Effect of chloroquine on cultured fibroblasts: Release of lysosomal hydrolases and inhibition of their uptake

Ulrich N. Wiesmann, Stephano DiDonato, Norbert N. Herschkowitz

Research output: Contribution to journalArticlepeer-review

Abstract

Incubation of normal human fibroblasts with 1-5 μM chloroquine at physiological pH for 8 hr produces granular cytoplasmic inclusions, release of lysosomal enzymes into the medium and decrease of intracellular lysosomal enzyme activities. The effects are dose dependent and reversible. The uptake of arylsulfatase A into fibroblasts genetically deficient in arylsulfatase A (grown from skin biopsies of patients with metachromatic leukodystrophy) is completely inhibited by pretreating the cells with 5 μM chloroquine. Arylsulfatase A, which has been taken up as exogenous enzyme from the medium into the cells, is partially released into the culture medium upon incubation with chloroquine. The data suggest that chloroquine competes with the binding of lysosomal enzymes to the cell membrane and to the membranes of pinocytotic vacuoles and causes release of previously internalized exogenous enzyme.

Original languageEnglish
Pages (from-to)1338-1343
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume66
Issue number4
DOIs
Publication statusPublished - Oct 27 1975

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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