title: G-CSF treatment can attenuate dexamethasone-induced reduction in C2C12 myotube protein synthesis.
abstract: Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to enhance skeletal muscle recovery following injury and increases muscle function in the context of neuromuscular disease in rodent models. However, understanding of the underlying mechanisms used by G-CSF to mediate these functions remains poor. G-CSF acts on responsive cells through binding to a specific membrane spanning receptor, G-CSFR. Recently identified, the G-CSFR is expressed in myoblasts, myotubes and mature skeletal muscle tissue. Therefore, elucidating the actions of G-CSF in skeletal muscle represents an important prerequisite to consider G-CSF as a therapeutic agent to treat skeletal muscle. Here we show for the first time that treatment with moderate doses (4 and 40ng/ml) of G-CSF attenuates the effects of dexamethasone in reducing protein synthesis in C2C12 myotubes. However, a higher dose (100ng/ml) of G-CSF exacerbates the dexamethasone-induced reduction in protein synthesis. In contrast, G-CSF had no effect on basal or dexamethasone-induced protein degradation, nor did G-CSF influence the phosphorylation of Akt, STAT3, Erk1/2, Src, Lyn and Erk5 in C2C12 myotubes. In conclusion, physiologically relevant doses of G-CSF may attenuate reduced skeletal muscle protein synthesis during catabolic conditions, thereby improving recovery.
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Victoria, Australia.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Wright
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Victoria, Australia.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Brown
authors.affiliation: Molecular and Medical Research SRC, School of Medicine, Deakin University, Waurn Ponds, 3216 Victoria, Australia.
authors.forename: Alister C
authors.initials: AC
authors.lastname: Ward
authors.affiliation: Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood 3125, Victoria, Australia. Electronic address: aaron.russell@deakin.edu.au.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Russell
mesh_terms: D000818:Animals; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D059748:Proteolysis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: C2C12; G-CSF; Protein degradation; Protein synthesis; Skeletal muscle