GLUTATHIONE REDOX STATUS IN THE HUMAN CELL LINE, A549, FOLLOWING INTRACELLULAR GLUTATHIONE DEPLETION AND EXTRACELLULAR GLUTATHIONE ADDITION

Author: Pendergrass J. A.   Srinivasan Jr. V.   Clark E. P.   Kumar K. S.  

Publisher: Taylor & Francis Ltd

ISSN: 1091-7659

Source: Toxic Substance Mechanisms, Vol.18, Iss.1, 1999-01, pp. : 11-20

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Abstract

The redox status of glutathione (L-gamma-glutamyl-L-cysteinylglycine, GSH) plays an im portant role in a number of different cellular reactions including cellular oxidative stress. Using A549 human sm all cell lung carcinoma fibroblasts, we investigated the role of exogenous GSH on the intracellular GSH/glutathione disulfide (oxidized glutathione, GSSG) redox ratio in GSH-depleted cells by treating with L-buthionine-(S,R)-sulfoximine (BSO). GSH levels decreased after BSO treatment. Although BSO is a well-recognized inhibitor of GSH biosynthesis and has no known effect on GSSG reductase, surprisingly, the levels of GSSG also decreased. Incubation of control or GSH-depleted cells with exogenous GSH did not alter intracellular GSH or GSSG levels to any significant extent. Therefore, the ratio of GSH/GSSG also was not altered significantly either in the controls or the BSO-treated cells. It appears that there m ay be cellular hom eostatic mechanisms that would maintain a constant GSH/GSSG ratio, irrespective of the changes in intracellular GSH concentration.