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Peroxiredoxin III and Sulfiredoxin Together Protect Mice from Pyrazole-Induced Oxidative Liver Injury

 Soo Han Bae  ;  Su Haeng Sung  ;  Hye Eun Lee  ;  Ha Tan Kang  ;  Se Kyoung Lee  ;  Sue Young Oh  ;  Hyun Ae Woo In Sup Kil  ;  Sue Goo Rhee 
 Antioxidants & Redox Signaling, Vol.17(10) : 1351-1361, 2012 
Journal Title
 Antioxidants & Redox Signaling 
Issue Date
Aims: To define the mechanisms underlying pyrazole-induced oxidative stress and the protective role of peroxiredoxins (Prxs) and sulfiredoxin (Srx) against such stress. Results: Pyrazole increased Srx expression in the liver of mice in a nuclear factor erythroid 2–related factor 2 (Nrf2)-dependent manner and induced Srx translocation from the cytosol to the endoplasmic reticulum (ER) and mitochondria. Pyrazole also induced the expression of CYP2E1, a primary reactive oxygen species (ROS) source for ethanol-induced liver injury, in ER and mitochondria. However, increased CYP2E1 levels only partially accounted for the pyrazole-mediated induction of Srx, prompting the investigation of CYP2E1-independent ROS generation downstream of pyrazole. Indeed, pyrazole increased ER stress, which is known to elevate mitochondrial ROS. In addition, pyrazole up-regulated CYP2E1 to a greater extent in mitochondria than in ER. Accordingly, among Prxs I to IV, PrxIII, which is localized to mitochondria, was preferentially hyperoxidized in the liver of pyrazole-treated mice. Pyrazole-induced oxidative damage to the liver was greater in PrxIII−/− mice than in wild-type mice. Such damage was also increased in Srx−/− mice treated with pyrazole, underscoring the role of Srx as the guardian of PrxIII. Innovation: The roles of Prxs, Srx, and ER stress have not been previously studied in relation to pyrazole toxicity. Conclusion: The concerted action of PrxIII and Srx is important for protection against pyrazole-induced oxidative stress arising from the convergent induction of CYP2E1-derived and ER stress-derived ROS in mitochondria.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
길인섭(Kil, In Sup)
배수한(Bae, Soo Han) ORCID logo https://orcid.org/0000-0002-8007-2906
성수행(Sung, Su Haeng)
이서구(Rhee, Sue Goo)
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