Glutathione redox potential in response to differentiation and enzyme inducers

Ward G. Kirlin, Jiyang Cai, Sally A. Thompson, Dolores Diaz, Terrance J. Kavanagh, Dean P. Jones

Research output: Contribution to journalArticle

282 Scopus citations

Abstract

The reduced glutathione (GSH)/oxidized glutathione (GSSG) redox state is thought to function in signaling of detoxification gene expression, but also appears to be tightly regulated in cells under normal conditions. Thus it is not clear that the magnitude of change in response to physiologic stimuli is sufficient for a role in redox signaling under nontoxicologic conditions. The purpose of this study was to determine the change in 2GSH/GSSG redox during signaling of differentiation and increased detoxification enzyme activity in HT29 cells. We measured GSH, GSSG, cell volume, and cell pH, and we used the Nernst equation to determine the changes in redox potential E(h) of the 2GSH/GSSG pool in response to the differentiating agent, sodium butyrate, and the detoxification enzyme inducer, benzyl isothiocyanate. Sodium butyrate caused a 60-mV oxidation (from -260 to -200 mV), an oxidation sufficient for a 100-fold change in protein dithiols:disulfide ratio. Benzyl isothiocyanate caused a 16-mV oxidation in control cells but a 40-mV oxidation (to -160 mV) in differentiated cells. Changes in GSH and mRNA for glutamate:cysteine ligase did not correlate with E(h); however, correlations were seen between E(h) and glutathione S-transferase (GST) and nicotinamide adenine dinucleotide phosphate (NADPH):quinone reductase activities (N:QR). These results show that 2GSH/GSSG redox changes in response to physiologic stimuli such as differentiation and enzyme inducers are of a sufficient magnitude to control the activity of redox-sensitive proteins. This suggests that physiologic modulation of the 2GSH/GSSG redox poise could provide a fundamental parameter for the control of cell phenotype. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)1208-1218
Number of pages11
JournalFree Radical Biology and Medicine
Volume27
Issue number11-12
DOIs
StatePublished - 1999

Keywords

  • Benzyl isothiocyanate
  • Differentiation
  • Free radicals
  • Glutamate:cysteine ligase
  • Glutathione
  • Glutathione S-transferase
  • NADPH:quinone reductase
  • Redox potential

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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  • Cite this

    Kirlin, W. G., Cai, J., Thompson, S. A., Diaz, D., Kavanagh, T. J., & Jones, D. P. (1999). Glutathione redox potential in response to differentiation and enzyme inducers. Free Radical Biology and Medicine, 27(11-12), 1208-1218. https://doi.org/10.1016/S0891-5849(99)00145-8