NF-~B-Induced LOSS of My0D few py. Here targets wehave-been investigateidentified the potential forrole thera-of Messenger RNA: Possible Role NF-KB as a downstream effector of TNFmediated skeletal muscle dysfunction. -TNF was recently shown to inhibit skeletal in Muscle Decay and Cachexia myogenesis in vitro (6, 14). We therefore investigated the potential role of NF-KB in this Denis C. ~uttridge,'Marty W. Mayol1 Lee V. adr rid,'.' regulatory process. The addition of TNF to Cun-Yu Wangll*

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... S. Baldwin ~r . ' * ~* ~t mouse C2C12 myocytes completely blocked their SMD program, as evidenced by the re-MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair duced expression of the differentiationmarkers of damaged tissue. The transcription factor nuclear factor kappa B (NF-KB)is myogenin and the cyclin-dependent kinase inactivated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal hibitor p21, and by the complete absence of the muscle wasting in cachexia. Here, the role of NF-KBin cytokine-induced muscle late-stage differentiationmarker myosin heavy degeneration was explored. In differentiating CZClZ myocytes, TNF-induced chain (MHC) (Fig. 1A). TNF also caused a activation of NF-KB inhibited SMD by suppressing MyoD mRNA at the post-severe reduction in MyoD protein levels (Fig. transcriptional level. In contrast, in differentiated myotubes, TNF plus inter-1B) but had no effect on the transcription facferon-y (IFN-y) signaling was required for NF-KB-dependent down-regulation tors Myf5 or MEF2D, which are also expressed of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-but are inactive in undifferentiated myoblasts.