Pyruvate prevents cardiac dysfunction and AMP-activated protein kinase activation by hydrogen peroxide in isolated rat hearts.
Can J Physiol Pharmacol
; 82(6): 409-16, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15381965
ABSTRACT
Ischemia-reperfusion injury in the heart results in enhanced production of H2O2 and activation of AMP-activated protein kinase (AMPK). Since mutations in AMPK result in cardiovascular dysfunction, we investigated whether the activation of AMPK mediates the H2O2-induced reduction in cardiac mechanical function. Isolated working rat hearts were perfused at 37 degrees C with Krebs-Henseleit solution. Following a 20-minute equilibration period, a single bolus of H2O2 (300 micromol/L) was added and the hearts were perfused for an additional 5 min. H2O2 induced a dramatic and progressive reduction in cardiac function. This was accompanied by rapid and significant activation of AMPK, an increase in Thr-172 phosphorylation of AMPK, and an increase in the creatine to phosphocreatine (Cr/PCr) ratio. Addition of pyruvate (5 mmol/L) to the perfusate prevented the H2O2-mediated reduction in cardiac mechanical dysfunction, activation of myocardial AMPK activity, increase in AMPK phosphorylation and the increase in the Cr/PCr ratio. Hearts challenged with H2O2 (300 micromol/L) in presence of either AMPK inhibitor Compound C (10 micromol/L) or its vehicle (dimethyl sulfoxide (DMSO), 0.1%) showed reduced impairment in cardiac mechanical function. Compound C but not its vehicle significantly inhibited myocardial AMPK activity. Thus, H2O2 induces cardiac dysfunction via both AMPK-dependent and independent mechanisms.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
/
Monofosfato de Adenosina
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Proteínas Serina-Treonina Quinases
/
Ácido Pirúvico
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Inibidores Enzimáticos
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Peróxido de Hidrogênio
/
Complexos Multienzimáticos
Limite:
Animals
Idioma:
En
Revista:
Can J Physiol Pharmacol
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Canadá