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.
We examined patterns of phosphorylation of key MAP kinase proteins in cultured myotubes responding to oxidative stress, and in muscle tissue in vivo.
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.
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: 374–383, 2012