Structural changes in lysosomes from cultured human fibroblasts in Duchenne's muscular dystrophy

B. B. Gelman, M. H. Davis, R. E. Morris, E. Gruenstein

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

We have previously reported a decreased activity of the lysosomal enzyme dipeptidyl aminopeptidase-I (DAP-I) in cultured fibroblasts from patients with Duchenne's muscular dystrophy (DMD). Here we report that electron microscope examination of these cells reveals the presence of abundant lamellar bodies, a morphologic abnormality commonly associated with impaired lysosomal function. Morphometric analysis of these cytoplasmic figures in dystrophic cells shows a sevenfold increase relative to normal controls (P < 0.01). Analysis of lysosomal density profiles by density gradient centrifugation reveals similar patterns in normal and DMD cells. Treatment of lysosomes with the nonionic detergent Triton X-100 causes an activation of DAP-I. This activation, attributable to structure-linked latency, is markedly diminished in DMD cells which show an optimal activation of only 180% compared to 255% for control fibroblasts (P < 0.01). These data suggest an alteration in the properties of the lysosomal membrane in DMD fibroblasts. This suggestion is also supported by studies on the release of DAP-I from lysosomes by osmotic shock which show it to be a membrane-associated enzyme with membrane-binding characteristics intermediate between those of tightly bound β-glucosidase and those of unbound N-acetylgalactosaminidase. The latency characteristics of these other lysosomal enzymes are not altered in the DMD cells, indicating that the effect is specific for DAP-I.

Original languageEnglish (US)
Pages (from-to)329-337
Number of pages9
JournalJournal of Cell Biology
Volume88
Issue number2
DOIs
StatePublished - 1981

ASJC Scopus subject areas

  • Cell Biology

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