Expression of Antioxidant Enzymes in Patients with Uterine Polyp, Myoma, Hyperplasia, and Adenocarcinoma.

Ana Todorović,Ljubica Gavrilović,Nataša Popović,Ivan Pavlović,Vesna Stojiljković,Snežana Pejić,Snežana B Pajović

doi:10.3390/antiox8040097

Abstract

We previously found that compared to patients with benign uterine diseases (polyps, myomas), patients with premalignant (hyperplasia simplex and complex) and malignant (adenocarcinoma) lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme (AOE) activities. To further elucidate the mechanism of the observed changes, we examined protein and mRNA levels of copper-zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and transcription factor Nrf2. We also examined correlations of AOE expression with AOE activity, lipid hydroperoxides (LOOH) level, and level of Nrf2. Our results showed decreased CuZnSOD, CAT, and Nrf2 levels, and increased GPx and GR levels in hyperplasias, while in patients with adenocarcinoma, the level of CAT was decreased and GR was increased, compared to benign groups. Similar changes in mRNA levels were also detected, indicating predominantly translational control of the AOE expression. The positive correlation of enzyme expression/activity was recorded for CuZnSOD, GPx, and GR, but only among groups with benign diseases. Only GR and GPx expressions were positively correlated with LOOH. Nrf2 protein was positively correlated with mRNA levels of CuZnSOD and GR. Observed results indicate involvement of diverse redox mechanisms in etiopathogenesis of different gynecological diseases, and may improve redox-based approaches in current clinical practice.

Highlights

During the life cycle, aerobic organisms are exposed to a number of endogenous and exogenous sources of reactive oxygen species (ROS)
Endometrial protein level of CuZnSOD in patients with myoma was comparable to that observed in patients with polyps and adenocarcinoma, whereas in patients with simple or complex hyperplasia
glutathione peroxidase (GPx) (C), and glutathione reductase (GR) (D) in endometrium of patients diagnosed with polypus endometrii (PE), uterus myomatosus (UM), simple hyperplasia (SH), complex hyperplasia (CH), and adenocarcinoma myomatosus (UM), simple hyperplasia (SH), complex hyperplasia (CH), and adenocarcinoma endometrii (ACE)

Summary

Introduction

Aerobic organisms are exposed to a number of endogenous and exogenous sources of reactive oxygen species (ROS). To achieve redox homeostasis they developed a powerful antioxidant system (AOS) [1], whose main enzyme components are superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The transcription factor Nrf is responsible for regulating a battery of antioxidant and detoxification enzymes [2,3], as well as processes such as stress response, proliferation, and proteasomal degradation [4,5]. Nrf was identified as an important transcription factor regulating development, progression, and chemoresistance of cancer [6]. Cancer develops over three stages, initiation, promotion, and progression, and oxidative stress is associated with each of them [7]. Endometrial cancer ranks as the fourth most common neoplasm in women from European countries [8]. It has been shown that premalignant changes precede the malignant transformation of the uterus, which is why hyperplasia may be considered as a precursor of Antioxidants 2019, 8, 97; doi:10.3390/antiox8040097 www.mdpi.com/journal/antioxidants

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