GSNOR Deficiency Enhances In Situ Skeletal Muscle Strength, Fatigue Resistance, and RyR1 S-Nitrosylation Without Impacting Mitochondrial Content and Activity
Nitric oxide (NO) plays important, but incompletely defined roles in skeletal muscle. NO exerts its regulatory effects partly though S-nitrosylation, which is balanced by denitrosylation by enzymes such as S-nitrosoglutathione reductase (GSNOR), whose functions in skeletal muscle remain to be fully deciphered.
GSNOR null (GSNOR-⁄-) tibialis anterior (TA) muscles showed normal growth and were stronger and more fatigue resistant than controls in situ. However, GSNOR-⁄- lumbrical muscles showed normal contractility and Ca2+ handling in vitro suggesting important differences in GSNOR function between muscles or between in vitro and in situ environments. GSNOR-⁄- TA muscles exhibited normal mitochondrial content, and capillary densities, but reduced type IIA fiber content. GSNOR inhibition did not impact mitochondrial respiratory complex I, III or IV ac-tivity. These findings argue that enhanced GSNOR-⁄- TA contractility is not driven by changes in mitochondrial content or activity, fiber type or blood vessel density. However, loss of GSNOR led to RyR1 hypernitrosylation which is thought to increase muscle force output under physiolog-ical conditions. cGMP synthesis by soluble guanylate cyclase (sGC) was decreased in resting GSNOR-⁄- muscle and was more responsive to agonist (DETANO, BAY 41 and BAY 58) stimulation suggesting that GSNOR modulates cGMP production in skeletal muscle.
GSNOR may act as a "brake" on skeletal muscle contractile performance under physiological conditions by modulating nitrosylation/denitrosylation balance.
GSNOR may play important roles in skeletal muscle contractility, RyR1 S-nitrosylation, fiber type specification and sGC activity.
Pharmacology, Toxicology and Pharmaceutical Science
2
7%
Biochemistry, Genetics and Molecular Biology
2
7%
Other
5
18%
Unknown
8
29%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 August 2017.
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