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

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.

Serum trace element levels and activity of enzymes associated with oxidative stress in endometriosis and endometrial cancer

“…Increased GSH levels may thus reflect the allowance of survival of cells with altered metabolism [38] and reflect GSH-associated cytoprotection. Nevertheless, since the free glutathione in the serum is not directly reflecting the redox state inside the endometrial cells, its levels and the activity of the related enzymes (GPx, GR, and GST) in the tissue do not correlate with the results reported herein [39].…”

Fructose‐1,6‐bisphosphate induces generation of reactive oxygen species and activation of p53‐dependent cell death in human endometrial cancer cells

“…Considering that most types of tumor cells have low intrinsic levels of antioxidant enzymes compared with non‐tumor cells, tumor cells may not be able to efficiently detoxify higher concentrations of H 2 O 2 (Marklund, Westman, Lundgren, & Roos, 1982; Oberley & Oberley, 1997). A study evaluated the expression of antioxidant enzymes in gynecological disorders and identified that endometrial adenocarcinoma cells have low levels of catalase (CAT) enzyme, responsible for the decomposition of H 2 O 2 in water and oxygen (Todorović et al, 2019). Cancer cells that have a limited amount of CAT are sensitive to a high level of H 2 O 2 and end up being attacked by the generated hydroxyl radicals and induced to cell death (Birben, Sahiner, Sackesen, Erzurum, & Kalayci, 2012).…”

Uterine myomas and sarcomas – clinical and ultrasound characteristics and differential diagnosis using pulsed and color Doppler techniques

“…The study found that the advancement of uterine lesion formation depends on both the type of enzymes involved and the course of endometrial transformation. These observations will contribute to the understanding of the molecular mechanisms underlying oxidative stress mediated disorders (17) .…”