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Life Sci. 2015 Jun 1;130:57-65. doi: 10.1016/j.lfs.2015.03.014. Epub 2015 Mar 26.

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

Author information

1
Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
2
Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia. Electronic address: ana.saric@irb.hr.
3
Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia.

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.

KEYWORDS:

17β-estradiol; Cat; Keap1; Nrf2; ROS; Sex-related; Sod-1; Sod-2

PMID:
25818184
DOI:
10.1016/j.lfs.2015.03.014
[Indexed for MEDLINE]

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