Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In conclusion, many specialized tests for the evaluation of anemia and RBC abnormalities can readily be performed in-house or by commercial laboratories. Tests include RBC indices, examination of blood smears (for morphological changes, infectious agents, basophilic stippling, and polychromasia), reticulocyte counts, iron stains, serum iron determinations, Heinz body counts, and methemoglobin tests. These diagnostic tests should routinely be used for the evaluation of hematologic abnormalities that are detected by a CBC. Accurate interpretation of test results will provide vital information on the pathophysiological and/or etiologic mechanisms of disease and point the way to successful therapeutic intervention. Failure to adequately resolve some hematologic abnormalities, particularly in breeds in which heritable disease is a consideration, may require additional tests, including serum haptoglobin, ferritin and erythropoietin measurement, or assays for RBC enzymes, such as methemoglobin reductase, PK, and PFK. These tests usually are available only through research laboratories or hematology specialists, and it is advisable to consult with a veterinary clinical pathologist for referral to the appropriate individual or laboratory.
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PMID:Specialized hematology tests. 147 Jul 72

Bovine heart microsomes have been found to contain a non-heme iron protein which serves as an electron acceptor for NADPH-cytochrome P-450 reductase and therefore stimulates NADPH oxidation. This protein, tentatively referred to as Microsomal Iron Protein (MIP), has been extracted with Triton N-101 and purified by ion exchange chromatography on CM- and DEAE-celluloses and gel filtration on Sepharose 6B. MIP is an Mr = 66,000 monomer with 17 atoms of Fe(III)/molecule. Incubation with dithionite removes iron from MIP and abolishes the stimulation of NADPH oxidation, but subsequent incubation with nitrilotriacetic-Fe(III) reincorporates iron and restores the stimulation of NADPH oxidation. Oxygen is the ultimate electron acceptor. In the presence of oxygen, the enzymatic reduction of MIP Fe(III) is followed by the reoxidation of Fe(II) at the expense of oxygen, generating superoxide anion and regenerating MIP Fe(III) for the continuous oxidation of NADPH. In the absence of oxygen, electron transfer from the reductase to MIP Fe(III) causes the release of Fe(II), which limits the ability of MIP to serve as an electron acceptor and stimulate NADPH oxidation. The--NH2-terminal of MIP has been sequenced, and no homology has been found with the sequence of other iron storage or transport proteins such as ferritin or transferrin.
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PMID:Bovine heart microsomes contain an Mr = 66,000 non-heme iron protein which stimulates NADPH oxidation. 193 64

Thiourea and superoxide dismutase were effective antidotes to paraquat toxicity in an HL60 cell culture system, whereas other hydroxyl scavengers were ineffective. The efficacy of thioureas was not due to blockage of intracellular paraquat uptake, inhibition of NADPH-P-450 reductase, or reaction with the paraquat radical. Thiourea also competitively inhibited the reduction of cytochrome c by the xanthine/xanthine oxidase superoxide-generating system, and the release of iron from ferritin by superoxide radicals. The reaction of superoxide with thiourea produced a sulfhydryl compound distinct from products formed by hydrogen peroxide or hydroxyl radicals. Spectrophotometric and chromatographic studies indicated the carbon-sulfide double bond was converted to a sulfhydryl group which reacted with Ellman's reagent. Additional confirmatory evidence for the sulfhydryl compound was obtained with carbon-13 NMR and mass spectroscopies. Thus, thioureas are direct scavengers of superoxide radicals as well as hydroxyl radicals and hydrogen peroxide. The rate constant for the reduction of thiourea by superoxide was estimated at 1.1 x 10(3) M-1 s-1. The implication of this finding on free radical studies, the mechanism of paraquat toxicity, and the metabolism of thioureas is discussed.
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PMID:Thioureas react with superoxide radicals to yield a sulfhydryl compound. Explanation for protective effect against paraquat. 215 25

Rat heart microsomes were found to contain nonheme iron and two lines of evidence suggested that this iron was involved in NADPH oxidation. As first evidence, pretreatment of rats with iron gluconate increased microsomal iron content and NADPH oxidation. As second evidence, treatment of microsomes with nonionic detergent Triton N-101 decreased membrane iron content and NADPH oxidation. Triton N-101-solubilized nonheme iron was nondialyzable and ammonium sulfate-precipitable, indicative of association with protein(s). This protein-bound iron per se did not oxidize NADPH but its addition to detergent-treated microsomes restored very high rates of NADPH oxidation, that were abolished by inhibiting NADPH-cytochrome P450 reductase with p-hydroxymercuribenzoate. Since heart microsomes did not contain cytochrome P450, these results suggested that stimulation of NADPH oxidation was mediated by direct electron transfer from reductase to iron. Purified rat heart ferritin and hemosiderin did not stimulate NADPH oxidation and the stimulation observed with detergent-solubilized microsomal iron was much higher than that observed with EDTA-Fe3+, a very effective electron acceptor for the reductase. This suggested that (i) microsomal iron was different from other intracellular iron-storage proteins, and (ii) microsomal iron was unusually permissive to one-electron transfer from reductase.
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PMID:Microsomal iron-dependent NADPH oxidation: evidence for the involvement of membrane-bound nonheme iron in NADPH oxidation by rat heart microsomes. 217 78

Increasing evidence points to a major role for free radicals in the pathogenesis of alcohol-induced liver injury. In vitro, free radicals may be generated during ethanol metabolism by the further metabolism of acetaldehyde by molybdenum-dependent oxidases such as xanthine oxidase. Ferritin iron mobilized by such free radicals may serve as catalytic iron. Increased stores of ferritin iron and induction of microsomal P-450 reductase activity are mechanisms by which chronic alcohol feeding may potentiate the acute effects of alcohol.
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PMID:Lipid peroxidation, iron mobilization and radical generation induced by alcohol. 255 83

The number of gene assignments to human chromosome 20 has increased slowly until recently. Only seven genes and one fragile site were confirmed assignments to chromosome 20 at the Ninth Human Gene Mapping Workshop in September 1987 (HGM9). One fragile site, 13 additional genes, and 10 DNA sequences that identify restriction fragment length polymorphisms (RFLPs), however, were provisionally added to the map at HGM9. Five mutated genes on chromosome 20 have a relation to disease: a mutation in the adenosine deaminase gene results in a deficiency of the enzyme and severe combined immune deficiency; mutations in the gene for the growth hormone releasing factor result in some forms of dwarfism; mutations in the closely linked genes for the hormones arginine vasopressin and oxytocin and their neurophysins are probably responsible for some diabetes insipidus; and mutations in the gene that regulates both alpha-neuraminidase and beta-galactosidase activities determine galactosialidosis. The gene for the prion protein is on chromosome 20; it is related to the infectious agent of kuru, Creutzfeld-Jacob disease, and Gertsmann-Straussler syndrome, although the nature of the relationship is not completely understood. Two genes that code for tyrosine kinases are on the chromosome, SRC1 the proto-oncogene and a gene (HCK) coding for haemopoietic kinase (an src-like kinase), but no direct relation to cancer has been shown for either of these kinases. The significance of non-random loss of chromosome 20 in the malignant diseases non-lymphocytic leukaemia and polycythaemia vera is not understood. Twenty-four additional loci are assigned to the chromosome: five genes that code for binding proteins, one for a light chain of ferritin, genes for three enzymes (inosine triphosphatase, s-adenosylhomocysteine hydrolase, and sterol delta 24-reductase), one for each of a secretory protein and an opiate neuropeptide, a cell surface antigen, two fragile sites, and 10 DNA sequences (one satellite and nine unique) that detect RFLPs.
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PMID:The map of chromosome 20. 307 44

A newborn female, the second child of consanguineous parents, exhibited general muscle hypotonia, apathy, hepatomegaly and failure to thrive from birth and signs of craniofacial dysmorphia were present. Pipecolic and trihydroxicoprostanoic acid were excreted in the urine and serum transferrin, ferritin and iron were markedly elevated. At the age of 7 weeks the baby died of respiratory insufficiency. Besides malformations of the brain, renal cysts, liver damage with hypoplastic intrahepatic bile ducts and cholestasis, increased storage of iron and cytochemically proven deficiency of peroxisomes in liver and kidney, morphological studied provided evidence of a mitochondrial myopathy in striated muscle with the accumulation of enlarged bizarre mitochondria, showing only minor structural abnormalities. No defects of NADH-reductase, succinate-dehydrogenase or cytochrome-c-oxidase were demonstrated histochemically. Cytochemical-ultrastructural investigation of mitochondrial ATPase revealed activation of the ATP-synthesising enzyme even before the addition of an uncoupler, this indicating loosely coupled oxidative phosphorylation. In addition a high rate of subcellular autophagy with segregation of mitochondria and focal loss of fibrils was present. Muscle damage in Zellweger syndrome appears to be the consequence of complex, interacting metabolic processes. The mitochondrial myopathy thereby induced allows a better understanding of general muscle hypotonia, one of the leading symptoms of this disorder.
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PMID:Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study. 614 41

Nonheme iron is synergistic with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing hepatotoxicity in mice. Fe2+ rather than Fe3+ is the probable toxin and we speculated that TCDD, an inducer of microsomal electron transport, might favour reduction of iron. We have defined a system which will release Fe2+ from ferritin (Fe3+) under anaerobic conditions and in the presence of added flavin mononucleotide (FMN). The rate of reduction iron was proportional (a) to microsomal protein from 0.5 to greater than 3 mg/mL, (b) to the activity of NADPH-cytochrome c reductase over 0.1 U/mL, (c) to ferritin at concentrations exceeding iron concentrations greater than 200 mumol/L, and (d) to the concentration of FMN when it was less than 125 mumol/L. The system was approximately twice as active with NADPH as with NADH as electron donor. The linear phase of iron release did not commence immediately, but followed a delay (+/- 0.5 min) after adding FMN to an anaerobic mixture containing microsomes, ferritin, an NADPH-generating system, and an oxygen-scavenging system. When microsomes from untreated, phenobarbital-treated (3 days), or TCDD-treated (1 or 3 weeks) rats were compared, iron release correlated most closely with the cytochrome P-450 concentration. However, when the microsomal proteins were solubilized and the NADPH-cytochrome c reductase and cytochrome P-450 activities were separated, reduction of ferritin iron was shown to be a function only of the reductase fraction, except that the delay in initiating release of Fe2+ was increased with purified reductase and decreased when a monooxygenase system was reconstituted with cytochrome (phenobarbital or TCDD induced) and lipid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of ferrous iron from ferritin by liver microsomes: a possible role in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 644 9

NADPH-cytochrome c reductase was purified from rat liver microsomes and the monospecific antibodies to the reductase were prepared from the antiserum by affinity chromatography using immunoadsorbent gel. Ferritin was coupled to the specific antibodies and the approximately equimolar conjugates were isolated by gel filtration. By direct ferritin-immunoelectron microscopy, using these conjugates, it was revealed that the ferritin particles are localized exclusively on the microsomal vesicles and the outer nuclear envelope. In contrast, binding of ferritin particles to Golgi membranes, outer mitochondrial membranes and plasma membranes was slight and at control level. On each microsomal vesicle, the ferritin particles were distributed heterogeneously, sometimes forming clusters. An assay of the binding of equimolar conjugates with microsomes showed that microsomes bind approximately 1 mol of antibody per mol of reductase. From these data the maximum number of ferritin particles that can bind with microsomes was calculated. This number is in agreement with the average number of ferritin particles bound per microsome, as determined experimentally by observing a number of cross-sectional profiles of microsomal vesicles previously incubated with the conjugates at saturation level. This showed that the distribution of the reductase could be analysed semi-quantitatively by the present ferritin-immunoelectron-microscopical analyses. It was also shown that smooth microsomes can bind more conjugates than rough microsomes. The average number of ferritin particles on each microsomal vesicle increased in proportion to the increase in the amount of reductase in the microsomes after treatment with phenobarbital. Finally, the non-random distribution of ferritin particles on microsomal vesicles was confirmed by statistical analysis of electron micrographs of a number of the labelled microsomes.
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PMID:Intracellular distribution of NADPH-cytochrome c reductase in rat hepatocytes studied by direct ferritin-immunoelectron microscopy. 679 45

The reduction of exogenous ferric iron by Listeria monocytogenes, a Gram-positive food-borne pathogen, was investigated. Using an assay incorporating the ferrous iron chelator ferrozine, we showed that intact cells of L. monocytogenes, when exposed to ferric iron, were able to rapidly reduce and solubilize the iron to the ferrous form. Reduction occurred only after direct contact between the bacteria and the iron source. A number of different ferric iron chelates, including transferrin and lactoferrin-bound iron, haemoglobin, ferritin, and iron complexed to siderophores, could be reduced. The ferric reductase activity was expressed by both reference strains and clinical isolates of L. monocytogenes and by all other species of Listeria, although significant quantitative differences were observed. In L. monocytogenes, the expression of ferric reductase was not affected by the growth phase of the bacteria nor by the presence or absence of iron in the growth medium. However, expression was greatly reduced in bacteria grown anaerobically and when cultured in media of reduced pH. In addition, bacteria grown at a cold temperature displayed greater ferric reductase activity than cells grown at higher temperatures. A surface-associated ferric reductase system may be one component of a general iron scavenging mechanism which can be used by Listeria growing in a variety of environments.
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PMID:Reduction of exogenous ferric iron by a surface-associated ferric reductase of Listeria spp. 755 Oct 61


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