title: Basal peroxisome proliferator activated receptor gamma coactivator 1α expression is independent of calcineurin in skeletal muscle.
abstract: 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.
authors.affiliation: Institut de Recherche Biomédicale des Armées, BP 73-91223 Brétigny sur Orge France. sbanzet@crssa.net
authors.forename: Sébastien
authors.initials: S
authors.lastname: Banzet
authors.forename: Hervé
authors.initials: H
authors.lastname: Sanchez
authors.forename: Rachel
authors.initials: R
authors.lastname: Chapot
authors.forename: André
authors.initials: A
authors.lastname: Peinnequin
authors.forename: Xavier
authors.initials: X
authors.lastname: Bigard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Koulmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; C548050:RCAN1 protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016572:Cyclosporine; D019703:Calcineurin; D016559:Tacrolimus