Activation of ERK by sodium tungstate induces protein synthesis and prevents protein degradation in rat L6 myotubes.
The balance between the rates of protein synthesis and degradation in muscle is regulated by PI3K/Akt signaling. Here we addressed the effect of ERK activation by sodium tungstate on protein turnover in rat L6 myotubes. Phosphorylation of ERK by this compound increased protein synthesis by activating MTOR and prevented dexamethasone-induced protein degradation by blocking FoxO3a activity, but it did not alter Akt phosphorylation. Thus, activation of ERK by tungstate improves protein turnover in dexamethasone-treated cells. On the basis of our results, we propose that tungstate be considered an alternative to IGF-I and its analogs in the prevention of skeletal muscle atrophy.
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain.
Rafael
R
Salto
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain.
José D
JD
Vílchez
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain.
Elena
E
Cabrera
Institute for Research in Biomedicine, University of Barcelona and CIBER de Diabetes y Enfermedades Metabólicas (CIBERDEM), Barcelona, Spain.
Joan J
JJ
Guinovart
Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain. Electronic address: mgiron@ugr.es.
María D
MD
Girón
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009133:Muscular Atrophy / Q000517:prevention & control; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D059748:Proteolysis / Q000187:drug effects*; D051381:Rats; D000071456:Sequestosome-1 Protein; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D017973:Tungsten Compounds / Q000494:pharmacology*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism
D003907:Dexamethasone; D048049:Extracellular Signal-Regulated MAP Kinases; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D005938:Glucocorticoids; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D046988:Proteasome Endopeptidase Complex; D000071456:Sequestosome-1 Protein; D058570:TOR Serine-Threonine Kinases; D017973:Tungsten Compounds; D025801:Ubiquitin; C499515:FOXO3 protein, rat; C526109:Anxa3 protein, rat; C491079:Sqstm1 protein, rat; C025399:sodium tungstate(VI); C546845:mTOR protein, rat
Extracellular signal-regulated kinases 1 and 2; Forkhead box O Family of Transcription Factors; LC3; Mechanistic target of rapamycin; Skeletal muscle; Sodium tungstate