Saini Amarjit, Al-Shanti Nasser, Faulkner Steve H, Stewart Claire E
Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Cheshire, UK.
Growth Factors. 2008 Oct;26(5):239-53. doi: 10.1080/08977190802291634.
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.
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.
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.
骨骼肌稳态的概念——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——并非彼此独立发生，而是由复杂的信号网络精细协调。
我们使用啮齿动物肌肉细胞系研究了肿瘤坏死因子-α（TNF-α）/胰岛素样生长因子-I（IGF-I）的相互作用，试图模拟并理解消瘦过程背后的机制。
当成肌细胞与TNF-α（10 ng/ml）一起孵育时，会诱导最大损伤（约21%±0.7%的成肌细胞死亡，p<0.05）。TNF-α（10 ng/ml）与IGF-I共同孵育可使细胞存活（成肌细胞死亡减少约50%，p<0.05），然而，肌管形成并不明显。相比之下，已确定IGF-I的一个新作用，即肌肉细胞与IGF-I（1.5 ng/ml）和非凋亡剂量的TNF-α（1.25 ng/ml；足以阻断分化）共同孵育时，出乎意料地发现不仅不能挽救分化阻滞，反而会促进显著的成肌细胞死亡（p<0.05）。有趣的是，预先给予MAPK信号阻断剂PD98059，然后将1.25 ng/ml的TNF-α和1.5 ng/ml的IGF-I共同孵育，可使死亡降至基线水平（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可能具有凋亡作用。
