Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemin allows maximal protein synthesis in intact rabbit reticulocytes and their cell-free lysate preparations by retarding the formation of a translational repressor (HCR) found in the postribosomal supernate. In order to evaluate the role of HCR in the pathogenesis of hypochromic anemias, HCR was isolated and partially purified from intact rabbit reticulocytes incubated in vitro with either 0.1 mM alpha,alpha-dipyridyl (an iron-chelating agent) or 0.1 M ethanol. Both of these agents inhibit reticulocyte protein synthesis. Hemin (50 muM) protects against the inhibition by both agents. A ferrous iron-transferrin mixture, however, protects only against alpha,alpha-dipyridyl. Both alpha,alpha-dipyridyl and ethanol inhibit heme synthesis before the time that protein synthesis is affected, while neither lowers either ATP or GSH levels. These results indicate that while both agents inhibit heme synthesis, alpha,alpha-dipyridyl does so by inducing iron deficiency while ethanol works at a non-iron-requiring step. When HCR was isolated from intact cells and assayed in the reticulocyte cell-free systems, plus and minus hemin, premature appearance of HCR was found in cells incubated in vitro with alpha,alpha-dipyridyl or ethanol. When hemin was present in the intact cell incubation, the appearance of HCR was retarded. The HCR from alpha,alpha-dipyridyl ethanol-treated cells was partially purified and eluted at the same location on a Sephadex G-200 column (molecular weight approximately 3 x 10(5)) as that from postribosomal supernates incubated minus hemin. In addition rabbits with phenylhydrazine-induced hemolytic anemia were given intravenous ethanol in vivo at a dose of 0.4 ml/kg. This concentration of alcohol resulted in an inhibition of the rate of heme synthesis and protein synthesis as well as an acceleration of HCR formation in reticulocytes. The HCR from these in vivo treated rabbits was isolated, partially purified, and assayed in an identical fashion as the in vitro experiments. These in vivo experiments further support the physiological and pathophysiological role of HCR in reticulocytes. On the basis of these results a model for a role of HCR in some of the hypochromic anemias is proposed. In iron deficiency or chronic disease (where iron is not available to the erythroblast for heme synthesis) HCR appears prematurely and inhibits protein synthesis. When heme synthesis is inhibited by ethanol but there is sufficient intracellular iron, HCR appears prematurely and inhibits protein synthesis, iron accumulates in the erythroblast, and the end result is sideroblastic anemia.
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PMID:A rabbit reticulocyte model for the role of hemin-controlled repressor in hypochromic anemias. 0 17

Blood samples were collected monthly over a nine-month period from 19 high-producing Holstein-Friesian dairy cows. Dry cows on the lowest (13 per cent) protein ration had the highest mean values for packed cell volume (PCV), haemoglobin (Hb) and red blood cells (RBC). Among the lactating cows, the group on the 13 per cent protein diet had the highest mean PCV, Hb and RBC values. Other constituents were not affected significantly by dietary protein levels. Packed cell volume, RBC, Hb, serum iron (SI), iron binding capacity (IBC) and serum albumin concentrations decreased early in lactation and rose to pre-lactation levels by mid-lactation. PCV and Hb concentrations remained low for periods up to four months. RBC count was lowest in the second month while albumin concentration was lowest in the first month and remained low up to the second month. IBC was lowest in the first month of lactation while SI concentrations were lowest in the third month. There were no significant variations in the activities of erythrocyte glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and reduced glutathione (GSH). The 13 per cent protein ration had no anaemia-inducing effect on the cows.
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PMID:Effects of dietary protein and stage of lactation on the haematology and erythrocyte enzymes activities of high-producing dairy cattle. 47 89

Cases showing erythrocyte glutathione peroxidase (GSH-Px) defects have been previously described. Our experiments demonstrate that a number of non genetic factors may influence the GSH-Px activity in human erythrocytes. Selenium administration in vivo was followed in four subjects by elevation in erythrocyte GSH-Px activity ranging from 30% to 1400%. Selenium operates mainly in the bone marrow erythroblasts by facilitating the synthesis of active GSH-Px molecules; experiments in vivo demonstrate that, in the youngest erythrocytes, selenium can raise the enzyme activity, but by a different mechanism. The reticulocyte GSH-Px activity appears to depend on selenium availability and may vary over a wide range. In some normal and iron deficient subjects the GSH-Px activity in the youngest erythrocyte fraction was equal or lower than that previously found in whole erythrocytes of patients affected by haemolytic anaemia. During erythrocyte life, GSH-Px activity may either diminish or increase, and these variations are inversely related to the initial GSH-Px activity in youngest cells. In vitro experiments with the addition of acetyl-phynyl-hydrazine strongly suggest that elevation of GSH-Px activity may be due to allosteric enzyme activation by activated oxygen.
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PMID:In vivo and in vitro variations of human erythrocyte glutathione peroxidase activity as result of cells ageing, selenium availability and peroxide activation. 69 17

Erythrocytic glutathione-peroxidase (GSH-Px) activity and plasma selenium concentrations were measured in 14 patients: 7 with iron deficiency and 7 with raised serum iron levels. The decreased enzymatic activity in iron deficiency was confirmed. Plasma selenium was significantly lower in patients with lower serum iron; furthermore there is a significant correlation between serum iron and plasma selenium concentrations. Another correlation even more significant was found between plasma selenium and enzyme activity in all the cases we studied. These data suggests that the importance of iron for GSH-Px activity may be merely due to its relationship with selenium and that plasma selenium concentration may be of critical importance for enzyme activity.
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PMID:Erythrocytic glutathione peroxidase: its relationship to plasma selenium in man. 88 36

The red cell glutathione-peroxidase (GSH-Px) activity of 9 normal subjects is compared with that of 15 cases of iron deficiency anaemia and with 13 cases of heterozygous beta-thalassemia with the same degree of anaemia and hypochromia. 2 cases of sideroblastic anaemia with high serum iron levels were also examined. Enzymatic activity was found to be significantly decreased in iron deficiency anaemia (about 55% of normal range), while it was not affected in heterozygous beta thalassaemia and it was increased in the 2 cases of sideroblastic anaemia. Moreover, GSH-Px activity exhibited a significant correlation with serum iron levels in all the patients studied. The observed modifications in GSH-Px activity are not correlated with erythrocyte ageing because reticulocyte-poor fractions exhibited GSH-Px activity which was not significantly reduced in respect of the reticulocyte-rich ones. These data seem to suggest that iron has a crucial connection with erythrocyte GSH-Px and that the enzyme deficiency may be of some importance in explaining the decreased red cell survival observed in severe iron-deficiency anaemias.
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PMID:Plasma iron and erythrocytic glutathione peroxidase activity. A possible mechanism for oxidative haemolysis in iron deficiency anemia. 96 43

A method is described for purification of sulfhydryl oxidase from bovine milk which consistently yields preparations with greater than 3000-fold purification over skim milk. A concentration-dependent association-dissociation of the enzyme was adapted to the development of an isolation procedure. Purified preparations exhibited two zones, both of which displayed activity, upon polyacrylamide disc gel electrophoresis, but only one zone following disc gel electrophoresis in sodium dodecyl sulfate. Its mobility indicated a subunit weight of 89,000. Several lines of evidence suggest that iron is an integral part of the enzyme. Treatment of the enzyme with EDTA resulted in complete loss of activity which could be subsequently restored by dialysis against 1 muM ferrous sulfate. Furthermore, atomic absorption analysis and neutron activation analysis of separate enzyme preparations each indicated 0.5 atom of iron per subunit. Chemical analyses of sulfhydryl oxidase accounted for 97% of the sample weight, of which 89% could be attributed to amino acid residues and 11% to carbohydrate residues. Five half-cystine residues per subunit were indicated by cysteic acid analysis and by sulfhydryl group determination following reaction with sodium borohydride. Comparison of this value to the total sulfhydryl groups without reduction tentatively suggests the presence of one disulfide bond. Sulfhydryl oxidase was found to catalyze the oxidation of sulfhydryl groups in both small compounds and proteins, using O2 as oxidant and producing, in equimolar quantities, H2O2 and the corresponding disulfide. A Michaelis constant of 90 muM was obtained using reduced glutathione as substrate, under conditions of optimal pH and temperature, viz., pH 7.0 and 35 degrees. Substrate inhibition was apparent at GSH concentrations above 0.8 mM. In the presence of sulfhydryl oxidase, reductively denatured RNase was reoxidized and fully reactivated within 1 hour, whereas in the absence of the oxidase under otherwise identical conditions, full recovery of RNase activity required 24 hours. The presence of reducing agent was not required for this activity, nor was prior reduction of the sulfhydryl oxidase. Based on the observed activity, it appears that the enzyme could be involved in the biosynthesis of disulfide bonds in certain proteins.
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PMID:Isolation and characterization of sulfhydryl oxidase from bovine milk. 112 23

Ethanol, in concentrations of 0.05-0.8 M, inhibited intact human and rabbit reticulocyte protein synthesis in the presence of iron-transferrin for endogenous haem synthesis. Associated with this effect there was a conversion of polyribosomes to monoribosomes and a decreased incorporation of radioactive leucine into nascent globin chains. When physiological levels of ethanol (0.05-0.1 M) were used, these effects were prevented by incubation with 50 muM haemin and reversed by removing the alcohol and reincubating with iron-transferrin or haemin. The polyribosomal disaggregation was also prevented by stopping ribosomal movement with 5 mM cycloheximide. Neither ATP nor GSH levels were altered in the presence of ethanol. When non-physiological levels of 0.8 M ethanol were used, haemin did not prevent the inhibition of protein synthesis. Likewise, in the rabbit reticulocyte cell-free lysate system containing haemin inhibition was noted at concentrations greater than 0.05 M ethanol. The polyribosomal disaggregation in reticulocytes incubated with 0.8 M ethanol was associated with decreased dissociation of monoribosomes into subunits. Similarly, when ribosomes were directly suspended cell-free in 0.1 or 0.8 M ethanol there was a decreased percentage of subunits. These results indicate that physiological concentrations of ethanol inhibit initiation of reticulocyte protein synthesis secondary to a block in haem synthesis. When intact cells are exposed to high non-physiological concentrations of ethanol the inhibition is secondary to decreased ribosomal dissociation. The cell-free lysate inhibition is also through this effect on ribosomal dissociation. This study supports the view that alcohol is a direct toxin to developing red cell precursors via its effect on mitochondrial haem synthesis. The physiological role of the decreased dissociation of monoribosomes into subunits is not yet clear.
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PMID:Ethanol inhibition of reticulocyte protein synthesis: the role of haem. 120 Dec 18

The changes in trace elements, free radicals, and neurophysiological function were investigated in rats with liver damage induced by D-galactosamine (GalN). The elevated results showed that all the parameters related to free radical metabolism changed after administration of GalN. Relative free radical concentration, malonaldehyde (MDA), and oxidized glutathione (GSSG) elevated, but reduced glutathione (GSH) decreased. Concurrently, zinc, copper, manganese, and selenium contents in liver were significantly reduced, whereas iron was elevated. In rats with hepatic encephalopathy (HE) owing to fulminant hepatic failure (FHF) induced by a high dosage of GalN, the latencies of VEPs were delayed. Moreover, there is a correlation between Zn content of brain and the latencies of VEPs. The results of this study suggested that lipid peroxidation by free radicals might be responsible for GalN-induced liver damage in which trace elements were involved, and that change in brain Zn might play a role in the neural inhibition of HE owing to FHF.
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PMID:Changes in free radicals, trace elements, and neurophysiological function in rats with liver damage induced by D-galactosamine. 138 18

The antineoplastic drug Carboplatin (CBDCA) was encapsulated in human erythrocytes by means of transient hypotonic hemolysis, followed by isotonic resealing. Up to 5 mg/ml of packed cells could be entrapped, with about 70% cell recovery. In vitro incubation of the CBDCA-loaded erythrocytes in autologous plasma caused a very slow release of the drug from the cells (12% approximately in 3 h). The encapsulation conditions, performed at a low hematocrit, in order to obtain high amounts of the drug inside the carriers, impaired the metabolic properties of the loaded erythrocytes significantly. In particular, an almost complete disappearance of GSH was observed. Analysis of the intraerythrocytic metabolism of CBDCA showed that, in spite of its relatively high stability in aqueous solutions, in hemolysates and in the loaded erythrocytes a significant percentage of CBDCA is rapidly converted to other species that still retain an antiproliferative activity in vitro. This fast conversion could be extensively inhibited by previous conversion of oxyhemoglobin to methemoglobin or carbomonoxyhemoglobin, suggesting an important role of heme iron in this process. Encapsulation of CBDCA in selectively targeted human erythrocytes may represent a therapeutic strategy for increasing the drug concentration in specific organs, notably liver.
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PMID:Interaction of carboplatin with carrier human erythrocytes. 138 19

Alkaline sucrose density gradient and agarose gel electrophoresis methods were used to observe lambda deoxyribonucleic acid (DNA) strand breaks by the reaction system of reduced glutathione (GSH) with alloxan in the presence of Fe(3+)-ethylenediaminetetraacetic acid (EDTA). When DNA was incubated in the reaction system for 10 min, DNA strand breaks were easily induced. The increasing concentrations of GSH up to 1.0 mM in the reaction system in the presence of 1.0 mM alloxan caused DNA strand breaks in a concentration-dependent fashion and GSH beyond 2.0 mM caused in the strand breaks of DNA by which the fragments with multiple ranges of molecular weight were produced. The strand breaks of DNA in the reaction system containing low concentrations of GSH were protected by catalase and hydroxyl radical (HO.) scavengers but superoxide dismutase (SOD) did not, indicating that such breaks were induced by HO.generated from the Fenton reaction. On the other hand, the strand breaks of DNA at high concentrations of GSH were protected by ethanol and desferrioxamine, but not effectively by SOD and HO.scavengers, suggesting the possible participation of some oxidizing species of iron rather than HO.. These results indicate that HO.or oxidizing species of iron generated in the GSH-alloxan system depending on the concentration of GSH attacks DNA to produce strand breaks.
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PMID:Effect of glutathione on lambda deoxyribonucleic acid strand breaks in the reaction system of glutathione-alloxan in the presence of Fe(3+)-ethylenediaminetetraacetic acid. 142 70


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