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

UN Wiesmann, S DiDonato… - … and Biophysical Research …, 1975 - Elsevier
UN Wiesmann, S DiDonato, NN Herschkowitz
Biochemical and Biophysical Research Communications, 1975Elsevier
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 …
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.
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