title: Changes in muscle proteomics in the course of the Caudwell Research Expedition to Mt. Everest.
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, 19 d at 5300 m altitude; B, n = 6, 66 d 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 2 alpha, 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.
authors.affiliation: Centre for Altitude, Space, and Extreme Environment Medicine, University College London (UCL), Institute of Child Health, University College London, London, UK; Anaesthesia and Critical Care Research Unit, University Hospital Southampton, NHS Foundation Trust, Southampton, UK.
authors.forename: Denny Z H
authors.initials: DZ
authors.lastname: Levett
authors.forename: Agnese
authors.initials: A
authors.lastname: Viganò
authors.forename: Daniele
authors.initials: D
authors.lastname: Capitanio
authors.forename: Michele
authors.initials: M
authors.lastname: Vasso
authors.forename: Sara
authors.initials: S
authors.lastname: De Palma
authors.forename: Manuela
authors.initials: M
authors.lastname: Moriggi
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Martin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murray
authors.forename: Paolo
authors.initials: P
authors.lastname: Cerretelli
authors.forename: Mike P W
authors.initials: MP
authors.lastname: Grocott
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gelfi
mesh_terms: D000064:Acclimatization; D000328:Adult; D000531:Altitude; D005260:Female; D006801:Humans; D007656:Ketoglutaric Acids / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000032:analysis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D040901:Proteomics; D013312:Stress, Physiological
chemical_list: D007656:Ketoglutaric Acids; D009124:Muscle Proteins
keywords: Altitude hypoxia; Biomedicine; α-Ketoglutarate