The calcineurin antagonist RCAN1-4 is induced by exhaustive exercise in rat skeletal muscle.

The aim of this work was to study the regulation of the calcineurin antagonist regulator of calcineurin 1 (RCAN1) in rat skeletal muscles after exhaustive physical exercise, which is a physiological modulator of oxidative stress. Three skeletal muscles, namely extensor digitorum longus (EDL), gastrocnemius, and soleus, were investigated. Exhaustive exercise increased RCAN1-4 protein levels in EDL and gastrocnemius, but not in soleus. Protein oxidation as an index of oxidative stress was increased in EDL and gastrocnemius, but remained unchanged in soleus. However, lipid peroxidation was increased in all three muscles. CuZnSOD and catalase protein levels were increased at 3 h postexercise in soleus, whereas they remained unchanged in EDL and gastrocnemius. Calcineurin enzymatic activity declined in EDL and gastrocnemius but not in soleus, and its protein expression was decreased in all three muscles. The level of PGC1-α protein remained unchanged, whereas the protein expression of the transcription factor NFATc4 was decreased in all three muscles. Adiponectin expression was increased in all three muscles. RCAN1-4 expression in EDL and gastrocnemius muscles was augmented by the oxidative stress generated from exhaustive exercise. We propose that increased RCAN1-4 expression and the signal transduction pathways it regulates represent important components of the physiological adaptation to exercise-induced oxidative stress.