Tissue Iron Distribution and Adaptation of Iron Absorption in Rats Exposed to a High Dietary Level of NaFeEDTA

2005 ◽  
Vol 53 (20) ◽  
pp. 8087-8091 ◽  
Author(s):  
Chi Kong Yeung ◽  
Le Zhu ◽  
Raymond P. Glahn ◽  
Dennis D. Miller
Keyword(s):  
Iron Absorption ◽  
Dietary Level ◽  
Iron Distribution ◽  
High Dietary Level ◽  
Tissue Iron

scholarly journals Ineffective erythropoiesis in β-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin

Blood ◽  
2007 ◽  
Vol 109 (11) ◽  
pp. 5027-5035 ◽  
Author(s):  
Sara Gardenghi ◽  
Maria F. Marongiu ◽  
Pedro Ramos ◽  
Ella Guy ◽  
Laura Breda ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Content ◽  
Iron Absorption ◽  
Regulatory Gene ◽  
Regulatory Genes ◽  
Ineffective Erythropoiesis ◽  
Transfusion Therapy ◽  
Iron Distribution ◽  
Tissue Iron

Abstract Progressive iron overload is the most salient and ultimately fatal complication of β-thalassemia. However, little is known about the relationship among ineffective erythropoiesis (IE), the role of iron-regulatory genes, and tissue iron distribution in β-thalassemia. We analyzed tissue iron content and iron-regulatory gene expression in the liver, duodenum, spleen, bone marrow, kidney, and heart of mice up to 1 year old that exhibit levels of iron overload and anemia consistent with both β-thalassemia intermedia (th3/+) and major (th3/th3). Here we show, for the first time, that tissue and cellular iron distribution are abnormal and different in th3/+ and th3/th3 mice, and that transfusion therapy can rescue mice affected by β-thalassemia major and modify both the absorption and distribution of iron. Our study reveals that the degree of IE dictates tissue iron distribution and that IE and iron content regulate hepcidin (Hamp1) and other iron-regulatory genes such as Hfe and Cebpa. In young th3/+ and th3/th3 mice, low Hamp1 levels are responsible for increased iron absorption. However, in 1-year-old th3/+ animals, Hamp1 levels rise and it is rather the increase of ferroportin (Fpn1) that sustains iron accumulation, thus revealing a fundamental role of this iron transporter in the iron overload of β-thalassemia.

scholarly journals Molecular liaisons between erythropoiesis and iron metabolism

Blood ◽  
2014 ◽  
Vol 124 (4) ◽  
pp. 479-482 ◽  
Author(s):  
Leon Kautz ◽  
Elizabeta Nemeth
Keyword(s):  
Blood Plasma ◽  
Iron Metabolism ◽  
Iron Absorption ◽  
Iron Distribution ◽  
Plasma Iron ◽  
Iron Supply ◽  
Tissue Iron ◽  
Made In ◽  
In Blood Plasma ◽  
Iron Concentrations

Abstract Although most circulating iron in blood plasma is destined for erythropoiesis, the mechanisms by which erythropoietic demand modulates the iron supply (“erythroid regulators”) remain largely unknown. Iron absorption, plasma iron concentrations, and tissue iron distribution are tightly controlled by the liver-produced hormone hepcidin. During the last decade, much progress has been made in elucidating hepcidin regulation by iron and inflammation. This review discusses the less understood mechanisms and mediators of hepcidin suppression in physiologically and pathologically stimulated erythropoiesis.

scholarly journals PS1298 TISSUE IRON DISTRIBUTION IN PATIENTS WITH LOW-RISK MDS

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 593
Author(s):  
R. Grosse ◽  
A.M. Asemissen ◽  
C.G. Ganster ◽  
J. Starekova ◽  
P. Schafhausen ◽  
...  
Keyword(s):  
Low Risk ◽  
Iron Distribution ◽  
Tissue Iron

scholarly journals Iron and Zinc Homeostasis and Interactions: Does Enteric Zinc Excretion Cross-Talk with Intestinal Iron Absorption?

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1885 ◽  
Author(s):  
Palsa Kondaiah ◽  
Puneeta Singh Yaduvanshi ◽  
Paul A Sharp ◽  
Raghu Pullakhandam
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
The Body ◽  
Zinc Homeostasis ◽  
Iron Accumulation ◽  
Intestinal Cell ◽  
Deficiency Anemia ◽  
Intestinal Iron Absorption ◽  
Tissue Iron ◽  
Iron And Zinc

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation and food fortification. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly, increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating intestinal iron absorption and mobilization from tissues. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN1) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN1 axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.

A possible role for secreted ferritin in tissue iron distribution

2011 ◽  
Vol 118 (3) ◽  
pp. 337-347 ◽  
Author(s):  
Esther G. Meyron-Holtz ◽  
Shirly Moshe-Belizowski ◽  
Lyora A. Cohen
Keyword(s):  
Iron Distribution ◽  
Tissue Iron

scholarly journals Circulating Human Hepcidin-25 Concentrations Display a Diurnal Rhythm, Increase with Prolonged Fasting, and Are Reduced by Growth Hormone Administration

2012 ◽  
Vol 58 (8) ◽  
pp. 1225-1232 ◽  
Author(s):  
Jason S Troutt ◽  
Mats Rudling ◽  
Lena Persson ◽  
Lars Ståhle ◽  
Bo Angelin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Iron Absorption ◽  
Early Morning ◽  
Diurnal Changes ◽  
Prolonged Fasting ◽  
Healthy Human ◽  
Rapid Variation ◽  
Hormone Administration ◽  
Tissue Iron ◽  
Human Volunteers

Abstract BACKGROUND Hepcidin-25 reduces iron absorption by binding to the intestinal iron transporter ferroportin and causing its degradation. Currently, little is known about the basal regulation of circulating hepcidin-25. In addition, although erythropoietin administration has been reported to decrease the circulating hepcidin concentration, information is limited regarding how other stimulators of erythropoiesis, such as growth hormone (GH), might alter hepcidin-25 concentrations. METHODS We used a sensitive and specific hepcidin-25 dual–monoclonal antibody sandwich immunoassay to measure hepcidin-25 in healthy human volunteers at various time points throughout the day and during 3 days of fasting and subsequent refeeding. We also measured hepcidin-25 concentrations in healthy volunteers after GH administration. RESULTS In healthy individuals, hepcidin-25 concentrations displayed a diurnal variation, with concentrations being lowest in the early morning and steadily increasing throughout the day before declining during the evening hours, a pattern that was not influenced by food intake. Prolonged fasting produced statistically significant increases in hepcidin-25 concentrations. Refeeding reversed this process, and GH administration markedly decreased hepcidin-25 concentrations. CONCLUSIONS Our results indicate that in humans, hepcidin-25 exhibits diurnal changes that can be altered by prolonged fasting, which increases hepcidin-25 concentrations approximately 3-fold after 3 days of fasting, possibly owing to a suppression of erythropoiesis that may occur during the fasting state to preserve tissue iron concentrations. In contrast, GH administration decreased hepcidin-25 concentrations by approximately 65%, presumably by stimulating erythropoiesis. These results indicate that circulating hepcidin-25 concentrations display much more dynamic and rapid variation than might have been anticipated previously.

scholarly journals Iron Overload in the Face of Anemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-38-SCI-38
Author(s):  
Yatrik Shah
Keyword(s):  
Transcription Factors ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Iron Absorption ◽  
Conflicts Of Interest ◽  
Iron Accumulation ◽  
Cell Disease ◽  
Divalent Metal Transporter 1 ◽  
Tissue Iron

Abstract Several distinct congenital disorders can lead to tissue-iron overload with anemia including β-thalassemia and sickle cell disease. We show that intestinal absorption of iron is highly increased and significantly contributes to tissue iron accumulation in these disorders. The present work describes a novel pathway by which oxygen sensing transcription factors are highly upregulated in iron overload anemias and are subsequently essential for the increase intestinal iron absorption. Oxygen signaling is mediated through well-conserved hypoxia driven transcription factors, hypoxia-inducible factor (HIF)1a and HIF2a. In the intestine, HIF2a directly activates divalent metal transporter 1 (DMT1), duodenal ferric reductase (DcytB), and Fpn1, which are iron transporters critical for adaptive changes in iron absorption. We demonstrate that HIF2a and its downstream target gene, DMT1 are essential for iron accumulation in mouse models of β-thalassemia and sickle cell disease. Furthermore, studies of thalassemic mouse model with established iron overload demonstrated that loss of intestinal HIF2a and DMT1 signaling led to decreased tissue iron accumulation in the livers. Interestingly, disrupting intestinal HIF2a not only improves tissue iron accumulation, but a marked improvement of anemia was also observed. These novel findings suggests that inhibition of HIF2a signaling pathway could be a novel and robust treatment strategy for several conditions that cause iron overload with anemia. Disclosures No relevant conflicts of interest to declare.

Effects of hypoxia on iron absorption and mobilization in the rat

1964 ◽  
Vol 207 (1) ◽  
pp. 55-61 ◽  
Author(s):  
Georg W. Strohmeyer ◽  
Stephen A. Miller ◽  
Robert W. Scarlata ◽  
Edward W. Moore ◽  
Mortimer S. Greenberg ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Oxidase Activity ◽  
Iron Absorption ◽  
Test Dose ◽  
Oral Iron ◽  
Base Line ◽  
Tissue Storage ◽  
Iron Load ◽  
Tissue Iron ◽  
Iron Deficient

Rats exposed to an atmosphere of 10% oxygen increase their absorption of a test dose of iron after 6 8 hr. Release of tissue storage iron begins within 2 hr of the start of hypoxia and continues for at least 8 hr. An oral iron load does not prevent the release of tissue iron in response to hypoxia. Iron-loaded rats also release iron from storage depots and increase their minimal absorption in response to hypoxia. Iron-deficient rats apparently have a diminished tissue release and also increase absorption above their elevated base-line levels. Xanthine loading had no effect on the release of tissue iron or changes in absorption with hypoxia, and there was no evidence that changes in xanthine oxidase activity in the liver or bowel were directly associated with tissue release or absorption of iron.

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