Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize the vitamin E-responsive anemia occurring in owl monkeys (Aotus trivirgatus), osmotic fragility, and H2O2-induced and time-dependent hemolysis, as well as RBC lipid peroxidation, were compared in anemic and nonanemic owl monkeys. Whereas vitamin E serves as a lipid-soluble antioxidant, the glutathione peroxidase system functions in the water-soluble phase of the cell. Thus, activity of glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase, as well as reduced glutathione concentrations in owl monkeys' RBC, were compared with those of rhesus macaques and cebus and squirrel monkeys fed the same diet and maintained under the same management scheme. Osmotic fragility did not differ between anemic and nonanemic owl monkeys. The H2O2-induced and time-dependent hemolysis was approximately 10-fold greater among anemia owl monkeys than among their nonanemic counterparts, and lipid peroxidation values tended to be higher in the anemic monkeys. Owl monkeys, as a species and independent of anemia, exhibited higher RBC peroxidation than did 2 other New World species, cebus and squirrel monkeys. The glutathione peroxidase system was not depressed in owl monkey RBC. The only observed difference in this system was in the glucose-6-phosphate dehydrogenase activity, which was 3- to 6-fold higher in the owl monkey than in the other species, indicating an increased activity of the peroxidase system. Thus, a defect in the glutathione peroxidase system could not be identified.
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PMID:Erythrocyte characteristics in vitamin E-responsive anemia of the owl monkey (Aotus trivirgatus). 710 34

In the present study we demonstrated that human erythrocytes possess a NO synthase (NOS) that can be activated by oxidative stress and Ca2+ accumulation to produce nitric oxide (NO), and that this activation could be involved in the pathogenesis of toxic anaemia in breast cancer patients. By causing oxidative stress in human erythrocytes with hydrogen peroxide (H2O2) (100 microM), or by increasing the intracellular calcium concentration using various doses (up to 100 microM) of the calcium ionophore A23187, a gradual increase in both NO and peroxynitrite (ONOO-) release that was inhibited by N-monomethyl-L-arginine (L-NMMA) (1mM) was observed. Time-dependent experiments using hemolysates showed a linear rise of NO production which was elevated by 60% in the presence of superoxide dismutase (SOD) (100 U). NOS isolated from hemolysates was constitutively expressed and was dependent on NADPH, Ca2+/calmodulin, tetrahydrobiopterin and flavins. In reconstitution experiments, when purified NOS, isolated from erythrocytes, was added to purified soluble guanylate cyclase (sGC), isolated from endothelial cells, in the presence of the appropriate cofactors and substrates, a linear increase in cGMP production at various concentrations (up to 50 microM) of H2O2 was observed. Furthermore, it was shown that erythrocytes from breast cancer patients were subjected to higher oxidative stress by ONOO- (100 microM), with a consequential increase of membrane rigidity, than erythrocytes from healthy individuals. Such mechanic changes may result in shortening of the lifespan of erythrocytes, a feature of toxic anemia in cancer patients.
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PMID:Nitric oxide and peroxynitrite production by human erythrocytes: a causative factor of toxic anemia in breast cancer patients. 754 67

Activation of K+/Cl- cotransport was studied after exposure of normal human erythrocytes to the oxidative action of acetylphenylhydrazine (APH), menadione sodium bisulfite (MSB), hydrogen peroxide (H2O2) or phenazine metasulfate (PMS). In order to better define the relative contributions of K+/Cl- cotransport on ouabain and bumetanide-resistant (OBR) K+ efflux induced by oxidation, we used (dihydroindenyl)oxyalkanoic acid (DIOA) and carbocyanine as specific inhibitors, respectively, of cotransport system and Ca(2+)-activated K+ channel. APH, MSB and - to much less extent - H2O2 promoted a K+ efflux pathway with features corresponding to those of K+/Cl- cotransport. This pathway showed: (i) kinetics of efflux compatible with a specific cation transport system; (ii) requirement for chloride anion; (iii) resistance to ouabain, bumetanide and carbocyanine inhibition; (iv) stimulation by hypotonic challenge; (v) susceptibility to inhibition by DIOA. Dithiothreitol (DTT) or 2-mercaptoethanol (2-ME) decreased K+/Cl- cotransport activation, suggesting that oxidative mechanisms affected crucial SH groups of the transporter. These data suggest that oxidation represents a factor capable of modulating activation of K+/Cl- cotransport. Its possible contribution in situations with high oxidative risk, such as sickle-cell anaemia or beta thalassemia, is discussed.
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PMID:Activation of K+/Cl- cotransport in human erythrocytes exposed to oxidative agents. 845 77

Many inflammatory diseases are associated with a hypoproliferative anaemia. Patients with this anaemia often present with serum erythropoietin (EPO) concentrations that are too low for the degree of their anaemia. Proinflammatory cytokines, in addition to their inhibitory effects on proliferation of erythroid progenitors, could contribute to the pathogenesis of this anaemia by reducing EPO production. Because several cytokines stimulate nitric oxide (NO) synthase we propose that nitric oxide might mediate the suppression of EPO production during inflammation. In order to test this hypothesis we investigated the effects of NO donors on 24-h hypoxia-induced EPO production in the hepatocellular carcinoma cell line HepG2. Following application of the NO donors sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1), and S-nitroso-N-acetyl-D,L-penicillamine (SNAP), EPO production was dose-dependently reduced: compared to the untreated control EPO production was lowered by 89% with SNP (1000 microM), by 66% with SIN-1 (1000 microM), and by 72% with SNAP (500 microM). In contrast, 8-bromo-cGMP did not inhibit EPO formation. Since pyrogallol (300 microM) and H2O2 (250 microM) showed a comparable suppression of EPO synthesis, we propose that NO might affect EPO production either by a similar direct influence on the cellular redox state or via increasing the cellular content of reactive oxygen species.
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PMID:Nitric oxide donors suppress erythropoietin production in vitro. 878 Nov 91

Copper, zinc, selenium, and molybdenum are involved in many biochemical processes supporting life. The most important of these processes are cellular respiration, cellular utilization of oxygen, DNA and RNA reproduction, maintenance of cell membrane integrity, and sequestration of free radicals. Copper, zinc, and selenium are involved in destruction of free radicals through cascading enzyme systems. Superoxide radicals are reduced to hydrogen peroxide by superoxide dismutases in the presence of copper and zinc cofactors. Hydrogen peroxide is then reduced to water by the selenium-glutathione peroxidase couple. Efficient removal of these superoxide free radicals maintains the integrity of membranes, reduces the risk of cancer, and slows the aging process. On the other hand, excess intake of these trace elements leads to disease and toxicity; therefore, a fine balance is essential for health. Trace element--deficient patients usually present with common symptoms such as malaise, loss of appetite, anemia, infection, skin lesions, and low-grade neuropathy, thus complicating the diagnosis. Symptoms for intoxication by trace elements are general, for example, flu-like and CNS symptoms, fever, coughing, nausea, vomiting, diarrhea, anemia, and neuropathy. A combination of observation, medical and dietary history, and analyses for multiple trace elements is needed to pinpoint the trace element(s) involved. Serum, plasma, and erythrocytes may be used for the evaluation of copper and zinc status, whereas only serum or plasma is recommended for selenium. Whole blood is preferred for molybdenum. When trace element levels are inconsistent with medical evaluations, a test for activity of the suspected enzyme(s) would support the differential diagnosis. Furthermore, it is important to differentiate whether trace element deficiency or toxicity is the primary cause of the disorder, or is secondary to other underlying diseases. Only successful treatment of the primary disorder will lead to complete recovery. In the event of sample contamination during collection or analysis, the physician may be misled by falsely elevated results. Royal blue top evacuated tubes containing negligibly low concentrations of the trace element or acid-washed plastic sterilized syringes should be used for blood, serum, or plasma collection. Powdered gloves must be avoided. When possible, mineral supplements are not to be administered to the patient for a minimum of 3 days prior to sample collection. Serum and plasma specimens are to be transported in acid-washed polypropylene and polyethylene tubes. Analysis is performed in a controlled environment to minimize or eliminate contamination. During analysis, all laboratory wares should be acid-washed for decontamination. A detailed description of these precautions may be found in reviews by Aitio and Jarvisalo and by Chan and Gerson. Copper and zinc analysis on serum and plasma are commonly performed by flame atomic absorption spectrometry, inductively coupled plasma-atomic emission spectrometry, and inductively coupled plasma-mass spectrometry. Serum and plasma selenium levels are determined by graphite furnace atomic absorption with Zeeman background correction and neutron activation analysis. Molybdenum levels are best determined by neutron activation and highly sensitive inductively coupled plasma-mass spectrometry. The reader is referred to reviews by Tsalev and Jarvis.
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PMID:The role of copper, molybdenum, selenium, and zinc in nutrition and health. 989 6

Blood erythrocytes of 25 confirrhed malarial patients infested with P. vivax were analyzed for peroxidation and hemolysis and results compared with 10 uninfected normal control samples. Results indicated significant increase in peroxide formation measured as malondialdehyde, both in presence and absence of H2O2, in parasite infested erythrocytes. These changes induced hemolysis of infected erythrocytes which was increased manifold in presence of H2O2 and could probably be the reason for extensive anemia reported in malaria.
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PMID:In vitro studies on peroxidative changes leading to hemolysis of erythrocytes infested with malarial parasite Plasmodium vivax. 1052 62

Fanconi anemia (FA) is an autosomal recessive disorder manifested by chromosomal breakage, birth defects, and susceptibility to bone marrow failure and cancer. At least seven complementation groups have been identified, and the genes defective in four groups have been cloned. The most common subtype is complementation group A. Although the normal functions of the gene products defective in FA cells are not completely understood, a clue to the function of the FA group A gene product (FANCA) was provided by the detection of limited homology in the amino terminal region to a class of heme peroxidases. We evaluated this hypothesis by mutagenesis and functional complementation studies. We substituted alanine residues for the most conserved FANCA residues in the putative peroxidase domain and tested their effects on known biochemical and cellular functions of FANCA. While the substitution mutants were comparable to wild-type FANCA with regard to their stability, subcellular localization, and interaction with FANCG, only the Trp(183)-to-Ala substitution (W183A) abolished the ability of FANCA to complement the sensitivity of FA group A cells to mitomycin C. By contrast, TUNEL assays for apoptosis after exposure to H2O2 showed no differences between parental FA group A cells, cells complemented with wild-type FANCA, and cells complemented with the W183A of FANCA. Moreover, semiquantitative RT-PCR analysis for the expression of the peroxide-sensitive heme oxygenase gene showed appropriate induction after H2O2 exposure. Thus, W183A appears to be essential for the in vivo activity of FANCA in a manner independent of its interaction with FANCG. Moreover, neither wild-type FANCA nor the W183A mutation appears to alter the peroxide-induced apoptosisor peroxide-sensing ability of FA group A cells.
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PMID:Functional analysis of the putative peroxidase domain of FANCA, the Fanconi anemia complementation group A protein. 1116 29

Cells harvested from Fanconi anemia (FA) patients show an increased hypersensitivity to the multifunctional DNA damaging agent mitomycin C (MMC), which causes cross-links in DNA as well as 7,8-dihydro-8-oxoguanine (8-oxoG) adducts indicative of escalated oxidative DNA damage. We show here that the Drosophila multifunctional S3 cDNA, which encodes an N-glycosylase/apurinic/apyrimidinic (AP) lyase activity was found to correct the FA Group A (FA(A)) and FA Group C (FA(C)) sensitivity to MMC and hydrogen peroxide (H2O2). Furthermore, the Drosophila S3 cDNA was shown to protect AP endonuclease deficient E. coli cells against H(2)O(2) and MMC, and also protect 8-oxoG repair deficient mutM E. coli strains against MMC and H2O2 cell toxicity. Conversely, the human S3 protein failed to complement the AP endonuclease deficient E. coli strain, most likely because it lacks N-glycosylase activity for the repair of oxidatively-damaged DNA bases. Although the human S3 gene is clearly not the genetic alteration in FA cells, our results suggest that oxidative DNA damage is intimately involved in the overall FA phenotype, and the cytotoxic effect of selective DNA damaging agents in FA cells can be overcome by trans-complementation with specific DNA repair cDNAs. Based on these findings, we would predict other oxidative repair proteins, or oxidative scavengers, could serve as protective agents against the oxidative DNA damage that occurs in FA.
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PMID:The Drosophila S3 multifunctional DNA repair/ribosomal protein protects Fanconi anemia cells against oxidative DNA damaging agents. 1118 42

Visceral leishmaniasis is accompanied by severe anemia and pancytopenia. Reactive oxygen species are known to contribute to the pathogenesis of several red blood cell (RBCs) disorders. The present study reveals the extent of oxidative stress and the efficacy of the primary antioxidant system in erythrocytes of hamsters in the progressive anemic response at different stages of leishmanial infection. Increased intracellular precipitation of Heinz bodies secondary to oxidative denaturation of hemoglobin and enhanced formation of malonyldialdehyde suggest oxidative damage of erythrocytes, both in the hemoglobin and cell membrane, respectively. Decreased activities of superoxide dismutase and catalase in the infected animals indicate the generation of O2*- and H2O2, which in turn may produce the highly reactive *OH species. Decreases in the reduced glutathione level along with the decreased activities of glutathione reductase and glutathione peroxidase point to a deficient antioxidant defense system during the post-infection period. Accentuated degradation of both cytoskeletal and integral membrane proteins after 3 months of infection may eventually lead to membrane destabilization and early lysis of erythrocytes in experimental visceral leishmaniasis.
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PMID:Oxidative damage of erythrocytes: a possible mechanism for premature hemolysis in experimental visceral leishmaniasis in hamsters. 1123 73

Many monogeneans are pathogenic to economically important fish in Japan. However no other monogenean is comparable with the diclidophorids, Heterobothrium okamotoi and Neoheterobothrium hirame, on the scale of impacts they inflict on Japanese fisheries. The shared importance of the two monogenean infections lies in their pathogenicity, fecundity and tolerance to chemical treatment. Heterobothrium okamotoi infects the gills and wall of the branchial cavity of the tiger puffer, Takifugu rubripes (Tetraodontidae), which is widely cultured in western Japan. The main presenting signs of infected fish are anaemia and extensive necrosis caused by adult worms. This monogenean deposits long strings of eggs, which reach lengths of almost 3 m. Egg entanglement with the mesh of culture nets increases the chance of hatched larvae encountering susceptible fish. The oncomiracidium maintains infectivity for up to 4 days after hatching. Hydrogen peroxide is the only commercially available chemical able to control the infection, but can only kill immature worms on the gills. Neoheterobothrium hirame infects the gills and wall of the buccal cavity of the Japanese flounder, Paralichthys olivaceus (Paralichthyidae). Since the first known occurrence of this monogenean in 1993, the species has been recorded from almost all areas where the host is distributed. Neoheterobothrium hirame has the potential to produce 781 eggs per day at 20 degree C. In the western Sea of Japan, wild young-of-the-year flounder became infected in early summer, followed by a sharp increase in prevalence in late summer. By late summer, juvenile flounder have nearly disappeared from the area, strongly suggesting that N. hirame is responsible for mortality of young fish. This is in good agreement with the recent decline in the local flounder population. Neoheterobothrium hirame has also been considered the causative agent of anaemia among wild Japanese flounder since the late 1990s.
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PMID:Impacts of diclidophorid monogenean infections on fisheries in Japan. 1183 77


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