Effect of EUK-134 on Insulin Signaling and Morphology Alterations by 7 Days of Hindlimb Unloading in the Rat Soleus
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abstract
Removal of mechanical loading causes rapid and profound atrophy of skeletal muscle due to an increase in contractile protein degradation coupled with a decrease in protein synthesis. Emerging data suggest that oxidative stress may contribute to unloadinginduced translocation of nNOS from the sarcolemma, FoxO3a activation, and fiber atrophy. Insulin resistance can altered in unloaded skeletal muscle and could contribute to atrophy; however, the mechanisms are unknown. We hypothesized that oxidative stress may contribute to insulin signaling and morphological changes in the rat soleus with 7 days of unloading. F344 rats were divided (n=9/gr) into ambulatory control (CON), hindlimb unloaded (HU), and HU + EUK134 (HUE) groups. The superoxide dismutase/catalase mimetic EUK134 was injected daily (3 mg/kg/d) beginning 24 hours prior to HU. HU significantly decreased muscle weight/body weight ratio (18%) and fiber crosssectional area (32%) in the soleus, effects ameliorated by EUK134. GLUT4 colocalization with the membrane protein sarcoglycan significantly increased with HU; while HUE muscles were not different than CON. Akt phosphorylation (Ser473) was elevated by HU, with a lesser effect in HUE. Our data suggest a complex relationship between HUrelated alterations in insulin signaling and oxidative stress that may be independent of protective effects against atrophy. Supported by NASA (NNX13AE45G), NIH (AR054084).
