Health & Environmental Research Online (HERO)


Print Feedback Export to File
2833329 
Journal Article 
Oxidative stress induces phosphorylation of neuronal NOS in cardiomyocytes through AMP-activated protein kinase (AMPK) 
Kar, R; Kellogg, DL; Roman, LJ 
2015 
Yes 
Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 
459 
3 
393-397 
English 
25732085 
WOS:000353085300007 
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. 
Neuronal nitric oxide synthase; Oxidative stress; Cardiomyocyte; Phosphorylation; AMP-Activated protein kinase