Cystinotic fibroblasts accumulate cystine from intracellular protein degradation.

Abstract

Fibroblasts derived from patients with cystinosis, an autosomal recessive condition, accumulate the disulfide amino acid cystine within lysosomes. The metabolic defect leading to the cystine accumulation and the source from which the cystine is derived are unknown. In this report we present data showing that cystine in these cells accumulates from the degradation of endogenous protein. This conclusion is based upon: (i) no demonstrable synthesis of cystine from serine; (ii) no difference in cystine reaccumulation between glutathione-depleted and non-glutathione-depleted cystinotic cells; (iii) recovery of labeled cystine only when the protein pool is labeled; (iv) reversible inhibition of cystine reaccumulation by known inhibitors of lysosomal protein degradation (chloroquine and NH4Cl).

• Authors: J G Thoene, R G Oshima, D G Ritchie, J A Schneider
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 74 Issue 10 Pg. 4505-7 (Oct 1977) ISSN: 0027-8424 [Print] United States
• PMID: 270698 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Proteins
• Cystine
• Chloroquine
• Glutathione

Topics

• Biodegradation, Environmental
• Cells, Cultured
• Chloroquine (pharmacology)
• Cystine (metabolism)
• Cystinosis (metabolism)
• Fibroblasts (metabolism)
• Glutathione (physiology)
• Humans
• Proteins (metabolism)
• Time Factors