Serveur d'exploration Chloroquine

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Effects of lysosomotropic agents on lipogenesis

Identifieur interne : 003434 ( Main/Exploration ); précédent : 003433; suivant : 003435

Effects of lysosomotropic agents on lipogenesis

Auteurs : Grace L. Chen [États-Unis] ; Sarah L. Sutrina ; Karen L. Frayer [États-Unis] ; Winston W. Chen

Source :

RBID : ISTEX:2A304F5FB0F6C56F038ECA09A7210CE6C7018C92

English descriptors

Abstract

Abstract: Chloroquine, quinine, and NH4Cl are lysosomotropic agents which inhibit lysosomal function, apparently by raising the intralysosomal pH. We found that preincubation of cultured human skin fibroblasts with these lysosomotropic agents under serum-free conditions induced about a 10-fold stimulation of lipogenesis. A similar stimulatory effect on the incorporation of 3H2O, [14C]acetate, [14C]pyruvate, [14C]palmitate, and [14C]choline into cellular lipids was observed. The effect was both time and dose dependent, and was reversible. The concentrations of chloroquine, quinine, and NH4Cl resulting in half-maximal stimulation were about 3 μm, 30 μm, and 9 mm, respectively. At these concentrations, stimulation of lipogenesis correlated with impairment of lysosomal function. At a concentration of 10 μm chloroquine, the half-time for maximal stimulation was about 4 h. Most of the [14C]acetate was incorporated into phosphatidylcholine and other cellular lipids; less than 10% was found in cholesterol and cholesterol ester. Nevertheless, incorporation of [14C]acetate into cholesterol showed a chloroquine-induced stimulation parallel to that observed for phospholipids, suggesting that stimulation of both lipogenesis and cholesterogenesis occurred. The stimulatory effect of lysosomotropic agents on lipogenesis appeared to depend on active synthesis of cellular proteins. In the presence of cycloheximide, an inhibitor of protein synthesis, the stimulation was completely abolished.

Url:
DOI: 10.1016/0003-9861(86)90190-6


Affiliations:


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<div type="abstract" xml:lang="en">Abstract: Chloroquine, quinine, and NH4Cl are lysosomotropic agents which inhibit lysosomal function, apparently by raising the intralysosomal pH. We found that preincubation of cultured human skin fibroblasts with these lysosomotropic agents under serum-free conditions induced about a 10-fold stimulation of lipogenesis. A similar stimulatory effect on the incorporation of 3H2O, [14C]acetate, [14C]pyruvate, [14C]palmitate, and [14C]choline into cellular lipids was observed. The effect was both time and dose dependent, and was reversible. The concentrations of chloroquine, quinine, and NH4Cl resulting in half-maximal stimulation were about 3 μm, 30 μm, and 9 mm, respectively. At these concentrations, stimulation of lipogenesis correlated with impairment of lysosomal function. At a concentration of 10 μm chloroquine, the half-time for maximal stimulation was about 4 h. Most of the [14C]acetate was incorporated into phosphatidylcholine and other cellular lipids; less than 10% was found in cholesterol and cholesterol ester. Nevertheless, incorporation of [14C]acetate into cholesterol showed a chloroquine-induced stimulation parallel to that observed for phospholipids, suggesting that stimulation of both lipogenesis and cholesterogenesis occurred. The stimulatory effect of lysosomotropic agents on lipogenesis appeared to depend on active synthesis of cellular proteins. In the presence of cycloheximide, an inhibitor of protein synthesis, the stimulation was completely abolished.</div>
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