scholarly journals Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient

2016 ◽  
Author(s):  
Jignesh H. Parmar ◽  
Grey Davis ◽  
Hope Shevchuk ◽  
Pedro Mendes
Keyword(s):  
Blood Cells ◽  
Iron Homeostasis ◽  
Essential Element ◽  
Iron Regulation ◽  
Infectious Agents ◽  
Iron Distribution ◽  
Regulatory Interactions ◽  
High Iron ◽  
Body Distribution ◽  
Living Organisms

AbstractBackgroundIron is an essential element of most living organisms but is a dangerous substance when poorly liganded in solution. The hormone hepcidin regulates the export of iron from tissues to the plasma contributing to iron homeostasis and also restricting its availability to infectious agents. Disruption of iron regulation in mammals leads to disorders such as anemia and hemochromatosis, and contributes to the etiology of several other diseases such as cancer and neurodegenerative diseases. Here we test the hypothesis that hepcidin alone is able to regulate iron distribution in different dietary regimes in the mouse using a computational model of iron distribution calibrated with radioiron tracer data.ResultsA model was developed and calibrated to the data from adequate iron diet, which was able to simulate the iron distribution under a low iron diet. However simulation of high iron diet shows considerable deviations from the experimental data. Namely the model predicts more iron in red blood cells and less iron in the liver than what was observed in experiments.ConclusionsThese results suggest that hepcidin alone is not sufficient to regulate iron homeostasis in high iron conditions and that other factors are important. The model was able to simulate anemia when hepcidin was increased but was unable to simulate hemochromatosis when hepcidin was suppressed, suggesting that in high iron conditions additional regulatory interactions are important.

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 The Functional Versatility of Transferrin Receptor 2 and Its Therapeutic Value

2018 ◽  
Vol 11 (4) ◽  
pp. 115 ◽  
Author(s):  
Antonella Roetto ◽  
Mariarosa Mezzanotte ◽  
Rosa Pellegrino
Keyword(s):  
Transferrin Receptor ◽  
Iron Homeostasis ◽  
Hereditary Hemochromatosis ◽  
Iron Regulation ◽  
Role Taking ◽  
Therapeutic Value ◽  
Living Organisms ◽  
Type 3 ◽  
Functional Versatility ◽  
Transferrin Receptor 2

Iron homeostasis is a tightly regulated process in all living organisms because this metal is essential for cellular metabolism, but could be extremely toxic when present in excess. In mammals, there is a complex pathway devoted to iron regulation, whose key protein is hepcidin (Hepc), which is a powerful iron absorption inhibitor mainly produced by the liver. Transferrin receptor 2 (Tfr2) is one of the hepcidin regulators, and mutations in TFR2 gene are responsible for type 3 hereditary hemochromatosis (HFE3), a genetically heterogeneous disease characterized by systemic iron overload. It has been recently pointed out that Hepc production and iron regulation could be exerted also in tissues other than liver, and that Tfr2 has an extrahepatic role in iron metabolism as well. This review summarizes all the most recent data on Tfr2 extrahepatic role, taking into account the putative distinct roles of the two main Tfr2 isoforms, Tfr2α and Tfr2β. Representing Hepc modulation an effective approach to correct iron balance impairment in common human diseases, and with Tfr2 being one of its regulators, it would be worthwhile to envisage Tfr2 as a therapeutic target.

In vivo Experiments of Natural Products Protection of Antagonistic Effects of Lead on Iron

2018 ◽  
Vol 68 (12) ◽  
pp. 2747-2751
Author(s):  
Marioara Nicula ◽  
Nicolae Pacala ◽  
Lavinia Stef ◽  
Ioan Pet ◽  
Dorel Dronca ◽  
...  
Keyword(s):  
Aquatic Environment ◽  
Iron Homeostasis ◽  
Iron Concentration ◽  
Antagonistic Effect ◽  
Tissue Samples ◽  
Antagonistic Effects ◽  
In Vivo Experiments ◽  
Living Organisms ◽  
Toxic Potential

Living organisms take nutrients from the environment, and together with them, substances with toxic potential � such as heavy metals. Lead is one common metal pollutant especially in aquatic environment, from where the fish can be intoxicated very easily. Bioavailability, distribution, toxic action, synergistic and antagonistic effects are characteristics which can alter the fish health. Our experimental study followed the effects of lead overload in water on iron distribution, in different tissues sample Carassius gibelio Bloch fish. We performed the experiment in four different fish groups: control C; lead � Pb (administration of lead in water 0.075mg/mL of water, as Pb(NO3)2 x � H2O); lead (the same dose) and 2% of freeze-dry garlic incorporated into fishes� food � Pb+garlic; lead (the same dose) and 2% chlorella incorporated into fishes� food � Pb+chlorella, for 21 consecutive days. The iron concentration was analysed with AAS (Atomic Absorption Spectroscopy) from gills, muscle, skin (and scales), intestine, liver, heart, brain, ovary, testicles, and kidney. The obtained data presented a significantly decrease of iron content in all tested tissue samples that demonstrated, alteration of iron homeostasis, explained by a strong antagonistic effect of lead on iron. Our experiment showed that biologic active principles from garlic and chlorella act like natural protectors, and potentiate the iron deficiency even in the case of lead overload in aquatic environment, for fish.

Abstract 293: Mammalian Target of Rapamycin and Tristetraprolin Regulate Iron Homeostasis in Cardiac Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Marina Bayeva ◽  
Arineh Khechaduri ◽  
Hossein Ardehali
Keyword(s):  
Energy Metabolism ◽  
Iron Homeostasis ◽  
Heart Function ◽  
Iron Regulation ◽  
Mrna Levels ◽  
Iron Regulatory Proteins ◽  
Regulatory Pathways ◽  
Genetic Knockout ◽  
Cellular Iron ◽  
Vital Functions

Introduction: Iron is essential for normal heart function, and disruption of iron homeostasis can lead to cardiomyopathy. However, our understanding of iron regulation on a cellular level is incomplete, with a single model involving iron regulatory proteins (IRP) described to date. Here, we report the existence of a parallel iron regulatory pathway by energy sensor mTOR and inflammatory mediator trsitetraprolin (TTP). Results: To examine the role of energy metabolism in the regulation of cellular iron, we used rapamycin to inhibit mTOR pathway in H9c2 cardiac myoblasts and mouse embryonic fibroblasts (MEFs). Rapamycin treatment significantly elevated cellular iron content through a coordinated reduction in iron import (transferrin receptor, TfR1) and iron export (ferroportin, Fpn1), leading to deceleration of iron flux and net iron accumulation. We found that the primary action of rapamycin was to reduce TfR1 through destabilization of its mRNA. Surprisingly, this effect was not mediated by IRP1/2, the “classical” sensors of cellular iron levels, as TfR1 mRNA levels were significantly reduced by rapamycin even in cells with the genetic knockout of IRP1 and IRP2. In yeast, a tandem zinc finger (TZF) protein Cth2 was found to conserve cellular iron in states of deficiency by preferentially degrading mRNA of non-essential iron-containing proteins thus reducing iron requirements and liberating iron for vital functions. We found that the mammalian TZF protein TTP, an established mediator of inflammation, was greatly induced by iron deficiency, enhanced degradation of iron-containing proteins, and complemented Cth2 deletion in yeast, thus establishing TTP as the functional homolog of Cth2 in mammalian iron regulation. Finally, TTP levels were increased by rapamycin in IRP1/2-independent manner, and genetic knockout of TTP in MEFs significantly reversed the effects of rapamycin on TfR1 mRNA levels and stability. These findings establish TTP as the mediator of iron-regulatory effects of mTOR and provide a novel link between energy metabolism, inflammation and iron regulatory pathways. Conclusions: We identified a novel pathway of cellular iron regulation by mTOR and TTP, which complements the “classical” IRP1/2 model.

Magnitude and variation of ratio of total body potassium to fat-free mass: a cellular level modeling study

2001 ◽  
Vol 281 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
Zimian Wang ◽  
F. Xavier Pi-Sunyer ◽  
Donald P. Kotler ◽  
Jack Wang ◽  
Richard N. Pierson ◽  
...  
Keyword(s):  
Body Fat ◽  
Essential Element ◽  
Physiological Model ◽  
Cellular Level ◽  
Fat Free Mass ◽  
Total Body Potassium ◽  
Fluid Compartment ◽  
Total Body Fat ◽  
Total Body ◽  
Living Organisms

Potassium is an essential element of living organisms that is found almost exclusively in the intracellular fluid compartment. The assumed constant ratio of total body potassium (TBK) to fat-free mass (FFM) is a cornerstone of the TBK method of estimating total body fat. Although the TBK-to-FFM (TBK/FFM) ratio has been assumed constant, a large range of individual and group values is recognized. The purpose of the present study was to undertake a comprehensive analysis of biological factors that cause variation in the TBK/FFM ratio. A theoretical TBK/FFM model was developed on the cellular body composition level. This physiological model includes six factors that combine to produce the observed TBK/FFM ratio. The ratio magnitude and range, as well as the differences in the TBK/FFM ratio between men and women and variation with growth, were examined with the proposed model. The ratio of extracellular water to intracellular water ( E/I) is the major factor leading to between-individual variation in the TBK/FFM ratio. The present study provides a conceptual framework for examining the separate TBK/FFM determinants and suggests important limitations of the TBK/FFM method used in estimating total body fat in humans and other mammals.

scholarly journals Change of mineral and organic nitrogen forms in a long term fertilization experiment (literature)

2014 ◽  
pp. 43-47
Author(s):  
Judit Horváth ◽  
János Kátai
Keyword(s):  
Organic Nitrogen ◽  
Inorganic Nitrogen ◽  
Essential Element ◽  
Nitrogen Forms ◽  
Organic Form ◽  
The Sustainable Development ◽  
Nitrogen Turnover ◽  
Mineralization Processes ◽  
Living Organisms

The research topic has timeliness, since the rational utilization and protection of the soil, besides the conservation of its diverse functions is part of the sustainable development. Research of the long-term experiments is esentially important, because it can model the term effects in the same place, under the same conditions. If we want to get accurate informations about the occured changes, way and danger of changes, we should track the resupply and effect of the mineral nutrients and the removed quantity of nutrients with the harvest. Nitrogen is an essential element for living organisms, it is present in the soil mainly in organic form. In general only only a low percentage of the total nitrogent content can be used directly by plants in the soil. This inorganic nitrogen is produced by the transformation of organic contents through mineralization processes and it get into the soil by the fertilization. The plants incorporote the mineral nitrogen into our bodies. This is how nitrogen turnover is realized when mineral forms become organic and organic forms become mineral. The purpose of our paper is to make a literature before our research.

scholarly journals The Ins and Outs of Iron Homeostasis

Physiology ◽  
2006 ◽  
Vol 21 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Adriana Donovan ◽  
Cindy N. Roy ◽  
Nancy C. Andrews
Keyword(s):  
Iron Transport ◽  
Iron Homeostasis ◽  
Essential Element ◽  
Regulatory Mechanisms ◽  
Health And Disease ◽  
And Storage ◽  
Different Tissues

Iron is an essential element that is toxic when it accumulates in excess. Intricate regulatory mechanisms have evolved to maintain iron homeostasis within cells and between different tissues of complex organisms. This review discusses the proteins involved in iron transport and storage and their regulation in health and disease.

Paleolimnology in Deep Time: The Evolution of Lacustrine Ecosystems

2003 ◽  
Author(s):  
Andrew S. Cohen
Keyword(s):  
Fossil Record ◽  
World Ocean ◽  
Biological Evolution ◽  
Body Distribution ◽  
Freshwater Organisms ◽  
History Of ◽  
Living Organisms ◽  
Lake Basins ◽  
Lake Beds

Most lakes are geologically ephemeral; even the longest-lived individual lakes persist only for tens of millions of years. However there is a continuity to lake systems that transcends the geologically short history of individual lake basins. This continuity comes from the long-term biological evolution of life in freshwater, and fittingly, forms the final subject of this treatment of paleolimnology. Like the oceans, lakes have provided habitats for living organisms for most of the earth’s history. Yet the patterns of aquatic ecosystem evolution in rivers and lakes have differed dramatically from those of the oceans. In large part this can be traced to the fundamentally ephemeral nature of most continental aquatic habitats and the ‘‘disconnectedness’’ in both time and space that exists between individual lakes and rivers compared with the world ocean. This pattern of temporal and spatial patchiness in water body distribution on the continents has shaped the evolution of lacustrine species and communities. Some understanding of this history can be gleaned from the study of modern ecology and molecular genetics of living freshwater organisms. But to understand long-term trends in lacustrine biodiversity and their relationship to the history of the lacustrine environment we must turn to the pre- Quaternary fossil record. Understanding this history, the timing and tempo of major species diversification and extinction events, and the evolution of key ecological innovations is critical for correctly interpreting ancient lake deposits. The fossil record of pre-Quaternary lakes is more difficult to interpret than that of more recent lake basins. Robust phylogenies are largely unavailable for clades of ancient lacustrine fossils, hindering our ability to test hypotheses of evolutionary ecology, although that situation hopefully will improve in coming years. Many major clades of fossil lacustrine organisms are extinct, and ecologies must be inferred from their depositional context. Even for organisms that have close-living relatives, our certainty in making inferences about habitat and relationship with other species weakens as we go back in time. Also the record we have to work with deteriorates with age, the result of (a) a declining volume of lake beds available for study with increasing age, (b) difficulties associated with processing lithified lake beds for their fossil content, and (c) an increasing likelihood of destruction by diagenesis with increasing age.

scholarly journals Iron as a Central Player and Promising Target in Cancer Progression

2019 ◽  
Vol 20 (2) ◽  
pp. 273 ◽  
Author(s):  
Michaela Jung ◽  
Christina Mertens ◽  
Elisa Tomat ◽  
Bernhard Brüne
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Cancer Progression ◽  
Crucial Role ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Essential Element ◽  
Major Function ◽  
Iron Pool

Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a crucial role in tumor progression and metastasis due to its major function in tumor cell survival and reprogramming of the tumor microenvironment. Therefore, pathways of iron acquisition, export, and storage are often perturbed in cancers, suggesting that targeting iron metabolic pathways might represent opportunities towards innovative approaches in cancer treatment. Recent evidence points to a crucial role of tumor-associated macrophages (TAMs) as a source of iron within the tumor microenvironment, implying that specifically targeting the TAM iron pool might add to the efficacy of tumor therapy. Here, we provide a brief summary of tumor cell iron metabolism and updated molecular mechanisms that regulate cellular and systemic iron homeostasis with regard to the development of cancer. Since iron adds to shaping major hallmarks of cancer, we emphasize innovative therapeutic strategies to address the iron pool of tumor cells or cells of the tumor microenvironment for the treatment of cancer.

scholarly journals Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2601
Author(s):  
Tanja Grubić Kezele ◽  
Božena Ćurko-Cofek
Keyword(s):  
Iron Metabolism ◽  
Neurological Disorders ◽  
Healthy Aging ◽  
Iron Homeostasis ◽  
Essential Element ◽  
Molecular Alterations ◽  
Age Related ◽  
Faster Development ◽  
Brain Iron Metabolism ◽  
Age Related Changes

Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.

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