Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metal ions are essential cofactors for a wealth of biological processes, including oxidative phosphorylation, gene regulation and free-radical homeostasis. Failure to maintain appropriate levels of metal ions in humans is a feature of hereditary haemochromatosis, disorders of metal-ion deficiency, and certain neurodegenerative diseases. Despite their pivotal physiological roles, however, there is no molecular information on how metal ions are actively absorbed by mammalian cells. We have now identified a new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+. DCT1 mediates active transport that is proton-coupled and depends on the cell membrane potential. It is a 561-amino-acid protein with 12 putative membrane-spanning domains and is ubiquitously expressed, most notably in the proximal duodenum. DCT1 is upregulated by dietary iron deficiency, and may represent a key mediator of intestinal iron absorption. DCT1 is a member of the 'natural-resistance-associated macrophage protein' (Nramp) family and thus its properties provide insight into how these proteins confer resistance to pathogens.
 ...
PMID:Cloning and characterization of a mammalian proton-coupled metal-ion transporter. 924 8

There is still debate in the literature on whether or not endurance athletes tend to have low iron stores. In this article, we propose that endurance athletes really are at risk of becoming iron deficient due to an imbalance between absorption of dietary iron and exercise-induced iron loss. The purpose of this article is to present a critical review of the literature on iron supplementation in sport. The effect of iron deficiency on performance, its diagnosis and suggestions for treatment are also discussed. Studies of the nutritional status of athletes in various disciplines have shown that male, but not female, athletes clearly achieve the recommended dietary intake of iron (10 to 15 mg/day). This reflects the situation in the general population, with menstruating women being the main risk group for mild iron deficiency, even in developed countries. Whereas the benefit of iron supplementation in athletes with iron deficiency anaemia is well established, this is apparently not true for non-anaemic athletes who have exhausted iron stores alone (prelatent iron deficiency); most of the studies in the literature show no significant changes due to supplementation in the physical capacity of athletes with prelatent iron deficiency. However, the treatment protocols used in some of these studies do not meet the general recommendations for the optimal clinical management of iron deficiency, that is, with respect to adequate daily dosage, mode of administration and treatment period. For future studies, we recommend a prolonged treatment period (> or = 3 months) with standardised conditions of administration (use of a pharmaceutical iron preparation with known high bioavailability and a dosage of ferrous (Fe++) iron 100 mg/day, taken on an empty stomach). Currently, decisions regarding iron supplementation are best made on the basis of taking care of individual athletes. We believe that there are sufficient arguments to support controlled iron supplementation in all athletes with low serum ferritin levels. Firstly, the development of iron deficiency is prevented. Secondly, the nonspecific upregulation of intestinal metal ion absorption is reverted to normal, thus limiting the hyperabsorption of potentially toxic lead and cadmium even in individuals with mild iron deficiency.
 ...
PMID:Iron supplementation in athletes. Current recommendations. 982 Sep 21

The molecular basis for the transport of manganese across membranes in plant cells is poorly understood. We have found that IRT1, an Arabidopsis thaliana metal ion transporter, can complement a mutant Saccharomyces cerevisiae strain defective in high-affinity manganese uptake (smf1 delta). The IRT1 protein has previously been identified as an iron transporter. The current studies demonstrated that IRT1, when expressed in yeast, can transport manganese as well. This manganese uptake activity was inhibited by cadmium, iron(II) and zinc, suggesting that IRT1 can transport these metals. The IRT1 cDNA also complements a zinc uptake-deficient yeast mutant strain (zrt1zrt2), and IRT1-dependent zinc transport in yeast cells is inhibited by cadmium, copper, cobalt and iron(III). However, IRT1 did not complement a copper uptake-deficient yeast mutant (ctr1), implying that this transporter is not involved in the uptake of copper in plant cells. The expression of IRT1 is enhanced in A. thaliana plants grown under iron deficiency. Under these conditions, there were increased levels of root-associated manganese, zinc and cobalt, suggesting that, in addition to iron, IRT1 mediates uptake of these metals into plant cells. Taken together, these data indicate that the IRT1 protein is a broad-range metal ion transporter in plants.
 ...
PMID:The IRT1 protein from Arabidopsis thaliana is a metal transporter with a broad substrate range. 1039 43

Iron uptake from the soil is a tightly controlled process in plant roots, involving specialized transporters. One such transporter, IRT1, was identified in Arabidopsis thaliana and shown to function as a broad-range metal ion transporter in yeast. Here we report the cloning and characterization of the IRT2 cDNA, a member of the ZIP family of metal transporters, highly similar to IRT1 at the amino-acid level. IRT2 expression in yeast suppresses the growth defect of iron and zinc transport yeast mutants and enhances iron uptake and accumulation. However, unlike IRT1, IRT2 does not transport manganese or cadmium in yeast. IRT2 expression is detected only in roots of A. thaliana plants, and is upregulated by iron deficiency. By fusing the IRT2 promoter to the uidA reporter gene, we show that the IRT2 promoter is mainly active in the external cell layers of the root subapical zone, and therefore provide the first tissue localization of a plant metal transporter. Altogether, these data support a role for the IRT2 transporter in iron and zinc uptake from the soil in response to iron-limited conditions.
 ...
PMID:Arabidopsis IRT2 gene encodes a root-periphery iron transporter. 1138 59

DMT1 has four names, transports as many as eight metals, may have four or more isoforms and carries out its transport for multiple purposes. This review is a start at sorting out these multiplicities. A G185R mutation results in diminished gastrointestinal iron uptake and decreased endosomal iron exit in microcytic mice and Belgrade rats. Comparison of mutant to normal rodents is one analytical tool. Ectopic expression is another. Antibodies that distinguish the isoforms are also useful. Two mRNA isoforms differ in the 3' UTR: +IRE DMT1 has an IRE (Iron Responsive Element) but -IRE DMT1 lacks this feature. The +/-IRE proteins differ in the distal 18 or 25 amino acid residues after shared identity for the proximal 543 residues. A major function is serving as the apical iron transporter in the lumen of the gut. The +IRE isoform appears to have that role. Another role is endosomal exit of iron. Some evidence indicts the -IRE isoform for this function. In our ectopic expression assay for metal uptake, four metals--Fe2+, Mn2+, Ni2+ and Co2+--respond to the normal DMT1 cDNA but not the G185R mutant. Two metals did not--Cd2+ and Zn2+--and two--Cu2+ and Pb2+--remain to be tested. In competition experiments in the same assay, Cd2+, Cu2+ and Pb2+ inhibit Mn2+ uptake but Zn2+ did not. In rodent mutants, Fe and Mn appear more dependent on DMT1 than Cu and Zn. Experiments based on ectopic expression, specific antibodies that inhibit metal uptake and labeling data indicate that Fe3+ uptake depends on a different pathway in multiple cells. Two isoforms localize differently in a number of cell types. Unexpectedly, the -IRE isoform is in the nuclei of cells with neuronal properties. While the function of -IRE DMT1 in the nucleus is speculative, one may safely infer that this localization identifies new role(s) for this multifunctional transporter. Management of toxic challenges is another function related to metal homeostasis. Airways represent a gateway tissue for metal entry. Preliminary evidence using specific PCR primers and antibodies specific to the two isoforms indicates that -IRE mRNA and protein increase in response to exposure to metal in lungs and in a cell culture model; the +IRE form is unresponsive. Thus the -IRE form could be part of a detoxification system in which +IRE DMT1 does not participate. How does iron status affect other metals' toxicity? In the case of Mn, iron deficiency may enhance cellular responses.
 ...
PMID:DMT1: a mammalian transporter for multiple metals. 1257 63

The Arabidopsis FRO2 gene encodes the low-iron-inducible ferric chelate reductase responsible for reduction of iron at the root surface. Here, we report that FRO2 and IRT1, the major transporter responsible for high-affinity iron uptake from the soil, are coordinately regulated at both the transcriptional and posttranscriptional levels. FRO2 and IRT1 are induced together following the imposition of iron starvation and are coordinately repressed following iron resupply. Steady-state mRNA levels of FRO2 and IRT1 are also coordinately regulated by zinc and cadmium. Like IRT1, FRO2 mRNA is detected in the epidermal cells of roots, consistent with its proposed role in iron uptake from the soil. FRO2 mRNA is detected at high levels in the roots and shoots of 35S-FRO2 transgenic plants. However, ferric chelate reductase activity is only elevated in the 35S-FRO2 plants under conditions of iron deficiency, indicating that FRO2 is subject to posttranscriptional regulation, as shown previously for IRT1. Finally, the 35S-FRO2 plants grow better on low iron as compared with wild-type plants, supporting the idea that reduction of ferric iron to ferrous iron is the rate-limiting step in iron uptake.
 ...
PMID:Overexpression of the FRO2 ferric chelate reductase confers tolerance to growth on low iron and uncovers posttranscriptional control. 1452 17

The effects of latent iron deficiency combined with parenteral subchronic or acute cadmium exposure during pregnancy on maternal and fetal tissue distribution of cadmium, iron and zinc, and on fetal viability were evaluated. Timed-pregnant Sprague-Dawley rats were fed on semisynthetic test diets with either high iron (240 mg kg) or low iron (10 mg kg), and concomitantly exposed to 0, 3 or 5 mg cadmium (as anhydrous CdCl2) per kilogram body weight. Animals were exposed to cadmium from gestation day 1 through 19 by subcutaneously implanted mini pumps (Subchronic exposure) or on gestation day 15 by a single subcutaneous injection (Acute exposure). All rats were killed on gestation day 19. Blood samples, selected organs and fetuses were removed and prepared for element analyses by atomic absorption spectrometry. Low iron diet caused decreases in maternal body weight, maternal and fetal liver weights, placental weights and tissue iron concentrations. By cadmium exposure, both subchronic and acute, tissue cadmium concentrations were increased and the increase was dose-related, maternal liver and kidney zinc concentrations were increased, and fetal zinc concentration was decreased. Cadmium concentration in maternal liver was additionally increased by low iron diet. Acute cadmium exposure caused lower maternal body and organ weights, high fetal mortality, and decreased fetal weights of survivors. In conclusion, parenteral cadmium exposure during pregnancy causes perturbations in essential elements in maternal and fetal compartments. Acute cadmium exposure in the last trimester of gestation poses a risk for fetal viability especially when combined with low iron in maternal diet.
 ...
PMID:Low iron diet and parenteral cadmium exposure in pregnant rats: the effects on trace elements and fetal viability. 1497 57

The absorption rate of dietary cadmium (Cd) was investigated among 38 female farmers who had been exposed to Cd at levels close to the current provisional tolerable weekly intake (PTWI); these levels were much higher than those examined in previous studies. The study group composed of 7 diabetics and their 13 age-matched controls and 6 anemic subjects and their 12 controls. With their informed consent, the study participants were confined in an inn for 7 nights and 8 days to collect all feces and urine and duplicates of all food consumed. The dietary Cd absorption rate was calculated for each subject from her total Cd intake and fecal excretion. The means and 95% confidence intervals (CI) of the diabetic group and the anemic group did not differ significantly from those of their respective controls. By individual analysis using all 38 subjects, however, significant Pearson's correlation coefficients were observed between Cd absorption rate and age, serum ferritin, serum iron, and blood and urine Cd levels. Among these, multiple regression analysis revealed that only age was a significant factor contributing to Cd absorption rate. The actual Cd absorption rate in the youngest age group (20-39 years) was 44.0%, which was highly accelerated compared with the rate in the total subject group of 6.5%, while zero to negative balance was observed in the older subjects. These results demonstrate that age, rather than iron deficiency, diabetes mellitus (DM), or Cd burden, is the only independent factor affecting the Cd absorption rate, suggesting that young women are always at high risk.
 ...
PMID:Comprehensive study of the effects of age, iron deficiency, diabetes mellitus, and cadmium burden on dietary cadmium absorption in cadmium-exposed female Japanese farmers. 1569 66

Absorption from food is an important route for entry of the toxic metal, cadmium, into the body. Both cadmium and iron are believed to be taken up by duodenal enterocytes via the iron regulated, proton-coupled transporter, DMT1. This means that cadmium uptake could be enhanced in conditions where iron absorption is increased. We measured pH dependent uptake of (109)Cd and (59)Fe by duodenum from mice with an in vitro method. Mice with experimental (hypoxia, iron deficiency) or hereditary (hypotransferrinaemia) increased iron absorption were studied. All three groups of mice showed increased (59)Fe uptake (p<0.05) compared to their respective controls. Hypotransferrinaemic and iron deficient mice exhibited an increase in (109)Cd uptake (p<0.05). Cadmium uptake was not, however, increased by lowering the medium pH from 7.4 to 6. In contrast, (59)Fe uptake (from (59)FeNTA(2)) and ferric reductase activity was increased by lowering medium pH in control and iron deficient mice (p<0.05). The data show that duodenal cadmium uptake can be increased by hereditary iron overload conditions. The uptake is not, however, altered by lowering medium pH suggesting that DMT1-independent uptake pathways may operate.
 ...
PMID:Iron and cadmium uptake by duodenum of hypotransferrinaemic mice. 1693 61

Anemia is commonly induced by chronic cadmium (Cd) intoxication. Three main factors are involved in the development of Cd-induced anemia: hemolytic, iron-deficiency, and renal. Intravascular hemolysis can occur at the early stage of Cd exposure owing to the direct damaging effect on erythrocytes. In addition, Cd that accumulates in erythrocytes affects membrane cytoskeletons and decreases cell deformability, and these cells are then trapped and destroyed in the spleen. Iron deficiency can be detected in animals after an oral exposure to Cd, which competes with iron for absorption in the intestines, leading to anemia. However, an increase in body iron content along with anemia is often observed in cases of parenteral exposure or itai-itai disease. Therefore, it is estimated that Cd disrupts the efficient usage of iron in hemoglobin synthesis in the body. Renal anemia is observed during the very last phase of chronic, severe Cd intoxication, such as itai-itai disease, showing a decrease in the production of erythropoietin from renal tubular cells. Because the renal anemia is based on the same pathophysiology as Cd-induced osteomalacia, which is derived from the disturbance of mineral metabolism due to renal tubular dysfunction, it is reasonable to include renal anemia in the criteria for the diagnosis of itai-itai disease. Hemodilution could also contribute to the development of Cd-induced anemia. Bone marrow hypoplasia or the inhibition of heme synthesis might only be involved in Cd-induced anemia in severe cases of Cd intoxication.
 ...
PMID:[Anemia induced by cadmium intoxication]. 1757 87


<< Previous 1 2 3 4 5 6 Next >>