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

 Soo Han Bae  ;  Su Haeng Sung  ;  Eun Jung Cho  ;  Se Kyoung Lee  ;  Hye Eun Lee  ;  Hyun Ae Woo  ;  Dae-Yeul Yu  ;  In Sup Kil  ;  Sue Goo Rhee 
 HEPATOLOGY, Vol.53(3) : 945-953, 2011 
Journal Title
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Animals ; Chemical and Drug Induced Liver Injury/metabolism ; Chemical and Drug Induced Liver Injury/prevention & control* ; Cytochrome P-450 CYP2E1/metabolism ; Ethanol/toxicity* ; Male ; Mice ; Oxidation-Reduction ; Oxidoreductases Acting on Sulfur Group Donors/deficiency ; Oxidoreductases Acting on Sulfur Group Donors/metabolism* ; Peroxiredoxin III ; Peroxiredoxins/metabolism* ; Reactive Oxygen Species/metabolism
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-SO(2) ) 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-SO(2) 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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kil, In Sup(길인섭)
Bae, Soo Han(배수한) ORCID logo https://orcid.org/0000-0002-8007-2906
Sung, Su Haeng(성수행)
Rhee, Sue Goo(이서구)
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