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.