Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury

Hong Zhu, Li Zhang, Michael A. Trush, Yunbo Li

Research output: Contribution to journalArticle

Abstract

This study was undertaken to investigate the inducibility of glutathione (GSH), glutathione reductase (GR) and glutathione peroxidase (GPx) by 3H-1,2-dithiole-3-thione (D3T) in beta-cells, and the resultant cytoprotection against oxidant injury. Incubation of the insulin-secreting RINm5F cells with D3T led to significant induction of GSH, GR and GPx. D3T-mediated induction of GSH was abolished by buthionine sulfoximine (BSO), suggesting a critical involvement of γ-glutamylcysteine ligase (γGCL). Consistently, incubation of RINm5F cells with D3T resulted in increased expression of γGCL protein and mRNA. Pretreatment of RINm5F cells with D3T provided remarkable protection against oxidant-elicited cytotoxicity. On the other hand, depletion of cellular GSH by BSO sensitized RINm5F cells to oxidant injury. Furthermore, cotreatment of RINm5F cells with BSO to reverse D3T-mediated GSH induction abolished the cytoprotective effects of D3T on oxidant injury. Taken together, this study demonstrates that upregulation of glutathione system by D3T is effective for protecting against oxidative beta-cell injury.

Original languageEnglish (US)
Pages (from-to)242-250
Number of pages9
JournalFree Radical Research
Volume41
Issue number2
DOIs
StatePublished - 2007

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Thiones
Insulin-Secreting Cells
Glutathione
Up-Regulation
Buthionine Sulfoximine
Oxidants
Wounds and Injuries
Glutathione Reductase
Ligases
Glutathione Peroxidase
Cytotoxicity
Cytoprotection
1,2-dithiol-3-thione
Insulin
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Upregulation of endogenous glutathione system by 3H-1,2-dithiole-3-thione in pancreatic RINm5F beta-cells as a novel strategy for protecting against oxidative beta-cell injury. / Zhu, Hong; Zhang, Li; Trush, Michael A.; Li, Yunbo.

In: Free Radical Research, Vol. 41, No. 2, 2007, p. 242-250.

Research output: Contribution to journalArticle

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