UMLS:C0027960 - FACTA Search

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Query: UMLS:C0027960 (mole)
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Glutathione peroxidase (glutathione:H2O2 oxidoreductase, E.C. 1.11.1.9), isolated from ovine and bovine erythrocytes, has recently been shown to contain 4 selenium atoms per mole, an average of 1 Se per protein subunit of about 22,000 molecular weight. Selenium deficiency in the rat, chick and sheep causes dramatic decreases in the activity of this enzyme in the tissues, but certain sites such as liver are affected more than others. Decreases in glutathione peroxidase correlate with lesions caused by selenium deficiency and appear useful in diagnosing selenium deficiency. Glutathione peroxidase is an important enzyme in destroying H2O2 and organic hydroperoxides such as lipid hydroperoxides. It therefore guards against oxidative damage to the cell membranes and other oxidant-sensitive sites in the cell. While this selenium-dependent system destroys lipid hydroperoxides and other peroxides, vitamin E is believed to protect against oxidant damage to membranes by preventing the formation of lipid hydroperoxides. A scheme is proposed, based on oxidant damage and its prevention, which accounts for the interaction between selenium, vitamin E, unsaturated lipids, sulfur-containing amino acids, and cell damaging agents such as oxidant stressors and toxicants such as silver and tri-o-cresyl phosphate. The background for such a scheme is reviewed.
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PMID:Biochemical function of selenium and its relation to vitamin E. 110 Apr 37

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

Dioleoyl phosphatidylcholine (PC) liposomes were ozonized and the ozonized liposomes were tested for their lytic potency on human red blood cells (RBC). Ozonation of PC liposomes generated approximately 1 mole equivalent of hydrogen peroxide (H2O2) and 2 mole equivalents of aldehydes, based on the moles of ozone consumed. The time necessary for 50% hemolysis induced by ozonized liposomes (a convenient measure of hemolytic activity) was found to depend on the extent of ozonation of the PC liposomes, indicating the formation and accumulation of hemolytic agents during ozonation. Hemolysis was also observed when RBC were incubated with nonanal, the expected product of the ozonation of oleic acid, the principle unsaturated fatty acid in the liposomes. Hydrogen peroxide, another product of PC ozonation, did not induce hemolysis; however, a combination of H2O2 and nonanal was significantly more hemolytic than nonanal alone. A ratio of 1:2 H2O2/nonanal (the ratio observed in the ozonized liposomes) provided hemolytic activity comparable to that observed with ozonized dioleoyl PC. Among different antioxidants tested, ascorbate, catalase, and glutathione peroxidase partially inhibited hemolysis induced by ozonized liposomes and by H2O2/nonanal mixtures, but they were not protective against the nonanal-induced hemolysis. Identification of H2O2 and aldehydes as cytotoxic chemical species generated from the ozonation of unsaturated fatty acids may have an important bearing on the in vivo toxicity of ozone on the lung as well as on extrapulmonary tissues.
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PMID:The mixture of aldehydes and hydrogen peroxide produced in the ozonation of dioleoyl phosphatidylcholine causes hemolysis of human red blood cells. 206 37

Selenium occurs normally in living things as a highly specific component of certain enzymes and amino acid transfer nucleic acids (tRNAs). In bacteria, biosynthesis of essential selenoenzymes has been shown to be unaffected by wide variations in sulfur levels. The naturally occurring selenoenzymes so far identified from bacterial sources include glycine reductase, certain formate dehydrogenases, a hydrogenase, nicotinic acid hydroxylase, xanthine dehydrogenase and thiolase. The selenoenzyme, glutathione peroxidase, and three other selenoproteins of unknown function have been isolated from animals. In certain enzymes, e.g. glycine reductase, formate dehydrogenase, hydrogenase and glutathione peroxidase, the chemical form of selenium has been identified as selenocysteine. One enzyme, a bacterial thiolase, contains selenomethionine rather than selenocysteine. A labile, unidentified form of selenium is present in nicotinic acid hydroxylase, and by inference, xanthine dehydrogenase. The seleno-tRNAs serve as examples of a different type of biological macromolecule that is specifically modified with selenium. The major seleno-tRNAs in Clostridium sticklandii and Escherichia coli have been identified as glutamate and lysine isoaccepting species. The selenium-modified nucleoside is 5-methyl-aminomethyl-2-selenouridine (mnm5Se2U), which is the chemical analog of 5-methylaminomethyl-2-thiouridine, a previously identified minor base of E. coli tRNA2Glu. The seleno-tRNAGlu of C. sticklandii contains one gram atom of Se per mole of biologically active tRNA. Loss of Se from the modified nucleoside, mnm5Se2U, in this tRNA results in concomitant loss of glutamate charging activity suggesting that selenium is essential for interaction of the synthetase and its cognate tRNA.
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PMID:New biologic functions--selenium-dependent nucleic acids and proteins. 622 14

Numerous experimental and clinical studies have reported a role of radical forms of oxygen in the etiology of the manifestations of reperfusion of the ischemic myocardium. However, clinical results remain controversial. The aim of this study was to ascertain the existence of reperfusion-related radical stress after thrombolysis with a marker that is easy to use and reliable. Thirty patients hospitalized for acute myocardial infarction were involved in the study. Of these, 18 had been subjected to intravenous thrombolysis (Group I) and 12 had not (Group II). They were compared to two control groups who had no history of myocardial infarction. Of these, 16 were patients with coronary heart disease hospitalized for stable angina (Group III) and 17 were patients free of any known cardiovascular disease (Group IV). Radical activity was assessed in plasma samples taken from a peripheral vein over a 10-day period of hospitalization by measuring (1) malondialdehydes (MDA) concentrations using fluorometry techniques or HPLC, (2) the antioxidant activity of glutathione peroxidase (GPx) and (3) the concentration of various antiradical compounds (beta-carotene, vitamins A and E, uric acid). All patients in Group I had a patent artery on coronary angiography and showed a significant increase in plasma MDA when compared to those who had not been subjected to thrombolysis (3.15 +/- 0.62 and 2.70 +/- 0.40 mole/l of plasma, respectively). Furthermore, GPx plasma activity was also significantly increased following thrombolysis. By contrast, there was no significant alteration in the antiradical compounds measured. These data suggest that MDA measurements (an early measurement 1-2 days and a late measurement 5-7 days after reperfusion) by fluorometry is a good marker of radical stress during reperfusion in man. The assessment of this marker in patients might represent a simple and reliable test of reperfusion efficacy following thrombolysis, and it might enable one to test the effect of various antioxidant therapies associated with thrombolytic treatment.
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PMID:Assessment of radical activity during the acute phase of myocardial infarction following fibrinolysis: utility of assaying plasma malondialdehyde. 858 62

The mechanism of oxidation or reduction using the electron method was investigated for (I) aniline; (II) nitrobenzene; (III) nitrate; (IV) sulphanilamide; (V) hydrogen peroxide; (VI) hydroxyl free radical; (VII) ferricyanide; (VIII) acetylphenylhydrazine; (IX) nitrite; (X) chlorate and (XI) hydroxylamine respectively. Substances (II), (III), (V), (VI), (VII), (IX), (X) and (XI) evolved as oxidants, with (II), nitrobenzene and (X), chlorate as the most powerful oxidants (number of moles of HbFe(2+)(haemoglobin) of 6 reacting with 1.0 mole of the substance). Substances (I), (IV) and (VII) evolved as reductants of equal reducing power (number of moles of HbFe(3+)(methaemoglobin) of 4 reacting with 1.0 mole of the substance). Using the following equations, the impact of oxidants and reductants on glutathione (GSH) peroxidase, glutathione (GSSC) reductase and NADHmetHb reductase respectively on methaemoglobinaemia generation was investigated. [Equation in text]. Redox potential change (DeltaE' (o)) of 1.77, -1.77 and 1.86 volt and free energy change (DeltaG(o)') of -81, 81 and -85.8 kcal/mol were calculated for GSH peroxidase, GSSG reductase and NADHmetHb reductase systems respectively. In sustained methaemoglobinaemia, these mechanisms predict low levels of NADHmetHb reductase and glutathione peroxidase respectively, but high levels of glutathione reductase in red blood cells on exposure to oxidants. The significance of these mechanisms was investigated in cord blood, neonatal, adult red blood cells and other biological systems. It was concluded that any reaction with a positive DeltaE(o)' and negative DeltaG(o)' with the Fe(3+): Fe(2+)couple will indicate methaemoglobin oxidizing power. The effects on red blood cells and white blood cells were manifested in the biochemical toxicology of nitroso (PhN = 0), arylamine glucuronide (PhNHG) and arene imine respectively.
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PMID:Theoretical mechanistic basis of oxidants of methaemoglobin formation. 1079 Jul 68

The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known [maximum lifespan potential (MLSP): >28 yr] and is a unique model of successful aging showing attenuated declines in most physiological function. This study addresses age-related changes in endothelial function and production of reactive oxygen species in NMR arteries and vessels of shorter-living Fischer 344 rats (MLSP: approximately 3 yr). Rats exhibit a significant age-dependent decline in acetylcholine-induced responses in carotid arteries over a 2-yr age range. In contrast, over a 10-yr age range nitric oxide (NO)-mediated relaxation responses to acetylcholine and to the NO donor S-nitrosopencillamine (SNAP) were unaltered in NMRs. Cellular superoxide anion (O(2)(*-)) and H(2)O(2) production significantly increased with age in rat arteries, whereas they did not change substantially with age in NMR vessels. Indicators of apoptotic cell death (DNA fragmentation rate, caspase 3/7 activity) were significantly enhanced ( approximately 250-300%) in arteries of 2-yr-old rats. In contrast, vessels from 12-yr-old NMRs exhibited only a approximately 50% increase in apoptotic cell death. In the hearts of NMRs (2 to 26 yr old), expression of endothelial NO synthase, antioxidant enzymes (Cu,Zn-SOD, Mn-SOD, catalase, and glutathione peroxidase), the NAD(P)H oxidase subunit gp91(phox), and mitochondrial proteins (COX-IV, ATP synthase, and porin, an indicator of mitochondrial mass) did not change significantly with age. Thus long-living NMRs can maintain a youthful vascular function and cellular oxidant-antioxidant phenotype relatively longer and are better protected against aging-induced oxidative stress than shorter-living rats.
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PMID:Vascular aging in the longest-living rodent, the naked mole rat. 1746 32

Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with (75)Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression.
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PMID:Reduced utilization of selenium by naked mole rats due to a specific defect in GPx1 expression. 2137 35

The oxidative damage hypothesis of aging posits that the accumulation of oxidative damage is a determinant of an animal species' maximum lifespan potential (MLSP). Recent findings in extremely long-living mammal species such as naked mole-rats challenge this proposition. Among birds, parrots are exceptionally long-living with an average MLSP of 25 years, and with some species living more than 70 years. By contrast, quail are among the shortest living bird species, averaging about 5-fold lower MLSP than parrots. To test if parrots have correspondingly (i) superior antioxidant protection and (ii) lower levels of oxidative damage compared to similar-sized quail, we measured (i) total antioxidant capacity, uric acid and reduced glutathione (GSH) levels, as well as the activities of enzymatic antioxidants (superoxide dismutase, glutathione peroxidase and catalase), and (ii) markers of mitochondrial DNA damage (8-OHdG), protein damage (protein carbonyls) and lipid peroxidation (lipid hydroperoxides and TBARS) in three species of long-living parrots and compared these results to corresponding measures in two species of short-living quails (average MLSP=5.5 years). All birds were fed the same diet to exclude differences in dietary antioxidant levels. Tissue antioxidants and oxidative damage were determined both 'per mg protein' and 'per g tissue'. Only glutathione peroxidase was consistently higher in tissues of the long-living parrots and suggests higher protection against the harmful effects of hydroperoxides, which might be important for parrot longevity. The levels of oxidative damage were mostly statistically indistinguishable between parrots and quails (67%), occasionally higher (25%), but rarely lower (8%) in the parrots. Despite indications of higher protection against some aspects of oxidative stress in the parrots, the pronounced longevity of parrots appears to be independent of their antioxidant mechanisms and their accumulation of oxidative damage.
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PMID:Does the oxidative stress theory of aging explain longevity differences in birds? II. Antioxidant systems and oxidative damage. 2223 Apr 89