Format

Send to

Choose Destination
Biochem Biophys Res Commun. 2015 Apr 10;459(3):393-7. doi: 10.1016/j.bbrc.2015.02.113. Epub 2015 Feb 27.

Oxidative stress induces phosphorylation of neuronal NOS in cardiomyocytes through AMP-activated protein kinase (AMPK).

Author information

1
Department of Biochemistry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. Electronic address: KarR@uthscsa.edu.
2
Department of Biochemistry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. Electronic address: KelloggDL@livemail.uthscsa.edu.
3
Department of Biochemistry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. Electronic address: roman@uthscsa.edu.

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.

KEYWORDS:

AMP-Activated protein kinase; Cardiomyocyte; Neuronal nitric oxide synthase; Oxidative stress; Phosphorylation

PMID:
25732085
PMCID:
PMC4380631
DOI:
10.1016/j.bbrc.2015.02.113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center