Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient
| Autor: | Pedro Mendes, Jignesh H. Parmar, Grey Davis, Hope Shevchuk |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Anemia Iron Systems biology Hepcidin Models Biological Mice 03 medical and health sciences 0302 clinical medicine Iron homeostasis Hepcidins Structural Biology hemic and lymphatic diseases medicine Animals Distribution (pharmacology) Dangerous substance lcsh:QH301-705.5 Molecular Biology Hemochromatosis 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species biology Applied Mathematics Modeling Iron Deficiencies Computer simulation Iron metabolism medicine.disease Computer Science Applications Diet Cell biology 030104 developmental biology Phenotype lcsh:Biology (General) chemistry Biochemistry Modeling and Simulation 030220 oncology & carcinogenesis Chronic Disease biology.protein Iron physiology Research Article Hormone |
| Zdroj: | BMC Systems Biology Parmar, J H, Davis, G, Shevchuk, H & Mendes, P 2017, ' Modeling the dynamics of mouse iron body distribution: hepcidin is necessary but not sufficient ', BMC Systems Biology, vol. 11, no. 1 . https://doi.org/10.1186/s12918-017-0431-3 BMC Systems Biology, Vol 11, Iss 1, Pp 1-13 (2017) |
| Popis: | BackgroundIron 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. |
| Databáze: | OpenAIRE |
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