Altered Expression, Intracellular Distribution and Activity of Lymphocyte Calpain II in Duchenne Muscular Dystrophy

Background: Calpain II is an calcium-dependent cysteine protease involved in essential regulatory or processing functions of the cell, mediated by physiological concentrations of Ca(2+). However, in an environment of abnormal intracellular calcium as in Duchenne muscular dystrophy (DMD), calpain is suggested to cause membrane alterations.

Methods: Twelve individuals with dystrophin gene deletion and an equal number of age and sex matched controls were chosen for the study. The expression pattern of calpain II (both at RNA and protein levels), its cellular location upon activation and its activity in lymphocytes were specifically assessed to know if our earlier report of increased calpain activity in DMD lymphocytes is a result of de novo synthesis or is due to basic defect in calcium handling.

Results: We found a significant increase in the expression, alteration in calpain II distribution and increased activity of this enzyme.

Conclusion: Membrane abnormalities and altered signaling pathways observed in DMD lymphocytes may be due to increased association of calpain II onto membrane and cytosol.