Manchester Metropolitan University's Research Repository

    Pro- and anti-apoptotic roles for IGF-I in TNF-α-induced apoptosis: A MAP kinase mediated mechanism

    Saini, Amarjit, Al-Shanti, Nasser, Faulkner, Steve H. and Stewart, Claire E. (2008) Pro- and anti-apoptotic roles for IGF-I in TNF-α-induced apoptosis: A MAP kinase mediated mechanism. Growth Factors, 26 (5). pp. 239-253. ISSN 1029-2292

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    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-α/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-α (10 ng ml− 1) maximal damage (21% ± 0.7 myoblast death, p < 0.05) was induced. Co-incubation of TNF-α (10 ng ml− 1) with IGF-I resulted in cell survival (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-α (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-α 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-α-induced cell death.

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