Calcium-binding proteins in skeletal muscles of the mdx mice: potential role in the pathogenesis of Duchenne muscular dystrophy

Author(s)

Pertille, Adriana ^[1] ; Tonizza de Carvalho, Candida Luiza ^[1] ; Matsumura, Cintia Yuri ^[1] ; Santo Neto, Humberto ^[1] ; Marques, Maria Julia ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Anat, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: International Journal of Experimental Pathology; v. 91, n. 1, p. 63-71, FEB 2010.
• Web of Science Citations: 14

Abstract

P>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 Ca2+-calmodulin activation and calsequestrin expression may be a valuable way to develop new therapeutic approaches to the dystrophinopaties. (AU)