Oxidative stress induces phosphorylation of neuronal NOS in cardiomyocytes through AMP-activated protein kinase (AMPK).
Biochem Biophys Res Commun
; 459(3): 393-7, 2015 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-25732085
ABSTRACT
Neuronal nitric oxide synthase (nNOS) plays a critical role in regulating cardiomyocyte function. nNOS was reported to decrease superoxide production in the myocardium by inhibiting the function of xanthine oxidoreductase. However, the effect of oxidative stress on nNOS in cardiomyocytes has not been determined. We report here that brief exposure of HL-1 cardiomyocytes to hydrogen peroxide (H2O2) induces phosphorylation of nNOS at serine 1412. This increase in phosphorylation was concomitant with increased nitric oxide (NO) production. Prolonged exposure to the oxidant, however, resulted in decreased expression of the protein. H2O2 treatment for short periods also stimulated phosphorylation of AKT and AMPK. H2O2-induced phosphorylation of nNOS was reduced when AMPK activity was inhibited by compound C, suggesting that AMPK is a mediator of oxidative stress-induced phosphorylation of nNOS. However, inhibition of AKT activity by the pan AKT inhibitor, AKTi, had no effect on nNOS phosphorylation caused by H2O2. These data demonstrate the novel regulation of nNOS phosphorylation and expression by oxidative stress.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Miócitos Cardíacos
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Óxido Nítrico Sintase Tipo I
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Proteínas Quinases Ativadas por AMP
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2015
Tipo de documento:
Article