Is oxidative stress a cause or consequence of disuse muscle atrophy in mice? A proteomic approach in hindlimb unloaded mice

Two dimensional proteomic maps of soleus (Sol), a slow oxidative muscle, and gastrocnemius (Gas), a fast glycolitic 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 HU. The most interesting adaptations regarded the cellular defense systems against oxidative stress and energy metabolism. In HU Sol, the antioxidant defense systems and heat shock proteins were down-regulated, and protein oxidation index and lipid peroxidation were higher compared to CTRL Sol. On the contrary, in HU Gas the antioxidant defense systems were up-regulated and protein oxidation index and lipid peroxidation were normal. Noteworthy, both Sol and Gas muscles and their muscle fibers 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 fiber 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.