RRC ID 12358
Author Bae SH, Sung SH, Cho EJ, Lee SK, Lee HE, Woo HA, Yu DY, Kil IS, Rhee SG.
Title Concerted action of sulfiredoxin and peroxiredoxin I protects against alcohol-induced oxidative injury in mouse liver.
Journal Hepatology
Abstract UNLABELLED: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.
Volume 53(3)
Pages 945-53
Published 2011-3-1
DOI 10.1002/hep.24104
PMID 21319188
MeSH 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
IF 14.679
Times Cited 54
Mice RBRC01390