Effect of zinc chloride on GSH synthesis rates in various lung cell lines.
Zinc toxicity has been linked to decreased reduced glutathione (GSH) and increased oxidized glutathione (GSSG) contents, which might be caused by a GSSG reductase inhibition by zinc. In this study we investigated zinc effects on GSH synthesis rates in various lung cell lines by thin-layer chromatography after (35)S-cysteine incorporation. Two alveolar epithelial cell lines (A549 and L2) and two human fibroblast-like lung cell lines (11Lu and 16Lu) were used in this study. Equipotent protein synthesis inhibition for the different cell lines was reached after 2 h (L2, 11Lu), 3 h (16Lu), and 4 h (A549) zinc exposure (15-200 microM) to cells. Here GSH depletion and GSSG increase in A549 cells were markedly lower than in the other cell lines tested. Incorporation of cysteine (Cys) into GSH was not different in the cell lines tested, while 11Lu cells only demonstrated a decrease of newly synthesized GSH after 1 h of (35)S-Cys exposure when cells were exposed to zinc. Only 11Lu cells showed a markedly decreased Cys availability as compared with the other cell lines. In all cell lines the availability of Cys was not affected by exposure to zinc. No compensating increase in GSH synthesis rates was found after zinc-mediated cellular GSH depletion.
Walther
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UI
Walther-Straub Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians, Universität München, Nussbaumstr. 26, 80336 München, Germany.
Wilhelm
B
B
Walther
S C
SC
Mückter
H
H
Forth
W
W
D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000494:pharmacology* / Q000633:toxicity; D002855:Chromatography, Thin Layer; D003545:Cysteine / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology* / Q000633:toxicity
D002712:Chlorides; D017967:Zinc Compounds; C016837:zinc chloride; D005978:Glutathione; D003545:Cysteine