Abstract
Neuronal nitric oxide synthase (nNOS) plays a crucial role in the maintenance of correct skeletal muscle function due, at least in part, to S-nitrosylation of specific protein targets. Similarly, we recently provided evidence for a muscular phenotype in mice lacking the denitrosylase S-nitrosoglutathione reductase (GSNOR). Here, we demonstrate that nNOS and GSNOR are concomitantly expressed during differentiation of C2C12. They colocalizes at the sarcolemma and co-immunoprecipitate in cells and in myofibers. We also provide evidence that GSNOR expression decreases in mouse models of muscular dystrophies and of muscle atrophy and wasting, i.e., aging and amyotrophic lateral sclerosis, suggesting a more general regulatory role of GSNOR in skeletal muscle homeostasis.
Highlights
The role of nitric oxide (NO) in skeletal muscle homeostasis has been deeply investigated, and findings of the last decades support the hypothesis that it is involved in both muscle contraction and atrophy[1,2,3,4]
We observed that two mouse models of genetic dystrophies, namely the mdx[13] and α-sarcoglycan-deficient (α-SG−/−) mice[14], showed excessive levels of S-nitrosylated proteins (PSNOs) similar to those detected in GSNOR-null (Gsnor−/−) mice, suggesting that aberrant S-nitrosylation is a hallmark of muscle wasting
We previously reported that skeletal muscles from mdx and αSG−/− dystrophic mice show PSNOs increase that correlates with a decrease in GSNOR expression[12]
Summary
The role of nitric oxide (NO) in skeletal muscle homeostasis has been deeply investigated, and findings of the last decades support the hypothesis that it is involved in both muscle contraction and atrophy[1,2,3,4]. In rat models of denervation- and disuse-induced atrophy[5], and in dystrophin-null (mdx) mouse models of genetic dystrophy[2,6,7], it has been observed that the skeletal muscle specific form of neuronal NO synthase (nNOS) dislocates from the dystrophin glycoprotein complex (DGC) located at the sarcolemma[8]. This leads first to the loss of NO beneficial effects, mostly exerted via cGMP signaling (e.g., vasodilation and satellite cell proliferation)[1,9], and second to nitration and hyper-S-nitrosylation of several proteins, including those involved in Ca2+ release These results strongly suggest that GSNOR and nNOS act in concert to dynamically regulate NO flux and convey it on specific targets
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
