In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models
Figure 4
GCase protein and activity in diltiazem-treated mice:
(A) The 4 wk old mice were administered diltiazem in drinking water (10mg/kg/day) for 4 wks. D409H livers had ∼1.2-fold increases of GCase activity. GCase activity in V394L liver decreased 38% after treatment. No significant changes in GCase activity were detected in WT, D409H and V394L brain, spleen, and lung. (B) Immunoblot analyses of GCase protein levels in WT liver. Diltiazem (10 mg/kg/d) increased GCase protein by ∼1.2 fold in WT liver. Fold change is presented as the ratio relative to untreated samples. Quantitation of blots was performed using Molecular Dynamics ImageQuant 5.0 Software and using the ratio of GCase/β-actin for normalization. Each experiment was repeated in triplicate. n = 3 to 7 mice. Student's t test, **, p<0.01; *, p<0.05.