Journal article
Endothelial nitric oxide synthase is involved in calcium-induced Akt signaling in mouse skeletal muscle
Nitric oxide, Vol.21(3), pp.192-200
2009
DOI: 10.1016/j.niox.2009.08.001
PMID: 19682597
Abstract
We hypothesized that targeted mutation of the endothelial nitric oxide synthase (eNOS) gene would reduce Akt-related signaling events in skeletal muscle cells, compared to wild type (WT) controls. Results show that slow myosin heavy chain (type I/β) expression and the abundance of slow-twitch fibers are reduced in plantaris muscle of eNOS
−/− mice, compared to WT. Further, basal phosphorylation of Akt (p-Akt (Ser-473)/total Akt) and GSK-3β (GSK-3β (Ser-9)/total GSK-3β) are reduced 60–70% in primary myotubes from eNOS
−/− mice. Treatment with the calcium ionophore, A23187 (0.4
μM, 1
h), increased phosphorylation of Akt and GSK-3β by ∼2-fold (
P
<
0.05) in myotubes from WT mice, but had no effect on phosphorylation of these proteins in eNOS
−/− myotubes. Additionally, A23187 treatment failed to induce nuclear translocation of the transcription factor, NFATc1, in eNOS
−/− myotubes. Treatment with the nitric oxide donor, propylamine propylamine NONOate (PAPA-NO; 1
μM for 1
h) increased Akt and GSK-3β phosphorylation, and induced NFATc1 nuclear translocation in WT and eNOS
−/− myotubes, and eliminated differences from WT in the NOS knockout cultures. Parallel experiments in C2C12 myotubes found that Akt phosphorylation induced by NO or the guanylate cyclase activator, YC-1, is prevented by co-treatment with either a guanylate cyclase or PI3K inhibitor (10
μM ODQ or 25
μM LY2904002, respectively). These data suggest that eNOS activity is necessary for calcium-induced activation of the Akt pathway, and that nitric oxide is sufficient to elevate Akt activity in primary myotubes. NO appears to influence Akt signaling through a cGMP, PI3K-dependent pathway.
Details
- Title: Subtitle
- Endothelial nitric oxide synthase is involved in calcium-induced Akt signaling in mouse skeletal muscle
- Creators
- Jason A DrenningVitor A LiraQuinlyn A SoltowClaire N CanonLauren M ValeraDana L BrownDavid S Criswell
- Resource Type
- Journal article
- Publication Details
- Nitric oxide, Vol.21(3), pp.192-200
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.niox.2009.08.001
- PMID
- 19682597
- ISSN
- 1089-8603
- eISSN
- 1089-8611
- Language
- English
- Date published
- 2009
- Academic Unit
- Health and Human Physiology
- Record Identifier
- 9984002484602771
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