Calcineurin A and CaMKIV transactivate PGC-1alpha promoter, but differentially regulate cytochrome c promoter in rat skeletal muscle.
In skeletal muscle, slow-twitch fibers are highly dependent on mitochondrial oxidative metabolism suggesting the existence of common regulatory pathways in the control of slow muscle-specific protein expression and mitochondrial biogenesis. In this study, we determined whether peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) could transactivate promoters of nuclear-encoded mitochondrial protein (cytochrome c) and muscle-specific proteins (fast troponin I, MyoD). We also investigated if calcineurin A (CnA) and calcium/calmodulin kinase IV (CaMKIV) were involved in the regulation of PGC-1alpha and cytochrome c promoter. For this purpose, we took advantage of the gene electrotransfer technique, which allows acute expression of a gene of interest. Electrotransfer of a PGC-1alpha expression vector into rat Tibialis anterior muscle induced a strong transactivation of cytochrome c promoter (P < 0.001) independent of nuclear respiratory factor 1. PGC-1alpha gene electrotransfer did not transactivate fast troponin I promoter, whereas it did transactivate MyoD promoter (P < 0.05). Finally, whereas electrotransfers of CnA or CaMKIV expression vectors transactivated PGC-1alpha promoter (P < 0.001), gene electrotransfer of CaMKIV was only able to transactivate cytochrome c promoter. Taken together, these data suggest that CnA triggers PGC-1alpha promoter transactivation to drive the expression of non-mitochondrial proteins.
Guerfali
Ibtissem
I
Unité Physiologie et Physiopathologie de l'Exercice et Handicap EA 3062, Faculté de Médecine, Université Jean Monnet, 15 rue Ambroise Paré, 42023 Saint-Etienne Cedex 2, France.
Manissolle
Chloé
C
Durieux
Anne-Cécile
AC
Bonnefoy
Régis
R
Bartegi
Aghleb
A
Freyssenet
Damien
D
D000818:Animals; D001483:Base Sequence; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D045304:Cytochromes c / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051266:Nuclear Respiratory Factor 1 / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D019210:Troponin I / Q000235:genetics / Q000378:metabolism
D017570:MyoD Protein; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D019210:Troponin I; D045304:Cytochromes c; D008156:Luciferases; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517686:Camk4 protein, rat; D019703:Calcineurin