in chronic lymphocytic leukemia (B-CLL) cells Modulation of the activity of calcium-activated neutral proteases (calpains)

ABSTRACTDecreased susceptibility to apoptosis and impaired proliferative control are thought to be responsible for prolonged lifespan and accumulation of chronic lymphocytic leukemia (B-CLL) cells. The activity of calpains (calcium-dependent, neutral proteases, active in the cells responding to signals inducing a rise of cytoplasmic Ca 2+ ) is involved in the regulation of apoptosis of some cell types by interaction with caspase-3. This work verifies the hypothesis of the abnormal activity of calpains and its role in reduced apoptosis of the B-CLL cells. Casein zymography, RT-PCR and western blotting were used for identification and quantification of the activity and expression of calpains in B-CLL cells and purified normal B-lymphocytes. The activity and expression of ∝ -calpain (requiring micromolar Ca 2+ for activation) are significantly higher in the leukemic than in non-malignant cells. Contrarily, the activity and expression of m-calpain (requiring millimolar Ca