At the moment there are few studies describing the involvement of different transcriptional factors in muscle wasting. Penner et al.  reported an increase in NFkB and AP-1 transcription factors during sepsis in experimental animals. Recent data from our laboratory do not support an involvement of NFkB in skeletal muscle during cancer cachexia (unpublished data). However, tumour burden results in a significant increase in the binding activity of AP-1. Interestingly, inhibition of NFkB is not able to revert muscle wasting in cachectic tumour-bearing animals ; however, inhibition of AP-1 results in a partial reversal of protein degradation in skeletal muscle associated with tumour growth (unpublished data). The increase in NFkB observed in skeletal muscle during sepsis can be mimicked by TNF-a. Indeed, TNF-a addition to C2C12 muscle cultures results
Fig. 2. Interactions between proinflammatory cytokines and PIF. Both humoural (TNF-a and IL-6) and tumoural (PIF) factors have been shown to activate intracellu-lar muscle proteolysis by different mechanisms, but possibly sharing common pathways. For abbreviations, see text
Fig. 2. Interactions between proinflammatory cytokines and PIF. Both humoural (TNF-a and IL-6) and tumoural (PIF) factors have been shown to activate intracellu-lar muscle proteolysis by different mechanisms, but possibly sharing common pathways. For abbreviations, see text in a short-term increase in NFkB [47,48]; however, whether or not this increase in NFkB promoted by TNF-a is associated with increased proteolysis and/or increased apoptosis in skeletal muscle remains to be established. In relation to AP-1 activation, TNF-a has been shown to increase c-jun expression in C2C12 cells ; in turn, the effects of c-jun overexpression mimic those of TNF-a on differentiation, i.e. decreased myoblast differentiation . Tumour mediators, PIF in particular, also seem to be able to increase NFkB expression in cultured muscle cells, this possibly being linked with increased proteolysis (M. Tisdale, personal communication). Other transcriptional factors reported to be involved in muscle changes associated with catabolic conditions include c/EBPp and c/EBPS, which are increased in skeletal muscle during sepsis , PW-1, and PGC-1. TNF-a decreases MyoD content in cultured myoblasts  and blocks differentiation by a mechanism that seems to be independent of NFkB and that involves PW-1, a transcriptional factor related to p53-induced apoptosis . Cytokine action on muscle cells, therefore, seems to rely most likely on satellite cells blocking muscle differentiation or, in other words, regeneration.
Finally, the transcription factor PGC-1 has been associated with the activation of UCP2 and UCP3 and with increased oxygen consumption by cytokines in cultured myotubes . This tran-scriptional factor is involved as an activator of PPAR-y in the expression of uncoupling proteins.
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