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NF‐κB inhibition and ischemic preconditioning ameliorate ischemia‐reperfusion injury in dystrophin‐deficient muscles of mdx mice
Author(s) -
Ye Jianfeng,
Thomas Gail D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.782.9
Subject(s) - dystrophin , duchenne muscular dystrophy , ischemia , pharmacology , reperfusion injury , chemistry , mdx mouse , muscular dystrophy , ischemic preconditioning , medicine , endocrinology
Mutations of the dystrophin gene cause Duchenne muscular dystrophy, but the pathogenetic mechanisms are poorly understood. We previously reported that ischemia and reperfusion (I/R) cause excessive injury to dystrophin‐deficient muscles, which is ameliorated by antioxidant treatment. We therefore hypothesized that the enhanced susceptibility of the dystrophin‐deficient muscles of mdx mice to I/R‐induced injury is mediated by activation of the redox‐sensitive transcription factor NF‐κB. Because brief exposure to ischemia induces tolerance to subsequent I/R and is thought to be mediated in part by reactive oxygen species, we also hypothesized that I/R‐induced injury would be reduced by ischemic preconditioning (IPC). In anesthetized mdx and C57BL10 mice, I/R (1 h/2 h) induced greater sarcolemmal damage as reflected by Evans blue dye (EBD) uptake (EBD + area: 29±3% vs 6±2%; P<0.05) and greater activation of NF‐κB (+115±32% vs +36±16%; P<0.05). I/R‐induced injury in mdx mice was attenuated by pharmacological inhibition of NF‐κB (EBD + area: 17±3%; P<0.05 vs I/R alone) and by 3 cycles of IPC consisting of 5 min ischemia and 10 min reperfusion (EBD + area: 11±4%; P<0.05 vs I/R alone). These data suggest that activation of NF‐κB plays a role in the excessive I/R‐induced injury in dystrophin‐deficient muscle and provide support for a protective effect of IPC to ameliorate this muscle damage. Supported by NIH AR051034.