title: The role of 17β-estradiol in the regulation of antioxidant enzymes via the Nrf2-Keap1 pathway in the livers of CBA/H mice.
abstract: OBJECTIVE
  We aimed to explore the impact of surgical 17β-estradiol (E2) deprivation/administration on the expression of antioxidant enzymes with an emphasis on the alteration of the NF-E2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) pathway under physiological conditions in the livers of CBA/H mice of both sexes.
  
  
  METHODS
  Hepatic oxidative stress markers were determined by measuring lipid peroxidation and DNA damage using the comet assay. The expression and activities of two isoforms of superoxide dismutase (Sod-1, Sod-2) and catalase (Cat) were studied using real-time PCR, Western blot and spectrophotometrical analyses. The effect of E2 on Nrf2/Keap1 protein levels and localization was assessed using cytosolic and nuclear fractions.
  
  
  RESULTS
  We demonstrate the E2-mediated repression of the antioxidant enzymes Sod-1, Sod-2 and Cat in the livers of ovariectomized mice treated with E2 and its association with a decreased level of Nrf2/Keap1 proteins in the nucleus. We observed beneficial effects of long-term E2 administration on lipid peroxidation but not on DNA damage in the livers of ovariectomized mice.
  
  
  CONCLUSIONS
  The results of this study may additionally confirm the protective ability of E2 in prolonging the onset of age-related disease in females that ultimately contributes to their longer lifespan.
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sobočanec
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia. Electronic address: ana.saric@irb.hr.
authors.forename: Ana
authors.initials: A
authors.lastname: Šarić
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Željka
authors.initials: Ž
authors.lastname: Mačak Šafranko
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Marijana
authors.initials: M
authors.lastname: Popović Hadžija
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Abramić
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Balog
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D000072019:Kelch-Like ECH-Associated Protein 1; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000975:Antioxidants; D003598:Cytoskeletal Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D004958:Estradiol; D013482:Superoxide Dismutase
keywords: 17β-estradiol; Cat; Keap1; Nrf2; ROS; Sex-related; Sod-1; Sod-2