Gayle M Smythe1, Jade K Forwood. 1. School of Community Health, Charles Sturt University, P.O. Box 789, Albury, NSW, 2640, Australia. gsmythe@csu.edu.au
Abstract
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.
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.
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