Activation of an alternative NF-κB pathway in skeletal muscle during disuse atrophy

Although cytokine-induced nuclear factor κB (NF-κB) pathways are involved in muscle wasting subsequent to disease, their potential role in disuse muscle atrophy has not been characterized. Seven days of hind limb unloading led to a 10-fold activation of an NF-κB-dependent reporter in rat soleus muscle but not the atrophy-resistant extensor digitorum longus muscle. Nuclear levels of p50 were markedly up-regulated, c-Rel was moderately up-regulated, Rel B was down-regulated, and p52 and p65 were unchanged in unloaded solei. The nuclear IκB protein Bcl-3 was increased. There was increased binding to an NF-κB consensus oligonucleotide, and this complex bound antibodies to p50, c-Rel, and Bcl-3 but not other NF-κB family members. Tumor necrosis factor alpha (TNF-α) and TNF receptor-associated factor 2 protein were moderately down-regulated. There was no difference in p38, c-Jun NH2-terminal kinase or Akt activity, nor were activator protein 1 or nuclear factor of activated T cell-dependent reporters activated....