Abstract
Nephropathic cystinosis is associated with extreme intracellular (lysosomal) storage of cystine (CySS). Reduced dithiothreitol (DTTSH) and cysteamine both decrease cellular CySS in cystinosis patients in vivo and may ameliorate the natural course of the disease. The mutant cellular function remains undefined. We studied survival of normal (n=4) and cystinotic (n=3) fibroblast lines in selective medium (CySS-free) with or without DTTSS or DTTSH in the medium. Control and cystinotic cells were matched for site of biopsy, age of donor, and passage number in culture. Cells plated at low density were washed and refed at 24 h with either control or selective media. Cell density was measured after further incubation (24 h). CySS-free medium was selective and caused detachment (>90%) of cystinotic and control cells; DTTSS (1-8 mM) and DTTSH (0.5-2 mM) both protected cystinotic cells but not control cells in the selective medium. Cystinotic cells preincubated with cysteamine (1 mM × 4 h) were not protected by DTT in CySS-free medium. These findings imply that cystinotic cells have the capability (presumably cytoplasmic in origin) to reduce DTTSS and use it to liberate CySS from their expanded intracellular pools to support growth. If CySS accumulation, or other events related to abnormal -SH metabolism are important facets of the cystinosis phenotype, there is a rationale for treatment with DTT, and like agents, in vivo.
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Lancaster, G., Scriver, C. 737 DITHIOTHREITOL (DTT) PROTECTS CYSTINOTIC FIBROBLASTS IN CYSTINE-FREE MEDIUM. Pediatr Res 15 (Suppl 4), 565 (1981). https://doi.org/10.1203/00006450-198104001-00760
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DOI: https://doi.org/10.1203/00006450-198104001-00760