Basal peroxisome proliferator activated receptor gamma coactivator 1α expression is independent of calcineurin in skeletal muscle

Both calcineurin-A and peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) are key players in the acquisition and maintenance of slow-oxidative skeletal muscle phenotype. Whether calcineurin can control PGC-1α expression has been proposed but is still controversial. Our aim was to examine the relationship between calcineurin activation and PGC-1α expression in nonexercising skeletal muscles of rats. We first examined PGC-1α and modulatory calcineurin-interacting protein-1 messenger RNA (mRNA) (a marker of calcineurin activity) expression patterns within rat single myofibers, classified according to their phenotype (type I, IIa, IIx, and IIb). Secondly, we measured PGC-1α mRNA and protein in soleus and plantaris muscles of rats treated or not by cyclosporin A or FK506, 2 pharmacological inhibitors of calcineurin activity. In single myofibers, no differences were found in PGC-1α mRNA levels, whereas modulatory calcineurin-interacting protein-1 mRNA was substantially higher in type I and IIa compared with type IIx and IIb fibers. In cyclosporin A- and FK506-treated animals, no decrease in PGC-1α mRNA and protein was found, despite an efficient blockade of calcineurin activity. Taken together, our results show that, in weight-bearing skeletal muscles, basal PGC-1α expression, necessary to maintain slow-oxidative phenotype, is independent of calcineurin activity.