Iron Homeostasis and Disorders in Dogs and Cats: A Review

2011 ◽  
Vol 47 (3) ◽  
pp. 151-160 ◽  
Author(s):  
Jennifer L. McCown ◽  
Andrew J. Specht
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Diagnostic Testing ◽  
Clinical Manifestations ◽  
Essential Element ◽  
The Body ◽  
Deficiency Anemia ◽  
Enzyme Systems ◽  
Living Organisms

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

scholarly journals Molecular Mechanisms Regulating Hepcidin Revealed by Hepcidin Disorders

2011 ◽  
Vol 11 ◽  
pp. 1357-1366 ◽  
Author(s):  
Clara Camaschella ◽  
Laura Silvestri
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Transcriptional Control ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Human Life ◽  
Genetic Diseases ◽  
The Body ◽  
Deficiency Anemia ◽  
Iron Regulatory Proteins

Iron is essential for human life, but toxic if present in excess. To avoid iron overload and maintain iron homeostasis, all cells are able to regulate their iron content through the post-transcriptional control of iron genes operated by the cytosolic iron regulatory proteins that interact with iron responsive elements on iron gene mRNA. At the systemic level, iron homeostasis is regulated by the liver peptide hepcidin. Disruption of these regulatory loops leads to genetic diseases characterized by iron deficiency (iron-refractory iron-deficiency anemia) or iron overload (hemochromatosis). Alterations of the same systems are also found in acquired disorders, such as iron-loading anemias characterized by ineffective erythropoiesis and anemia of chronic diseases (ACD) associated with common inflammatory conditions. In ACD, iron is present in the body, but maldistributed, being deficient for erythropoiesis, but sequestered in macrophages. Studies of the hepcidin regulation by iron and inflammatory cytokines are revealing new pathways that might become targets of new therapeutic intervention in iron disorders.

scholarly journals Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 647-650 ◽  
Author(s):  
Anne Lenoir ◽  
Jean-Christophe Deschemin ◽  
Léon Kautz ◽  
Andrew J. Ramsay ◽  
Marie-Paule Roth ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Serine Protease ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Hepatic Iron ◽  
Master Regulator ◽  
Liver Iron ◽  
The Relationship

Abstract Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (encoded by Tmprss6). To determine the relationship between Bmp6 and matriptase-2 pathways, Tmprss6−/− mice (characterized by increased hepcidin levels and anemia) and Bmp6−/− mice (exhibiting severe iron overload because of hepcidin deficiency) were intercrossed. We showed that loss of Bmp6 decreased hepcidin levels; increased hepatic iron; and, importantly, corrected hematologic abnormalities in Tmprss6−/− mice. This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway.

Modulation of the HIF2-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis

Blood ◽  
2022 ◽  
Author(s):  
Nupur K Das ◽  
Chesta Jain ◽  
Amanda D. Sankar ◽  
Andrew J Schwartz ◽  
Naiara Santana-Codina ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Mouse Model ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Hypoxia Inducible Factor ◽  
Whole Body ◽  
Deficiency Anemia ◽  
Null Mouse ◽  
Intestinal Iron Absorption

Intestinal iron absorption is activated during increased systemic iron demand. The best-studied example is iron-deficiency anemia, which increases intestinal iron absorption. Interestingly, the intestinal response to anemia is very similar to that of iron overload disorders, as both the conditions activate a transcriptional program that leads to a hyperabsorption of iron via the transcription factor hypoxia-inducible factor (HIF)2a. However, pathways to selectively target intestinal-mediated iron overload remain unknown. Nuclear receptor co-activator 4 (NCOA4) is a critical cargo receptor for autophagic breakdown of ferritin (FTN) and subsequent release of iron, in a process termed ferritinophagy. Our work demonstrates that NCOA4-mediated intestinal ferritinophagy is integrated to systemic iron demand via HIF2a. To demonstrate the importance of intestinal HIF2a/ferritinophagy axis in systemic iron homeostasis, whole body and intestine-specific NCOA4-null mouse lines were generated and assessed. These analyses revealed that the intestinal and systemic response to iron deficiency was not altered following disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency.

An Essential Role For Transferrin Receptor 2 In Erythropoiesis During Iron Restriction

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 429-429
Author(s):  
Daniel F Wallace ◽  
Cameron J McDonald ◽  
Eriza S Secondes ◽  
Lesa Ostini ◽  
Gautam Rishi ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Deficiency Anemia ◽  
Transferrin Receptor ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Deficiency Anemia ◽  
Erythroid Cells ◽  
Iron Restriction ◽  
Extramedullary Erythropoiesis

Abstract Iron deficiency and iron overload are common clinical conditions that impact on the health and wellbeing of up to 30% of the world’s population. Understanding mechanisms regulating iron homeostasis will provide improved strategies for treating these disorders. The liver-expressed proteins matriptase-2 (encoded by TMPRSS6), HFE and transferrin receptor 2 (TFR2) play important and opposing roles in systemic iron homeostasis by regulating expression of the iron regulatory hormone hepcidin. Mutations in TMPRSS6 lead to iron refractory iron deficiency anemia, whereas mutations in HFE and TFR2 lead to the iron overload disorder hereditary hemochromatosis. To elucidate the competing roles of these hepcidin regulators, we created mice lacking matriptase-2, Hfe and Tfr2. Tmprss6 -/-/Hfe-/-/Tfr2-/- mice had iron deficiency anemia resulting from hepatic hepcidin over-expression and activation of Smad1/5/8, indicating that matriptase-2 predominates over Hfe and Tfr2 in hepcidin regulation. Surprisingly, this anemia was more severe than in the Tmprss6-/- mice, demonstrated by more extensive alopecia, lower hematocrit and significant extramedullary erythropoiesis in the spleen. There was increased expression of erythroid-specific genes in the spleens of Tmprss6-/-/Hfe-/-/Tfr2-/- mice, consistent with the extramedullary erythropoiesis. Expression of Tfr2 but not Hfe in the spleen was increased in the Tmprss6-/- mice compared to wild type and correlated with the expression of erythroid genes, suggesting that Tfr2 is expressed in erythroid cells. Further analysis of gene expression in the bone marrow suggests that the loss of Tfr2 in the erythroid cells of Tmprss6-/-/Hfe-/-/Tfr2-/- mice causes a delay in the differentiation process leading to a more severe phenotype. In conclusion, our results indicate that Hfe and Tfr2 act upstream of matriptase-2 in hepcidin regulation or in a way that is overridden when matriptase-2 is deleted. These results indicate that inhibition of matriptase-2 would be useful in the treatment of iron overload conditions such as hereditary hemochromatosis. We have also identified a novel role for Tfr2 in erythroid differentiation that is separate from its canonical role as a regulator of iron homeostasis in the liver. This important role of Tfr2 in erythropoiesis only becomes apparent during conditions of iron restriction. Our results provide novel insights into mechanisms regulating and linking iron homeostasis and erythropoiesis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Hepcidin-Ferroportin System as a Therapeutic Target in Anemias and Iron Overload Disorders

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 538-542 ◽  
Author(s):  
Tomas Ganz ◽  
Elizabeta Nemeth
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Therapeutic Target ◽  
Iron Homeostasis ◽  
Kidney Diseases ◽  
Hereditary Hemochromatosis ◽  
Deficiency Anemia ◽  
Therapeutic Targeting ◽  
Chronic Kidney Diseases

Abstract The review summarizes the current understanding of the role of hepcidin and ferroportin in normal iron homeostasis and its disorders. The various approaches to therapeutic targeting of hepcidin and ferroportin in iron-overload disorders (mainly hereditary hemochromatosis and β-thalassemia) and iron-restrictive anemias (anemias associated with infections, inflammatory disorders, and certain malignancies, anemia of chronic kidney diseases, and iron-refractory iron-deficiency anemia) are also discussed.

scholarly journals A genome-wide meta-analysis yields 46 new loci associating with biomarkers of iron homeostasis

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Steven Bell ◽  
◽  
Andreas S. Rigas ◽  
Magnus K. Magnusson ◽  
Egil Ferkingstad ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Meta Analysis ◽  
Deficiency Anemia ◽  
Genome Wide Association Studies ◽  
Independent Sequence ◽  
Genome Wide ◽  
A Genome

AbstractIron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation.

scholarly journals Systemic iron homeostasis in female athletes: hepcidin, exercise and sex influence

2020 ◽  
Vol 37 (5) ◽  
pp. 348-353
Author(s):  
L Barba-Moreno ◽  
VM Alfaro-Magallanes ◽  
FJ Calderón ◽  
AB Peinado
Keyword(s):  
Iron Deficiency ◽  
Iron Homeostasis ◽  
Female Athletes ◽  
Iron Absorption ◽  
The Body ◽  
Deficiency Anemia ◽  
Hormonal Changes ◽  
Sexual Hormones ◽  
Susceptible Population ◽  
And Performance

Iron is necessary for adequate deliver oxygen to the tissues since it is an essential component of the haemoglobin. However, iron deficiency remains a common problem among athletes, particularly for women experiencing the menstrual bleeding every month. The iron losses through menstrual blood loss during the early follicular phase (or menses) and an inadequate dietary intake of iron are two important factors contributing to this disease. Furthermore, the large hormonal changes that women experience along the menstrual cycle, especially in oestrogen and progesterone may influence on the optimization of iron absorption. Iron absorption is mainly mediated by hepcidin hormone, which seems to be affected by several stimulus and factors such as oestrogen and progesterone concentrations. Moreover, the regular practice of exercise is another important modulator of this hormone. Therefore, premenopausal active females are the most susceptible population to develop an iron deficiency or iron deficiency anemia, affecting their health and performance due to the less iron availability within the body and consequently a reduction of haemoglobin which compromise the oxygen transport. To date, most studies have not explored the acute post-exercise hepcidin response taking endogenous and exogenous sexual hormones influence into account. This narrative review will focus on how iron homeostasis is modulated by different factors mainly influenced by exercise and female sexual hormones.

scholarly journals Correction of iron deficiency in the clinical picture of internal medicine

2021 ◽  
Vol 17 (3) ◽  
pp. 64-70
Author(s):  
Z.P. Mandziy ◽  
O.H. Boichuk ◽  
V.V. Myhovych
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Malignant Tumors ◽  
Clinical Manifestations ◽  
The Body ◽  
Comprehensive Approach ◽  
Deficiency Anemia ◽  
Peptic Ulcers ◽  
Liposomal Form ◽  
Systematic Analysis

Background. The purpose was to theoretically and practically substantiate the existing approaches to the problem of prevalence, causes, clinical manifestations, as well as diagnosis and use of the latest methods of treatment of iron deficiency anemia (IDA) based on studying scientific ideas. Materials and methods. We used systematic analysis, synthesis, and generalization of scientific and medical literature to make it possible to consider modern views on the problem of IDA among different populations in terms of its epidemiology, etiology, presentation of iron metabolism in the body, and pathogenetic mechanisms of clinical and laboratory symptoms as well as modern methods of laboratory diagnosis of anemia and conclusions on a comprehensive approach to the treatment and prevention. Results. The most common blood disease is iron deficiency anemia. Iron deficiency occurs as a result of a mismatch between the body’s needs for iron and its intake or loss. According to the WHO, more than half of the population in different countries suffers from iron deficiency anemia. It covers all age groups but is most common in children, adolescents, and pregnant women. The symptoms of anemia are pale skin, fatigue, dizziness, shortness of breath, loss of consciousness, dysfunction of many organs. The most common causes of iron deficiency anemia are bleeding from wounds or peptic ulcers, hemorrhoidal bleeding, excessive blood loss during menstruation, uterine fibroids, ulcerative colitis, malignant tumors, gastrectomy, and others. In this disease, the iron depot in the body decreases. According to data from domestic and foreign scientists, as well as the WHO, IDA of varying severity is observed in 20 % of the population. The treatment of IDA should first eliminate the cause of bleeding, prescribe a protein-enriched diet, vitamins, and trace elements. In many countries, the prevention and treatment of anemia are becoming a social challenge. The presence of iron deficiency reduces the quality of life of patients, disrupts their ability to work, causes functional disorders of many organs and systems. To prevent and eliminate iron deficiency, a whole group of iron-containing drugs is successfully used, the range of which is constantly replenishing and updating, as well as a comprehensive approach to treatment with modern iron drugs is discussing. Conclusions. The main pathological and physiological conditions that lead to the development of iron deficiency in different population groups are analyzed. Therefore, the treatment of IDA is aimed not only at eliminating anemia as a symptom, but also at eliminating iron deficiency and replenishing its reserves in the body, which can be achieved by taking a liposomal form of iron.

scholarly journals ГЕПСИДИН, ТРАНСФЕРИН, ФЕРИТИН: ФІЗІОЛОГІЧНА РОЛЬ ЯК ЦЕНТРАЛЬНИХ РЕГУЛЯТОРІВ ОБМІНУ ЗАЛІЗА В ОРГАНІЗМІ

2019 ◽  
pp. 8-16
Author(s):  
Станіслав Видиборець ◽  
Дмитро Борисенко
Keyword(s):  
Iron Deficiency ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Physiological Role ◽  
Clinical Importance ◽  
Dynamic Parameter ◽  
The Body ◽  
Deficiency Anemia ◽  
Laboratory Diagnostics ◽  
The Given

The knowledge about mammalian iron metabolism has advanced dramatically over the past decades. Studies of genetics, biochemistry and molecular biology allowed us the identification and characterization of many of the molecules involved in regulation of iron homeostasis. Important progresses were made after the discovery in 2000 of a small peptide – hepsidin – that has been proved to play a central role in orchestration on iron metabolism also providing a link between iron metabolism and inflammation and innate immunity. Hepsidin directly interacts with ferroportin, the only known mammalian iron exporter, which is expressed by enterocytes, macrophages and hepatocytes. The direct hepsidin- ferroportin interaction allows an adaptative response from the body in situations that alter normal iron homeostasis (hypoxia, anemia, iron deficiency, iron overload, and inflammation). In clause the items of information on transport protein of iron - transferrin are stated. Its physiological role and clinical importance is shown. Dynamics of the contents of the hepsidin, transferrin, ferritin in persons with latent deficiency of iron. The conclusion about importance of the given parameter for laboratory diagnostics of iron deficiency condition is made. In the article the items of information about the ferritin - protein - depot of iron in body are given. Its physiological role and clinical importance is displayed. Dynamics of changes of the contents ferritin during treatment of the patients with iron deficiency anemia and persons with latent deficiency of iron is shown. The conclusion about the level of the ferritin in serum of blood is the important dynamic parameter for laboratory diagnostics iron deficiency of condition is made.

scholarly journals Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

2018 ◽  
Vol 115 (12) ◽  
pp. 3000-3005 ◽  
Author(s):  
Benjamin H. Hudson ◽  
Andrew T. Hale ◽  
Ryan P. Irving ◽  
Shenglan Li ◽  
John D. York
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Reduction ◽  
Genetic Basis ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Sulfur Assimilation ◽  
Nucleotide Hydrolysis ◽  
Evolutionarily Conserved ◽  
Organismal Development

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis.

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