title: The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms.
abstract: In order to get a comprehensive picture of the complex adaptations of human skeletal muscle to disuse and further the understanding of the underlying mechanisms, we participated in two bed rest campaigns, one lasting 35 days and one 24 days. In the first bed rest (BR) campaign, myofibrillar proteins, metabolic enzymes and antioxidant defence systems were found to be down-regulated both post-8 days and post-35 days BR by proteomic analysis of vastus lateralis muscle samples from nine subjects. Such profound alterations occurred early (post-8 days BR), before disuse atrophy developed, and persisted through BR (post-35 days BR). To understand the mechanisms underlying the protein adaptations observed, muscle biopsies from the second bed rest campaign (nine subjects) were used to evaluate the adaptations of master controllers of the balance between muscle protein breakdown and muscle protein synthesis (MuRF-1 and atrogin-1; Akt and p70S6K), of autophagy (Beclin-1, p62, LC3, bnip3, cathepsin-L), of expression of antioxidant defence systems (NRF2) and of energy metabolism (PGC-1α, SREBP-1, AMPK). The results indicate that: (i) redox imbalance and remodelling of muscle proteome occur early and persist through BR; (ii) impaired energy metabolism is an early and persistent phenomenon comprising both the oxidative and glycolytic one; (iii) although both major catabolic systems, ubiquitin proteasome and autophagy, could contribute to the progression of atrophy late into BR, a decreased protein synthesis cannot be ruled out; (iv) a decreased PGC-1α, with the concurrence of SREBP-1 up-regulation, is a likely trigger of metabolic impairment, whereas the AMPK pathway is unaltered.
authors: Department of Molecular Medicine, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors: Lorenza
authors: L
authors: Brocca
authors: Jessica
authors: J
authors: Cannavino
authors: Luisa
authors: L
authors: Coletto
authors: Gianni
authors: G
authors: Biolo
authors: Marco
authors: M
authors: Sandri
authors: Roberto
authors: R
authors: Bottinelli
authors: Maria Antonietta
authors: MA
authors: Pellegrino
mesh_terms: D000328:Adult; D001510:Bed Rest; D004734:Energy Metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000378:metabolism*; D020966:Muscular Disorders, Atrophic / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020543:Proteome; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D006360:Heat-Shock Proteins; D009124:Muscle Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020543:Proteome; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors