tretinoin and carboprostacyclin

Catecholamine-induced and beta-adrenergic receptor (beta-AR)-mediated thermogenesis in skeletal muscle is a significant component of whole-body energy expenditure. Skeletal muscle expresses uncoupling protein (UCP) 2 and UCP3, which can dissipate the transmitochondrial electrochemical gradient and thereby may be involved in regulation of energy metabolism. We investigated the effects of beta-AR stimulation on UCP2 and UCP3 expression in L6 myotubes. Stimulation of the cells with epinephrine increased the UCP3 mRNA level transiently at 6 h, and also the UCP2 mRNA level at 6-24 h. The stimulatory effects of epinephrine were also observed in the presence of carbacyclin and 9-cis retinoic acid, and mimicked by isoproterenol and salbutamol (beta2-AR agonists), but abolished by propranolol and ICI-118,551 (beta2-AR antagonists). Pharmacological and mRNA analyses revealed the existence of beta2-AR, but not beta1- and beta3-ARs, in L6 myotubes. These results suggested that catecholamines up-regulate UCP2 and UCP3 expression through direct action on the beta2-AR in skeletal muscle.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Albuterol; Alitretinoin; Animals; Carrier Proteins; Cell Line; Cyclic AMP; Energy Metabolism; Epinephrine; Epoprostenol; Ion Channels; Isoproterenol; Membrane Transport Proteins; Mitochondrial Proteins; Muscle, Skeletal; Propanolamines; Propranolol; Proteins; Rats; Receptors, Adrenergic, beta; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; RNA, Messenger; Time Factors; Transcription Factors; Tretinoin; Uncoupling Protein 2; Uncoupling Protein 3; Up-Regulation

Uncoupling protein 3 (UCP3), expressed abundantly in the skeletal muscle, is one of the carrier proteins dissipating the transmitochondrial electrochemical gradient as heat, and thereby has been implicated in the regulation of energy metabolism. We have investigated UCP3 mRNA expression in the widely used L6 myocyte cell line by Northern blot analysis. UCP3 mRNA was not detected in L6 myoblasts, but appeared after their differentiation to myotubes. The UCP3 mRNA level was increased when L6 myotubes were treated with increasing concentrations of triiodothyronine (T3), oleic acid, alpha-bromopalmitate and carbacyclin, a non-selective ligand of peroxisome proliferator-activated receptors (PPARs), whereas it was not influenced when treated with selective ligands of PPARalpha (WY 14¿ omitted¿643) and PPARgamma (troglitazone). A ligand of retinoid X receptor (RXR), 9-cis retinoic acid, was also effective by itself and in combination with carbacyclin in stimulating UCP3 mRNA expression. The mRNA analysis of individual PPAR isoforms revealed that L6 cell expressed a significant level of PPARdelta but undetectable levels of PPARalpha and PPARgamma. These results suggest that UCP3 expression in myocytes is differentiation-dependent and regulated by the T3 receptor, RXR and PPARdelta.

Topics: Alitretinoin; Animals; Carrier Proteins; Cells, Cultured; Chromans; Dimerization; Drug Synergism; Epoprostenol; Gene Expression Regulation; Ion Channels; Mitochondrial Proteins; Muscle, Skeletal; Oleic Acid; Palmitates; Protein Isoforms; Rats; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; RNA, Messenger; Thiazoles; Thiazolidinediones; Transcription Factors; Tretinoin; Triiodothyronine; Troglitazone; Uncoupling Protein 3