title: The effect of 17β-estradiol on the expression of dipeptidyl peptidase III and heme oxygenase 1 in liver of CBA/H mice.
abstract: BACKGROUND
  17β-estradiol (E₂) has well-established cardioprotective, antioxidant and neuroprotective role, and exerts a vast range of biological effects in both sexes. Dipeptidyl peptidase III (DPP III) is protease involved as activator in Keap1-Nrf2 signalling pathway, which is important in cellular defense to oxidative and electrophilic stress. It is generally accepted that oxidative stress is crucial in promoting liver diseases.
  
  
  OBJECTIVE
  To examine the effect of E₂ on the expression of DPP III and haeme oxygenase 1 (HO-1) in liver of adult CBA/H mice of both sexes.
  
  
  METHODS
  Gene and protein expressions of studied enzymes were determined by quantitative real-time PCR and Western blot analysis. Immunohistochemistry was performed to analyse the localization of both proteins in different liver cell types.
  
  
  RESULTS
  Ovariectomy diminished expression of DPP III and HO-1 proteins. E₂ administration abolished this effect, and even increased these proteins above the control. A significant enhancement in DPP III protein was found in E₂-treated males, as well. A decrease in the expression of HO-1, but not of the DPP III gene, was detected in the liver of ovariectomized females. HO-1 protein was found localized in the pericentral areas of hepatic lobules (Kupffer cells and hepatocytes), whilst DPP III showed a uniform distribution within hepatic tissue.
  
  
  CONCLUSIONS
  We demonstrate for the first time that E₂ influences the protein level of DPP III in vivo, and confirm earlier finding on HO-1 gene upregulation by 17β-estradiol. These results additionally confer new insights into complexity of protective action of E₂.
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Ž
authors.initials: Ž
authors.lastname: Mačak Šafranko
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia. ssoboc@irb.hr.
authors.forename: S
authors.initials: S
authors.lastname: Sobočanec
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: A
authors.initials: A
authors.lastname: Šarić
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: N
authors.initials: N
authors.lastname: Jajčanin-Jozić
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Ž
authors.initials: Ž
authors.lastname: Krsnik
authors.affiliation: Department of Pathology, Medical School University of Zagreb and University Hospital, Dubrava, Zagreb, Croatia.
authors.forename: G
authors.initials: G
authors.lastname: Aralica
authors.affiliation: Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: T
authors.initials: T
authors.lastname: Balog
authors.affiliation: Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: M
authors.initials: M
authors.lastname: Abramić
mesh_terms: D000818:Animals; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010052:Ovariectomy; D015854:Up-Regulation
chemical_list: D004967:Estrogens; D004958:Estradiol; D051547:Heme Oxygenase-1; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100152:dipeptidyl peptidase III
keywords: Antioxidant enzyme; Gene and protein expression; Immunohistochemistry; Ovariectomy; Sex-related; Steroid hormone; Zinc peptidase