OBJECTIVE The concept of skeletal muscle homeostasis--often viewed as the net balance between two separate processes, namely protein degradation and protein synthesis--are not occurring independently of each other, but are finely co-ordinated by a web of intricate signalling networks. MATERIALS AND METHODS Using rodent muscle cell lines we have investigated TNF-alpha/IGF-I interactions, in an attempt to mimic and understand mechanisms underlying the wasting process. RESULTS AND CONCLUSION When myoblast cells are incubated with TNF-alpha (10 ng ml(- 1)) maximal damage ( approximately 21% +/- 0.7 myoblast death, p < 0.05) was induced. Co-incubation of TNF-alpha (10 ng ml(- 1)) with IGF-I resulted in cell survival ( approximately 50% reduction in myoblast death, p < 0.05), however, myotube formation was not evident. In contrast, a novel role of IGF-I has been identified whereby co-incubation of muscle cells with IGF-I (1.5 ng ml(- 1)) and a non-apoptotic dose of TNF-alpha (1.25 ng ml(- 1); sufficient to block differentiation) unexpectedly were shown not to rescue a block on differentiation but to facilitate significant myoblast death (p < 0.05). Interestingly, pre-administration of PD98059, a MAPK signal-blocking agent followed by co-incubation of 1.25 ng ml(- 1) TNF-alpha and 1.5 ng ml(- 1) IGF-I, reduced death to baseline levels (p < 0.05). We show for the first time that IGF-I can be apoptotic in the absence of TNF-alpha-induced cell death.

中文翻译：

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IGF-1在TNF-α诱导的凋亡中的促凋亡和抗凋亡作用：MAP激酶介导的机制。

目的骨骼肌动态平衡的概念（通常被视为两个独立过程，即蛋白质降解和蛋白质合成）之间的净平衡，并不是彼此独立发生的，而是由复杂的信号网络完美协调的。材料和方法我们使用啮齿动物肌肉细胞系研究了TNF-α/ IGF-I相互作用，以试图模拟和理解浪费过程的潜在机制。结果与结论当成肌细胞与TNF-α（10 ng ml（-1））一起孵育时，会引起最大损伤（约21％+/- 0.7成肌细胞死亡，p <0.05）。TNF-α（10 ng ml（-1））与IGF-I共同孵育可导致细胞存活（成肌细胞死亡减少约50％，p <0.05），但是肌管形成并不明显。相反，已经确定了IGF-I的新作用，从而将肌肉细胞与IGF-I（1.5 ng ml（-1））和非凋亡剂量的TNF-α（1.25 ng ml（-1））共同孵育；足够（阻止分化）出乎意料地显示，它不能挽救分化的障碍，但可以促进成肌细胞的大量死亡（p <0.05）。有趣的是，预先施用M980信号阻断剂PD98059，然后共同孵育1.25 ng ml（-1）TNF-α和1.5 ng ml（-1）IGF-1，可将死亡降至基线水平（p < 0.05）。我们首次表明，在没有TNF-α诱导的细胞死亡的情况下，IGF-I可以凋亡。足以阻止分化）意外地显示，它不能挽救分化的障碍，但可以促进成肌细胞的大量死亡（p <0.05）。有趣的是，预先施用M980信号阻断剂PD98059，然后共同孵育1.25 ng ml（-1）TNF-α和1.5 ng ml（-1）IGF-1，可将死亡降至基线水平（p < 0.05）。我们首次表明，在没有TNF-α诱导的细胞死亡的情况下，IGF-I可以凋亡。足以阻止分化）意外地显示，它不能挽救分化的障碍，但可以促进成肌细胞的大量死亡（p <0.05）。有趣的是，预先施用M980信号阻断剂PD98059，然后共同孵育1.25 ng ml（-1）TNF-α和1.5 ng ml（-1）IGF-1，可将死亡降至基线水平（p < 0.05）。我们首次表明，在没有TNF-α诱导的细胞死亡的情况下，IGF-I可以凋亡。