Chemoprotective 3H-1,2-dithiole-3-thione induces antioxidant genes in vivo

Monicah A. Otieno, Thomas W Kensler, Kathryn Z. Guyton

Research output: Contribution to journalArticle

Abstract

Several 1,2-dithiole-3-thiones are potent inhibitors of chemical-induced tumors in multiple tissues. Chemoprotection by 1,2-dithiole-3-thiones has been associated with induction of detoxication enzymes, although several studies suggest that additional mechanisms may be involved. In this study, we examined the induction of hepatic antioxidant genes in rats treated with 3H-1,2-dithiole-3-thione (D3T). After a 24 h D3T treatment, a 2.4-fold increase in catalase mRNA was observed, which was accompanied by a 1.5-fold increase in catalase protein expression and a 2.3-fold increase in catalase activity. D3T also mediated 2.9-, 5.9-, and 3.7-fold increases in the 1.0, 3.0, and 4.0 kb mRNA species of manganese superoxide dismutase (MnSOD), respectively. The induction of MnSOD mRNA by D3T was coincident with 1.7-fold and 4.6-fold increases in MnSOD protein and enzyme activity, respectively. Induction of γ-glutamylcysteine synthetase mRNA by D3T was accompanied by an increase in glutathione levels. Nuclear run-on assays provided evidence that D3T enhances the transcription rate from MnSOD, catalase, and γ-glutamylcysteine synthetase. In support of this view, D3T also activated an MnSOD promoter-reporter construct in transiently transfected HepG2 cells. In light of observations that antioxidant enzyme regulation may be altered during carcinogenesis, induction of these genes could provide a potentially important mechanism of action of chemoprotective 1,2-dithiole-3-thiones. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)944-952
Number of pages9
JournalFree Radical Biology and Medicine
Volume28
Issue number6
DOIs
StatePublished - Mar 15 2000

Fingerprint

Thiones
Antioxidants
Genes
Superoxide Dismutase
Catalase
Glutamate-Cysteine Ligase
Messenger RNA
Enzyme Induction
Hep G2 Cells
Enzyme activity
Enzymes
Transcription
Glutathione
1,2-dithiol-3-thione
Rats
Tumors
Assays
Carcinogenesis
Proteins
Tissue

Keywords

  • 2-dithiole-3-thione
  • 3H-1
  • Antioxidants
  • Catalase
  • Chemoprotection
  • Free radical
  • MnSOD

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Chemoprotective 3H-1,2-dithiole-3-thione induces antioxidant genes in vivo. / Otieno, Monicah A.; Kensler, Thomas W; Guyton, Kathryn Z.

In: Free Radical Biology and Medicine, Vol. 28, No. 6, 15.03.2000, p. 944-952.

Research output: Contribution to journalArticle

Otieno, Monicah A. ; Kensler, Thomas W ; Guyton, Kathryn Z. / Chemoprotective 3H-1,2-dithiole-3-thione induces antioxidant genes in vivo. In: Free Radical Biology and Medicine. 2000 ; Vol. 28, No. 6. pp. 944-952.
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