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

To gain insights at the molecular level into the expression of iron-regulated genes [transferrin (Tf), transferrin receptor (TfR), and ferritin H and L subunits] in human intestinal areas relevant to iron absorption, the steady-state levels of specific messenger RNAs (mRNAs) were analyzed in gastric and duodenal samples obtained from 6 normal subjects, or 10 patients with anemia, 14 patients with untreated iron overload, and 8 patients with various gastrointestinal disorders. No Tf mRNA was detected in human gastroduodenal tissue, confirming earlier findings in the rat. In normal subjects, although higher levels of ferritin H- and L-subunit mRNAs were consistently found in duodenal than in gastric samples, no differences in the content of TfR transcripts were detected. However, a dramatic increase in TfR mRNA levels was specifically found in duodenal samples from subjects with mild iron deficiency but severe anemia. This response of the TfR gene is presumably secondary to decreased cellular iron content due to its accelerated transfer into the bloodstream, as also indicated by the low levels of ferritin subunit mRNAs found in the same tissue samples, and is not linked to faster growth rate of mucosal cells because no changes in duodenal expression of histone, a growth-related gene, were detected. In patients with secondary iron overload, a down-regulation of duodenal TfR gene expression and a concomitant increase in ferritin mRNA content were documented. On the contrary, a lack of TfR gene down-regulation and an abnormally low accumulation of ferritin H- and L-subunit mRNAs were detected in the duodenums of subjects with idiopathic hemochromatosis. Whether these molecular abnormalities in idiopathic hemochromatosis are relevant to the metabolic defect(s) of the disease is presently unknown.
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PMID:Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum. 153 99

We investigated the effects of iron deficiency in mice on protein kinase C (PKC) activation, an enzyme required for optimal lymphocyte proliferation. C57BL/6 mice were fed either an iron-deficient diet (ID; 10 mg Fe/kg diet), a control diet (C; 50 mg/kg diet), or were pair fed (PF) to ID mice for 34 d. PKC activity was studied in spleen cells by histone phosphorylation. Iron deficiency significantly reduced cytosol activity in unstimulated cells and membrane-bound activity in cells stimulated by concanavalin A (Con A) or phorbol-12-myristate-13-acetate (PMA), and the ratio of membrane-bound over cytosol activity in mitogen-stimulated cells. In PF mice the ratio of membrane-bound activity to cytosol activity was greater than normal in Con A-treated cells and only slightly decreased in PMA-treated cells. PKC activity positively correlated with iron status. We conclude that reduced PKC activity and poor translocation results in aberrant signal transduction, which in turn might be responsible for the impaired lymphocyte proliferation associated with iron deficiency.
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PMID:Impaired protein kinase C activation as one of the possible mechanisms of reduced lymphocyte proliferation in iron deficiency in mice. 195 Nov 69

Neonatal brain iron deficiency occurs after insufficient maternal dietary iron intake, maternal hypertension, and maternal diabetes mellitus and results in short and long-term neurologic and behavioral deficits. Early iron deficiency affects the genomic profile of the developing hippocampus that persists despite iron repletion. The purpose of the present study was threefold: 1) quantitative PCR confirmation of our previous microarray results, demonstrating upregulation of a network of genes leading to beta-amyloid production and implicated in Alzheimer disease etiology in iron-deficient anemic rat pups at the time of hippocampal differentiation; 2) investigation of the potential contributions of iron deficiency anemia and iron treatment to this differential gene expression in the hippocampus; and 3) investigation of these genes over a developmental time course in a mouse model where iron deficiency is limited to hippocampus, is not accompanied by anemia and is not repletable. Quantitative PCR confirmed altered regulation in 6 of 7 Alzheimer-related genes (Apbb1, C1qa, Clu, App, Cst3, Fn1, Htatip) in iron-deficient rats relative to iron-sufficient controls at P15. Comparison of untreated to treated iron-deficient animals at this age suggested the strong role of iron deficiency, not treatment, in the upregulation of this gene network. The non-anemic hippocampal iron-deficient mouse demonstrated upregulation of all 7 genes in this pathway from P5 to P25. Our results suggest a role for neonatal iron deficiency in dysregulation of genes that may set the stage for long-term neurodegenerative disease and that this may occur through a histone modification mechanism.
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PMID:Iron deficiency alters expression of genes implicated in Alzheimer disease pathogenesis. 1872 4

Because both iron deficiency and iron excess are deleterious to normal cell function, the intracellular level of iron must be tightly controlled. Ferritin, an iron binding protein, regulates iron balance by storing iron in a bioavailable but nontoxic form. Ferritin protein comprises two subunits: ferritin H, which contains ferroxidase activity, and ferritin L. Here we demonstrate that ferritin H mRNA and protein are induced by histone deacetylase inhibitors (HDAC inhibitors), a promising class of anti-cancer drugs, in cultured human cancer cells. Deletion analysis and EMSA assays reveal that the induction of ferritin H occurs at a transcriptional level via Sp1 and NF-Y binding sites near the transcriptional start site of the human ferritin H promoter. Classically, HDAC inhibitors modulate gene expression by increasing histone acetylation. However, ChIP assays demonstrate that HDAC inhibitors induce ferritin H transcription by increasing NF-Y binding to the ferritin H promoter without changes in histone acetylation. These results identify ferritin H as a new target of HDAC inhibitors, and recruitment of NF-Y as a novel mechanism of action of HDAC inhibitors.
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PMID:Ferritin H induction by histone deacetylase inhibitors. 2038 7

Nonsense-mediated mRNA decay (NMD) prevents the accumulation of transcripts bearing premature termination codons. Here we show that Saccharomyces cerevisiae NMD mutants accumulate 5'-extended RNAs (CD-CUTs) of many subtelomeric genes. Using the subtelomeric ZRT1 and FIT3 genes activated in response to zinc and iron deficiency, respectively, we show that transcription of these CD-CUTs mediates repression at the bona fide promoters, by preventing premature binding of RNA polymerase II in conditions of metal repletion. Expression of the main ZRT1 CD-CUT is controlled by the histone deacetylase Rpd3p, showing that histone deacetylases can regulate expression of genes through modulation of the level of CD-CUTs. Analysis of binding of the transcriptional activator Zap1p and insertion of transcriptional terminators upstream from the Zap1p binding sites show that CD-CUT transcription or accumulation also interferes with binding of the transcriptional activator Zap1p. Consistent with this model, overexpressing Zap1p or using a constitutively active version of the Aft1p transcriptional activator rescues the induction defect of ZRT1 and FIT3 in NMD mutants. These results show that cryptic upstream sense transcription resulting in unstable transcripts degraded by NMD controls repression of a large number of genes located in subtelomeric regions, and in particular of many metal homeostasis genes.
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PMID:Cryptic transcription mediates repression of subtelomeric metal homeostasis genes. 2173 94

Histone modifications play critical roles in the perception of environmental cues by plants. Here, we report that Shk1 binding protein 1 (SKB1/AtPRMT5), which catalyzes the symmetric dimethylation of histone H4R3 (H4R3sme2), is involved in iron homeostasis in Arabidopsis. The SKB1 lesion mutant exhibited higher iron accumulation in shoots and greater tolerance to iron deficiency than the wild type. The expression of SKB1 was not affected by iron, but the level of H4R3sme2 mediated by SKB1 was related to iron status in plants. We showed by chromatin immunoprecipitation (ChIP) and genome-wide ChIP-seq that SKB1 associated with the chromatin of the Ib subgroup bHLH genes (AtbHLH38, AtbHLH39, AtbHLH100 and AtbHLH101), and symmetrically dimethylated histone H4R3. The quantity of SKB1 that associated with chromatin of the Ib subgroup bHLH genes and the level of H4R3sme2 corresponded to the iron status of plants (higher with increased iron supply and lower when iron was removed). We conclude that SKB1-mediated H4R3sme2 regulates iron homeostasis in Arabidopsis in the context of increasing or decreasing expression of Ib subgroup bHLH genes. Iron deficiency may cause an increase in the disassociation of SKB1 from chromatin of the bHLH genes and a decrease in the level of H4R3sme2, thereby elevating their transcription and enhancing iron uptake. Our findings provide new insight into the molecular mechanisms of iron homeostasis in strategy I plants.
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PMID:SKB1/PRMT5-mediated histone H4R3 dimethylation of Ib subgroup bHLH genes negatively regulates iron homeostasis in Arabidopsis thaliana. 2429 97

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency.
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PMID:Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus. 2551 36

Modern definitions of epigenetics incorporate models for transient but biologically important changes in gene expression that are unrelated to DNA code but responsive to environmental changes such as injury-induced stress. In this scheme, changes in oxygen levels (hypoxia) and/or metabolic co-factors (iron deficiency or diminished 2-oxoglutarate levels) are transduced into broad genetic programs that return the cell and the organism to a homeostatic set point. Over the past two decades, exciting studies have identified a superfamily of iron-, oxygen-, and 2-oxoglutarate-dependent dioxygenases that sit in the nucleus as modulators of transcription factor stability, co-activator function, histone demethylases, and DNA demethylases. These studies have provided a concrete molecular scheme for how changes in metabolism observed in a host of neurological conditions, including stroke, traumatic brain injury, and Alzheimer's disease, could be transduced into adaptive gene expression to protect the nervous system. We will discuss these enzymes in this short review, focusing primarily on the ten eleven translocation (TET) DNA demethylases, the jumonji (JmJc) histone demethylases, and the oxygen-sensing prolyl hydroxylase domain enzymes (HIF PHDs). This article is part of a Special Issue entitled SI: Neuroprotection.
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PMID:Metabolism and epigenetics in the nervous system: Creating cellular fitness and resistance to neuronal death in neurological conditions via modulation of oxygen-, iron-, and 2-oxoglutarate-dependent dioxygenases. 2623 72

Iron (Fe) is one of the most important microelement required for plant growth and development because of its unique property of catalyzing oxidation/reduction reactions. Iron deficiency impairs fundamental processes which could lead to a decrease in chlorophyll production and pollen fertility, thus influencing crop productivity and quality. However, iron in excess is toxic to the cell and is harmful to the plant. To exactly control the iron content in all tissues, plants have evolved many strategies to regulate iron homeostasis, which refers to 2 successive steps: iron uptake at the root surface, and iron distribution in vivo. In the last decades, a number of transporters and regulatory factors involved in this process have been isolated and identified. To cope with the complicated flexible environmental conditions, plants apply diverse mechanisms to regulate the expression and activity of these components. One of the most important mechanisms is epigenetic regulation of iron homeostasis. This review has been presented to provide an update on the information supporting the involvement of histone modifications in iron homeostasis and possible future course of the field.
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PMID:Epigenetic regulation of iron homeostasis in Arabidopsis. 2631 98

Early-life iron deficiency results in long-term abnormalities in cognitive function and affective behavior in adulthood. In preclinical models, these effects have been associated with long-term dysregulation of key neuronal genes. While limited evidence suggests histone methylation as an epigenetic mechanism underlying gene dysregulation, the role of DNA methylation remains unknown. To determine whether DNA methylation is a potential mechanism by which early-life iron deficiency induces gene dysregulation, we performed whole genome bisulfite sequencing to identify loci with altered DNA methylation in the postnatal day (P) 15 iron-deficient (ID) rat hippocampus, a time point at which the highest level of hippocampal iron deficiency is concurrent with peak iron demand for axonal and dendritic growth. We identified 229 differentially methylated loci and they were mapped within 108 genes. Among them, 63 and 45 genes showed significantly increased and decreased DNA methylation in the P15 ID hippocampus, respectively. To establish a correlation between differentially methylated loci and gene dysregulation, the methylome data were compared to our published P15 hippocampal transcriptome. Both datasets showed alteration of similar functional networks regulating nervous system development and cell-to-cell signaling that are critical for learning and behavior. Collectively, the present findings support a role for DNA methylation in neural gene dysregulation following early-life iron deficiency.
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PMID:Dysregulation of Neuronal Genes by Fetal-Neonatal Iron Deficiency Anemia Is Associated with Altered DNA Methylation in the Rat Hippocampus. 3113 89


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