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      Roles of selenoprotein K and selenium status in the etiopathogenesis of preeclampsia: Their relationships with maternal lipid peroxidation, oxidative DNA damage, and glutathione peroxidase

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          Abstract

          Abstract. Objective: Preeclampsia (PE) is a complex disease and the underlying mechanisms are not known yet. It is well known that selenium and oxidative stress play a role in the pathogenesis of various diseases as well as PE. The aim of the study was to investigate the changes in selenium status, as an essential trace element, and selenoprotein K (SelK), a newly described selenoprotein which has been suggested to have an antioxidant function in some tissues in patients with preeclampsia. We also aimed at investigating their relationships with maternal lipid peroxidation, oxidative DNA damage, and glutathione peroxidase (GPx) activities. Materials and methods: 38 healthy pregnant and 48 pregnant women with PE were included in the study. Serum selenium levels were measured by graphite-furnace atomic absorption spectrophotometry. Plasma TBARS levels were analyzed by spectrophotometric method; GPx activities, 8OHdG, and SelK levels were determined by ELISA. Results: Plasma TBARS and 8OHdG levels were found to be increased in the PE group compared to the healthy pregnant group. Plasma SelK levels and GPx activities were found to be lower in the PE group than in the healthy control group. However, there was no significant difference in serum selenium levels between two groups. Furthermore, a significant correlation was determined between plasma SelK levels and GPx activities in PE patients group (r = 0.743; p < 0.01). Likewise, a significant positive correlation was found between plasma 8OHdG and TBARS levels (r = 0.457; p < 0.01), serum selenium levels and plasma GPx activities (r = 0.663; p < 0.01), serum selenium and plasma SelK levels (r = 0.851; p < 0.01) in PE. Conclusion: Our findings indicated that a selenoprotein SelK and a selenoenzyme GPx play a role in the etiopathogenesis of PE. Decreases in these antioxidant systems were associated with increase in lipid and DNA oxidation in PE patients. Underlying mechanisms of SelK and its interactions with selenium status and GPx in PE should be clarified in details with further studies.


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          Most cited references29

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          ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002.

          (2002)
          Hypertensive disease occurs in approximately 12-22% of pregnancies, and it is directly responsible for 17.6% of maternal deaths in the United States (1,2). However, there is confusion about the terminology and classification of these disorders. This bulletin will provide guidelines for the diagnosis and management of hypertensive disorders unique to pregnancy (ie, preeclampsia and eclampsia), as well as the various associated complications. Chronic hypertension has been discussed elsewhere (3).
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            Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses.

            Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K(-/-) mice were generated and found to be similar to wild-type controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K(-/-) mice. Receptor-mediated Ca(2+) flux was decreased in T cells, neutrophils, and macrophages from Sel K(-/-) mice compared with controls. Ca(2+)-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcγ receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K(-/-) mice compared with that in cells from controls. West Nile virus infections were performed, and Sel K(-/-) mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, West Nile virus-infected Sel K(-/-) mice demonstrated significantly lower survival (2 of 23; 8.7%) compared with that of wild-type controls (10 of 26; 38.5%). These results establish Sel K as an endoplasmic reticulum-membrane protein important for promoting effective Ca(2+) flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses.
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              Trace elements as an activator of antioxidant enzymes.

              Oxidative stress is a state of impaired balance between the formation of free radicals and antioxidant capacity of the body. It causes many defects of the body, e.g. lipid peroxidation, DNA and protein damage. In order to prevent the effects of oxidative stress, the organism has developed defence mechanisms. These mechanisms capture and inhibit the formation of free radicals and also chelate ion metals that catalyse free radical reactions. Trace elements are components of antioxidant enzymes involved in antioxidant mechanisms. Selenium, as a selenocysteine, is a component of the active site of glutathione peroxidase (GPx). The main function of GPx is neutralization of hydrogen peroxide (H2O2) and organic peroxide (LOOH). Furthermore, selenium is a structural part of a large group of selenoproteins that are necessary for proper functioning of the body. Manganese, copper and zinc are a part of the group of superoxide dismutase enzymes (MnSOD, Cu/ZnSOD), which catalyse the superoxide anion dismutation into hydrogen peroxide and oxygen. Formed hydrogen peroxide is decomposed into water and oxygen by catalase or glutathione peroxidase. An integral component of catalase (CAT) is iron ions. The concentration of these trace elements has a significant influence on the activity of antioxidant enzymes, and thus on defence against oxidative stress. Even a small change in the level of trace elements in the tissue causes a disturbance in their metabolism, leading to the occurrence of many diseases.
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                Author and article information

                Journal
                Trace Elements and Electrolytes
                TE
                Dustri-Verlgag Dr. Karl Feistle
                0946-2104
                November 20 2017
                Article
                10.5414/TEX01512
                e3836d0d-4964-448f-94ec-0398b8d5a4a6
                © 2017
                History

                Endocrinology & Diabetes,General medicine,Medicine,Gastroenterology & Hepatology,Nutrition & Dietetics
                GPx,SelK,8OHdG,TBARS,selenium,preeclampsia

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