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The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms

Publication ,  Journal Article
Brocca, L; Cannavino, J; Coletto, L; Biolo, G; Sandri, M; Bottinelli, R; Pellegrino, MA
Published in: Journal of Physiology
October 1, 2012

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 p70 S6K), 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. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.

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Published In

Journal of Physiology

DOI

EISSN

1469-7793

ISSN

0022-3751

Publication Date

October 1, 2012

Volume

590

Issue

20

Start / End Page

5211 / 5230

Related Subject Headings

  • Physiology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 06 Biological Sciences
 

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Brocca, L., Cannavino, J., Coletto, L., Biolo, G., Sandri, M., Bottinelli, R., & Pellegrino, M. A. (2012). The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. Journal of Physiology, 590(20), 5211–5230. https://doi.org/10.1113/jphysiol.2012.240267
Brocca, L., J. Cannavino, L. Coletto, G. Biolo, M. Sandri, R. Bottinelli, and M. A. Pellegrino. “The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms.” Journal of Physiology 590, no. 20 (October 1, 2012): 5211–30. https://doi.org/10.1113/jphysiol.2012.240267.
Brocca L, Cannavino J, Coletto L, Biolo G, Sandri M, Bottinelli R, et al. The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. Journal of Physiology. 2012 Oct 1;590(20):5211–30.
Brocca, L., et al. “The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms.” Journal of Physiology, vol. 590, no. 20, Oct. 2012, pp. 5211–30. Scopus, doi:10.1113/jphysiol.2012.240267.
Brocca L, Cannavino J, Coletto L, Biolo G, Sandri M, Bottinelli R, Pellegrino MA. The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms. Journal of Physiology. 2012 Oct 1;590(20):5211–5230.
Journal cover image

Published In

Journal of Physiology

DOI

EISSN

1469-7793

ISSN

0022-3751

Publication Date

October 1, 2012

Volume

590

Issue

20

Start / End Page

5211 / 5230

Related Subject Headings

  • Physiology
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
  • 06 Biological Sciences