Mammalian selenoproteins

Department of Biochemistry, Medical School, Bydgoszcz, Poland.
Journal of trace elements and electrolytes in health and disease 10/1992; 6(3):137-51.
Source: PubMed


Selenium (Se) is an essential trace element for animals and humans. Its biological role was established following the discovery that Se is a structural component of the active center of the enzyme glutathione peroxidase (GSH-Px). During the last decade remarkable progress has been made in the recognition of the structure and function of several selenoproteins. Cellular GSH-Px was the first enzyme recognized as a selenoprotein. In it Se was found in the form of selenocysteine. The enzyme is a tetrameric protein and is composed of four apparently identical subunits each containing one gram atom of Se. Plasma GSH-Px also has a tetrameric form with identical subunits and with one atom of Se per subunit. It is, however, a glycosylated protein, and is distinct from cellular enzyme. Both enzymes catalyze the reduction of hydrogen peroxide and a variety of organic hydroperoxides by glutathione. A third GSH-Px, called phospholipid hydroperoxide glutathione peroxidase (PHGSH-Px), is a monomeric, membrane-associated enzyme containing one atom of Se per mole of protein. This enzyme destroys esterified lipid hydroperoxides. The fourth known mammalian selenoenzyme is a type I iodothyronine 5'-deiodinase that catalyzes the deiodination of L-thyroxine to the biologically active hormone 3,3',5-triiodothyronine. It is a monomeric enzyme and contains one atom of Se per mole of protein. Selenoprotein P, a fifth known selenoprotein, is a glycosylated, monomeric protein containing ten atoms of Se per molecule. The function of this protein is not known, but it may play a role in Se transport or be connected with a protective activity against free radicals. In all these selenoproteins the Se is incorporated into the protein molecule via the selenocysteinyl-tRNA which recognizes the specific UGA codons in mRNAs to insert selenocysteine into the primary structure of selenoproteins.

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    • "While GPx and CATs utilize H 2 O 2 as substrate, SODs promote superoxide dismutation . GPx is a selenium-containing enzyme [9], while CAT possesses an iron(III) protoporphyrin IX or a dinuclear manganese active site [10] [11]. In SODs, iron, manganese, copper/zinc, or nickel are found in the active site [12] [13] [14] [15]. "
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    ABSTRACT: Due to their aerobic life style, eukaryotic organisms have evolved different strategies to overcome oxidative stress. The recruitment of some specific metalloenzymes such as superoxide dismutases (SODs) and catalases (CATs) is of great importance to eliminate harmful reactive oxygen species (hydrogen peroxide and superoxide anion). Using the ligand HPClNOL {1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol}, we have synthesized three coordination compounds containing iron(III), copper(II) and manganese(II) ions, which are also present in the active site of the above mentioned metalloenzymes. These compounds were evaluated as SOD and CAT mimetics. The manganese and iron compounds showed both SOD and CAT activities, while copper showed just SOD activity. The copper and manganese in vitro SOD activities are very similar (IC50 ~0.4μmol dm(-3)) and about 70-fold higher than the iron one. The manganese compound showed CAT activity higher than the iron species. Analyzing their capacity to protect Saccharomyces cerevisiae cells against oxidative stress (H2O2 and the O2(•-) radical), we observed that all compounds act as antioxidants, increasing the resistance of yeast cells mainly due to a reduction of lipid oxidation. Especially for the iron compound, the data indicate complete protection when wild-type cells were exposed to H2O2 or O2(•-) species. Interestingly, these compounds also compensate for both superoxide dismutase and catalase deficiencies; their antioxidant activity is metal ion-dependent, in the order iron(III) > copper(II) > manganese(II). The protection mechanism employed by the complexes proved to be independent of the activation of transcription factors (such as Yap1, Hsf1, Msn2/Msn4) and protein synthesis. There is no direct relation between the in vitro and in vivo antioxidant activities. Copyright © 2014 Elsevier Inc. All rights reserved.
    Free Radical Biology and Medicine 12/2014; 80. DOI:10.1016/j.freeradbiomed.2014.12.005 · 5.74 Impact Factor
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    • "The selenium-containing peroxidases are a broad group of enzymes that utilizes hydrogen peroxide (H 2 O 2 ) as a substrate along with an endogenous source of reducing equivalence [1]. Glutathione peroxidases (GPx) are one of the best studied families of peroxidases. "
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    ABSTRACT: The role of glutathione peroxidase-1 (GPx1) in limiting the oxidative risk for atherogenesis is increasingly recognized. Therapeutic strategies, designed to augment cellular endogenous defense systems have been identified as a promising approach to control oxidative stress-associated diseases, including atherosclerosis. Ozone therapy regulates oxidative metabolism and prevents oxidative stress-associated-chronic diseases. Thus, the present study was aimed to test the hypothesis that ozone-oxidative conditioning up-regulates GPx1 synthesis in apolipoprotein E deficient mice (apoE−/−), protecting the vasculature against atherosclerosis. Male apoE−/− mice were treated with 1 mL of ozone/oxygen containing 40 μg/mL of ozone by rectal insufflation. As controls, mice were untreated or insufflated with oxygen only. Results showed a significant increase (P < 0.05) of aortic GPx1 gene expression in ozone-treated mice, whereas only minor atherosclerotic lesions were observed. Furthermore, GPx1 activity and GSH levels were significant increased (P < 0.05) in ozone receiving group compared with controls. In addition, lipid peroxidation was attenuated by ozone treatment, whereas serum lipids were similar among experimental groups. These results altogether suggest that ozone therapy attenuated atherogenesis by a mechanism that involved, at least, the improvement of aortic GPx1 expression/activity. Further studies are needed in order to assess the possible link of cellular redox-sensitive pathways with the antiatherogenic effect of ozone therapy.
    Biomedicine and Aging Pathology 08/2014; 4(4). DOI:10.1016/j.biomag.2014.07.001
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    • "Therefore, the conjugated enzyme system glutathione peroxidase/glutathione reductase must be very important in the regulation of the equilibrium between the oxidized and the reduced forms of glutathione during epididymal maturation and, particularly in vespertilionid and rhinolophid species of bats, during the long periods of spermatozoon epididymal storage. Activity of GPx depends on the presence of at least four isozymes (Faure et al. 1991; Zachara 1992): classical cellular GPx, plasma glutathione peroxidase, phospholipid–hydroperoxide glutathione peroxidase , and an epididymal-specific, androgen-regulated isozyme that is expressed only in the caput epididymides (Vernet et al. 1999). The intracellular level of GSH participates in several important ways in the normal spermatozoon maturation process . "
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    ABSTRACT: We studied the activities of reactive oxygen species (ROS) scavenging enzymes during epididymal spermatozoon maturation and storage in Corynorhinus mexicanus (G.M. Allen, 1916), a vespertilionid bat that stores spermatozoa in the epididymides for several months after regression of the testes. Depending on the phase of the epididymal reproductive cycle, two different patterns of antioxidant enzyme activities were observed in C. mexicanus. Catalase activity is clearly present in both caput and cauda epididymides throughout the entire annual reproductive cycle, being particularly high during the post-testicular phase of epididymal function. Superoxide dismutase (SOD) activity, present during the testicular phase of epididymal transport and maturation of spermatozoa, is almost completely absent or inhibited in both epididymal segments during the post-testicular epididymal storage period. GPx activity is low during the testicular phase of epididymal spermatozoon maturation and is high in both epididymal segments during the storage phase of epididymal function. From our results, we postulate that (i) the pattern of epididymal antioxidant enzyme activities in C. mexicanus is significantly different from the pattern that is proposed to be unique for mammals; (ii) epididymal function in these species of bats can be clearly divided into two phases, a testicular-dependent phase that is related to the spermatozoon maturation function of the epididymides and a testicular-independent phase that is related to the long-term spermatozoon storage function observed in these mammals; (iii) the study of the regulation of the redox potential of the microenvironment, associated with mammalian spermatozoa as they transit through the epididymides, must be particularly focused on the anatomical region where ROS generation scavenging and spermatozoon maturation storage processes take place.
    Canadian Journal of Zoology 02/2011; 83(12):1556-1565. DOI:10.1139/z05-152 · 1.30 Impact Factor
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