Abstract | AIM: RESULTS: GC1, but not GC2, expression was higher in oxidative than glycolytic muscles. GC1 was found in a complex with nNOSĪ¼ and targeted to nNOS compartments at the Golgi complex and neuromuscular junction. Baseline GC activity and GC agonist responsiveness was reduced in the absence of nNOS. Structural analyses revealed aberrant microtubule directionality in GC1-/- muscle. Functional analyses of GC1-/- muscles revealed reduced fatigue resistance and postexercise force recovery that were not due to shifts in type IIA-IIX fiber balance. Force deficits in GC1-/- muscles were also not driven by defects in resting mitochondrial adenosine triphosphate ( ATP) synthesis. However, increasing muscle cGMP with sildenafil decreased ATP synthesis efficiency and capacity, without impacting mitochondrial content or ultrastructure. INNOVATION: GC may represent a new target for alleviating muscle fatigue and that NO-cGMP signaling may play important roles in muscle structure, contractility, and bioenergetics. CONCLUSIONS: These findings suggest that GC activity is nNOS dependent and that muscle-specific control of GC expression and differential GC targeting may facilitate NO-cGMP signaling diversity. They suggest that nNOS regulates muscle fiber type, microtubule organization, fatigability, and postexercise force recovery partly through GC1 and suggest that NO-cGMP pathways may modulate mitochondrial ATP synthesis efficiency. Antioxid. Redox Signal. 26, 966-985.
|
Authors | Younghye Moon, Jordan E Balke, Derik Madorma, Michael P Siegel, Gary Knowels, Peter Brouckaert, Emmanuel S Buys, David J Marcinek, Justin M Percival |
Journal | Antioxidants & redox signaling
(Antioxid Redox Signal)
Vol. 26
Issue 17
Pg. 966-985
(06 10 2017)
ISSN: 1557-7716 [Electronic] United States |
PMID | 27393340
(Publication Type: Journal Article, Review, Research Support, N.I.H., Extramural)
|
Chemical References |
- Nitric Oxide
- Adenosine Triphosphate
- Nitric Oxide Synthase Type I
- Nos1 protein, mouse
- Guanylate Cyclase
- Cyclic GMP
|
Topics |
- Adenosine Triphosphate
(metabolism)
- Animals
- Cyclic GMP
(metabolism)
- Gene Expression Regulation
- Guanylate Cyclase
(metabolism)
- Humans
- Mice
- Microtubules
(metabolism)
- Mitochondria
(metabolism)
- Muscle Fatigue
- Muscle, Skeletal
(physiology)
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type I
(genetics)
|