Characterization of multiple cysteine and cystine transporters in rat alveolar type II cells

The American Journal of Physiology
R G KnickelbeinJ B Warshaw

Abstract

Cysteine availability is rate limiting for the synthesis of glutathione, an important antioxidant in the lung. We used rat alveolar epithelial 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 degrees C and by micromolar levels of amino acids or analogs known to be substrates for a specific transporter. A unique system XAG was found that transports cysteine and cystine (as well as glutamate and aspartate, the only substrates previously described for system XAG). We also identified a second Na(+)-dependent cysteine transporter system, system ASC, and two Na(+)-independent transporter systems, system xc for cystine and system L for cysteine. In the presence of glutathione at levels measured in rat plasma and alveolar lining fluid, cystine was reduced to cysteine and was transported on systems ASC and XAG, doubling the transport rate. Cysteinylglycine, released from glutathione at the cell surface by gamma-glutamyl transpeptidase, also stimulated uptake after reduction of cystine. These findings suggest that, under physiological conditions, cysteine and cystine transport is influenc...Continue Reading

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Citations

Oct 29, 2000·American Journal of Physiology. Lung Cellular and Molecular Physiology·X JiangS M O'Grady
Oct 27, 2009·Antioxidants & Redox Signaling·Yuka KimuraHideo Kimura
Nov 8, 2001·American Journal of Physiology. Cell Physiology·A C RimaniolG Gras
Apr 29, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Olivia M GranilloRichard L Auten
Aug 9, 2002·American Journal of Physiology. Renal Physiology·Esperanza FernándezJosep Chillarón
Oct 22, 2020·Cancers·Janine M DeBlasi, Gina M DeNicola
Jul 1, 2007·Environmental Toxicology and Pharmacology·Malin Hultberg

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