Lysosomal cystine storage in cystinosis and mucolipidosis type II.
Cultured fibroblasts from mucolipidosis II (ML-II) patients demonstrated an elevated cystine content which increased with time in culture compared to fibroblasts from cystinotic patients or normal controls under the same conditions. In both cystinotic and ML-II cells the increased levels of cystine could be derived either from endogenous proteolysis or from in vitro supplementation of the cultured cells with cysteine-glutathione mixed disulfide. Cystine was depleted from both cell types by cysteamine. When cysteamine was replaced with complete medium, the cystine reaccumulated in both cystinotic and ML-II cells within 24 h, although a lag of 4 h was seen with ML-II cells. The intracellular location of the increased cystine in cultured fibroblasts was examined utilizing free-flow electrophoresis and found to be in the purified population of secondary lysosomes of both cystinotic and ML-II cells. White blood cell and hepatic cystine, which was greatly increased in cystinotic patients, was not elevated in ML-II patients. Compared to normal control fibroblasts the efflux of cystine from isolated granular fractions was virtually absent in cystinotic fibroblasts and considerably reduced in ML-II fibroblasts. The examination of such similarities and differences in cystine accumulation and transport in tissues from cystinotic and ML-II patients has provided some insight into the defects in these diseases.
D002478:Cells, Cultured; D003543:Cysteamine / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D003553:Cystine / Q000378:metabolism*; D003554:Cystinosis / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D009081:Mucolipidoses / Q000378:metabolism*
D003553:Cystine; D003543:Cysteamine; D003545:Cysteine