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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1982 Oct;79(20):6246–6249. doi: 10.1073/pnas.79.20.6246

Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis.

J M Williamson, B Boettcher, A Meister
PMCID: PMC347097  PMID: 6959113

Abstract

Depletion of glutathione by inhibition of its synthesis by buthionine sulfoximine, an irreversible inhibitor of gamma-glutamylcysteine synthetase, leads to increased sensitivity to (i) irradiation and (ii) oxidative stress. In the present work, an intracellular cysteine delivery system was used to promote glutathione synthesis, and this was found to protect against toxicity. Thus, administration of L-2-oxothiazolidine-4-carboxylate protected against acetaminophen toxicity in mice; the thiazolidine, which is converted to L-cysteine by the enzyme 5-oxo-L-prolinase (present in many animal tissues and in plants) promotes the synthesis of glutathione, which is the actual protectant. The effect of this thiazolidine in increasing the level of glutathione is prevented by administration of buthionine sulfoximine. This thiazolidine may be useful in the treatment of other toxicities and in the treatment of certain diseases. It may also be valuable as a component of amino acid mixtures used in therapy and as a safener in agriculture.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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