Identification of differentially expressed genes in response to dietary iron deprivation in rat duodenum

2005 ◽  
Vol 288 (5) ◽  
pp. G964-G971 ◽  
Author(s):  
James F. Collins ◽  
Christina A. Franck ◽  
Kris V. Kowdley ◽  
Fayez K. Ghishan
Keyword(s):  
Iron Deficiency ◽  
Real Time ◽  
Real Time Pcr ◽  
Iron Transport ◽  
Dietary Iron ◽  
Cancer Resistance ◽  
Novel Genes ◽  
Copper Absorption ◽  
Iron Deprivation ◽  
Iron Deficient

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.

Developmental iron deficiency dysregulates TET activity and DNA hydroxymethylation in the rat hippocampus and cerebellum

2022 ◽  
Author(s):  
Amanda K. Barks ◽  
Montana M. Beeson ◽  
Timothy C. Hallstrom ◽  
Michael K. Georgieff ◽  
Phu V. Tran
Keyword(s):  
Iron Deficiency ◽  
Neural Circuit ◽  
Epigenetic Modification ◽  
Rat Hippocampus ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Dna Hydroxymethylation ◽  
Iron Treatment ◽  
Iron Deficient ◽  
Increased Risk

Iron deficiency (ID) during neurodevelopment is associated with lasting cognitive and socioemotional deficits, and increased risk for neuropsychiatric disease throughout the lifespan. These neurophenotypical changes are underlain by gene dysregulation in the brain that outlasts the period of ID; however, the mechanisms by which ID establishes and maintains gene expression changes are incompletely understood. The epigenetic modification 5-hydroxymethylcytosine (5hmC), or DNA hydroxymethylation, is one candidate mechanism because of its dependence on iron-containing TET enzymes. The aim of the present study was to determine the effect of fetal-neonatal ID on regional brain TET activity, Tet expression, and 5hmC in the developing rat hippocampus and cerebellum, and to determine whether changes are reversible with dietary iron treatment. Timed pregnant Sprague-Dawley rats were fed iron deficient diet (ID; 4 mg/kg Fe) from gestational day (G)2 to generate iron deficient anemic (IDA) offspring. Control dams were fed iron sufficient diet (IS; 200 mg/kg Fe). At postnatal day (P)7, a subset of ID-fed litters was randomized to IS diet, generating treated IDA (TIDA) offspring. At P15, hippocampus and cerebellum were isolated for subsequent analysis. TET activity was quantified by ELISA from nuclear proteins. Expression of Tet1, Tet2, and Tet3 was quantified by qPCR from total RNA. Global %5hmC was quantified by ELISA from genomic DNA. ID increased DNA hydroxymethylation (p=0.0105), with a corresponding increase in TET activity (p<0.0001) and Tet3 expression (p<0.0001) in the P15 hippocampus. In contrast, ID reduced TET activity (p=0.0016) in the P15 cerebellum, with minimal effect on DNA hydroxymethylation. Neonatal dietary iron treatment resulted in partial normalization of these changes in both brain regions. These results demonstrate that the TET/DNA hydroxymethylation system is disrupted by developmental ID in a brain region-specific manner. Differential regional disruption of this epigenetic system may contribute to the lasting neural circuit dysfunction and neurobehavioral dysfunction associated with developmental ID.

Duodenal expression of HFE by real time PCR is not increased in hereditary hemochromatosis or iron deficiency anaemia

2003 ◽  
Vol 124 (4) ◽  
pp. A713-A714
Author(s):  
Barry Kelleher ◽  
Sharon Barrett ◽  
Michael Sweeney ◽  
Valerie Byrnes ◽  
Eleanor Ryan ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Real Time ◽  
Real Time Pcr ◽  
Iron Deficiency Anaemia ◽  
Hereditary Hemochromatosis ◽  
Deficiency Anaemia

scholarly journals Bacterial Compound N,N-Dimethylhexadecylamine Modulates Expression of Iron Deficiency and Defense Response Genes in Medicago truncatula Independently of the Jasmonic Acid Pathway

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 624 ◽  
Author(s):  
Vicente Montejano-Ramírez ◽  
Ernesto García-Pineda ◽  
Eduardo Valencia-Cantero
Keyword(s):  
Gene Expression ◽  
Salicylic Acid ◽  
Iron Deficiency ◽  
Jasmonic Acid ◽  
Pseudomonas Syringae ◽  
Medicago Truncatula ◽  
Abiotic Stresses ◽  
Biotic And Abiotic Stresses ◽  
Iron Deprivation ◽  
Iron Deficient

Plants face a variety of biotic and abiotic stresses including attack by microbial phytopathogens and nutrient deficiencies. Some bacterial volatile organic compounds (VOCs) activate defense and iron-deficiency responses in plants. To establish a relationship between defense and iron deficiency through VOCs, we identified key genes in the defense and iron-deprivation responses of the legume model Medicago truncatula and evaluated the effect of the rhizobacterial VOC N,N-dimethylhexadecylamine (DMHDA) on the gene expression in these pathways by RT-qPCR. DMHDA increased M. truncatula growth 1.5-fold under both iron-sufficient and iron-deficient conditions compared with untreated plants, whereas salicylic acid and jasmonic acid decreased growth. Iron-deficiency induced iron uptake and defense gene expression. Moreover, the effect was greater in combination with DMHDA. Salicylic acid, Pseudomonas syringae, jasmonic acid, and Botrytis cinerea had inhibitory effects on growth and iron response gene expression but activated defense genes. Taken together, our results showed that the VOC DMHDA activates defense and iron-deprivation pathways while inducing a growth promoting effect unlike conventional phytohormones, highlighting that DMHDA does not mimic jasmonic acid but induces an alternative pathway. This is a novel aspect in the complex interactions between biotic and abiotic stresses.

The Mask Mutation Identifies TMPRSS6 as an Essential Suppressor of Hepcidin Gene Expression, Required for Normal Uptake of Dietary Iron.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3-3 ◽  
Author(s):  
Ernest Beutler ◽  
Pauline Lee ◽  
Terri Gelbart ◽  
Xin Du ◽  
Bruce Beutler
Keyword(s):  
Iron Deficiency ◽  
Serine Protease ◽  
Positional Cloning ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Dietary Iron ◽  
Iron Deficient ◽  
Total Body ◽  
Hepcidin Gene ◽  
Hepcidin Mrna

Abstract Hepcidin, the central negative regulator of iron absorption and iron release from macrophages, is upregulated by iron. Mutations in hemojuvelin, Hfe, transferrin receptor 2, and SMAD4 are known to prevent upregulation. Additionally, the bone morphogenetic proteins (BMPs), and the inflammatory cytokines IL-1 and IL-6 stimulate hepcidin gene activation. Downregulation of hepcidin is effected by anemia and hypoxia, but nothing is known of the mechanism through which this occurs. Here we describe the recessive ENU-induced phenotype Mask, so called because affected homozygotes developed regional alopecia in which truncal hair was shed while facial hair was retained. The Mask phenotype was found to be a manifestation of iron deficiency, and was eliminated by correcting the iron deficiency. When fed an iron deficient diet, mutant mice absorbed less iron than controls, as measured by total body 59Fe counting. After reaching a plateau total body counts stabilized, indicating that blood loss did not play a role in the iron deficiency. The level of liver hepcidin mRNA of iron deficient mice is normally greatly decreased; in contrast, the Mask mouse had high liver hepcidin mRNA levels. By positional cloning, we were able to ascribe the Mask phenotype to a splicing error in the Tmprss6 gene, which encodes a membrane-bound serine protease of previously unknown function. The mutation truncates the protein, eliminating the serine protease domain. Transfecting HepG2 cells to express the wildtype TMPRSS6 protein decreased baseline hepcidin reporter activity and almost entirely blunted the hepcidin inducing effect of IL-6, IL-1, hemojuvelin, and the BMPs. A construct encoding the Mask truncation mutant had diminished activity. Thus, TMPRSS6 powerfully down-regulates hepcidin gene transcription in the baseline state and prevents its upregulation by all known stimulators. TMPRSS6 is a non-redundant component of a hepcidin suppression pathway that exerts dominant effect over all known hepcidin inducing pathways, and is required for normal absorption of dietary iron.

scholarly journals An Analysis of the Etiology of Anemia and Iron Deficiency in Young Women of Low Socioeconomic Status in Bangalore, India

2007 ◽  
Vol 28 (3) ◽  
pp. 328-336 ◽  
Author(s):  
Prashanth Thankachan ◽  
Sumithra Muthayya ◽  
Thomas Walczyk ◽  
Anura V. Kurpad ◽  
Richard F. Hurrell
Keyword(s):  
Socioeconomic Status ◽  
Iron Deficiency ◽  
Dietary Intake ◽  
Serum Ferritin ◽  
Young Women ◽  
Low Socioeconomic Status ◽  
Dietary Iron ◽  
Low Socioeconomic ◽  
Blood Hemoglobin ◽  
Iron Deficient

Background Anemia and iron deficiency are significant public health problems in India, particularly among women and children. Recent figures suggest that nearly 50% of young Indian women are anemic. Objectives Few studies have comprehensively assessed etiologic factors contributing to anemia and iron deficiency in India. Hence, this study assessed the relative importance of various factors contributing to these problems in young women of low socioeconomic status in Bangalore, India. Methods A random sample of 100 nonpregnant, nonlactating women 18 to 35 years of age, selected from among 511 women living in a poor urban settlement, participated in this study. Data were obtained on demography, socioeconomic status, anthropometry, three-day dietary intake, blood hemoglobin, hemoglobinopathies, serum ferritin, serum C-reactive protein, and stool parasites. Results The prevalence rates of anemia and iron deficiency were 39% and 62%, respectively; 95% of the anemic women were iron deficient. The mean dietary iron intake was 9.5 mg per day, predominantly from the consumption of cereals, pulses, and vegetables (77%). The estimated bioavailability of nonheme iron in this diet was 2.8%. Dietary intakes were suboptimal for several nutrients. Blood hemoglobin was significantly correlated with dietary intake of fat, riboflavin, milk and yogurt, and coffee. Serum ferritin was significantly correlated with intake of niacin, vitamin B12, and selenium. Parasitic infestation was low. Conclusions An inadequate intake of dietary iron, its poor bioavailability, and concurrent inadequate intake of dietary micronutrients appear to be the primary factors responsible for the high prevalence of anemia and iron deficiency in this population.

scholarly journals An in Vitro Study on the Role of Angiogenesis in Iron Deficiency Induced Reactive Thrombocytosis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2450-2450
Author(s):  
Pedro De Alarcon ◽  
Manu Gnanamony ◽  
Jessica Garcia
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Iron Deficiency ◽  
Real Time ◽  
Real Time Pcr ◽  
Tube Formation ◽  
Reactive Thrombocytosis ◽  
Serum Free

Abstract Introduction: Iron deficiency (ID) is one of the recognized causes of reactive thrombocytosis in children. Factors that are commonly associated with megakaryopoiesis such as thrombopoietin (TPO), interleukin 6 (IL-6) and IL-11 are not altered in patients with iron deficiency and thrombocytosis suggesting the role of alternate mechanisms in controlling this process. We have previously shown using an ID rat model that ID increased the number of megakaryocytes in the bone marrow. We have also shown an increase in VEGFR (FLT1) and CXCR4 staining in bone marrow slides of ID rats. This data suggests that angiogenesis plays a vital role in the development of reactive thrombocytosis in response to ID. In this report, we have expanded our study to identify specific angiogenic signaling molecules associated with ID and used functional assays to validate it. Methods: For this study, we used the megakaryoblast cell line MEG-01 as an in vitro model of megakaryopoiesis. MEG-01 cells were adapted to grow in chemically defined serum free medium containing iron (iron replete media). For iron deficiency, serum free iron free media was mixed with iron replete media at a 1% v/v concentration (iron deplete media). For our experiments, MEG-01 cells were grown in both iron replete and depleted media for 7 days. Cell viability was measured using the trypan blue exclusion assay. Messenger-RNA expression of iron-related markers (TFR1, TFR2, FLT1, FLT3, FTL, FTH1, TF, HMOX1 and HMOX2) and angiogenic markers (VEGFA, VEGFB, VEGFC, PDGF, ANGPTL1, ANGPTL2, FGF2) was studied using real time PCR. We performed functional validation of angiogenesis with an in vitro tube formation assay using human umbilical vein endothelial (HUVEC) cells. For statistical analysis of the data we performed the t test using graph pad prism software and we considered p<0.05 as statistically significant. Results: In low iron conditions, MEG-01 cells showed a significant increase in FLT1 (4 fold) and FLT3 (3 fold) expression using real time PCR (p<0.001). Iron deficiency also induced a 2 fold increase in the mRNA expression of angiogenic molecules VEGFB, VEGFC, FGF2 and PDGFA (p<0.001). Using the tube formation assay, we also show that conditioned media collected from iron deficient MEG-01 cells induced increased vessel formation in endothelial cells. Conclusion: In this study, we were able to validate our earlier in vivo findings on iron deficiency induced reactive thrombocytosis. We show that cells adapt to low iron conditions by upregulating FLT1, FLT3 and FTL. We also show that several markers in the angiogenesis pathway like VEGFB, VEGFC, FGF2 and PDGFA are upregulated in response to iron deficiency. We were also able to show that an increase in these angiogenic molecules induced increased vessel formation in endothelial cells. This report, along with our previous findings, points to the importance of the angiogenic pathway in reactive thrombocytosis induced by iron deficiency. Disclosures No relevant conflicts of interest to declare.

Dietary iron-deficient anemia induces a variety of metabolic changes and even apoptosis in rat liver: a DNA microarray study

2010 ◽  
Vol 42 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Asuka Kamei ◽  
Yuki Watanabe ◽  
Tomoko Ishijima ◽  
Mariko Uehara ◽  
Soichi Arai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Iron Deficiency ◽  
Dna Microarray ◽  
Global Analysis ◽  
Control Diet ◽  
Diet Group ◽  
Iron Level ◽  
Dietary Iron ◽  
Deficient Diet ◽  
Iron Deficient

Anemia can be induced by dietary iron deficiency, as well as by hemorrhagia. It may also be associated with changes in lipid metabolism. However, no global analysis detailing the consequences of iron deficiency in the liver has yet been conducted. Since the liver is a metabolically important organ and also a major iron-storing organ, we performed a comprehensive transcriptome analysis to determine the effects of iron deficiency on hepatic gene expression. Four-week-old rats were fed an iron-deficient diet, ∼3 ppm iron, ad libitum for 16 days. These rats were compared with similar rats pair-fed a control diet with a normal iron level, 48 ppm iron. The 16-day iron-deficient diet apparently induced anemia. On day 17, the rats were killed under anesthesia, and their livers were dissected for DNA microarray analysis. We identified 600 upregulated and 500 downregulated probe sets that characterized the iron-deficient diet group. In the upregulated probe sets, genes involved in cholesterol, amino acid, and glucose metabolism were significantly enriched, while genes related to lipid metabolism were significantly enriched in the downregulated probe sets. We also found that genes for caspases 3 and 12, which mediate endoplasmic reticulum (ER)-specific apoptosis, were upregulated in the iron-deficient group. Combined, these results suggest that iron deficiency exerts various influences, not only on nutrient metabolism but also on apoptosis, as a consequence of ER stress in the liver.

DISTRIBUTION OF CYTOCHROME C AND MYOGLOBIN IN RATS WITH DIETARY IRON DEFICIENCY

PEDIATRICS ◽  
1965 ◽  
Vol 35 (4) ◽  
pp. 677-686
Author(s):  
Peter R. Dallman ◽  
Herbert C. Schwartz
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome C ◽  
Intestinal Mucosa ◽  
Dietary Iron ◽  
Cell Turnover ◽  
Organ Function ◽  
Diaphragmatic Muscle ◽  
Iron Deprivation ◽  
Iron Deficient ◽  
Significant Impairment

A decrease in cytochrome c and myoglobin concentrations was observed in young rats made anemic on a low-iron diet. The degree of depletion of hemeprotein varied according to tissue. In the iron-deficient rat, myoglobin and cytochrome c were most depleted in skeletal muscle which contains the major portion of these proteins. Cytochrome c expressed as percentage of corresponding control mean concentrations was 44% in skeletal muscle, 61% in intestinal mucosa, 69% in kidney, 79% in diaphragm, 89% in heart, and 97% in brain. Myoglobin in the iron-deficient rats was 44% of the corresponding control concentration in skeletal muscle, 63% in diaphragmatic muscle, and 80% in heart muscle. The variations in degree of hemeprotein depletion in response to iron deprivation appeared to be related to organ function, growth rate, and cell turnover. Cardiac and diaphragmatic muscle, whose function is essential to survival, resisted the loss of myoglobin and cytochrome c to a greater extent than did skeletal muscle. Severe depletion of hemeprotein was observed in tissues with a rapid rate of growth such as skeletal muscle or a rapid cell turnover as in the case of intestinal mucosa. Brain, which grows minimally during the period of iron deprivation, was unchanged in its cytochrome c content. A significant impairment of oxidative metabolism in the iron deficient rat was suggested by a reduction in the rate of respiration of muscle homogenates.

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