Effect of chloroquine on handling of cystine by cystinotic fibroblasts.
Cystinotic fibroblasts when incubated in complete medium with 100 microM chloroquine rapidly lose their stored cystine, 50% or more disappearing in 2 hr and 80% in 4 hr. During the same 2 to 4 hr period of incubation with chloroquine, no change in intracellular pools of acidic and neutral amino acids was observed. However, after 5 hr the cellular pools of these amino acids became diminished and by 24 hr became markedly depleted. Chloroquine inhibited the uptake of 35S cystine by cystinotic cells during one hour incubations in phosphate buffered saline medium. Chloroquine altered the intracellular fate of exogenous 35S cystine into cystine, cysteine and glutathione (GSH) in cystinotic cells grown in both complete medium for 24 hr or placed in buffered saline for 2 hr. In the complete medium, chloroquine suppressed incorporation of label into cystine, cysteine and GSH pools after 1 hr. In the short-term study, the drug prevented the incorporation of label into cystine and cysteine pools after 45 min.
D000596:Amino Acids / Q000378:metabolism; D002648:Child; D002738:Chloroquine / Q000494:pharmacology*; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans
D000596:Amino Acids; D003553:Cystine; D002738:Chloroquine