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Treatment with IFN‐γ prevents insulin‐dependent PKB, p70 S6k phosphorylation and protein synthesis in mouse C2C12 myogenic cells
Author(s) -
GrzelkowskaKowalczyk Katarzyna,
WieteskaSkrzeczyńska Wioletta
Publication year - 2010
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20090135
Subject(s) - p70 s6 kinase 1 , protein kinase b , myogenesis , medicine , insulin , protein kinase a , phosphorylation , mapk/erk pathway , endocrinology , c2c12 , biology , glucose uptake , chemistry , microbiology and biotechnology , myocyte
The purpose of the present study was to examine the potential effect of IFN‐γ (interferon‐γ) on the cellular content and phosphorylation of PKB (protein kinase B), p70 S6k (p70 S6 kinase) and MAPK (mitogen‐activated protein kinase), and on the ability of insulin to stimulate the glucose uptake and protein synthesis in mouse C2C12 myotubes. Insulin (100 nmol/l) stimulated glucose uptake in C2C12 myotubes by 203.4%. Glucose uptake in cells differentiated in the presence of IFN‐γ (10 ng/ml) was increased by 165.8% and was not further significantly modified by the addition of insulin (183.4% of control value). Insulin increased the rate of protein synthesis by 198.8%. The basal rate of protein synthesis was not affected by IFN‐γ; however, this cytokine abolished the insulin effect. Cellular levels of PKB, p70 S6k , p42 MAPK and p44 MAPK were not modified by IFN‐γ. Insulin caused the phosphorylation of PKB and the activation of p70 S6k , but not p42 MAPK and p44 MAPK . In cells differentiated in the presence of IFN‐γ, the insulin‐mediated PKB phosphorylation was significantly diminished, whereas the phosphorylation of p70 S6k was completely prevented. Pretreatment of C2C12 myogenic cells with IFN‐γ led to the marked increase in p42 MAPK phosphorylation. Exposure of C2C12 myoblasts to IFN‐γ impaired MyoD and myogenin expression and decreased the fusion index on the fifth day of differentiation. In conclusion, (i) IFN‐γ present in the extracellular environment during C2C12 myoblast differentiation prevents the stimulatory action of insulin on protein synthesis; (ii) IFN‐γ‐induced insulin resistance of protein synthesis in myogenic cells can be associated with the decreased phosphorylation of PKB and p70 S6k , as well as with the augmented basal phosphorylation of p42 MAPK ; (iii) this cytokine effect can be partly explained by alterations in the differentiation process.