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Molecular and Cellular Biochemistry

, Volume 307, Issue 1–2, pp 185–191 | Cite as

Generation of superoxide from reaction of 3H-1,2-dithiole-3-thione with thiols: implications for dithiolethione chemoprotection

  • Zhenquan Jia
  • Hong Zhu
  • Michael A. Trush
  • Hara P. Misra
  • Yunbo Li
Article

Abstract

3H-1,2-Dithiole-3-thione (D3T), a potent member of dithiolethiones, induces phase 2 enzymes by activating an Nrf2/Keap1-dependent signaling pathway. It was proposed that interaction between D3T and two adjacent sulfhydryl groups of Keap1 might cause dissociation of Keap1 from Nrf2, leading to Nrf2 activation. This study was undertaken to investigate the reactions between D3T and thiols, including the dithiol compound, dithiothreitol (DTT), and the monothiol, glutathione (GSH). We reported here that under physiologically relevant conditions incubation of D3T with DTT caused remarkable oxygen consumption, indicating a redox reaction between D3T and the dithiol molecule. Incubation of D3T with GSH also led to oxygen consumption, but to a less extent. Electron paramagnetic resonance (EPR) studies showed that the redox reaction between D3T and DTT generated superoxide. Superoxide was also formed from the redox reaction of D3T with GSH. These findings demonstrate that D3T reacts with thiols, particularly a dithiol, generating superoxide, which may provide a mechanistic explanation for induction of Nrf2-dependent phase 2 enzymes by D3T.

Keywords

EPR Superoxide D3T Oxygen consumption Thiols 

Abbreviations

ARE

Antioxidant response element

D3T

3H-1,2-Dithiole-3-thione

DEPMPO

5-(Diethoxyphosphoryl)-5-methylpyrroline N-oxide

DTPA

Diethylenetriaminepentaacetic acid

DTT

Dithiothreitol

EPR

Electron paramagnetic resonance

GSH

Glutathione

MAPKs

Mitogen-activated protein kinases

NBT

Nitroblue tetrazolium

PBS

Phosphate-buffered saline

ROS

Reactive oxygen species

SOD

Superoxide dismutase

Notes

Acknowledgments

This work was supported in part by NIH grant HL71190 (Y. L.). M. A. T. was supported by NIH grants ES03760, ES03819 and ES08078.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Division of Biomedical Sciences, Edward Via Virginia College of Osteopathic MedicineVirginia Tech Corporate Research CenterBlacksburgUSA
  2. 2.Division of Toxicology, Department of Environmental Health SciencesThe Johns Hopkins University Bloomberg School of Public HealthBaltimoreUSA

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