Calcium-binding proteins in skeletal muscles of the mdx mice: potential role in the pathogenesis of Duchenne muscular dystrophy.
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.
Pertille
Adriana
A
Departamento de Anatomia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil.
de Carvalho
Candida Luiza Tonizza
CL
Matsumura
Cintia Yuri
CY
Neto
Humberto Santo
HS
Marques
Maria Julia
MJ
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
D002147:Calmodulin; D002155:Calsequestrin