TEMPERATURE-DEPENDENT INFLUENCE OF THIOLS UPON GLUTATHIONE LEVELS IN CHINESE-HAMSTER OVARY CELLS AT CYTO-TOXIC CONCENTRATIONS
- 1 January 1985
- journal article
- research article
- Vol. 45 (12) , 6219-6224
Abstract
Chinese hamster ovary cells were exposed to the sulfhydryl compound cysteamine at different temperatures (5.degree. C, 37.degree. C, 44.degree. C) at concentrations known to generate activated oxygen species. At 37.degree. C, the cellular glutathione (GSH) content increased linearly over the time of drug exposure(2 h) as compared to untreated cells or to cells kept at 5.degree. C during drug treatment. The 2-4 fold increase in GSH induced by cysteamine was more rapid at 44.degree. C than at 37.degree. C and showed a saturation effect at the higher temperature. The elevation of GSH could be completely blocked by DL-buthionine-S,R-sulfoximine, an inhbitor of .gamma.-glutamylcysteine synthetase, or by incubation in a cystine-free medium during the period of drug treatment. The increased cellular GSH content induced by cysteamine alone at 37.degree. C or combined with heat at 44.degree. C decreased to the range of control values within 22 h after either treatment. Other thiols like cysteamine, namely cysteine, N-acetylcysteine, and dithiotheitol, werd found to be similar in their potential to induce GSH elevation in Chinese hamster ovary cells. Cytotoxic effects of these sulfhydryl compounds were observed in the same concentration range as that for cysteamine(0-2 mM), but only if cells were plated at low densities (102-104 cells/flask), and were completely blocked by the addition of catalase (50 .mu.g/ml). In contrast, the elevation of GSH after thiol treatment (0.8 mM) was not modified by catalase. The data suggest that thiol treatment combined with hyperthermia leads to a rapid increase of GSH biosynthesis in Chinese hamster ovary cells which seems to be independent of the simultaneous generation of activated oxygen species by thiol autoxidation.This publication has 17 references indexed in Scilit:
- Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis.Published by Elsevier ,2021
- Intracellular cysteine delivery system that protects against toxicity by promoting glutathione synthesis.Proceedings of the National Academy of Sciences, 1982
- Increase in hepatic mixed disulphide and glutathione disulphide levels elicited by paraquatBiochemical Pharmacology, 1982
- Mechanism of growth stimulation of L1210 cells by 2-mercaptoethanol in vitro. Role of the mixed disulfide of 2-mercaptoethanol and cysteine.Journal of Biological Chemistry, 1981
- Influence of cysteine upon the glutathione status of isolated rat hepatocytesBiochemical Pharmacology, 1981
- Formation of sulfhydryl groups in the culture medium by human diploid fibroblastsJournal of Cellular Physiology, 1980
- THERMOSENSITIZATION BY SULFHYDRYL COMPOUNDS OF EXPONENTIALLY GROWING CHINESE-HAMSTER CELLS1979
- Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo.Journal of Clinical Investigation, 1976
- Effect of Heat and Radiation on Synchronous Chinese Hamster Cells: Killing and RepairRadiation Research, 1975
- PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENTJournal of Biological Chemistry, 1951