Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver

Authors

  • Soo Han Bae,

    Corresponding author
    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
    • Soo Han Bae, Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea===

      Sue Goo Rhee, Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea===

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  • Su Haeng Sung,

    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
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  • Eun Jung Cho,

    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
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  • Se Kyoung Lee,

    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
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  • Hye Eun Lee,

    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
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  • Hyun Ae Woo,

    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
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  • Dae-Yeul Yu,

    1. Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
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  • In Sup Kil,

    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
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  • Sue Goo Rhee

    Corresponding author
    1. Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea
    • Soo Han Bae, Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea===

      Sue Goo Rhee, Division of Life and Pharmaceutical Sciences, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea===

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    • fax: +82-2-3277-3760


  • Potential conflict of interest: Nothing to report.

Abstract

Peroxiredoxins (Prxs) are peroxidases that catalyze the reduction of reactive oxygen species (ROS). The active site cysteine residue of members of the 2-Cys Prx subgroup (Prx I to IV) of Prxs is hyperoxidized to cysteine sulfinic acid (Cys-SO2) during catalysis with concomitant loss of peroxidase activity. Reactivation of the hyperoxidized Prx is catalyzed by sulfiredoxin (Srx). Ethanol consumption induces the accumulation of cytochrome P450 2E1 (CYP2E1), a major contributor to ethanol-induced ROS production in the liver. We now show that chronic ethanol feeding markedly increased the expression of Srx in the liver of mice in a largely Nrf2-dependent manner. Among Prx I to IV, only Prx I was found to be hyperoxidized in the liver of ethanol-fed wildtype mice, and the level of Prx I-SO2 increased to ≈30% to 50% of total Prx I in the liver of ethanol-fed Srx−/− mice. This result suggests that Prx I is the most active 2-Cys Prx in elimination of ROS from the liver of ethanol-fed mice and that, despite the up-regulation of Srx expression by ethanol, the capacity of Srx is not sufficient to counteract the hyperoxidation of Prx I that occurs during ROS reduction. A protease protection assay revealed that a large fraction of Prx I is located together with CYP2E1 at the cytosolic side of the endoplasmic reticulum membrane. The selective role of Prx I in ROS removal is thus likely attributable to the proximity of Prx I and CYP2E1. Conclusion: The pivotal functions of Srx and Prx I in protection of the liver in ethanol-fed mice was evident from the severe oxidative damage observed in mice lacking either Srx or Prx I. (HEPATOLOGY 2011)

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