Journal
MUSCLE & NERVE
Volume 34, Issue 3, Pages 298-303Publisher
WILEY
DOI: 10.1002/mus.20579
Keywords
muscle damage; muscular dystrophy; supplement; transcription factor
Categories
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL059878] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR049022] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL59878] Funding Source: Medline
- NIAMS NIH HHS [AR49022] Funding Source: Medline
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Skeletal muscle of patients with Duchenne-type muscular dystrophy and mdx mice exhibits elevated activity of the transcription factor NF-kappa B (nuclear factor-kappa B), which may play a role in muscle catabolism. We measured skeletal muscle NF-kappa B activity in mdx mice at three ages (10 days, 4 weeks, and 8 weeks) to test the hypothesis that NF-kappa B activity is elevated in an age-dependent manner in these mice. In addition, we tested the hypothesis that NF-kappa B 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-kappa B 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-kappa B 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-kappa B 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.
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