title: Nitrosative stress in human skeletal muscle attenuated by exercise countermeasure after chronic disuse.
abstract: Activity-induced nitric oxide (NO) imbalance and "nitrosative stress" are proposed mechanisms of disrupted Ca(2+) homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO) functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study) without and with exercise as countermeasure in order to assess (i) the negative effects of chronic muscle disuse by nitrosative stress, (ii) to test for possible attenuation by exercise countermeasure in bed rest and (iii) to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre) and at end (End) from a bed rest disuse control group (CTR, n=9) and two bed rest resistive exercise groups either without (RE, n=7) or with superimposed vibration stimuli (RVE, n=7). At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, -SERCA1 and -PMCA) and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.
authors.affiliation: Charité - Universitätsmedizin Berlin, Center for Space Medicine Berlin (ZWMB) Germany ; Charité - Universitätsmedizin Berlin, Department of Anatomy, Neuromuscular Group, Berlin, Germany.
authors.forename: Michele
authors.initials: M
authors.lastname: Salanova
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schiffl
authors.forename: Martina
authors.initials: M
authors.lastname: Gutsmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Felsenberg
authors.forename: Sandra
authors.initials: S
authors.lastname: Furlan
authors.forename: Pompeo
authors.initials: P
authors.lastname: Volpe
authors.forename: Andrew
authors.initials: A
authors.lastname: Clarke
authors.forename: Dieter
authors.initials: D
authors.lastname: Blottner
mesh_terms: D000328:Adult; D001510:Bed Rest; D002118:Calcium / Q000378:metabolism*; D005081:Exercise Therapy; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism / Q000534:rehabilitation*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D052097:Quadriceps Muscle / Q000166:cytology; D055815:Young Adult
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009569:Nitric Oxide; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D002118:Calcium
keywords: Calcium ATPase; Calcium homeostasis; Calcium-release channels; Nitric oxide synthase; Nitrosative stress; Nrf-2; Skeletal muscle