The effect of chloroquine on the metabolism of [35S]cystine in normal and cystinotic human skin fibroblasts.
The present study concerns the effect of the lysosomotropic drug chloroquine on the uptake and metabolism of [35S]cystine in vitro by normal human fibroblasts and those from patients suffering from the lysosomal storage disease cystinosis. When the cells were cultured with [35S]cystine for periods in excess of 4 h, it was found that chloroquine considerably increased (up to 30-fold) the labelling of the intracellular cystine pool in cystinotic cells, with no increase or a much smaller increase in normal cells. For this effect chloroquine had an optimum concentration of 20 microM, with a small effect still being noticeable at 1 microM. A quinoline analogue, 4-(dimethylaminoethylamino)-7-iodoquinoline, had a similar effect to chloroquine. However, NH4Cl at concentrations of between 100 microM and 50 mM showed either no effect (at the lower concentrations) or a depression of intracellular cystine labelling (at the higher concentrations). The differences between the effects of the quinolines on cystinotic acid normal cells were not due to differences in total cell uptake of drug.
D000634:Aminoquinolines / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology*; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013462:Sulfur Radioisotopes
D000634:Aminoquinolines; D013462:Sulfur Radioisotopes; D003553:Cystine; C034401:4-(dimethylaminoethylamino)-7-iodoquinoline; D002738:Chloroquine