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Query: UNIPROT:P36969 (phospholipid hydroperoxide glutathione peroxidase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Mammalian selenoproteins. 148 33

The metabolic relationships among the antioxidant nutrients selenium, sulfur, and vitamin E are particularly close. Selenium and vitamin E have long been known to spare one another in certain nutritional diseases of animals, and selenium has been considered to have a key antioxidant defense function as a component of glutathione peroxidase. However, the antioxidant role of glutathione peroxidase has been questioned and new proteins containing selenium have been identified: phospholipid hydroperoxide glutathione peroxidase, selenoprotein P, and iodothyronine deiodinase. Glutathione peroxidase activity independent of selenium resides in the glutathione S-transferases. Glutathione participates in both enzymatic and nonenzymatic antioxidant defense systems. Some low-molecular weight selenium compounds (e.g., ebselen) exhibit glutathione peroxidase-like action. Certain low molecular weight thiols decompose peroxides nonenzymatically (e.g., the ovothiols). Murine malaria appears to be a useful experimental model for investigating interrelationships of selenium and vitamin E. Vitamin E deficiency protects against the parasite, especially when the mice are concurrently fed peroxidizable fat such as fish or linseed oils. Selenium deficiency, on the other hand, has little or no protective effect against the parasite. Any practical utility of pro-oxidant diets in combating human malaria remains to be determined.
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PMID:Selenium and sulfur in antioxidant protective systems: relationships with vitamin E and malaria. 157 91

Various rat and human tissues and cell lines naturally exposed to endogenous or exogenous oxidative stress were examined for their pattern of selenoprotein transcripts. Selenoprotein P mRNA was mainly expressed in rat kidney, testis, liver and lung. In testis, a high phospholipid hydroperoxide glutathione peroxidase (PHGPx) but only a weak cytosolic glutathione peroxidase (cGPx) signal was obtained. In kidney, spleen, heart, liver and lung cGPx mRNA levels were higher than those of PHGPx and for both only weak signals were obtained with brain mRNA. The Northern blot results concerning the tissue distribution of cGPx in the rat were fully supported by activity measurements. None of the human tissues revealed a PHGPx mRNA signal, whereas selenoprotein P transcripts were present in all human tissues with the highest abundance in heart, liver, and lung, tissues which also exhibited strong cGPx signals. The gastrointestinal glutathione peroxidase (GPx-GI) was only expressed in human liver and colon liver. Liver, the organ that showed the broadest repertoire of selenoproteins, has to cope with reactive oxygen intermediates produced during detoxification reactions. Human cell lines of the myeloic system that may be exposed to oxidative stress during inflammatory processes showed distinct cGPx signals: epithelial cells showed low cGPx signals. Similar cGPx mRNA levels were found in normal human thyroid tissue and thyroid carcinoma cells. Among the human cell lines selenoprotein P expression was detected in HepG2 and HTh74 thyroid cells. Our data confirm the necessity of getting specific information on distinct tissue- and cell-specific patterns of selenoprotein expression as endpoints of selenium supply and biological function of the selenoprotein family. Analysis of total selenium contents of tissues or body fluids only provides integrative information on the global selenium status of individuals.
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PMID:Expression of selenoproteins in various rat and human tissues and cell lines. 928 88

Selenoprotein P is an extracellular protein containing presumably 10 selenocysteines that are encoded by the UGA stop codon in the open reading frame of the mRNA. The function of selenoprotein P is currently unknown, although several indirect lines of evidence suggest that selenoprotein P is a free radical scavenger. We first developed a conventional procedure to isolate selenoprotein P from human plasma. Next, we investigated the reactivities of selenoprotein P against various hydroperoxides in the presence of glutathione. Although selenoprotein P reduces neither hydrogen peroxide nor tertiary butyl hydroperoxide, it does reduce phospholipid hydroperoxide such as 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl)-3-phosphatidylcholine hydroperoxide. Kinetic analysis demonstrated a tert-uni ping-pong mechanism, similar to those described for classical glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase. Not only glutathione, but also dithiothreitol, mercaptoethanol, cysteine, and homocysteine, were effective as reducing substances, as in the case of phospholipid hydroperoxide glutathione peroxidase. These results show that selenoprotein P functions as a phospholipid hydroperoxide glutathione peroxidase in extracellular fluids.
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PMID:Selenoprotein P in human plasma as an extracellular phospholipid hydroperoxide glutathione peroxidase. Isolation and enzymatic characterization of human selenoprotein p. 991 22

Selenium functions within mammalian systems primarily in the form of selenoproteins. Selenoproteins contain selenium as selenocysteine and perform a variety of physiological roles. Eleven selenoproteins have been identified: cellular or classical glutathione peroxidase; plasma (or extracellular) glutathione peroxidase; phospholipid hydroperoxide glutathione peroxidase; gastrointestinal glutathione peroxidase; selenoprotein P; types 1, 2, and 3 iodothyronine deiodinase; selenoprotein W; thioredoxin reductase; and selenophosphate synthetase. Of these, cellular and plasma glutathione peroxidase are the functional parameters used for the assessment of selenium status. Glutathione peroxidases catalyze the reduction of peroxides that can cause cellular damage. Thioredoxin reductase provides reducing power for several biochemical processes and defends against oxidative stress. Selenoprotein P appears to play a role in oxidant defense. Selenoprotein W may play a role in oxidant defense and be involved with muscle metabolism. Thyroid deiodinases function in the formation and regulation of active thyroid hormone. Selenophosphate synthetase is an enzyme required for the incorporation of selenocysteine into selenoproteins. In addition, a protein in the sperm mitochondrial capsule, which is vital to the integrity of sperm flagella, may be a unique selenoprotein. Recommended intakes, food sources, and status assessment of selenium, as well as selenium's role in health and disease processes, are reviewed.
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PMID:The diverse role of selenium within selenoproteins: a review. 1076 94

Glutathione peroxidase catalyzes the reduction of hydrogen peroxide and organic hydroperoxide by glutathione and functions in the protection of cells against oxidative damage. Glutathione peroxidase exists in several forms that differ in their primary structure and localization. We have also shown that selenoprotein P exhibits a glutathione peroxidase-like activity (Saito, Y., Hayashi, T., Tanaka, A., Watanabe, Y., Suzuki, M., Saito, E., and Takahashi, K. (1999) J. Biol. Chem. 274, 2866-2871). To understand the physiological significance of the diversity among these enzymes, a comparative study on the peroxide substrate specificity of three types of ubiquitous glutathione peroxidase (cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, and extracellular glutathione peroxidase) and of selenoprotein P purified from human origins was done. The specific activities and kinetic parameters against two hydroperoxides (hydrogen peroxide and phosphatidylcholine hydroperoxide) were determined. We next examined the thiol specificity and found that thioredoxin is the preferred electron donor for selenoprotein P. These four enzymes exhibit different peroxide and thiol specificities and collaborate to protect biological molecules from oxidative stress both inside and outside the cells.
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PMID:A comparative study on the hydroperoxide and thiol specificity of the glutathione peroxidase family and selenoprotein P. 1218 74

Male Wistar rats fed with diets containing eight different levels of selenium(Se). Six rats in each group were killed after 20 weeks to obtain brains. The other 105 rats in the Se depleted group were then divided into four groups randomly and fed with diets containing four different levels of Se. The rats in these four groups were then killed at different time points to observe the kinetic change of selenoproteins. The lowest dietary Se required for reaching the plateau of the activities of cellular glutathione peroxidase (cGPX), phospholipid hydroperoxide glutathione peroxidase (PHGPX) and type II deiodinase (ID II) were 0.05, 0.03 and 0.01 mg/kg respectively. The lowest dietary Se required for reaching normal expression of selenoprotein P and selenoprotein W were 0.01 and 0.05 mg/kg respectively. While the rats were restored Se from diets supplemented with Se, the expression of selenoprotein P and type II deiodinase were in preference to PHGPX and cGPX, and the later two parameters were in preference to selenoprotein W. The results suggested that the function of selenoprotein P and ID II in brain were more important than the other three selenoproteins.
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PMID:[Selenoproteins in rat brain]. 1271 17

Selenium (Se) is involved in the process of male reproduction. Several studies have been carried out to find the mechanism of Se action through identified selenoproteins. Especially selenoenzyme phospholipid glutathione peroxidase (PHGPx, GPx-4) plays a pivotal role in regulating spermatogenesis. However, the action of selenium is best known as an antioxidant which acts through various selenoproteins viz. glutathione peroxidase, thioredoxin reductase and selenoprotein P. Oxidative stress is currently being considered a leading cause of male infertility. Presently, the involvement of redox active transcription factor, AP1 (Activator protein1) in testicular function was studied. AP1 is redox sensitive and also controls cell proliferation. The effects of Se might be mediated through it. Different Se status - deficient, adequate and excess Se - were generated in male Balb/c mice by feeding yeast based selenium deficient diet and deficient diet supplemented with Se as sodium selenite (0.2 and 1 ppm Se), respectively, for a period of 4 and 8 weeks. Se status was checked by measuring the Se levels and glutathione peroxidase (GSH-Px) activity in testis and liver. The reproductive potential of mice was affected at these changed Se levels. Changes in the activity of superoxide dismutase (SOD), levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were observed indicating increased oxidative stress at both the levels. Further, changes in the mRNA expression of GSH-Px, gamma-glutamylcysteine synthetase gammaGCS) and Mn superoxide dismutase (MnSOD) were observed. Decrease in cjun and cfos mRNA levels were observed at both the Se status (deficient and excess) which might be responsible for decreased germ cell number, differentiation and reduced fertility observed at the altered Se levels.
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PMID:Role of selenium in regulation of spermatogenesis: involvement of activator protein 1. 1641 Jun 37

The role of selenium in male fertility is reviewed with special emphasis on selenoprotein P and phospholipid hydroperoxide glutathione peroxidase (GPx4) in spermiogenesis. Inverse genetics reveal that selenoprotein P is required for selenium supply to the testis. GPx4 is abundantly synthesized in spermatids. As a moonlighting protein it is transformed in the later stages of spermiogenesis from an active selenoperoxidase into a structural protein that becomes a constituent of the mitochondrial sheath of spermatozoa. The transformation is paralleled by loss of glutathione. Mechanistically, the process is an alternate substrate inactivation of GPx4 resulting from reactions of its selenenic form with thiols of GPx4 itself and other proteins. Circumstantial evidence and ongoing experimental genetics indicate that the mitochondrially expressed form of the GPx4 gene is the most relevant one in spermiogenesis, with the nuclear form being dispensable for fertility and the role of cytosolic GPx4 remaining unclear. Clinical data reveal a strong association of low sperm GPx4 with infertility. Thus, impaired GPx4 biosynthesis, due to selenium deficiency or to genetic defects in gpx4 itself or in proteins involved in Se distribution and selenoprotein biosynthesis, causes male infertility, but can also be an epiphenomenon due to any perturbation of testicular function.
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PMID:Selenium in mammalian spermiogenesis. 1793 12

Human selenium (Se) requirements are currently based on biochemical markers of Se status. In rats, tissue glutathione peroxidase-1 (Gpx1) mRNA levels can be used effectively to determine Se requirements; blood Gpx1 mRNA levels decrease in Se-deficient rats, so molecular biology-based markers have potential for human nutrition assessment. To study the efficacy of molecular biology markers for assessing Se status in humans, we conducted a longitudinal study on 39 subjects (age 45 +/- 11) in Reading, UK. Diet diaries (5 day) and blood were obtained from each subject at 2, 8, 17 and 23 weeks, and plasma Se, glutathione peroxidase (Gpx3) enzyme activity, and selenoprotein mRNA levels were determined. There were no significant longitudinal effects on Se biomarkers. Se intake averaged 48 +/- 14 microg/d. Plasma Se concentrations averaged 1.13 +/- 0.16 micromol/l. Plasma Se v. energy-corrected Se intake (ng Se/kJ/d) was significantly correlated, but neither Gpx3 activity v. Se intake (ng Se/kJ/d) nor Gpx3 activity v. plasma Se was significantly correlated. Collectively, this indicates that subjects were on the plateaus of the response curves. Selenoprotein mRNAs were quantitated in total RNA isolated from whole blood, but mRNA levels for Gpx1, selenoprotein H, and selenoprotein W (all highly regulated by Se in rodents), as well selenoprotein P, Gpx3, and phospholipid hydroperoxide glutathione peroxidase were also not significantly correlated with plasma Se. Thus selenoprotein molecular biomarkers, as well as traditional biochemical markers, are unable to further distinguish differences in Se status in these Se replete subjects. The efficacy of molecular biomarkers to detect Se deficiency needs to be tested in Se-deficient populations.
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PMID:Longitudinal selenium status in healthy British adults: assessment using biochemical and molecular biomarkers. 1859 87


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