title: Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb-unloaded mice.
abstract: Two-dimensional proteomic maps of soleus (Sol), a slow oxidative muscle, and gastrocnemius (Gas), a fast glycolytic muscle of control mice (CTRL), of mice hindlimb unloaded for 14 days (HU mice) and of HU mice treated with trolox (HU-TRO), a selective and potent antioxidant, were compared. The proteomic analysis identified a large number of differentially expressed proteins in a pool of approximately 800 proteins in both muscles. The protein pattern of Sol and Gas adapted very differently to hindlimb unloading. The most interesting adaptations related to the cellular defense systems against oxidative stress and energy metabolism. In HU Sol, the antioxidant defense systems and heat shock proteins were downregulated, and protein oxidation index and lipid peroxidation were higher compared with CTRL Sol. In contrast, in HU Gas the antioxidant defense systems were upregulated, and protein oxidation index and lipid peroxidation were normal. Notably, both Sol and Gas muscles and their muscle fibres were atrophic. Antioxidant administration prevented the impairment of the antioxidant defense systems in Sol and further enhanced them in Gas. Accordingly, it restored normal levels of protein oxidation and lipid peroxidation in Sol. However, muscle and muscle fibre atrophy was not prevented either in Sol or in Gas. A general downsizing of all energy production systems in Sol and a shift towards glycolytic metabolism in Gas were observed. Trolox administration did not prevent metabolic adaptations in either Sol or Gas. The present findings suggest that oxidative stress is not a major determinant of muscle atrophy in HU mice.
authors.affiliation: Department of Physiology, Human Physiology Unit, University of Pavia, Via Forlanini 6, 27100 Pavia, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Brocca
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Pellegrino
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Desaphy
authors.forename: Sabata
authors.initials: S
authors.lastname: Pierno
authors.forename: Diana Conte
authors.initials: DC
authors.lastname: Camerino
authors.forename: Roberto
authors.initials: R
authors.lastname: Bottinelli
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D019417:Hindlimb Suspension; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D020966:Muscular Disorders, Atrophic / Q000503:physiopathology*; D018384:Oxidative Stress; D020543:Proteome / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins; D020543:Proteome