The role of hepcidin in iron transport of macrophages

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The role of hepcidin in iron transport of macrophages

 

Author: Wang, Qin
Title: The role of hepcidin in iron transport of macrophages
Degree: Ph.D.
Year: 2007
Subject: Hong Kong Polytechnic University -- Dissertations.
Peptides.
Iron -- Metabolism.
Iron in the body -- Transportation.
Macrophages.
Department: Dept. of Applied Biology and Chemical Technology
Pages: 388 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b2145876
URI: http://theses.lib.polyu.edu.hk/handle/200/1209
Abstract: The existence of a sensor for iron homeostasis has been suspected for a long time. The sensor is thought to be a soluble component of the plasma that would signal between different organs and tissues such as the intestine (iron absorption), liver (iron store), bone marrow (iron utilization) and reticuloendothelial (RE) macrophage (iron recycling). Recent studies showed that hepcidin might fulfill this important role. However, the biological roles of this peptide and the associated mechanisms have not been determined. The experiments in this thesis were designed to investigate the effect of hepcidin on iron uptake and release in the rat peritoneal macrophages and the possible mechanisms involved. It was found that the cells treated with hepcidin were significant lower in iron release as well as higher in iron uptake than those treated without hepcidin. Western blot analysis demonstrated that hepcidin has the ability to decrease the expression of the ferroportinl (FPN1) protein and increase the divalent metal transporter 1 (DMT1) and transferrin receptor (TfRl) protein. These indicate that hepcidin regulates iron metabolism in macrophage through the regulation of the iron transporters. To compare the differences of hepcidin regulation in vivo with that in vitro, we used LPS to induce hepcidin expression in rat and examined the iron metabolism changes in the peritoneal macrophages. Our results showed that iron release was decreased at 6 hours after LPS i.p, and the iron uptake was increased at 6 hours after LPS i.p. These data were consistent with changes of the expression of FPN1 and TfRl in vivo. In addition, the regulation of iron uptake and release, and iron transporters (DMT1, TfRl, FPN1, CP and hephaestin (Heph)) expression by hepcidin in heart H9C2 cells were investigated. Hepcidin decreased the iron uptake and release of H9C2 cells through regulating the TfRl and FPN1 expression in these cells. Studies in this thesis also demonstrated the synthesis and distribution of hepcidin in different regions of the rat brain. On the other hand, we studied the role of hepcidin on iron metabolism of C6 glioma cells in vitro. After treating with hepcidin, the iron uptake and release of C6 glioma cells were both decreased when compared to that of the control groups, which had not been treated with hepcidin. Western blot results showed that the levels of DMTl-IRE, TfRl and FPNl were all decreased at the same time.

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