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

Iron deficiency during pregnancy causes problems both for the mother and fetus. Iron deficiency is known to have secondary effects on copper metabolism. In this study, we use a rat model to examine the effect of iron deficiency on copper levels in maternal and fetal tissue. We assess whether the effects of iron deficiency on copper metabolism are due to alterations in mRNA levels of proteins of copper transport. Rowett Hooded Lister rats were fed diets with four different iron contents before and during pregnancy. Maternal and fetal samples were collected on day 21 of gestation. Copper and iron levels of liver and placenta were analyzed, mRNA levels of genes involved in copper transport were studied, and copper oxidase activity measured. Reduced dietary iron was found to increase maternal liver copper, inversely correlating with iron levels. Correspondingly, copper and ceruloplasmin increased in maternal serum. The placenta showed the greatest increase in copper levels. As the iron content of the maternal diet decreased so did the iron and copper levels in the fetal liver. In all tissues examined, mRNA expression for CTR1, ATOX1, ATP7A, and ATP7B was unchanged by iron deficiency. However, copper oxidase activity in maternal serum and placenta was increased. Our study in a rat model demonstrates that iron deficiency during pregnancy has a differential effect on copper metabolism in the mother and fetus. It is clear from this study that the changes in copper levels that accompany iron deficiency are not mediated by changes in transcription of the genes involved in copper transport.
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PMID:Iron deficiency in the pregnant rat has differential effects on maternal and fetal copper levels. 1515 43

Heme, the major functional form of iron, is synthesized in the mitochondria. Although disturbed heme metabolism causes mitochondrial decay, oxidative stress, and iron accumulation, all of which are hallmarks of ageing, heme has been little studied in nutritional deficiency, in ageing, or age-related disorders such as Alzheimer's disease (AD). Biosynthesis of heme requires Vitamin B(6), riboflavin, biotin, pantothenic acid, and lipoic acid and the minerals zinc, iron, and copper, micronutrients are essential for the production of succinyl-CoA, the precursor for porphyrins, by the TCA (Krebs) cycle. Only a small fraction of the porphyrins synthesized from succinyl-CoA are converted to heme, the rest are excreted out of the body together with the degradation products of heme (e.g. bilirubin). Therefore, the heme biosynthetic pathway causes a net loss of succinyl-CoA from the TCA cycle. The mitochondrial pool of succinyl-CoA may limit heme biosynthesis in deficiencies for micronutrients (e.g. iron or biotin deficiency). Ageing and AD are also associated with hypometabolism, increase in heme oxygenase-1, loss of complex IV, and iron accumulation. Heme is a common denominator for all these changes, suggesting that heme metabolism maybe altered in age-related disorders. Heme can also be a prooxidant: it converts less reactive oxidants to highly reactive free radicals. Free heme has high affinity for different cell structures (protein, membranes, and DNA), triggering site-directed oxidative damage. This review discusses heme metabolism as related to metabolic changes seen in ageing and age-related disorders and highlights the possible role in iron deficiency.
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PMID:Heme, iron, and the mitochondrial decay of ageing. 1523 Dec 38

Iron deficiency is a public health problem in infancy. We assessed the efficacy of iron supplements in infants with inflammation on iron status and subsequent inflammation. This was a prospective, nested, case-control study of 6- to 12-mo-old infants participating in the International Research on Infant Supplementation study, Indonesia. Cases (n = 46) were selected on the basis of their inflammation status at baseline, C-reactive protein (>5 mg/L) or alpha-1 acid glycoprotein (>1 g/L); there were 44 controls without inflammation. Infants received 10 mg/d of elemental iron alone or in combination with multimicronutrients, or placebo. Blood samples were collected at baseline and at 6 mo for determinations of plasma ferritin, zinc, copper, retinol, beta-carotene, alpha-tocopherol, and inflammation status. Data on breast-feeding and acute respiratory infections (ARI) were collected daily. At baseline, 33% of infants had iron deficiency, and those with inflammation had lower retinol, beta-carotene, higher concentrations of copper and higher rates of ARI compared with controls. After 6 mo, compared with infants given placebo, ferritin concentration increased significantly in infants administered iron alone independently of inflammation status at baseline or at the end of the study. In those given multimicronutrients with iron, ferritin increased significantly in infants who did not have inflammation at baseline or at the end of the study compared with those given placebo. Consequently, iron alone resolved iron deficiency, whereas multimicronutrients reduced the deterioration of iron stores compared with placebo (chi(2), P < 0.05), without enhancing inflammation. Iron alone is recommended in populations in which iron deficiency is a public health problem despite the presence of inflammation in infants who are still breast-feeding.
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PMID:Daily iron alone but not in combination with multimicronutrients increases plasma ferritin concentrations in indonesian infants with inflammation. 1528 76

The role of essential nutrient metal ions (Mg, Fe, Cu, Zn, Mn and Co) often deficient in our foodstuffs, although vitally essential in the function of the human organism as well as the different reasons for these deficiencies both in foods and in the human body have been studied. The most frequent nutritional disease is iron deficient anaemia. Inorganic salts, artificial synthetic monomer organic metal complexes of high stability or organic polymer complexes of high molecular mass are unsatisfactory for supplementation to the human body, owing to poor absorption, low availability and/or harmful side effects. In contrast, we have recently found that mixed metal complexes of oligo/polygalacturonic acids with medium molecular weight prepared from natural pectin of plant origin are efficient for oral supplementation. Sufficient absorption of essential metal ions from metal oligo/polygalacturonate mixed complexes with polynuclear innersphere structure is due to the high ionselectivity and medium stability values. Metal oligo/polygalacturonate mixed complexes contain all deficient essential metal ions in adequate amounts and ratios for higher bioavailability of metal ions and optimal vital function. Therefore, by oral administration of these complexes, metal ion homeostasis and optimal interactions with vitamins and hormones can be ensured. Prelatent or latent macroelement Mg deficiency can often be observed among clinical or ambulance patients. Latent or manifest mesoelement iron deficiency is the most common, however, the occurrence of microelement copper, zinc, manganese and cobalt latent deficiencies is not seldom either. Supplementation studies utilizing essential metal oligo/polygalacturonate complexes led to satisfactory outcome without harmful side effects.
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PMID:[The role of essential metal ions in the human organism and their oral supplementation to the human body in deficiency states]. 1528 49

A genetic screen for Chlamydomonas reinhardtii mutants with copper-dependent growth or nonphotosynthetic phenotypes revealed three loci, COPPER RESPONSE REGULATOR 1 (CRR1), COPPER RESPONSE DEFECT 1 (CRD1), and COPPER RESPONSE DEFECT 2 (CRD2), distinguished as regulatory or target genes on the basis of phenotype. CRR1 was shown previously to be required for transcriptional activation of target genes like CYC6, CPX1, and CRD1, encoding, respectively, cytochrome c(6) (which is a heme-containing substitute for copper-containing plastocyanin), coproporphyrinogen III oxidase, and Mg-protoporphyrin IX monomethylester cyclase. We show here that CRR1 is required also for normal accumulation of copper proteins like plastocyanin and ferroxidase in copper-replete medium and for apoplastocyanin degradation in copper-deficient medium, indicating that a single pathway controls nutritional copper homeostasis at multiple levels. CRR1 is linked to the SUPPRESSOR OF PCY1-AC208 13 (SOP13) locus, which corresponds to a gain-of-function mutation resulting in copper-independent expression of CYC6. CRR1 is required also for hypoxic growth, pointing to a physiologically meaningful regulatory connection between copper deficiency and hypoxia. The growth phenotype of crr1 strains results primarily from secondary iron deficiency owing to reduced ferroxidase abundance, suggesting a role for CRR1 in copper distribution to a multicopper ferroxidase involved in iron assimilation. Mutations at the CRD2 locus also result in copper-conditional iron deficiency, which is consistent with a function for CRD2 in a pathway for copper delivery to the ferroxidase. Taken together, the observations argue for a specialized copper-deficiency adaptation for iron uptake in Chlamydomonas.
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PMID:Genetic dissection of nutritional copper signaling in chlamydomonas distinguishes regulatory and target genes. 1551 54

Zinc and copper deficiency is associated with anaemia or iron deficiency and affects fetus growth and pregnant women during pregnancy. To examine iron, zinc and copper status of Chinese pregnant women with and without anaemia in the third trimester, 1185 subjects were enrolled for measurements of Hb, ferritin, transferrin, soluble transferrin receptor (sTfR), and serum iron, zinc and copper. The results showed that there were lower levels of ferritin (14.1 microg/L) and transferrin (3.33 g/L) in subjects with Hb<or=100g/L as compared with subjects with Hb>or=101 g/L. sTfR levels in subjects with Hb<or=100g/L were significantly higher than those in subjects with Hb>or=120 g/L (38.5 nmol/L vs. 25.04 nmol/L, P<0.001). Serum iron was lower in subjects with Hb<or=100 g/L than those with Hb>or=120 g/L (871 microg/L vs. 990 microg/L, P<0.01). Lower levels of serum iron and zinc were also found in anaemic (Hb<110 g/L) as compared with non-anaemic women (Hb>or=110 g/L). Frequencies of marginal deficiencies in serum iron and zinc were 41.58% and 51.05% respectively higher in anaemic than in non-anaemic subjects. Distribution of serum zinc and iron showed a decreasing trend as Hb decreased. Few anaemic as well as non-anaemic subjects had copper deficiency although copper and Hb levels were found inversely correlated and the ratio of copper/iron was higher in anaemic than in non-anaemic group. In conclusion, a lower level of serum zinc in anaemic pregnant women might be related to anaemia and iron deficiency during pregnancy. Therefore, combined zinc and iron supplementation should be recommended to Chinese pregnant women, especially those with anaemia.
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PMID:Comparison of serum levels of iron, zinc and copper in anaemic and non-anaemic pregnant women in China. 1556 39

We sought to identify novel genes involved in intestinal iron absorption by inducing iron deficiency in rats during postnatal development from the suckling period through adulthood. We then performed comparative gene chip analyses (RAE230A and RAE230B chips; Affymetrix) with cRNA derived from duodenal mucosa. Real-time PCR was used to confirm changes in gene expression. Genes encoding the apical iron transport-related proteins [divalent metal transporter 1 (DMT1) and duodenal cytochrome b] were strongly induced at all ages studied, whereas increases in mRNA encoding the basolateral proteins iron-regulated gene 1 and hephaestin were observed only by real-time PCR. In addition, transferrin receptor 1 and heme oxygenase 1 were induced. We also identified induction of novel genes not previously associated with intestinal iron transport. The Menkes copper ATPase (ATP7a) and metallothionein were strongly induced at all ages studied, suggesting increased copper absorption by enterocytes during iron deficiency. We also found significantly increased liver copper levels in 7- to 12-wk-old iron-deficient rats. Also upregulated at most ages examined were the sodium-dependent vitamin C transporter, tripartite motif protein 27, aquaporin 4, lipocalin-interacting membrane receptor, and the breast cancer-resistance protein (ABCG2). Some genes also showed decreased expression with iron deprivation, including several membrane transporters, metabolic enzymes, and genes involved in the oxidative stress response. We speculate that dietary iron deprivation leads to increased intestinal copper absorption via DMT1 on the brush-border membrane and the Menkes copper ATPase on the basolateral membrane. These findings may thus explain copper loading in the iron-deficient state. We also demonstrate that many other novel genes may be differentially regulated in the setting of iron deprivation.
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PMID:Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum. 1563 78

Hephaestin is a transmembrane copper-dependent ferroxidase necessary for effective iron transport from intestinal enterocytes into the circulation. Hephaestin is mutated in sex-linked anemia (sla) mice. The initial uptake of iron from the diet in these animals is normal, but the basolateral export of iron from enterocytes is defective, resulting in iron deficiency and microcytic hypochromic anemia. In addition to the small intestine, hephaestin is expressed to a lesser extent in colon, spleen, placenta and kidney but its role in these tissues remains unknown. So far, hephaestin has not been linked to a human disease.
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PMID:Hephaestin--a ferroxidase of cellular iron export. 1577 82

Iron deficiency and chronic mild carbon monoxide (CO) exposure are nutritional and environmental problems that can be experienced simultaneously. We examined the effects of chronic mild CO exposure and iron availability on auditory development in the rat. We propose that chronic mild CO exposure creates an oxidative stress condition that impairs the spiral ganglion neurons. The CO-exposed rat pups had decreased neurofilament proteins and increased copper, zinc-superoxide dismutase (SOD1) in the spiral ganglion neurons. We conclude that the increased amount of SOD1 causes an increase in hydrogen peroxide production that allows the Fenton reaction to occur. This reaction uses both iron and hydrogen peroxide to generate hydroxyl radicals and leads to the development of oxidative stress that impairs neuronal integrity. However, rat pups with decreased iron and CO exposure (ARIDCO) exhibited in their cochlea an up-regulation of transferrin, whereas their expression of neurofilament proteins and SOD1 were similar to control. Consequently, reduced iron availability and the normal expression of SOD1 do not promote oxidative stress in the cochlea. By using basal c-Fos expression as a marker for cellular activation we found a significant reduction in c-Fos expression in the central nucleus of the inferior colliculus in iron-adequate rat pups exposed to CO. By contrast, rather than being reduced, c-Fos expression in the ARIDCO group is the same as for controls. We conclude that the cochlea of rat pups with normal iron availability is selectively affected by mild CO exposure, causing a chronic oxidative stress, whereas limiting iron availability ameliorates the effect caused by mild CO exposure by averting conditions that facilitate oxidative stress.
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PMID:Limiting iron availability confers neuroprotection from chronic mild carbon monoxide exposure in the developing auditory system of the rat. 1588 Apr 90

We previously noted strong induction of genes related to intestinal copper homeostasis (Menkes Copper ATPase (Atp7a) and metallothionein) in the duodenal epithelium of iron-deficient rats across several stages of postnatal development (Collins, J. F., Franck, C. A., Kowdley, K. V., and Ghishan, F. K. (2005) Am. J. Physiol., 288, G964-G971). We now report significant copper loading in the livers and intestines of iron-deficient rats. These findings are consistent with the hypothesis that there is increased intestinal copper transport during iron deficiency. We additionally found that hepatic Atp7b gene expression does not change with iron deficiency, suggesting that liver copper excretion is not altered. We have developed polyclonal antibodies against rat ATP7A, and we demonstrate the specificity of the immunogenic reaction. We show that the ATP7A protein is present on apical domains of duodenal enterocytes in control rats and on brush-border and basolateral membrane domains in iron-deprived rats. This localization is surprising, as previous in vitro studies have suggested that ATP7A traffics between the trans-Golgi network and the basolateral membrane. We further demonstrate that ATP7A protein levels are dramatically increased in brush-border and basolateral membrane vesicles isolated from iron-deficient rats. Other experiments show that iron refeeding partially corrects the hematological abnormalities seen in iron-deficient rats but that it does not ameliorate ATP7A protein induction, suggesting that Atp7a does not respond to intracellular iron levels. We conclude that ATP7A is involved in copper loading observed during iron deficiency and that increased intestinal copper transport is of physiological relevance, as copper plays important roles in overall body iron homeostasis.
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PMID:Menkes Copper ATPase (Atp7a) is a novel metal-responsive gene in rat duodenum, and immunoreactive protein is present on brush-border and basolateral membrane domains. 1608 13


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