S-METHYLTHIO-CYSTEINE AND CYSTAMINE ARE POTENT STIMULATORS OF THIOL PRODUCTION AND GLUTATHIONE SYNTHESIS

The effects of methylthio-cysteine disulfide (MT-Cy) and cystamine (CA M) on the thiol production and glutathione content of a human T cell l ine (CEM-SS) have been investigated. MT-Cy per se and CAM in the prese nce of cystine greatly enhanced thiol production and glutathione conte nt of cells while cystine alone exerted no or slight influence in the first hours. The MT-Cy-or CAM-induced extracellular SH-generation was observed both in a complete nutrient medium and even more in SH-free D -PBS. The acid-soluble thiol level and glutathione content of cells el evated markedly (up to 5-6 fold in two hours) when incubating cells in complete medium. Inhibition of glutathione synthesis by DL-buthionine (S,R)-sulfoximine did not alter the MT-CSI-or CAM-induced extracellul ar thiol production indicating that glutathione synthesis is not invol ved in this effect. The results suggest that MT-Cy easily enters the c ells thus accelerating the thiol cycle in SH-poor medium while CAM pro motes cystine uptake into the cells. Phenylalanine and leucine inhibit ed both MT-Cy- and CAM-dependent thiol production in D-PBS most effect ively suggesting the involvement of the L membrane transport system in these effects. (C) 1998 Elsevier Science Inc.