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

Wiesmann, Ulrich; DiDonato, Stephano; Herschkowitz, N

doi:10.1016/0006-291x(75)90506-9

Cited by 106 publications

(37 citation statements)

References 11 publications

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“…(1 mmol/l), both substances which alkalinize lysosomes (Wiesmann et al, 1975;Sandeaux et al, 1981), enhance F>520 (Table 2) Table 2). The increase of F, 520 following the addition of NH3/NH4' is not significantly modified by a simultaneous increase of extracellular osmolarity (results not shown).…”

Section: As Illustrated Inmentioning

confidence: 96%

Effect of cell volume on Acridine Orange fluorescence in hepatocytes

Völkl

Friedrich

Häussinger

et al. 1993

Biochemical Journal

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Hepatic proteolysis is inhibited by cell swelling following a variety of experimental manoeuvres, such as reduction of extracellular osmolarity, concentrative uptake of amino acids, or blockade of K+ channels by barium. On the other hand, proteolysis is known to be accomplished by pH-sensitive lysosomal proteases. Accordingly, NH3/NH4+ inhibits proteolysis by intralysosomal alkalinization. The present study has been performed to test for an effect of cell volume on the pH of acidic intracellular compartments, as assessed by Acridine Orange fluorescence at > 520 nm (F > 520). F > 520 is enhanced by NH3/NH4+ (2 and 20 mmol/l respectively), by glutamine (2 mmol/l), by the K(+)-channel blocker barium (10 mmol/l) and by reduction of extracellular osmolarity (by 20 and 80 mosmol/l respectively). The observations point to release of Acridine Orange from acidic cellular compartments, which is indicative of alkalinization of these compartments during cell swelling. This effect may contribute to the regulation of proteolysis.

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Section: As Illustrated Inmentioning

confidence: 96%

Effect of cell volume on Acridine Orange fluorescence in hepatocytes

Völkl

Friedrich

Häussinger

et al. 1993

Biochemical Journal

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“…Several laboratories have found that chloroquine inhibits pinocytosis of exogenous enzyme [42][43][44][45]. Gonzalez-Noriega et a1 [44] recently reported experiments suggesting that this inhibition is due to inhibition of reutilization of cell-surface receptors following internalization of enzyme-receptor complexes.…”

Section: Lysosomotropic Amines Impair Receptor Reutilizationmentioning

confidence: 99%

The Phosphomannosyl Recognition System for Intracellular and Intercellular Transport of Lysosomal Enzymes

Sly

1982

J of Cellular Biochemistry

362

152

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“…These include calcitonin, colchicine, enzyme inhibitors, and synthetic substrates [4][5][6]. The present study was undertaken to test the effects of three drugs--chloroquine, hydroxystilbamidine, and dapsone--which have been found to affect the activity or release of lysosomal enzymes in other systems [7][8][9]. All three were found to inhibit the stimulation of release of 45Ca and the lysosomal enzyme /3-glucuronidase produced by parathyroid hormone (PTH) or prostaglandin E2 (PGE2) in cultured fetal rat long bones.…”

mentioning

confidence: 98%

Chloroquine, hydroxystilbamidine, and dapsone inhibit resorption of fetal rat bone in organ culture

Eilon

Raisz

1982

Calcif Tissue Int

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Three potential inhibitors of lysosomal enzyme release, chloroquine, hydroxystilbamidine, and dapsone were tested for their effects on the release of previously incorporated 45Ca and beta (beta)-glucuronidase from fetal rat long bones cultured in a chemically defined medium. At concentrations of 10(-5) to 10(-8)M, all three agents were able to inhibit the stimulation of bone resorption by parathyroid hormone (PTH) or prostaglandin E2 (PGE2). Inhibition was seen at concentrations which did not alter the uptake of (3H)-2-deoxy-glucose or the incorporation of (3H)-thymidine in bone. While the inhibitors blocked the stimulation of beta-glucuronidase release by PTH and PGE2, they could also cause a direct increase in total beta-glucuronidase content and release. Hence the usual strong correlation between the release of beta-glucuronidase and 45Ca was no longer seen in the presence of inhibitors. These data indicate that chloroquine, hydroxystilbamidine, and dapsone are potent inhibitors of bone resorption which may act by blocking the release of lysosomal enzymes in cells stimulated by PTH or PGE2, but may have a different effect on other cell populations.

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

Cited by 106 publications

References 11 publications

Effect of cell volume on Acridine Orange fluorescence in hepatocytes

Effect of cell volume on Acridine Orange fluorescence in hepatocytes

The Phosphomannosyl Recognition System for Intracellular and Intercellular Transport of Lysosomal Enzymes

Chloroquine, hydroxystilbamidine, and dapsone inhibit resorption of fetal rat bone in organ culture

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