Clenbuterol changes phosphorylated FOXO1 localization and decreases protein degradation in the sartorius muscle of neonatal chicks

Biosci Biotechnol Biochem. 2016 Aug;80(8):1499-504. doi: 10.1080/09168451.2016.1158629. Epub 2016 Apr 8.


To investigate the intracellular signaling mechanisms by which clenbuterol reduces muscle protein degradation, we examined the phosphorylation level and intracellular localization of FOXO1 in the sartorius muscle of neonatal chicks. One-day-old chicks were given a single intraperitoneal injection of clenbuterol (0.1 mg/kg body weight). Three hours after injection, AKT protein was phosphorylated in the sartorius muscle by clenbuterol injection. Coincidentally, clenbuterol increased cytosolic level of phosphorylated FOXO1 protein, while it decreased nuclear level of FOXO1 protein in the sartorius muscle. Furthermore, clenbuterol decreased the expression of mRNAs for muscle-specific ubiquitin ligases (atrogin-1/MAFbx and MuRF1) in the sartorius muscle accompanied by decreased plasma 3-methylhistidine concentration, an index of muscle protein degradation, at 3 h after injection. These results suggested that, in the sartorius muscle of the chicks, clenbuterol changed the intracellular localization of phosphorylated FOXO1, and consequently decreased protein degradation via suppressing the expression of genes encoding muscle-specific ubiquitin ligases.

Keywords: FOXO transcription factor; clenbuterol; skeletal muscle; β2-adrenergic receptor.

MeSH terms

  • Animals
  • Animals, Newborn
  • Avian Proteins / genetics*
  • Avian Proteins / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Chickens
  • Clenbuterol / pharmacology*
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Forkhead Box Protein O1 / genetics*
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Regulation
  • Injections, Intraperitoneal
  • Methylhistidines / blood
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Phosphorylation / drug effects
  • Proteolysis / drug effects
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • SKP Cullin F-Box Protein Ligases / antagonists & inhibitors
  • SKP Cullin F-Box Protein Ligases / genetics*
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Sympathomimetics / pharmacology*
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism


  • Avian Proteins
  • Forkhead Box Protein O1
  • Methylhistidines
  • Sympathomimetics
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases
  • Proto-Oncogene Proteins c-akt
  • 3-methylhistidine
  • Clenbuterol