The role of 17β-estradiol in the regulation of antioxidant enzymes via the Nrf2–Keap1 pathway in the livers of CBA/H mice

Sobočanec, Sandra; Šarić, Ana; Mačak Šafranko, Željka; Popović Hadžija, Marijana; Abramić, Marija; Balog, Tihomir (2015) The role of 17β-estradiol in the regulation of antioxidant enzymes via the Nrf2–Keap1 pathway in the livers of CBA/H mice. Life Sciences, 130 . pp. 57-65. ISSN 0024-3205

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Abstract

AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: 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.

Item Type:	Article
Additional Information:	The authors thank Iva Pesun Medimorec for her excellent technical contribution in performing the ovariectomy surgical procedures. This research was funded by the Croatian Ministry of Science, Education and Sports, Grant Nos. 098-0982464-1647, 098-0982464-2460 and 098-1191344-2938.
Uncontrolled Keywords:	17β-estradiol; Cat; Keap1; Nrf2; ROS; Sex-related; Sod-1; Sod-2
Subjects:	BIOMEDICINE AND HEALTHCARE BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Physiology BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Genetics, Genomics and Proteomics
Divisions:	Division of Molecular Medicine
Projects:	Project title Project leader Project code Project type Sustav citokroma P450 i pojava tumora u starenju i oksidacijskom stresu- Tihomir Balog 098-0982464-1647 MZOS Dobivanje struktura nalik Langerhansovim otočićima iz matičnih stanica miša- Mirko Hadžija 098-0982464-2460 MZOS Molekularna enzimologija i proteinske interakcije hidrolaza- Marija Abramić 098-1191344-2938 MZOS
Depositing User:	Sandra Sobočanec
Date Deposited:	06 Dec 2017 14:31
URI:	http://fulir.irb.hr/id/eprint/3724
DOI:	10.1016/j.lfs.2015.03.014

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