Decreased Lysosomal Dipeptidyl Aminopeptidase I Activity in Cultured Human Skin Fibroblasts in Duchenne's Muscular Dystrophy
Open Access
- 1 June 1980
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 65 (6), 1398-1406
- https://doi.org/10.1172/jci109804
Abstract
Several lysosomal enzymes were assayed in cultured human skin fibroblasts from patients with Duchenne's muscular dystrophy (DMD) and age- and sex-matched control patients (N). The activity of four glycosidases, cathepsin B1, and total autoproteolysis at pH 4.0 were unchanged between the groups, but dipeptidyl aminopeptidase I (DAP-I, or cathepsin C) in the DMD cells was found to be only 30% as active as in the control cells (P < 0.003). This difference is not the result of a redistribution or loss of enzyme during homogenization because the difference occurs in all homogenate fractions. DAP-I activity existing in N and DMD fibroblasts behaves identically with respect to activation by chloride ion, activation by the sulfhydryl reducing agent dithiothreitol, changes in hydrogen ion concentration (pH), changes in substrate concentration (i.e., apparent Km values), and changes in temperature (i.e., apparent activation energies). Mixtures of N and DMD cell sonicates display an additivity in DAP-I activity. These results support the conclusion that the catalytic function of the DAP-I molecule is equivalent between N and DMD fibroblasts, and that the decrease in tissue-specific DAP-I activity probably results from the fact that fewer enzyme molecules are present in the DMD cells. These results are also an indication that these nonmuscle cells are expressing some of the phenotypic aspects of the genetic defect in DMD. Cultured human skin fibroblasts may therefore be a useful cellular model in DMD research.This publication has 24 references indexed in Scilit:
- DUCHENNE'S MUSCULAR DYSTROPHY: STUDIES IN CULTURED FIBROBLASTSThe Lancet, 1977
- A calcium-activated neutral protease in normal and dystrophic human muscleClinica Chimica Acta; International Journal of Clinical Chemistry, 1976
- Adenyl cyclase abnormality in Duchenne muscular dystrophyNeurology, 1976
- PROTEIN SYNTHESIS IN MUSCLE CULTURES FROM PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHYActa Neurologica Scandinavica, 1976
- Duchenne dystrophyNeurology, 1975
- Fatty Acid Pattern of Lipids in Normal and Dystrophic Human MuscleEuropean Journal of Clinical Investigation, 1975
- LYSOSOMES OF THE ARTERIAL WALLThe Journal of Experimental Medicine, 1972
- Acid, Neutral and Alkaline Cathepsins in Normal and Diseased Human MuscleEnzyme, 1972
- New observations on the substrate specificity of cathepsin C (dipeptidyl aminopeptidase I). Including the degradation of beta-corticotropin and other peptide hormones.1969
- Purification and Properties of Dipeptidyl Transferase (Cathepsin C)*Biochemistry, 1966