Ž Mačak Šafranko1, S Sobočanec2, A Šarić1, N Jajčanin-Jozić3, Ž Krsnik4, G Aralica5, T Balog1, M Abramić3. 1. Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia. 2. Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia. ssoboc@irb.hr. 3. Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia. 4. Croatian Institute for Brain Research, University of Zagreb School of Medicine, Zagreb, Croatia. 5. Department of Pathology, Medical School University of Zagreb and University Hospital, Dubrava, Zagreb, Croatia.
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.
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.
Entities:
Keywords:
Antioxidant enzyme; Gene and protein expression; Immunohistochemistry; Ovariectomy; Sex-related; Steroid hormone; Zinc peptidase
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