{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:05:39Z","timestamp":1762542339792},"reference-count":0,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[1995,5,15]],"date-time":"1995-05-15T00:00:00Z","timestamp":800496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[1995,5,15]]},"abstract":"<jats:p>1. The roles of the gamma\u2010glutamyl cycle and the anionic amino acid transport system xc\u2010 in mediating L\u2010cystine uptake were investigated in cultured human pancreatic duct PaTu 8902 cells. This cell line exhibits morphological features of normal pancreatic duct cells and expresses gamma\u2010glutamyl transpeptidase (gamma\u2010GT, EC 2.3.2.2), an enzyme involved in the metabolism and regulation of intracellular glutathione (GSH). 2. Uptake of L\u2010cystine (10 microM) was linear for up to 10 min, temperature dependent, Na+ independent, saturable (Michaelis\u2010Menten constant (Km), 86 +\/\u2010 25 microM; maximal velocity (Vmax), 109 +\/\u2010 33 nmol (mg protein)\u20101 h\u20101) and reduced by 80\u201090% by a 50\u2010fold excess concentration of L\u2010glutamate and L\u2010homocysteic acid, but not L\u2010aspartate. These transport properties resemble those described for system xc\u2010, which exchanges cystine for intracellular glutamate. 3. Acivicin, a known inhibitor of gamma\u2010GT, decreased gamma\u2010GT activity from 2.58 +\/\u2010 0.96 to 0.97 +\/\u2010 0.11 mU (mg protein)\u20101 and decreased the initial rates of L\u2010cystine and L\u2010glutamine uptake by 41\u201055%. Anthglutin (1\u2010gamma\u2010L\u2010glutamyl\u20102\u2010(2\u2010carboxyphenylhyl)hydrazine), a structurally different inhibitor of gamma\u2010GT, also caused a concentration\u2010dependent (0.01\u20101 mM) decrease in gamma\u2010GT activity and L\u2010cystine uptake. 4. Neither acivicin nor anthglutin inhibited the uptake of L\u2010glutamate, a poor substrate for gamma\u2010GT. 5. In the presence of a 500\u2010fold excess concentration of glutamate, which should abolish entry of cystine via system xc\u2010, the remaining fraction of cystine transport was inhibited by 50% by acivicin, suggesting that transport is, in part, dependent on the activity of gamma\u2010GT. 6. Cystine transport was also 60\u201080% inhibited by a series of gamma\u2010glutamyl amino acids (5 mM) including gamma\u2010glutamyl\u2010glutamate, gamma\u2010glutamyl\u2010glutamine and gamma\u2010glutamyl\u2010glycine. alpha\u2010Dipeptides inhibited cystine transport by only 6\u201022%. 7. These findings demonstrate that in human pancreatic duct PaTu 8902 cells, cystine uptake is mediated by system xc\u2010 (50\u201060%) and the gamma\u2010glutamyl cycle. Our results provide the first evidence linking gamma\u2010GT with cystine transport in human epithelial cells and are of relevance in view of the importance of cystine as a sulphur amino acid source for GSH synthesis in cells exposed to oxidative stress.<\/jats:p>","DOI":"10.1113\/jphysiol.1995.sp020721","type":"journal-article","created":{"date-parts":[[2014,12,17]],"date-time":"2014-12-17T10:26:01Z","timestamp":1418811961000},"page":"167-177","source":"Crossref","is-referenced-by-count":37,"title":["A role for gamma\u2010glutamyl transpeptidase and the amino acid transport system xc\u2010 in cystine transport by a human pancreatic duct cell line."],"prefix":"10.1113","volume":"485","author":[{"given":"J H","family":"Sweiry","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Sastre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Vi\u00f1a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H P","family":"Els\u00e4sser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G E","family":"Mann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1995,5,15]]},"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.1995.sp020721","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.1995.sp020721","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T17:22:21Z","timestamp":1698254541000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.1995.sp020721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,5,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,5,15]]}},"alternative-id":["10.1113\/jphysiol.1995.sp020721"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.1995.sp020721","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,5,15]]}}}