Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Transcriptional Regulation of the AP-1 and Nrf2 Target Gene Sulfiredoxin

  • Soriano, Francesc X. (Centre for Integrative Physiology, University of Edinburgh) ;
  • Baxter, Paul (Centre for Integrative Physiology, University of Edinburgh) ;
  • Murray, Lyndsay M. (Centre for Integrative Physiology, University of Edinburgh) ;
  • Sporn, Michael B. (Dartmouth Medical School) ;
  • Gillingwater, Thomas H. (Centre for Integrative Physiology, University of Edinburgh) ;
  • Hardingham, Giles E. (Centre for Integrative Physiology, University of Edinburgh)
  • Received : 2009.02.12
  • Accepted : 2009.02.15
  • Published : 2009.03.31
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Abstract

"Two-cysteine" peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin's role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here, the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress.

Keywords

Acknowledgement

Supported by : Royal Society

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