Curcumin counteracts both atrophy and loss of force of soleus muscles after hindlimb unloading

Skeletal muscle atrophy induced by microgravity, immobilization or prolonged bed rest, represents a major invalidating condition. Although redox imbalance fosters disuse atrophy, anti-oxidant administration provided controversial results. Here we investigated the effects of curcumin, a vegetal polyphenol with pleomorphic biological activity, on rat soleus muscles exposed to simulated microgravity (tail-suspension) for 7 days. Curcumin treatment countered by approximately 30% the loss of soleus mass and myofiber cross-sectional area (CSA) following unloading (P < 0.02). In vitro contractile properties of unloaded soleus muscle showed a dramatic decrease of both absolute and specific maximal forces. Curcumin administration potently countered the force loss in unloaded muscles, whereas it did not affect muscle contractility of control rats. The recovery of tetanic force with curcumin indicates that the treatment favours the maintenance of both muscular mass and contractility. Indexes of muscle protein and lipid oxidation, such as protein carbonylation, revealed by Oxyblot, and malondialdehyde, measured with HPLC, were significantly blunted by curcumin in unloaded rats compared to sham-treated ones (P = 0.01). Furthermore, curcumin significantly antagonized in unloaded solei both the decrease of Grp94, a stress protein/chaperone involved in anti-oxidant cytoprotection, and the increase of HO-1, a recognized marker of oxidative stress. The mechanistically involvement of Grp94 in the curcumin-induced attenuation of myofiber atrophy was further suggested by the lower CSA displayed by myofibers transfected with antisense Grp94 cDNA in unloaded curcumin-treated rats. In conclusion, curcumin represents an effective and safe tool to upregulate muscle Grp94 level and maintain muscle function during exposure to microgravity.