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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutathione plays an important role in biology and medicine. Most cells of plants and animals contain high concentrations of reduced glutathione and a much smaller amount of oxidised glutathione. GSH is important for several metabolic functions of live cells, e.g. the protection of oxidative stress by peroxides, mediation of enzyme reactions, regulation of metabolic events, transport of amino acids across cell membranes via the gamma-glutamyl cycle, elimination of foreign compounds by GSH-conjugation, release of neurotransmitter substances. Irreversible perturbations of the glutathione metabolism may be the reason for severe clinical symptoms of hemolytic anemia or, perhaps, of central nervous disease.
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PMID:[Glutathione (author's transl)]. 0 May 43

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

Glutathione reductase plays an important role in protecting hemoglobin, red cell enzymes, and biological cell membranes against oxidative damage by increasing the level of reduced glutathone (GSSGR) in the process of aerobic glycolysis. The enzyme deficiency may result in mild to moderately severe hemolytic anemia upon exposure to certain drugs or chemicals. However, hereditary deficiency of the enzyme is extremely rare. Recent studies on glutathione reductase in the red cell have shown more insight in the understanding of red cell metabolism and interactions with other enzymes, especially glucose-6-phosphate dehydrogenase (G-6-PD). Glutathione reducatase in serum may be a source of error in any clinical laboratory test in which an enzyme activity is determined indirectly by measuring the change in reduced nicotinamide-adenine dinucleotide (NADH) or reduced nicotinamide adenine dinucleotide phosphate (NADPH) absorbance. Glutathione reductase levels are reduced in banked blood when citrate-phosphate-dextrose (CPD) is used as a preservative. Reviewed is the role of glutathione reductase in the metabolism of the red cell and its clinical implication and usefulness.
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PMID:Glutathione reductase in the red blood cells. 62 27

The effect of 6-methylprednisolone (GCC) was studied on erythropoietin (ESF) levels and on the metabolic functions of erythrocytes (RBC). GCC (U mg/kg/day for 15 days) was administered to 6 patients with the haemolytic-uraemic syndrome (group B) and to 6 patients with non-spherocytic haemolytic anaemia due to hereditary pyruvate kinase enzyme deficiency (group C). 6 healthy persons served as control (group A). The metabolic functions of RBC were investigated by assaying HMPS activity, GSH/GSSG and lactate/pyruvate ratios, relevant glycolytic intermediates, 2,3-DPG, ATP, and key enzymes. A significant increase in ESF was observed in group B patients after GCC therapy, correlating with an improvement in the haemolytic state, and consequent rectification of the secondary disturbances of RBC metabolism. Group C patients already had raised ESF levels before GCC therapy; no further increase occured in response to treatment and no other clinical or haematological change was recorded. Hence, no harmonal influence of GCC on the disturbed RBC metabolic process was detectable in the cases.
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PMID:[Glucocorticoid-induced effect of erythropoietin in haemolytic anaemia with uraemia and red cell enzyme deficiency (author's transl)]. 69 63

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

A case of congenital nonspherocytic haemolytic anaemia associated with a new abnormal glucosephosphate isomerase (GPI), GSH (reduced glutathione) deficiency, and instability and altered carbohydrate membrane composition is reported. The only functional abnormality of the mutant enzyme seems to be a marked instability to heat, urea, and guanidine-HCl. Family studies suggest that the propositus is doubly heterozygous for a maternal gene producing an inactive enzyme and a paternal gene responsible for a structural alteration causing marked lability of the coded enzyme. Experiments of incubation of normal GPI and the propositus's GPI with oxidizing and reducing agents seem to indicate that the abnormality resides in the SH groups of the mutant GPI.
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PMID:A new mutant erythrocyte glucosephosphate isomerase (GPI) associated with GSH abnormality. 74 79

A new case of a defect in red cell pyrimidine 5'-nucleotide (P5N) activity was found in a large family from Guadeloupe in the West Indies. The propositus presented a characteristic hemolytic anemia with red cell basophilic stippling, an increased GSH level, and a shift of the peak in absorbance of nucleotide. The enzyme activity from the deficient red cells differed from that of the normal. The P5N activity of the deficient red cells was about 14% that of normal. The electrophoretic pattern of P5N activity of the deficient red cells was distinct from that of the control in terms of its Km and of the effects of pH on its maximum activity and heat stability. The significance of such differences is discussed.
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PMID:Electrophoretic and kinetic studies of human erythrocytes deficient in pyrimidine 5'-nucleotidase. 90 67

Glutathione peroxidase activity was measured in blood and cultured fibroblasts from healthy persons of several different population groups. Individuals of Jewish ancestry and others of Mediterranean origin were found to manifest a decrease of red cell but not of leukocyte or fibroblast enzyme activity. Oriental populations differed in that the scatter in red cell enzyme activity was significantly lower than in Occidental populations. The erythrocyte enzyme of individuals with low activity was found to be less stable to heating than was the enzyme from persons with high activity. As a possible explanation for these data, a provisional genetic model is presented: a low GSH Px allele with a frequency of 0.556 in the Jewish population and of only 0.181 in the United States-Northern European population. Our results suggest that an association between GSH Px deficiency and hemolytic anemia need not represent a cause-and-effect relationship.
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PMID:Ethnic variation in red cell glutathione peroxidase activity. 113 21

Differential diagnosis of hemolytic anemia is discussed, with regard to the classification into corpuscular and extracorpuscular types of hemolysis. Presence of antibodies in a patient's serum, indicate extracorpuscular-acquired hemolytic anemia. Coombs test may be positive or negative according to the antibody present. A primary disease has to be excluded in each case. Abnormal hemoglobin, defect of the corpuscular-hereditary type. Direct laboratory enzyme estimation indicate enzyme deficiency (Glucose-6-P-dehydrogenase, Pyruvate-kinase, Glutathione-reductase). Hemoglobinelectrophoresis and special tests for unstable hemoglobins indicate this type of disturbance. For defect of the membrane measuring of osmotic fragility might be helpful. Activity of membrane enzymes and introduction of 32P in the fractionated membrane lipids, point out special types of a deficient membrane. 6 of our own cases are discussed.
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PMID:[On the differential diagnosis of hemolytic anemia (author's transl)]. 119 56

Dapsone hydroxylamine (DDS-NOH), a known metabolite of dapsone, has recently been shown to be a direct-acting hemotoxin responsible in part for dapsone-induced hemolytic anemia in the rat. The effect of DDS-NOH on the morphology, sulfhydryl status, and membrane skeletal proteins of the rat red cell has been investigated. Exposure of rat red cells to a TC50 of DDS-NOH induced transformation of about 50% of the cells to an extreme echinocyte morphology. Reduced glutathione content of the cells was rapidly lost with concomitant increase in the formation of mixed disulfide between glutathione and the soluble protein of the cell. Oxidized glutathione content of the cells did not increase at any time during exposure to DDS-NOH. Examination of the skeletal membrane proteins by SDS-PAGE indicated that DDS-NOH caused the apparent loss of band 4.2, decrease in peaks 1, 2.1, and 3, and the appearance of new bands at about 16, 27, 40, and 54 kDa. Bands 4.1 and 7 appeared unchanged. Treatment of DDS-NOH altered proteins with dithiothreitol, reversed the protein changes, and indicated that the observed alterations were due to the formation of disulfide-linked adducts between hemoglobin and the various skeletal proteins as well as between hemoglobin monomers. The possible significance of the parallel changes in cell morphology and in membrane skeletal proteins for the premature splenic sequestration of the injured rat red cells is discussed.
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PMID:Dapsone-induced hemolytic anemia: effect of N-hydroxy dapsone on the sulfhydryl status and membrane proteins of rat erythrocytes. 147 Nov 53


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