Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens

Abstract

The study included human lenses of ages ranging from newborn to 92 years. Protein-free reduced glutathione decreased 14-fold, whereas protein-free oxidized glutathione increased 2·6-fold with increasing age. l-Cyst(e)ine uptake g −1 lens of very old cultured lenses decreased 70% from that exhibited in newborn lenses, demonstrating a marked decline of l-cyst(e)ine uptake as a function of age. In these same lenses the synthesis of reduced glutathione (μmol g −1 lens) decreased 73% with age. It was concluded that the glutathione decrease observed in the aging human lens was associated with decreased uptake of l-cyst(e)ine, decreased glutathione synthesis and possibly an increase in protein-free oxidized glutathione. The high correlation of l-cyst(e)ine uptake and glutathione synthesis supports the hypothesis that l-cyst(e)ine uptake is a rate-limiting factor of glutathione synthesis in the intact human lens. By the use of buthionine sulfoximine, the half-life of glutathione was estimated to be 90 hr in the cultured human lens.