title: Calcium-binding proteins in skeletal muscles of the mdx mice: potential role in the pathogenesis of Duchenne muscular dystrophy.
abstract: Duchenne muscular dystrophy is one of the most common hereditary diseases. Abnormal ion handling renders dystrophic muscle fibers more susceptible to necrosis and a rise in intracellular calcium is an important initiating event in dystrophic muscle pathogenesis. In the mdx mice, muscles are affected with different intensities and some muscles are spared. We investigated the levels of the calcium-binding proteins calsequestrin and calmodulin in the non-spared axial (sternomastoid and diaphragm), limb (tibialis anterior and soleus), cardiac and in the spared extraocular muscles (EOM) of control and mdx mice. Immunoblotting analysis showed a significant increase of the proteins in the spared mdx EOM and a significant decrease in the most affected diaphragm. Both proteins were comparable to the cardiac muscle controls. In limb and sternomastoid muscles, calmodulin and calsequestrin were affected differently. These results suggest that differential levels of the calcium-handling proteins may be involved in the pathogenesis of myonecrosis in mdx muscles. Understanding the signaling mechanisms involving Ca(2+)-calmodulin activation and calsequestrin expression may be a valuable way to develop new therapeutic approaches to the dystrophinopaties.
authors.affiliation: Departamento de Anatomia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Pertille
authors.forename: Candida Luiza Tonizza
authors.initials: CL
authors.lastname: de Carvalho
authors.forename: Cintia Yuri
authors.initials: CY
authors.lastname: Matsumura
authors.forename: Humberto Santo
authors.initials: HS
authors.lastname: Neto
authors.forename: Maria Julia
authors.initials: MJ
authors.lastname: Marques
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002147:Calmodulin / Q000378:metabolism*; D002155:Calsequestrin / Q000378:metabolism*; D003964:Diaphragm / Q000378:metabolism; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis; D010641:Phenotype
chemical_list: D002147:Calmodulin; D002155:Calsequestrin