title: Early changes in costameric and mitochondrial protein expression with unloading are muscle specific.
abstract: We hypothesised that load-sensitive expression of costameric proteins, which hold the sarcomere in place and position the mitochondria, contributes to the early adaptations of antigravity muscle to unloading and would depend on muscle fibre composition and chymotrypsin activity of the proteasome. Biopsies were obtained from vastus lateralis (VL) and soleus (SOL) muscles of eight men before and after 3 days of unilateral lower limb suspension (ULLS) and subjected to fibre typing and measures for costameric (FAK and FRNK), mitochondrial (NDUFA9, SDHA, UQCRC1, UCP3, and ATP5A1), and MHCI protein and RNA content. Mean cross-sectional area (MCSA) of types I and II muscle fibres in VL and type I fibres in SOL demonstrated a trend for a reduction after ULLS (0.05 ≤ P < 0.10). FAK phosphorylation at tyrosine 397 showed a 20% reduction in VL muscle (P = 0.029). SOL muscle demonstrated a specific reduction in UCP3 content (-23%; P = 0.012). Muscle-specific effects of ULLS were identified for linear relationships between measured proteins, chymotrypsin activity and fibre MCSA. The molecular modifications in costamere turnover and energy homoeostasis identify that aspects of atrophy and fibre transformation are detectable at the protein level in weight-bearing muscles within 3 days of unloading.
authors.affiliation: Balgrist University Hospital, University of Zurich, Switzerland ; Laboratory for Muscle Plasticity, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland.
authors.forename: Martin
authors.identifier: 0000-0002-0479-7243
authors.initials: M
authors.lastname: Flück
authors.affiliation: Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Manchester, UK.
authors.forename: Ruowei
authors.initials: R
authors.lastname: Li
authors.affiliation: Balgrist University Hospital, University of Zurich, Switzerland.
authors.forename: Paola
authors.identifier: 0000-0001-9322-4510
authors.initials: P
authors.lastname: Valdivieso
authors.affiliation: National Aeronautics and Space Administration, Johnson Space Center, Houston, TX, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Linnehan
authors.affiliation: Laboratoire de Physiologie de l'Exercice, EA4338, Faculté de Médecine, Université Jean-Monnet, Saint Etienne Cedex, France.
authors.forename: Josiane
authors.initials: J
authors.lastname: Castells
authors.affiliation: Department of Health Sciences, Mid Sweden University, Östersund, Sweden ; Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Tesch
authors.affiliation: Department of Laboratory Medicine, Karolinska University Hospital, Clinical Physiology Karolinska Institute, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustafsson
mesh_terms: D000328:Adult; D002918:Chymotrypsin / Q000378:metabolism; D054974:Costameres / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009928:Organ Specificity; D010084:Oxidation-Reduction; D010641:Phenotype; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016474:Weight-Bearing
chemical_list: D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D019000:Phosphotyrosine; D051416:Focal Adhesion Protein-Tyrosine Kinases; D002918:Chymotrypsin; D046988:Proteasome Endopeptidase Complex