Impaired clearance of free cystine from lysosome-enriched granular fractions of I-cell-disease fibroblasts.

Abstract

Cultured fibroblasts from patients with I-cell disease (mucolipidosis II) accumulate excessive amounts of free cystine, similarly to cells from patients with nephropathic cystinosis, a disorder of lysosomal cystine transport. To clarify whether the intralysosomal accumulation of cystine in I-cell-disease fibroblasts was due to a defective disposal mechanism, we measured the rates of clearance of free [35S]cystine from intact normal, cystinotic and I-cell-disease fibroblasts. Loss of radioactivity from the two mutant cell types occurred slowly (t 1/2 = 500 min) compared with the rapid loss from normal cells (t 1/2 = 40 min). Lysosome-rich granular fractions isolated from three different cystine-loaded normal, cystinotic and I-cell-disease fibroblast strains were similarly examined for non-radioactive cystine egress. Normal granular fractions lost cystine rapidly (mean t 1/2 = 43 min), whereas cystinotic granular fractions did not lose any cystine (mean t 1/2 = infinity). I-cell-disease granular fractions displayed prolonged half-times for cystine disposal (mean = 108 min), suggesting that I-cell-disease fibroblasts, like cystinotic cells, possess a defective carrier mechanism for cystine transport.

• Authors: F Tietze, L H Rome, J D Butler, G S Harper, W A Gahl
• Journal: The Biochemical journal (Biochem J) Vol. 237 Issue 1 Pg. 9-15 (Jul 01 1986) ISSN: 0264-6021 [Print] England
• PMID: 3800891 (Publication Type: Journal Article)

Chemical References

• Cystine
• cystine dimethyl ester

Topics

• Cells, Cultured
• Cystine (analogs & derivatives, metabolism, pharmacology)
• Cystinosis (metabolism)
• Cytoplasmic Granules (metabolism)
• Fibroblasts (drug effects, metabolism)
• Humans
• Lysosomes (metabolism)
• Mucolipidoses (metabolism)
• Subcellular Fractions (metabolism)