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The Effects of IL‐6 Dosage and Duration on the Regulation of Protein Turnover in C2C12 Myotubes
Author(s) -
GAO SONG,
CARSON JAMES
Publication year - 2012
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.26.1_supplement.1075.18
Subject(s) - myogenesis , phosphorylation , c2c12 , protein kinase b , pi3k/akt/mtor pathway , medicine , endocrinology , protein turnover , chemistry , soleus muscle , anabolism , myocyte , myogenin , muscle atrophy , protein degradation , skeletal muscle , signal transduction , biology , protein biosynthesis , biochemistry
One of hallmarks of cachexia is skeletal muscle wasting caused by an imbalance between the rates of protein synthesis and degradation. Circulating IL‐6 is chronically elevated in many types of cachexia, and has emerged as a key regulator of muscle mass. The purpose of this study was to investigate the influence of IL‐6 dosage and duration of exposure on signaling pathways regulating protein turnover in cultured C2C12 myotubes. Differentiated C2C12 myotubes were treated with two doses (20ng/ml and 100ng/ml) of IL‐6 for 4h, 24h and 48h. Protein samples were analyzed by Western blots. The low dose (20ng/ml) IL‐6 treatment transiently (4h) increased phosphorylation of ERK1/2 (T202/Y204), mTOR (S2448) and p70S6K (T389), through an Akt independent mechanism. Inhibition of Stat3 signaling by pyrrolidine dithioicarbamate (PDTC) abolished these anabolic effects of IL‐6. Chronic treatment (24h) of IL‐6 at this dosage caused reduced activation of p70S6K phosphorylation, and inhibition of mTOR phosphorylation. However, 100ng/ml IL‐6 showed an inhibitory effect on p70S6K phosphorylation at 4h, 24h and 48h, and 4EBP‐1 phosphorylation (T37/46) at 48h. Finally, Atrogin‐1 protein expression was elevated by 100ng/ml IL‐6 at all three time points. These results demonstrate IL‐6 dosage and duration of exposure can differentially effect the regulation of protein turnover in C2C12 muscle cells.