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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimentally induced lead poisoning especially under simultaneous iron deficit leads to the development of secondary thiamine insufficiency. Erythrocyte riboflavin content and erythrocyte glutathion reductase and aspartate aminotransferase activities have been demonstrated to be increased. Lead treatment is accompanied with the increase of urinary excretion of riboflavin, 4-pyridoxic acid and 1-vtthylnicotinamide in rats fed with adequate diet. Thus lead intoxication and iron deficiency influence vitamin B group metabolism.
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PMID:[Influence of lead on metabolism of vitamins B group in alimentary iron deficient rats]. 927 79

The enzyme ferric reductase catalyses the reduction of Fe(III) as a prerequisite to its transportation across the cell membrane. Duodenal mucosal biopsies from iron overloaded patients with genetic haemochromatosis (GH) have increased ferric reductase activity and iron absorption compared with controls, yet the GH mucosa is iron deficient. A similar GH-related iron deficiency is also seen in macrophages. The aim of this study was to investigate whether macrophage ferric reductase activity is altered in GH, and to determine ferric reductase activity in monocytes and differentiated macrophages. The erythroleukaemic K562 cell line was studied as a clonal reference cell line. The basal K562 ferric reductase activity is characteristic of a membrane bound enzyme, being both temperature and protease sensitive. Ferric reductase activity was also demonstrated in human leucocyte, monocyte and macrophage preparations. Assays of K562 and macrophage cell supernatants confirmed that the ferric reductase activity was not due to a secreted factor. Assay of ferric reductase in normalized-iron and iron-enriched (100 microM ferric citrate) conditions showed no significant difference between Cys282Tyr (Cys282-->Tyr) homozygous GH macrophages and Cys282-Tyr negative control activities (P>0.05). However, a 900% increase in ferric reductase activity was observed during monocyte to macrophage differentiation (P<0.05), possibly reflecting the co-ordinate up-regulation of iron metabolism in these cells. The demonstration of approx. 25% activity after macrophage differentiation at high free-iron concentrations compared with 'normalized' iron is consistent with repression of human ferric reductase activity by iron. The identification of the human ferric reductase gene and its protein will ultimately provide insight into its regulation and role in mammalian iron metabolism.
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PMID:Monocyte-macrophage ferric reductase activity is inhibited by iron and stimulated by cellular differentiation. 984 63

A pathogen such as C. albicans needs an efficient mechanism of iron uptake in an iron-restricted environment such as is the human body. A ferric-reductase activity regulated by iron and copper, and analogous to that in S. cerevisiae, has been described in C. albicans. We have developed an in-plate protocol for the isolation of clones that complement an aft1 mutation in S. cerevisiae that makes cells dependent on iron for growth. After transformation of S. cerevisiae aft1 with a C. albicans library, we have selected clones that grow in conditions of iron deficiency and share an identical plasmid, pIRO1, with a 4500 bp insert containing the URA3 gene and an ORF (IRO1) responsible for the suppression of the iron dependency. IRO1 does not show homology with AFT1 or with other sequences in the databases. Northern analysis demonstrates constitutive expression of IRO1. CAI4, a C. albicans strain isolated as Deltaura3, also has a deletion of the 3' half of IRO1, and displays in YNB medium similar phenotypic characteristics to S. cerevisiae aft1 mutant strains. Therefore, we consider IRO1 as a gene of C. albicans involved in the utilization of iron. However, in extreme conditions of iron deprivation, CAI4 seems to activate alternative mechanisms of iron uptake that allow a better growth than the wild strain SC5314. Analysis of its predicted protein sequence is in agreement with a role of Iro1p as a transcription factor.
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PMID:Isolation of a Candida albicans gene, tightly linked to URA3, coding for a putative transcription factor that suppresses a Saccharomyces cerevisiae aft1 mutation. 1122 39

Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.
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PMID:The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. 1248 69

Dcytb has been identified as the mammalian transplasma ferric reductase that catalyzes the reduction of ferric to ferrous iron in the process of iron absorption. Its mRNA and protein levels are up-regulated by several independent stimulators of iron absorption. Furthermore, its cDNA encodes putative binding sites for heme and ascorbic acid. Using Northern and Western blots, RT-PCR and confocal microscopy, we studied the expression and localisation of Dcytb in cell lines and tissues of CD1 mice. Dcytb expression and function were modulated by iron. Dcytb and DMT1, both predominantly localised in the apical region of the duodenum were up-regulated in iron deficiency. Dcytb, the iron regulated ferric reductase may also utilize cytoplasmic ascorbate as electron donor for transmembrane reduction of iron. Dcytb expression was found in other tissues apart from the duodenum and its regulation and functions at these other sites are of interest in iron metabolism.
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PMID:Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism. 1254 25

Individuals with hereditary hemochromatosis suffer from systemic iron overload due to duodenal hyperabsorption. Most cases arise from a founder mutation in HFE (845G-->A; ref. 2) that results in the amino-acid substitution C282Y and prevents the association of HFE with beta2-microglobulin. Mice homozygous with respect to a null allele of Hfe (Hfe-/-) or homozygous with respect to the orthologous 882G-->A mutation (Hfe(845A/845A)) develop iron overload that recapitulates hereditary hemochromatosis in humans, confirming that hereditary hemochromatosis arises from loss of HFE function. Much work has focused on an exclusive role for the intestine in hereditary hemochromatosis. HFE deficiency in intestinal crypt cells is thought to cause intestinal iron deficiency and greater expression of iron transporters such as SLC11A2 (also called DMT1, DCT1 and NRAMP2) and SLC11A3 (also called IREG1, ferroportin and MTP1; ref. 3). Published data on the expression of these transporters in the duodenum of HFE-deficient mice and humans are contradictory. In this report, we used a custom microarray to assay changes in duodenal and hepatic gene expression in Hfe-deficient mice. We found unexpected alterations in the expression of Slc39a1 (mouse ortholog of SLC11A3) and Cybrd1, which encode key iron transport proteins, and Hamp (hepcidin antimicrobial peptide), a hepatic regulator of iron transport. We propose that inappropriate regulatory cues from the liver underlie greater duodenal iron absorption, possibly involving the ferric reductase Cybrd1.
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PMID:Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. 1270 90

Patients suffering from hereditary hemochromatosis (HH) show progressive iron overload as a consequence of increased duodenal iron absorption. It has been hypothesized that mutations in the HH gene HFE cause misprogramming of the duodenal enterocytes towards a paradoxical iron-deficient state, resulting in increased iron transporter expression. Previous reports concerning gene expression levels of the duodenal iron transporters DMT1 and IREG1 in HH patients and animal models are controversial, however, and in many cases only mRNA expression levels were investigated. To analyze the duodenal expression of DMT1, Ireg1, Dcytb, and hephaestin and the association with iron overload in adult Hfe(-/-) mice, an Hfe(-/-) mouse line was generated. Duodenal DMT1 and Ireg1 protein levels, duodenal DMT1, Ireg1, Dcytb, hephaestin, and TfR1 mRNA levels, and hepatic hepcidin mRNA levels were quantified and the correlation to liver iron contents was calculated. We report that duodenal DMT1 and Ireg1 mRNA levels and DMT1 and Ireg1 protein levels remained unaffected by the Hfe deletion. Furthermore, duodenal hephaestin and TfR1 mRNA expression and hepatic hepcidin mRNA expression remained unaltered, while the duodenal mRNA expression of the brush border ferric reductase Dcytb was significantly increased in Hfe(-/-) mice. We found no correlation between the expression level of any of the analyzed transcripts and the liver iron content. In conclusion, the lack of correlation between DMT1 and Ireg1 protein expression and the liver iron content suggests that elevated duodenal iron transporter expression is not required for high liver iron overload. Hfe(-/-) mice do not necessarily display features of iron deficiency in the duodenum, indicated by an increase in mRNA and protein levels of DMT1 and Ireg1. Rather, the duodenal ferric reductase Dcytb may act as a possible mediator of iron overload in Hfe deficiency.
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PMID:Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin. 1461 43

Ascorbate has long been thought to play an important role in intestinal iron absorption. The recent identification of a possible ascorbate-dependent duodenal ferric reductase suggests a role for intracellular ascorbate in the control of iron absorption. We set out to determine whether duodenal ascorbate concentrations are altered by treatments known to alter the rate of iron absorption and whether ascorbate levels affect duodenal reductase activity. Duodenal ascorbate was extracted and assayed by HPLC and/or a chemical assay. Ferric reductase was assayed in vitro with ferric nitrilotriacetate or nitroblue tetrazolium as substrates. Duodenal ascorbate concentrations were increased by iron deficiency, genetic hypotransferrinemia, and hypoxia. Parenteral iron overload increased iron stores but did not affect duodenal ascorbate concentrations. Hemolytic anemia induced in mice by phenylhydrazine injection also did not affect duodenal ascorbate concentrations. In vitro studies with incubated duodenum showed that decreased tissue ascorbate was associated with decreased mucosal ferric reductase activity, whereas incubation with dehydroascorbate prevented both the decrease in ascorbate concentration and reductase activity. Mouse duodenum ascorbate concentrations changed in response to treatments that altered iron absorption rates; in particular, ascorbate levels generally increased when iron absorption was increased by iron deficiency, hypoxia, or genetic hypotransferrinemia. We conclude that changes in ascorbate levels are associated with changes in ferric reductase activity. These findings are consistent with the proposal that duodenal ascorbate plays a role in intestinal iron absorption.
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PMID:Duodenal ascorbate levels are changed in mice with altered iron metabolism. 1498 37

Arabidopsis (Arabidopsis thaliana) and tomato (Lycopersicon esculentum) show similar physiological responses to iron deficiency, suggesting that homologous genes are involved. Essential gene functions are generally considered to be carried out by orthologs that have remained conserved in sequence and map position in evolutionarily related species. This assumption has not yet been proven for plant genomes that underwent large genome rearrangements. We addressed this question in an attempt to deduce functional gene pairs for iron reduction, iron transport, and iron regulation between Arabidopsis and tomato. Iron uptake processes are essential for plant growth. We investigated iron uptake gene pairs from tomato and Arabidopsis, namely sequence, conserved gene content of the regions containing iron uptake homologs based on conserved orthologous set marker analysis, gene expression patterns, and, in two cases, genetic data. Compared to tomato, the Arabidopsis genome revealed more and larger gene families coding for the iron uptake functions. The number of possible homologous pairs was reduced if functional expression data were taken into account in addition to sequence and map position. We predict novel homologous as well as partially redundant functions of ferric reductase-like and iron-regulated transporter-like genes in Arabidopsis and tomato. Arabidopsis nicotianamine synthase genes encode a partially redundant family. In this study, Arabidopsis gene redundancy generally reflected the presumed genome duplication structure. In some cases, statistical analysis of conserved gene regions between tomato and Arabidopsis suggested a common evolutionary origin. Although involvement of conserved genes in iron uptake was found, these essential genes seem to be of paralogous rather than orthologous origin in tomato and Arabidopsis.
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PMID:Analysis of sequence, map position, and gene expression reveals conserved essential genes for iron uptake in Arabidopsis and tomato. 1553 8

Regulation of iron uptake is critical for plant survival. Although the activities responsible for reduction and transport of iron at the plant root surface have been described, the genes controlling these activities are largely unknown. We report the identification of the essential gene Fe-deficiency Induced Transcription Factor 1 (FIT1), which encodes a putative transcription factor that regulates iron uptake responses in Arabidopsis thaliana. Like the Fe(III) chelate reductase FRO2 and high affinity Fe(II) transporter IRT1, FIT1 mRNA is detected in the outer cell layers of the root and accumulates in response to iron deficiency. fit1 mutant plants are chlorotic and die as seedlings but can be rescued by the addition of supplemental iron, pointing to a defect in iron uptake. fit1 mutant plants accumulate less iron than wild-type plants in root and shoot tissues. Microarray analysis shows that expression of many (72 of 179) iron-regulated genes is dependent on FIT1. We demonstrate that FIT1 regulates FRO2 at the level of mRNA accumulation and IRT1 at the level of protein accumulation. We propose a new model for iron uptake in Arabidopsis where FRO2 and IRT1 are differentially regulated by FIT1.
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PMID:The essential basic helix-loop-helix protein FIT1 is required for the iron deficiency response. 1553 73


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