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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

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

Nitrofurantoin is a widely utilized urinary antimicrobial drug which has been associated with pulmonary fibrosis, neuropathy, and hepatitis as well as hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient individuals. Incubation of freshly isolated rat hepatocytes with nitrofurantoin caused oxygen activation as a result of futile redox cycling. Glutathione disulfide (GSSG) was formed and rapidly exported from the cell resulting in complete glutathione (GSH) depletion followed by cell death. However, fructose prevented the export of GSSG from the cell and GSH levels recovered rapidly without cytotoxicity occurring. Fructose did not affect nitrofurantoin metabolism but rapidly depleted cellular ATP levels by approximately 80% which remained depressed during the incubation period. Fructose, however, did not protect hepatocytes from nitrofurantoin-induced cytotoxicity if GSH was depleted beforehand. Protection by fructose only occurred at concentrations which caused ATP depletion. These results suggest that fructose prevents nitrofurantoin-induced toxicity by depleting ATP and thereby preventing the ATP-dependent GSSG efflux. GSSG is retained enabling NADPH and glutathione-reductase to reduce the GSSG back to GSH, thereby protecting the cell from nitrofurantoin-induced oxidative stress.
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PMID:Prevention of nitrofurantoin-induced cytotoxicity in isolated hepatocytes by fructose. 189 74

During the delivery of oxygen by erythrocytes, highly reactive oxygen species such as superoxide anion arise. The presence of reactive species damages the cell constituents. Glutathione (GSH) functions to repair cells when they are attacked by oxidative stress. GSH is synthesized in erythrocytes and glutathione disulfide (GSSG) is transported outside the cells to maintain a high GSH/GSSG ratio. The redox cycle of GSH by glutathione reductase and glutathione peroxidase is closely related to G6PD. Hereditary enzyme deficiency related to GSH metabolism, with hemolytic anemia has been reported. G6PD deficiency causes hemolytic anemia due to insufficiency of the redox cycle of GSH. Deficiency of GSH synthesizing enzymes or glutathione reductase also causes hemolysis. Pyrimidine 5'-nucleotidase deficiency causes hemolytic anemia even when there is a high concentration of GSH. Accumulation of nucleotides in red cells causes inhibition of G6PD activity.
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PMID:[Impaired glutathione metabolism in hemolytic anemia]. 219 89

gamma-Glutamylcysteine synthetase is one of the enzymes of glutathione (GSH) synthesis. A deficiency of this enzyme has been found only once previously in humans: it was associated with spinocerebellar degeneration and hemolytic anemia. We report the case of a woman, daughter of fifth cousins, who was gamma-glutamylcysteine-synthetase-deficient. Modest decreases in the amount of GSH in cultured lymphoblasts and fibroblasts could be documented. The amount of residual enzyme was insufficient to permit detailed studies of the characteristics of the mutant enzymes, but no major abnormality in its Km for cysteine and glutamic acid or in its heat stability were found. In contrast to the earlier report, the only manifestation of the enzyme deficiency was hemolytic anemia. This leads us to conclude that either the occurrence of neurologic symptoms in the other reported family was a chance association or that the clinical expression of this rare defect is pleomorphic.
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PMID:Gamma-glutamylcysteine synthetase deficiency and hemolytic anemia. 229 91


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