CHARACTERIZATION OF MULTIPLE CYSTEINE AND CYSTINE TRANSPORTERS IN RATALVEOLAR TYPE-II CELLS

Cysteine availability is rate limiting for the synthesis of glutathion e, an important antioxidant in the lung. We used rat alveolar epitheli al type II cells to study the mechanism of cysteine and cystine uptake . Consistent with carrier-mediated transport, each uptake process was saturable with Michaelis-Menten kinetics and was inhibited at 4 degree s C and by micromolar levels of amino acids or analogs known to be sub strates for a specific transporter. A unique system X-AG was found tha t transports cysteine and cystine (as well as glutamate and aspartate, the only substrates previously described for system X-AG) We also ide ntified a second Na+-dependent cysteine transporter system, system ASC , and two Na+-independent transporter systems, system x(c) for cystine and system L for cysteine. In the presence of glutathione at levels m easured in rat plasma and alveolar lining fluid, cystine was reduced t o cysteine and was transported on systems ASC and X-AG, doubling the t ransport rate. Cysteinylglycine, released from glutathione at the cell surface by gamma-glutamyl transpeptidase, also stimulated uptake afte r reduction of cystine. These findings suggest that, under physiologic al conditions, cysteine and cystine transport is influenced by the ext racellular redox state.