Progressive nuclear factor-kappaB activation resistant to inhibition by contraction and curcumin in mdx mice

Skeletal muscle of patients with Duchenne-type muscular dystrophy and mdx mice exhibits elevated activity of the transcription factor NF-kappaB (nuclear factor-kappaB), which may play a role in muscle catabolism. We measured skeletal muscle NF-kappaB activity in mdx mice at three ages (10 days, 4 weeks, and 8 weeks) to test the hypothesis that NF-kappaB activity is elevated in an age-dependent manner in these mice. In addition, we tested the hypothesis that NF-kappaB activity could be reduced in mdx skeletal muscle by dietary supplementation with curcumin (1% w/v) or by fatiguing muscle contractions. We found that NF-kappaB activity was elevated at 4 and 8 weeks of age but not at 10 days, and was resistant to inhibition by either fatiguing contractions or dietary curcumin. We conclude that NF-kappaB activity is elevated in dystrophic skeletal muscle in an age-related manner and is resistant to inhibition by physiological and pharmacological means. These findings are consistent with a role for NF-kappaB activation in dystrophic muscle wasting but suggest that predicted interventions such as exercise or inhibitors of the early steps in the NF-kappa activation pathway may not be effective and that targeted research is needed to identify novel therapeutic strategies.