title: Uncoupling protein-3 mRNA up-regulation in C2C12 myotubes after etomoxir treatment.
abstract: Uncoupling proteins (UCPs) are mitochondrial membrane proton transporters that uncouple respiration from oxidative phosphorylation by dissipating the proton gradient across the membrane. Treatment of C2C12 myotubes for 24 h with 40 microM etomoxir, an irreversible inhibitor of carnitine palmitoyltransferase I (CPT-I), up-regulated uncoupling protein 3 (UCP-3) mRNA levels (2-fold induction), whereas UCP-2 mRNA levels were not modified. Etomoxir treatment also caused a 2.5-fold induction in M-CPT-I (muscle-type CPT-I) mRNA levels. In contrast, other well-known peroxisome proliferator-activated receptor alpha (PPAR alpha) target genes, such as acyl-CoA oxidase and medium-chain acyl-CoA dehydrogenase, were not affected, suggesting that this transcription factor was not involved in the effects of etomoxir. Since it has been reported that CPT-I inhibition by etomoxir leads to a further increase in ceramide synthesis, we test the possibility that ceramides were involved in the changes reported. Similarly to etomoxir, addition of 20 microM C(2)-ceramide to C2C12 myotubes for 3, 6 and 9 h resulted in increased UCP-3 and M-CPT-I mRNA levels. These results indicate that the effects on UCP-3 mRNA levels could be mediated by increased ceramide synthesis.
authors.affiliation: Pharmacology Unit, School of Pharmacy, University of Barcelona, Diagonal 643, 08028 Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cabrero
authors.forename: M
authors.initials: M
authors.lastname: Alegret
authors.forename: R
authors.initials: R
authors.lastname: Sánchez
authors.forename: T
authors.initials: T
authors.lastname: Adzet
authors.forename: J C
authors.initials: JC
authors.lastname: Laguna
authors.forename: M
authors.initials: M
authors.lastname: Vázquez
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002518:Ceramides / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology*; D007473:Ion Channels; D051379:Mice; D024101:Mitochondrial Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000071247:Uncoupling Protein 3; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D002518:Ceramides; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D007473:Ion Channels; D024101:Mitochondrial Proteins; C064769:N-acetylsphingosine; D012333:RNA, Messenger; C000604393:Ucp3 protein, mouse; D000071247:Uncoupling Protein 3; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir; D013110:Sphingosine