title: Glucocorticoids Enhance Muscle Proteolysis through a Myostatin-Dependent Pathway at the Early Stage.
abstract: Myostatin, a member of the TGF-β superfamily of secreted proteins, is expressed primarily in skeletal muscle. It negatively regulates muscle mass and is associated with glucocorticoid-induced muscle atrophy. However, it remains unclear whether myostatin is involved in glucocorticoid-induced muscle protein turnover. The aim of the present study was to investigate the role of myostatin in protein metabolism during dexamethasone (DEX) treatment. Protein synthesis rates and the expression of the genes for myostatin, ubiquitin-proteasome atrogin-1, MuRF1, FoxO1/3a and mTOR/p70S6K were determined. The results show that DEX decreased (P<0.05) protein synthesis rates while increasing the abundance of myostatin. DEX increased (P<0.05) the level of phospho-FoxO1/3a (Thr 24/32) and the expression of MuRF1. In contrast, DEX treatment had no detectable effect on atrogin-1 protein levels (P>0.05). The phosphorylation levels of mTOR and p70S6K were decreased by DEX treatment (P<0.05). Follistatin treatment inhibited the DEX-induced increase in myostatin (P<0.05) and the activation of phosphor-FoxO1/3a (Thr 24/32) (P< 0.05) and MuRF1 (P<0.05). Follistatin treatment had no influence on the protein synthesis rate or on the phosphorylation levels of mTOR (Ser 2448) and p70S6K (Thr 389) (P> 0.05). In conclusion, the present study suggests that the myostatin signalling pathway is associated with glucocorticoid-induced muscle protein catabolism at the beginning of exposure. Myostatin is not a main pathway associated with the suppression of muscle protein synthesis by glucocorticoids.
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong, 271018, P. R. China.
authors.forename: Ruxia
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong, 271018, P. R. China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong, 271018, P. R. China.
authors.forename: Jingpeng
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong, 271018, P. R. China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Animal Science, Shandong Agricultural University, Shandong Key Lab for Animal Biotechnology and Disease Control, Taian, Shandong, 271018, P. R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Lin
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D055435:Myostatin; D025801:Ubiquitin; D003907:Dexamethasone; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex