The roles of glutathione and antioxidant enzymes in menadione-induced oxidative stress

Tzeon Jye Chiou, Woan Fang Tzeng

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

We investigated the role of glutathione (GSH) and antioxidant enzymes in menadione-resistance by using K300 cells (menadione-resistant cells) and parental P19 cells (menadione-sensitive cells). We found that acquisition of resistance was associated with elevations in glutathione content and DT-diaphorase activity. The activity of glutathione S-transferase (GST) was significantly decreased, while the activities of glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase in K300 cells were maintained at the same levels as compared to the parental P19 cells. Using reactive oxygen species (ROS)-sensitive fluorescence dye 2,7- dichlorodihydrofluorescein diacetate (DCFH/DA), we demonstrated that K300 cells are characterized by reduced cellular ROS as compared to the parental P19 cells during menadione's action. Menadione depleted glutathione to a small extent in the K300 cells, but a rapid depletion was observed in P19 cells. Pretreatment of K300 cells with dicumarol, a DT-diaphorase inhibitor, or buthionine sulfoximine (BSO), an inhibitor of γ-glutamyl cysteine synthase, sensitized the cells to menadione. BSO treatment was less effective than dicumarol treatment in reversing menadione resistance in K300 cells. These results strongly support the belief that DT-diaphorase plays a central role in protecting cells against menadione-induced oxidative stress by decreasing the ROS formation. (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)75-84
Number of pages10
JournalToxicology
Volume154
Issue number1-3
DOIs
Publication statusPublished - Nov 2000
Externally publishedYes

Keywords

  • Antioxidant enzymes
  • DT-diaphorase
  • Glutathione
  • Menadione
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology

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