Altered activity of signaling pathways in diaphragm and tibialis anterior muscle of dystrophic mice.
Duchenne muscular dystrophy is a musculoskeletal disease caused by mutations in the dystrophin gene. The purpose of this study was to use the mouse model of muscular dystrophy (mdx) to determine if the progression of the dystrophic phenotype in the diaphragm (costal) versus limb skeletal muscle (tibialis anterior) is associated with specific changes in extracellular regulated kinase (ERK1/2), p70 S6 kinase (p70(S6k)), or p38 signaling pathways. The studies detected that consistent with an earlier dystrophic phenotype, phosphorylation of p70(S6k) is elevated by 40% in the diaphragm with no change in limb muscle. In addition, phosphorylation of p38 kinase was decreased by 33% in the mdx diaphragm muscle. Levels of ERK1/2 as well as phosphorylation states were elevated in the diaphragm and limb muscle of mdx mice compared with age-matched control muscles. These results indicate that distinct signaling pathways are differentially activated in skeletal muscle of mdx mice. The specificity of these responses, particularly in the diaphragm, provides insight for potential targets for blunting the progression of the muscular dystrophy phenotype.
Lang
Joshua M
JM
Muscle Biology Laboratory, School of Kinesiology, University of Illinois, Chicago, Illinois 60608, USA.
Esser
Karyn A
KA
Dupont-Versteegden
Esther E
EE
D000818:Animals; D003964:Diaphragm / Q000201:enzymology*; D005121:Extremities; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology*; D009137:Muscular Dystrophy, Animal / Q000201:enzymology*; D010641:Phenotype; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D013912:Threonine; D014443:Tyrosine; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases