Effects of formoterol on protein metabolism in myotubes during hyperthermia.
Proteolysis in skeletal muscle is mainly carried out by the activity of the ubiquitin-dependent proteolytic system. For the study of protein degradation through the ubiquitin-proteasome pathway, we used a model of hyperthermia in murine myotubes. In C2C12 cells, hyperthermia (41°C) induced a significant increase in both the rate of protein synthesis (18%) and degradation (51%). Interestingly, the addition of the β(2) -adrenoceptor agonist formoterol resulted in a significant decrease in protein degradation (21%) without affecting protein synthesis. The decrease in proteolytic rate was associated with decreases in gene expression of the different components of the ubiquitin-dependent proteolytic system. The effects of the β(2) -agonist on protein degradation were dependent exclusively on cAMP formation, because inhibition of adenylyl cyclase completely abolished the effects of formoterol on protein degradation. It can be concluded that hyperthermia is a suitable model for studying the anti-proteolytic potential of drugs used in the treatment of muscle wasting.
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona 08028, Spain.
Elisabet
E
Ametller
Sílvia
S
Busquets
Gemma
G
Fuster
Maria T
MT
Figueras
Cibely Cristine Fontes
CC
De Oliveira
Míriam
M
Toledo
Katarzyna
K
Korzeniewska
Josep M
JM
Argilés
Francisco J
FJ
López-Soriano
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D000242:Cyclic AMP / Q000378:metabolism; D003634:DDT / Q000031:analogs & derivatives / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology*; D000068759:Formoterol Fumarate; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006979:Hyperthermia, Induced; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D058666:Adrenergic beta-2 Receptor Agonists; D004983:Ethanolamines; D007166:Immunosuppressive Agents; D014452:Ubiquitins; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D000242:Cyclic AMP; D046988:Proteasome Endopeptidase Complex; D000068759:Formoterol Fumarate