Cystine accumulation and loss in normal, heterozygous, and cystinotic fibroblasts.

AUTOR(ES)

Jonas, A J

RESUMO

Cystinotic fibroblasts contain approximately 100 times more cystine than do normal control fibroblasts. When cystinotic fibroblasts were placed in the presence of 30 mM cysteine-glutathione mixed disulfide (CSSG) for 24 hr, their cystine content increased about 3-fold. Similar treatment of normal fibroblasts and fibroblasts from patients heterozygous for cystinosis resulted in a 6- to 7-fold increase in cystine content. In all three cell types, the intracellular free cystine is located within lysosomes. When placed in cystine-free medium after 24 hr in CSSG-containing medium, the normal and heterozygous fibroblasts rapidly lost their lysosomal cystine (t 1/2 = 20 min), but the cystine content of the cystinotic cells remained stable for over 90 min. In contrast to the findings in intact fibroblasts, cystine loss could not be demonstrated from isolated, cystine-loaded lysosomes from any of the three cell types.

Documentos Relacionados

• Cystine accumulation and clearance by normal and cystinotic leukocytes exposed to cystine dimethyl ester.
• Uptake and Utilization of Exogenous Cystine by Cystinotic and Normal Fibroblasts
• Cystinotic fibroblasts accumulate cystine from intracellular protein degradation.
• Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide.
• Inhibitors of protein synthesis also inhibit lysosomal proteolysis. Studies using cystinotic fibroblasts.