Effects of cysteamine and other thiols on cystine egress from isolated lysosome-rich fractions of cystinotic and normal leucocytes

Abstract

After loading isolated normal and cystinotic white blood cell lysosomes with radioactive amino acid methyl esters, egress of the corresponding amino acids was measured in the presence or absence of reducing agents. Cysteamine greatly enhanced disposal of cystine- and, to a lesser extent, cysteine-loaded lysosomes, resulting in final similar rates of radioactive clearance. Cysteamine did not alter leucine egress. Cysteamine comparably accelerated cystine egress from normal and cystinotic lysosomes. Reduced glutathione, ascorbic acid, coenzyme A and acetylcoenzyme A, which are much less effective cystine-depleting agents on intact cystinotic cells than cysteamine, failed to increase egress rates from isolated lysosomes loaded with cystine. We believe this in vitro system can help in the future in evaluating drug efficacy in reducing cystine content in cystinotics in addition to the already existing tissue culture technique.