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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.
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1 Danish Cancer Society Research Center, Cell Stress and Survival Unit, Copenhagen, Denmark (GRID:grid.417390.8) (ISNI:0000 0001 2175 6024); Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark (GRID:grid.411702.1) (ISNI:0000 0000 9350 8874)
2 Danish Cancer Society Research Center, Cell Stress and Survival Unit, Copenhagen, Denmark (GRID:grid.417390.8) (ISNI:0000 0001 2175 6024)
3 Tor Vergata University of Rome, Department of Biology, Rome, Italy (GRID:grid.6530.0) (ISNI:0000 0001 2300 0941); Fondazione Santa Lucia, IRCCS, Rome, Italy (GRID:grid.417778.a) (ISNI:0000 0001 0692 3437)
4 Sapienza University of Rome, Department of Translational and Precision Medicine (formerly Department of Clinical Medicine), Rome, Italy (GRID:grid.7841.a)
5 Sapienza University of Rome, DAHFMO-Unit of Histology and Medical Embryology, Rome, Italy (GRID:grid.7841.a)
6 University of Piemonte Orientale (UPO), Department of Orthopaedics and Traumatology, Hospital “Maggiore della Carità”, Novara, Italy (GRID:grid.16563.37) (ISNI:0000000121663741)
7 Danish Cancer Society Research Center, Cell Stress and Survival Unit, Copenhagen, Denmark (GRID:grid.417390.8) (ISNI:0000 0001 2175 6024); Tor Vergata University of Rome, Department of Biology, Rome, Italy (GRID:grid.6530.0) (ISNI:0000 0001 2300 0941); IRCCS Bambino Gesù Children’s Hospital, Department of Pediatric Hematology and Oncology, Rome, Italy (GRID:grid.414125.7) (ISNI:0000 0001 0727 6809)
8 Danish Cancer Society Research Center, Cell Stress and Survival Unit, Copenhagen, Denmark (GRID:grid.417390.8) (ISNI:0000 0001 2175 6024); Tor Vergata University of Rome, Department of Biology, Rome, Italy (GRID:grid.6530.0) (ISNI:0000 0001 2300 0941)