Increased gamma-glutamylcysteine synthetase and gamma-glutamyl transpeptidase activities enhance resistance of rat lung epithelial L2 cells to quinone toxicity.

• DOI: 10.1165/ajrcmb.14.2.8630270
• Publication Date: 2013-04-04T02:27:43Z
• Authors: R M Liu; H Hu; T W Robison; H J Forman
• Keywords: Buthionine sulfoximine

Tert-butylhydroquinone (TBHQ) is a monofunctional Phase II enzyme inducer, which produces reactive oxygen species. Incubation with sublethal concentration of TBHQ increased the activities both gamma-glutamyl transpeptidase (GGT) and gamma-glutamylcysteine synthetase (GCS), although mechanisms are different (Liu colleagues, accompanying manuscript). In this study, we found that intracellular glutathione (GSH) content in rat lung epithelial L2 cells. cells pretreated nontoxic (50 microM) acquired resistance to subsequent challenge normally lethal (200 microM). Pretreatment L-buthionine S,R-sulfoximine (BSO), an inhibitor GCS, prevented TBHQ-induced increase GSH markedly diminished 200 microM TBHQ. Similarly, pretreatment acivicin, GGT, also Nevertheless, blockage GGT by acivicin could be bypassed using 2-oxothiazolidine-4-carboxylate (procysteine) provide cell source cysteine. This allowed restored TBHQ-pretreated The results suggest elevation GCS participated quinone toxicity.