Glutathione efflux associated with a low gamma-glutamyl transpeptidase activity in human melanoma cells.
The cellular concentration of reduced glutathione (GSH) modulates the sensitivity of human melanoma cells to alkylating drugs in vitro. To investigate whether the membrane-associated enzyme gamma-glutamyl transpeptidase (gamma-GTP) involved in GSH breakdown was expressed in melanoma cells, the enzymatic activity of gamma-GTP as well as the secretion of GSH were measured in human melanoma cells from four different cell lines (Me8, JUSO, GLL19, Swift). All the cells showed low gamma-GTP activities (0-1 mU/mg protein) and released GSH in culture supernatants at significant rates. After incubation for 24 h in growth medium containing 0.1 mmol/L cystine, the levels of GSH in supernatants ranged from 56 to 111 nmol GSH/mg protein. The GSH metabolism of melanoma cells was also evaluated by measuring the levels of the melanogenesis intermediate 5-S-cysteinyldopa under different experimental conditions. The results of these experiments suggest that melanoma cells have a low ability to metabolize the tripeptide GSH, which appears to be responsible for GSH secretion and accumulation in culture supernatants.
Benathan
M
M
Department of Dermatology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
D002455:Cell Division / Q000187:drug effects; D003548:Cysteinyldopa / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D003548:Cysteinyldopa; D014442:Monophenol Monooxygenase; D005723:gamma-Glutamyltransferase; D005978:Glutathione