Mol. Cells 2009; 27(3): 279-282
Published online March 19, 2009
https://doi.org/10.1007/s10059-009-0050-y
© The Korean Society for Molecular and Cellular Biology
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 antioxidant response element, AP-1, Nrf2, oxidative stress, peroxiredoxin, sulfiredoxin
Mol. Cells 2009; 27(3): 279-282
Published online March 31, 2009 https://doi.org/10.1007/s10059-009-0050-y
Copyright © The Korean Society for Molecular and Cellular Biology.
Francesc X. Soriano, Paul Baxter, Lyndsay M. Murray, Michael B. Sporn, Thomas H. Gillingwater, and Giles E. Hardingham
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: antioxidant response element, AP-1, Nrf2, oxidative stress, peroxiredoxin, sulfiredoxin
Jae Hyun Kwon, Jooyoung Lee, Jiye Kim, Varvara A. Kirchner, Yong Hwa Jo, Takeshi Miura, Nayoung Kim, Gi-Won Song, Shin Hwang, Sung-Gyu Lee, Young-In Yoon, and Eunyoung Tak
Mol. Cells 2019; 42(9): 672-685 https://doi.org/10.14348/molcells.2019.0003Byung Chull An, Seung Sik Lee, Eun Mi Lee, Jae Taek Lee, Seung Gon Wi, Hyun Suk Jung, Woojun Park, and Byung Yeoup Chung*
Mol. Cells 2010; 29(2): 145-151 https://doi.org/10.1007/s10059-010-0023-1Aryatara Shakya, Nicholas W. McKee, Matthew Dodson, Eli Chapman, and Donna D. Zhang
Mol. Cells 2023; 46(3): 165-175 https://doi.org/10.14348/molcells.2023.0005