title: Differential expression of nitric oxide synthases (NOS 1-3) in human skeletal muscle following exercise countermeasure during 12 weeks of bed rest.
abstract: Adaptive changes of major body systems in astronauts during spaceflight can be simulated by strict anti-orthostatic head-down tilt (HDT) bed rest (BR), a ground-based microgravity (microG) model that provides a meaningful opportunity to study atrophy mechanisms and possible countermeasures under controlled experimental conditions. As nitric oxide (NO) signaling is linked to muscle activity, we investigated altered expression of the three major isoforms of nitric oxide synthase (NOS 1-3) at cellular compartments during prolonged HDT BR without (control group) and with resistance exercise interventions (exercise group) using a flywheel ergometer (FWE). Atrophy detected in mixed (fast-slow) m. vastus lateralis (VL) and slow-type m. soleus (SOL) myofiber Types I and II (minus 35-40% of myofiber cross-sectional area) was prevented by FWE training. Concomitant to muscle atrophy, reduced NOS 1 protein and immunostaining was found in VL not in SOL biopsies. In trained VL, NOS 1 protein and immunostaining at myofibers II were significantly increased at the end of BR. Exercise altered NOS 2/caveolin 3 co-immunostaining patterns of subsarcolemmal focal accumulations in VL or SOL myofibers, which suggests reorganization of sarcolemmal microdomains. In trained VL, increased capillary-to-fiber (C/F) ratio and NOS 3 protein content were documented. Activity-linked NO signaling may be widespread in skeletal muscle cellular compartments that may be directly or indirectly impacted by adequate exercise countermeasure protocols to offset the negative effects induced by disuse, immobilization, or extended exposure to microgravity.
authors.affiliation: Department of Anatomy, Campus Benjamin Franklin, Charité University Medicine Berlin, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Rudnick
authors.forename: Britta
authors.initials: B
authors.lastname: Püttmann
authors.forename: Per A
authors.initials: PA
authors.lastname: Tesch
authors.forename: Björn
authors.initials: B
authors.lastname: Alkner
authors.forename: Benedikt G H
authors.initials: BG
authors.lastname: Schoser
authors.forename: Michele
authors.initials: M
authors.lastname: Salanova
authors.forename: Karl
authors.initials: K
authors.lastname: Kirsch
authors.forename: Hanns-christian
authors.initials: HC
authors.lastname: Gunga
authors.forename: Gudrun
authors.initials: G
authors.lastname: Schiffl
authors.forename: Gabriele
authors.initials: G
authors.lastname: Lück
authors.forename: Dieter
authors.initials: D
authors.lastname: Blottner
mesh_terms: D000328:Adult; D001510:Bed Rest / Q000009:adverse effects*; D001707:Biopsy, Needle; D002196:Capillaries / Q000201:enzymology; D022461:Caveolins / Q000378:metabolism; D002451:Cell Compartmentation; D004790:Enzyme Induction; D016552:Ergometry / Q000295:instrumentation / Q000379:methods; D005081:Exercise Therapy; D018475:Head-Down Tilt / Q000009:adverse effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008833:Microcirculation; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology / Q000648:ultrastructure; D018657:Muscle Fibers, Slow-Twitch / Q000201:enzymology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D009133:Muscular Atrophy / Q000201:enzymology* / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012508:Sarcolemma / Q000201:enzymology; D014664:Vasodilation / Q000502:physiology; D018474:Weightlessness Simulation
chemical_list: D022461:Caveolins; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III