nNOS/GSNOR interaction contributes to skeletal muscle differentiation and homeostasis

Costanza Montagna; Salvatore Rizza; Claudia Cirotti; Emiliano Maiani; Maurizio Muscaritoli; Antonio Musarò; Maria Teresa Carrí; Elisabetta Ferraro; Francesco Cecconi; Giuseppe Filomeni

doi:10.1038/s41419-019-1584-3

nNOS/GSNOR interaction contributes to skeletal muscle differentiation and homeostasis

Cell Death Dis. 2019 May 1;10(5):354. doi: 10.1038/s41419-019-1584-3.

Authors

Costanza Montagna^{1

2}, Salvatore Rizza¹, Claudia Cirotti^{3

4}, Emiliano Maiani¹, Maurizio Muscaritoli⁵, Antonio Musarò⁶, Maria Teresa Carrí^{3

4}, Elisabetta Ferraro⁷, Francesco Cecconi^{1

3

8}, Giuseppe Filomeni^{9

10}

Affiliations

¹ Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark.
² Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, 2400, Copenhagen, Denmark.
³ Department of Biology, Tor Vergata University of Rome, 00133, Rome, Italy.
⁴ Fondazione Santa Lucia, IRCCS, 00143, Rome, Italy.
⁵ Department of Translational and Precision Medicine (formerly Department of Clinical Medicine), Sapienza University of Rome, 00185, Rome, Italy.
⁶ DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, 00161, Rome, Italy.
⁷ Department of Orthopaedics and Traumatology, Hospital "Maggiore della Carità", University of Piemonte Orientale (UPO), Novara, Italy.
⁸ Department of Pediatric Hematology and Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
⁹ Cell Stress and Survival Unit, Danish Cancer Society Research Center, 2100, Copenhagen, Denmark. giufil@cancer.dk.
¹⁰ Department of Biology, Tor Vergata University of Rome, 00133, Rome, Italy. giufil@cancer.dk.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics*
Aging / metabolism
Alcohol Dehydrogenase / antagonists & inhibitors
Alcohol Dehydrogenase / deficiency
Alcohol Dehydrogenase / genetics*
Animals
Cell Differentiation
Cell Line, Transformed
Disease Models, Animal
Dystrophin-Associated Proteins / genetics
Dystrophin-Associated Proteins / metabolism
Gene Expression Regulation
Homeostasis / genetics*
Humans
Mice
Mice, Inbred mdx
Mice, Knockout
Muscle Development / genetics*
Muscle, Skeletal / enzymology
Muscle, Skeletal / pathology
Muscular Dystrophies / genetics*
Muscular Dystrophies / metabolism
Muscular Dystrophies / pathology
Myoblasts / cytology
Myoblasts / enzymology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type I / genetics*
Nitric Oxide Synthase Type I / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Sarcolemma / enzymology
Signal Transduction
Superoxide Dismutase-1 / genetics
Superoxide Dismutase-1 / metabolism

Substances

Dystrophin-Associated Proteins
RNA, Small Interfering
syntrophin
Nitric Oxide
Adh5 protein, mouse
Alcohol Dehydrogenase
Nitric Oxide Synthase Type I
Nos1 protein, mouse
Sod1 protein, mouse
Superoxide Dismutase-1