Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

In a 26-year-old patient there have been benign enlargements of the lymphatic nodes and a splenomegaly since the end of the adolescence. In the 21st year of age the diagnosis of a Tangier disease was made. Allogenic HDL-rich serum fraction (COHN IV/1-fraction, prepared according to the modified method 6) infused under therapeutic aspect led to a prolonged increase of the serum total cholesterol and of the thrombocytes. The results pled for an activation of the reverse cholesterol transport. Excessively high malonic dialdehyde concentrations in the serum were relating to a "free radical"-associated metabolic defect, which was caused by the hypocholesterolaemia, the reduced transport capacity of vitamin E in the plasma and the nutrition poor in selenium and cholesterol, respectively. Under a nutritive antioxidant supplementation with sodium selenite and D-alpha-tocopherol a slight increase of the total cholesterol, of the thrombocytes as well as a normalization of the MDA values could be reached. The chronic oxidative stress appeared in the patient in a distinct lipofuscinosis of the skin and formations of naevus-cell naevi as an expression of massive denaturations of protein-lipids. In the Tangier disease we must reckon with an increased mutagenic effect of free radicals with an additional DNS repair capacity as well as an increased sensitivity to radical-generating cancerogenic xenobiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Tangier disease--a "free radical"-associated disease. Results of HDL and anti-oxidant therapy with selenium and D-alpha tocopherol]. 166 43

Anti-hepatitis effect of the olean-9(11),12-diene-3 b, 30-diol 3 b, o-hemisuccinate Na Salt (III b), a glycyrrhetinic acid derivative, was studied in CCl4 induced mouse. The mouse was administered i.p. with 0.1 mole/kg or 0.2 mole/kg of III b, then followed by 31.4 microliters/kg of CCl4. III b was shown to promote the activity of the glucose-6-phosphatase, lower the content of malondialdehyde, and prevent the activity from the soluble enzyme(i.e. GPT, GOT, LDH) from flowing out in the serum enzyme and liver homogenate. III b had the similar anti-peroxidation effect as vitamin E and can maintain the liver function.
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PMID:Effect of olean-9(11), 12-diene-3 beta, 30-diol 3 beta, o-hemisuccinate Na salt, a glycyrrhetinic acid derivative, on peroxidation in CCl4 induced mouse acute hepatitis. 166 46

The effects of ozone on human alpha 1-proteinase inhibitor (A-1-PI), alpha 1-antichymotrypsin (A-1-Achy), bronchial leukocyte proteinase inhibitor (BLPI), and Eglin C were studied using in vitro exposures in phosphate-buffered solutions. Following ozone exposure, inhibitory activities against human neutrophil elastase (HNE) and/or cathepsin G (Cat G) were measured. Exposure of A-1-PI to 50 mol O3/mol protein resulted in a complete loss of HNE inhibitory activity, whereas A-1-Achy lost only 50% of its Cat G inhibitory activity and remained half active even after exposure to 250 mol of O3. At 40 mol O3/mol protein, BLPI lost 79% of its activity against HNE and 87% of its Cat G inhibitory activity. Eglin C, a leech-derived inhibitor, lost 81% of its HNE inhibitory activity and 92% of its ability to inhibit Cat G when exposed to 40 mol O3/mol. Amino acid analyses of ozone-exposed inhibitors showed destruction of Trp, Met, Tyr, and His with as little as 10 mol O3/mol protein, and higher levels of O3 resulted in more extensive oxidation of susceptible residues. The variable ozone susceptibility of the different amino acid residues in the four proteins indicated that oxidation was a function of protein structure, as well as the inherent susceptibility of particular amino acids. Exposure of A-1-PI and BLPI in the presence of the antioxidants, Trolox C (water soluble vitamin E) and ascorbic acid (vitamin C), showed that antioxidant vitamins may protect proteins from oxidative inactivation by ozone. Methionine-specific modification of BLPI reduced its HNE and Cat G inhibitory activities. Two moles of N-chlorosuccinimide per mole of BLPI methionine caused an 80% reduction in activity against Cat G, but only a 40% reduction in HNE inhibitory activity.
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PMID:Ozone effects on inhibitors of human neutrophil proteinases. 349 63

Spin labeling methods were applied to study the structure and dynamics of phosphatidylcholine membranes as a function of temperature and the mole fraction of probucol. Multilamellar liposomes made of dimyristoylphosphatidyclcholine, dipalmitoylphosphatidylcholine both saturated, and egg yolk phosphatidylcholine, an unsaturated membrane, were used. In fluid phase membranes probucol was found to increase the order and decrease the motional freedom of alkyl chains of lipids as shown with stearic acid spin labels. The effect of probucol on order and motional freedom is more pronounced in the membrane center (16-doxylstearic acid spin label position) than in the near polar headgroup region (5-doxylstearic acid spin label position). The presence of unsaturation in alkyl chains significantly decreased the ordering effect of probucol. The main phase transition temperature of saturated bilayers was lowered by 2 degrees C in the presence of 3 mol% of probucol and significantly broadened at higher concentrations as measured with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) partitioning. Also, pretransition was no longer observed in the presence of probucol. In gel phase membranes, the effect of probucol was complex. Close to the main phase transition the motion of alkyl chains was increased, showing a regulatory effect of probucol on membrane fluidity. It is proposed that probucol is located in the membrane center as opposed to vitamin E, which locates its phenolic -OH group at the membrane surface; therefore, it inhibits lipid peroxidation in this region which is less accessible to vitamin E.
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PMID:Effects of probucol on phase transition and fluidity of phosphatidylcholine membranes: a spin label study. 804 34

Oxidative modification of human low density lipoprotein (LDL) has been implicated in plaque formation in blood vessels leading to atherogenesis. Conversely, there is increasing evidence that prevention of LDL oxidation reduces the incidence of coronary artery disease. Here, we have compared the effect of unconjugated bilirubin (Bu) and Trolox (a vitamin E analogue) on the oxidation of LDL after treatment with Cu2+ under defined conditions. We observed that Bu, at or near the normal serum level (i.e. 17 microM) effectively inhibits oxidation of LDL, while it takes at least 500 microM Trolox to achieve a similar effect. This means that, on a per mole basis, Bu is > 20 times more effective than Trolox in preventing LDL oxidation. The oxidation of LDL was assessed by agarose gel electrophoresis. This was further corroborated by assaying the malondialdehyde formed upon reacting the presumptive peroxidation product(s) of LDL with thiobarbituric acid. Thus, we have directly verified that Bu and, less so, Trolox, can each prevent the oxidative damage of LDL in vitro. Our result supports the contention that Bu as an endogenous antioxidant can prevent LDL oxidation and hence reduce the risk of atherogenesis.
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PMID:Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox. 820 41

The chain-breaking antioxidant potential of caeruloplasmin and bovine serum albumin (BSA) has been investigated in comparison with other well-established antioxidants. Their Oxygen Radical Absorbing Capacity (ORAC), was measured by using beta-phycocyanin (beta-PC) as a fluorescent indicator protein, 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) as a peroxyl radical generator and the water soluble vitamin E analogue, Trolox, as a reference standard. The relative peroxyl absorbing capacities/mole for Trolox, caeruloplasmin, heat-denatured caeruloplasmin (hCP), catalase, bovine serum albumin (BSA), superoxide dismutase (SOD), and deferoxamine were 1; 2.6; 3.3; 3.7; 1.2; 0.1; 0.2, respectively. Caeruloplasmin was far more effective as a peroxyl radical scavenger than SOD, deferoxamine and BSA, but slightly less effective than catalase. The peroxyl radical absorbing capacity of caeruloplasmin was enhanced by heat-denaturation of the protein. Electron paramagnetic resonance (EPR) spectroscopy using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin-trap, was applied in order to measure the scavenger abilities of caeruloplasmin on superoxide radical and hydroxyl radical production and the concentration required to inhibit by 50% oxygen free radical formation (IC50) was determined. The IC50 values of caeruloplasmin, hCP, and BSA for the superoxide radical were 12, 2, 260 microM and for the hydroxyl radical 15, 2, 200 microM. These results show that caeruloplasmin is an effective chain-breaking antioxidant for a variety of radicals, independently of its catalytic ferroxidase activity.
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PMID:Direct evidence of caeruloplasmin antioxidant properties. 987 63

Melatonin is a potent endogenous free radical scavenger, actions that are independent of its many receptor-mediated effects. In the last several years, hundreds of publications have confirmed that melatonin is a broad-spectrum antioxidant. Melatonin has been reported to scavenge hydrogen peroxide (H(2)O(2)), hydroxyl radical (HO(.)), nitric oxide (NO(.)), peroxynitrite anion (ONOO(-)), hypochlorous acid (HOCl), singlet oxygen ((1)O(2)), superoxide anion (O(2)(-).) and peroxyl radical (LOO(.)), although the validity of its ability to scavenge O(2)(-). and LOO(.) is debatable. Regardless of the radicals scavenged, melatonin prevents oxidative damage at the level of cells, tissues, organs and organisms. The antioxidative mechanisms of melatonin seem different from classical antioxidants such as vitamin C, vitamin E and glutathione. As electron donors, classical antioxidants undergo redox cycling; thus, they have the potential to promote oxidation as well as prevent it. Melatonin, as an electron-rich molecule, may interact with free radicals via an additive reaction to form several stable end-products which are excreted in the urine. Melatonin does not undergo redox cycling and, thus, does not promote oxidation as shown under a variety of experimental conditions. From this point of view, melatonin can be considered a suicidal or terminal antioxidant which distinguishes it from the opportunistic antioxidants. Interestingly, the ability of melatonin to scavenge free radicals is not in a ratio of mole to mole. Indeed, one melatonin molecule scavenges two HO. Also, its secondary and tertiary metabolites, for example, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine, N-acetyl-5-methoxykynuramine and 6-hydroxymelatonin, which are believed to be generated when melatonin interacts with free radicals, are also regarded as effective free radical scavengers. The continuous free radical scavenging potential of the original molecule (melatonin) and its metabolites may be defined as a scavenging cascade reaction. Melatonin also synergizes with vitamin C, vitamin E and glutathione in the scavenging of free radicals. Melatonin has been detected in vegetables, fruits and a variety of herbs. In some plants, especially in flowers and seeds (the reproductive organs which are most vulnerable to oxidative insults), melatonin concentrations are several orders of magnitude higher than measured in the blood of vertebrates. Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.
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PMID:Significance of melatonin in antioxidative defense system: reactions and products. 1089

Chronic renal failure induces a clinical state of immunodefi ciency that also depends upon a wide spectrum of dialysis membranes used during hemodialysis. Previous studies have shown that cellular immunodeficiency is caused by malfunc tion of the antigen presenting cells (monocytes or granulocytes). Subsequent activation of rolling mononuclear leuko cytes results in up-regulated expression of CD11b/CD18 (Mac-1) on endothelial cells. It is postulated that a VitE coated dialysis membrane might minimize the membrane biocompatibility, thereby generating a smaller amount of re active oxygen species (ROS). The purpose of this study was to evaluate the expression of the CD11b/CD18 adhesion mole cule on lymphocytes, monocytes, and granulocytes during HD in 10 patients, using flow cytometric analysis. The study protocol included the measurement of molecule expression using cellulose membrane (Clirans RS15, TERUMO Corp. Japan), and the same membrane coated by vitamin E (Exce brane, Clirans E15, TERUMO Corp., Japan) during 20 dialysi sessions each. Lymphocyte CD11 b/CD1 8 (Mac-1) expression did not change with either dialyzer type. However, monocyt (p = 0.046) and granulocyte (p = 0.018) CD11b/CD18 ex pression in the post HD period was significantly lower using the vitamin E coated membrane compared with the contro cellulose membrane. Our findings suggest a significant de crease in activation and migration of monocytes and granu locytes when using a vitamin E coated cellulose membrane.
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PMID:Effect of vitamin E modified cellulose membrane on human lymphocyte, monocyte, and granulocyte CD11b/CD18 adhesion molecule expression during hemodialysis. 1173 Jan 99

Numerous reports have established that lipid peroxidation contributes to cell injury by altering the basic physical properties and structural organization of membrane components. Oxidative modification of polyunsaturated phospholipids has been shown, in particular, to alter the intermolecular packing, thermodynamic, and phase parameters of the membrane bilayer. In this study, the effects of oxidative stress on membrane phospholipid and sterol organization were measured using small angle x-ray diffraction approaches. Model membranes enriched in dilinoleoylphosphatidylcholine were prepared at various concentrations of cholesterol and subjected to lipid peroxidation at physiologic conditions. At cholesterol-to-phospholipid mole ratios (C/P) as low as 0.4, lipid peroxidation induced the formation of discrete, membrane-restricted cholesterol domains having a unit cell periodicity or d-space value of 34 A. The formation of cholesterol domains correlated directly with lipid hydroperoxide levels and was inhibited by treatment with vitamin E. In the absence of oxidative stress, similar cholesterol domains were observed only at C/P ratios of 1.0 or higher. In addition to changes in sterol organization, lipid peroxidation also caused reproducible changes in overall membrane structure, including a 10 A reduction in the width of the surrounding, sterol-poor membrane bilayer. These data provided direct evidence that lipid peroxidation alters the essential organization and structure of membrane lipids in a manner that may contribute to changes in membrane function during aging and oxidative stress-related disorders.
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PMID:Lipid peroxidation induces cholesterol domain formation in model membranes. 1619 27


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