Study on the Iron-related Molecules in Iron Homeostasis：Mutation Spectrum and Low Oxygen Effect
Date Issued
2009
Date
2009
Author(s)
Chen, Hsin-Yu
Abstract
Iron is essential for living organisms to survive, e.g. it is involved in electron transport and energy metabolism. There is no excretory pathway for iron, the regulation of iron homeostasis should be tightly controlled. To prevent unbalanced iron concentration causing cells and tissues damage, the systemic iron metabolism is regulated by iron absorption, utilization, and recycling. Recently, several novel studies of iron-related moleculars and genes make the association between iron homeostasis and diseases more clear. Hepcidin, a 25-amino acid peptide hormone, is mainly produced in the liver and is considered to be the principal regulator of systemic iron concentration. To limit iron absorption in enterocytes and control iron release from macrophages, hepcidin would bind to the iron-exporter protein ferroportin and trigger entrocytosis to degrade ferroportin. The hepcidin expression is regulated through erythropoietic activity pathway, iron store pathway, and inflammation pathway. Additionally, severl moleculars are also involved in, such as transferring receptor 1 (TFR1), transferring receptor 2 (TFR2), hemochromatosis (HFE), hemojuvelin (HJV), bone morphogenetic protein (BMP), etc. Recently, the TMPRSS6 mutation is revealed to be related to iron-refractory iron deficiency anemia, subsequent reporters showed that the main function of TMPRSS6 is to inhibit hepcidin activation by cleaving m-HJV. The mutation of these genes were reported somewhere, however, there are few reporters to discover the mutations of HAMP, HJV, FPN1 and TMPRSS6 in Taiwan. The aim of the present research is to study iron-related genes in 47 patients with iron deficiency, especially the TMPRSS6. We didn’t find any meaningful mutations in the functional serine protease domain, besides some SNPs. Further, the second aim is to know the effect of differ oxygenation concentrations. We measured several genes mRNA of Hep G2 and Huh7 cell lines which are incubated in normoxia or hypoxia conditions. Compared with normoxia, hypoxia can induce the expression of TMPRSS6 and HAMP mRNA in both cell lines. As expected, we found ceruloplasmin mRNA increased under hypoxia in Hep G2 cells. Furthermore, hypoxia decreased TfR1 mRNA at first and then increased its expression.
Subjects
iron homeostasis
iron deficiency anemia
hypoxia
Hep G2 cells
hepcidin
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