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Dominant anabolic effects of low‐dose corticosteroid in C2C12 cells
Author(s) -
Zhu Ercheng,
Fang Liwei,
Caiozzo Vincent J,
Sassoon Catherine S.H.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1046.10
Subject(s) - pi3k/akt/mtor pathway , proteolysis , protein kinase b , methylprednisolone , c2c12 , messenger rna , endocrinology , medicine , chemistry , biology , myogenesis , signal transduction , microbiology and biotechnology , myocyte , biochemistry , gene , enzyme
High‐dose corticosteroid induces diaphragm muscle dysfunction, whereas low‐dose corticosteroid preserves function. To elucidate the mechanisms of the protective effects of low‐dose corticosteroid, in C2C12 cell cultures we tested the hypothesis that low‐dose methylprednisolone (MP) increases protein synthesis via IGF/PI3K/Akt/mTOR, and decreases proteolysis via IGF/PI3K/Akt/Foxo pathways. Methods Myotubes of normal control (NC) and dominant negative MAF‐box (shRNA MAF‐box‐targeted interference) were treated with 0, 10 (low‐dose), and 100 (high‐dose) μMol MP (MP0, MP10, and MP100, respectively) for 3 days in the presence of rhIGF‐1 (50 ng/ml), the former with or without of rapamycin (RP) (25 ng/ml). We measured total, cytoplasmic, and nuclear protein pools, MAF‐box protein expressions, and MAF‐box mRNA. Results Both mTOR‐mediated protein synthesis increased and MAF‐box‐mediated proteolysis decreased following MP10 administration (Figure). MP10 treatment did not increase MAF‐box protein despite enhanced MAF‐box mRNA levels. MP100 overexpressed both MAF‐box protein and mRNA levels. Conclusion Low‐dose methylprednisolone promotes protein synthesis and reduces proteolysis via Akt/mTOR and Akt/Foxo pathways, respectively. The reduced proteolysis is likely related to MAF‐box RNA stabilization. Funded By: VA Medical Research, NIH AR‐46856