Article

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

Departamento de Anatomia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, São Paulo, Brazil.
International Journal of Experimental Pathology (impact factor: 2.57). 12/2009; 91(1):63-71. DOI:10.1111/j.1365-2613.2009.00688.x
Source: PubMed

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.

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Keywords

Ca(2+)-calmodulin activation
 
calcium-binding proteins calsequestrin
 
calcium-handling proteins
 
calsequestrin expression
 
cardiac muscle controls
 
common hereditary diseases
 
different intensities
 
Duchenne muscular dystrophy
 
dystrophic muscle pathogenesis
 
initiating event
 
intracellular calcium
 
mdx mice
 
mdx muscles
 
muscles
 
new therapeutic approaches
 
non-spared axial
 
significant decrease
 
spared extraocular muscles
 
spared mdx EOM
 
sternomastoid muscles
 

Adriana Pertille