Decreased lysosomal dipeptidyl aminopeptidase I activity in cultured human skin fibroblasts in Duchenne's muscular dystrophy

Benjamin Gelman, L. Papa, M. H. Davis, E. Gruenstein

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 K(m) 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.

Original languageEnglish (US)
Pages (from-to)1398-1406
Number of pages9
JournalJournal of Clinical Investigation
Volume65
Issue number6
StatePublished - 1980
Externally publishedYes

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Cathepsin C
Duchenne Muscular Dystrophy
Fibroblasts
Skin
Enzymes
Cathepsin B
Dithiothreitol
Glycoside Hydrolases
Reducing Agents
Chlorides
Ions

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Decreased lysosomal dipeptidyl aminopeptidase I activity in cultured human skin fibroblasts in Duchenne's muscular dystrophy. / Gelman, Benjamin; Papa, L.; Davis, M. H.; Gruenstein, E.

In: Journal of Clinical Investigation, Vol. 65, No. 6, 1980, p. 1398-1406.

Research output: Contribution to journalArticle

Gelman, Benjamin ; Papa, L. ; Davis, M. H. ; Gruenstein, E. / Decreased lysosomal dipeptidyl aminopeptidase I activity in cultured human skin fibroblasts in Duchenne's muscular dystrophy. In: Journal of Clinical Investigation. 1980 ; Vol. 65, No. 6. pp. 1398-1406.
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