Altered mitogen-activated protein kinase signaling in dystrophic (mdx) muscle

作者：Smythe Gayle M^*; Forwood Jade K

来源：Muscle & Nerve, 2012, 46(3): 374-383.

DOI：10.1002/mus.23312

• Duchenne muscular dystrophy
• mdx
• mitogen-activated protein kinase
• myotube
• oxidative stress

Introduction: Duchenne muscular dystrophy (DMD) results from a deficiency in the protein, dystrophin. Dystrophic myotubes are susceptible to stressful stimuli. This may be partly due to altered regulation of pro-survival signaling pathways, but a role for mitogen-activated protein (MAP) kinases has not been investigated. Methods: We examined patterns of phosphorylation of key MAP kinase proteins in cultured myotubes responding to oxidative stress, and in muscle tissue in vivo. Results: Dystrophic (mdx) myotubes have an increased susceptibility to oxidant-induced death compared with wild-type (C57Bl/10ScSn) myotubes. This correlates with late phosphorylation of c-Jun N-terminal kinase (JNK), and persistently high p38 MAP kinase phosphorylation in mdx myotubes. JNK and extracellular signal-regulated kinase 1/2 (ERK1/2) also showed altered phosphorylation levels in mdx muscle tissue. Conclusions: We show altered patterns of MAP kinase protein phosphorylation in dystrophic muscle in vitro and in vivo. These pathways may be novel pharmacological targets for treating DMD. Muscle Nerve 46: 374383, 2012

• 出版日期2012-9