Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest

Denny Z H Levett, Agnese Viganò, Daniele Capitanio, Michele Vasso, Sara De Palma, Manuela Moriggi, Daniel S. Martin, Andrew J. Murray, Paolo Cerretelli, Mike P W Grocott, Cecilia Gelfi

Research output: Contribution to journalArticle

Abstract

This study employed differential proteomic and immunoassay techniques to elucidate the biochemical mechanisms utilized by human muscle (vastus lateralis) in response to high altitude hypoxia exposure. Two groups of subjects, participating in a medical research expedition (A, n = 5, 19d at 5300 m altitude; B, n = 6, 66d up to 8848 m) underwent a ≈ 30% drop of muscular creatine kinase and of glycolytic enzymes abundance. Protein abundance of most enzymes of the tricarboxylic acid cycle and oxidative phosphorylation was reduced both in A and, particularly, in B. Restriction of α-ketoglutarate toward succinyl-CoA resulted in increased prolyl hydroxylase 2 and glutamine synthetase. Both A and B were characterized by a reduction of elongation factor 2alpha, controlling protein translation, and by an increase of heat shock cognate 71 kDa protein involved in chaperone-mediated autophagy. Increased protein levels of catalase and biliverdin reductase occurred in A alongside a decrement of voltage-dependent anion channels 1 and 2 and of myosin-binding protein C, suggesting damage to the sarcomeric structures. This study suggests that during acclimatization to hypobaric hypoxia the muscle behaves as a producer of substrates activating a metabolic reprogramming able to support anaplerotically the tricarboxylic acid cycle, to control protein translation, to prevent energy expenditure and to activate chaperone-mediated autophagy.

Original languageEnglish
Pages (from-to)160-171
Number of pages12
JournalProteomics
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Keywords

  • Altitude hypoxia
  • Biomedicine
  • α-Ketoglutarate

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Medicine(all)

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  • Cite this

    Levett, D. Z. H., Viganò, A., Capitanio, D., Vasso, M., De Palma, S., Moriggi, M., Martin, D. S., Murray, A. J., Cerretelli, P., Grocott, M. P. W., & Gelfi, C. (2015). Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest. Proteomics, 15(1), 160-171. https://doi.org/10.1002/pmic.201400306