Treatment with IFN‐γ prevents insulin‐dependent PKB, p70S6k phosphorylation and protein synthesis in mouse C2C12 myogenic cells
Treatment with IFN‐γ prevents insulin‐dependent PKB, p70S6k phosphorylation and protein synthesis in mouse C2C12 myogenic cells
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IFN-γ治疗可预防小鼠 C2C12 肌原细胞中胰岛素依赖性 PKB、p70S6k 磷酸化和蛋白质合成
DOI：
10.1042/cbi20090135
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发表时间：
2009
影响因子：
3.9
通讯作者：
W. Wieteska
中科院分区：
文献类型：
--
作者：
K. Grzelkowska;W. Wieteska
本研究的目的是检查 IFN-γ（干扰素-γ）对 PKB（蛋白激酶 B）、p70S6k（p70 S6 激酶）和 MAPK（丝裂原激活蛋白激酶）的细胞含量和磷酸化的潜在影响，以及对胰岛素刺激小鼠 C2C12 肌管中葡萄糖摄取和蛋白质合成的能力的潜在影响。胰岛素 (100 nmol/l) 刺激 C2C12 肌管中葡萄糖的摄取达 203.4%。在 IFN-γ (10 ng/ml) 存在下分化的细胞中的葡萄糖摄取增加了 165.8%，并且添加胰岛素后没有进一步显着改变（对照值的 183.4%）。胰岛素使蛋白质合成率提高198.8%。蛋白质合成的基础速率不受IFN-γ的影响；然而，这种细胞因子消除了胰岛素的作用。 PKB、p70S6k、p42MAPK 和 p44MAPK 的细胞水平不受 IFN-γ 的影响。胰岛素引起 PKB 磷酸化和 p70S6k 激活，但不引起 p42MAPK 和 p44MAPK。在存在 IFN-γ 的情况下分化的细胞中，胰岛素介导的 PKB 磷酸化显着减弱，而 p70S6k 的磷酸化则完全被阻止。用 IFN-γ 预处理 C2C12 肌原细胞导致 p42MAPK 磷酸化显着增加。 C2C12 成肌细胞暴露于 IFN-γ 会损害 MyoD 和肌细胞生成素的表达，并降低分化第五天的融合指数。总之，(i) C2C12 成肌细胞分化过程中细胞外环境中存在的 IFN-γ 阻止了胰岛素对蛋白质合成的刺激作用； (ii) IFN-γ诱导的肌原细胞中蛋白质合成的胰岛素抵抗可能与 PKB 和 p70S6k 磷酸化的减少以及 p42MAPK 基础磷酸化的增强有关； (iii)这种细胞因子效应可以部分地通过分化过程的改变来解释。
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), p70S6k (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, p70S6k, p42MAPK and p44MAPK were not modified by IFN‐γ. Insulin caused the phosphorylation of PKB and the activation of p70S6k, but not p42MAPK and p44MAPK. In cells differentiated in the presence of IFN‐γ, the insulin‐mediated PKB phosphorylation was significantly diminished, whereas the phosphorylation of p70S6k was completely prevented. Pretreatment of C2C12 myogenic cells with IFN‐γ led to the marked increase in p42MAPK 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 p70S6k, as well as with the augmented basal phosphorylation of p42MAPK; (iii) this cytokine effect can be partly explained by alterations in the differentiation process.
DOI：
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发表时间：
2002
期刊：
--
影响因子：
--
作者：
S. Kimball;P. Farrell;L. Jefferson
通讯作者：
S. Kimball;P. Farrell;L. Jefferson
影响因子：
3.3
作者：
Frost, R A;Lang, C H
通讯作者：
Lang, C H