upregulation. It is concluded that PPARß/δ activation exerts a cytoprotective effect in adult rat cardiac myocytes subjected to oxidative stress via inhibition of oxidative stress, MMP expression, and apoptosis. Our data suggest that the novel connection between PPAR signaling and MMP down-regulation in cardiac myocytes might represent a new target for the management of oxidative stress-induced cardiac dysfunction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Espécies Reativas de Oxigênio
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Apoptose
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Estresse Oxidativo
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Metaloproteinases da Matriz
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Espécies Reativas de Nitrogênio
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Miócitos Cardíacos
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PPAR beta
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PPAR delta
Limite:
Animals
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Grécia