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|Title:||CONTROL OF IRON EFFLUX FROM CNS GLIA|
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|Authors/Affiliations:||1 Katrin Schulz*; 1 Samuel David; |
1 Center for Research in Neuroscience, The Research Institute of the McGill University Health Center, Montreal, QC, Canada
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|Content:||Iron is essential for many biological processes. However, because of its redox activity, its levels must be tightly regulated. Ferroxidases, which convert toxic ferrous iron into its non-toxic ferric form, are involved in maintaining iron homeostasis. One of these ferroxidases is Hephaestin (Hp), a transmembrane copper-dependent enzyme that is required for the export of iron from intestinal enterocytes into the circulation. Hp is thought to facilitate iron efflux from enterocytes by oxidizing the ferrous iron transported across the cell membrane via the iron exporter ferroportin1 (FPN1). Ceruloplasmin (Cp), a homologue of Hp, is another ferroxidase that plays an important role in maintaining iron homeostasis in the liver. A secreted form of Cp is expressed by the liver, whereas a glycosylphosphatidylinositol (GPI)-anchored form is expressed by astrocytes of the central nervous system (CNS). GPI-Cp has been shown to efflux iron from astrocytes through its interaction with FPN1 and to play a role in iron homeostasis in the CNS. |
Objective: The aim of the study is to analyze the role of Hp in regulating iron homeostasis in the CNS.
Materials and Methods: Expressions of Hp, as well as FPN1, were analyzed in purified primary cell cultures from rat cortex and in spinal cord sections of C57BL/6 mice by double immunofluorescence.
Results: Our findings indicate that Hp is expressed exclusively in oligodendrocytes and microglia, but not in astrocytes or neurons. Furthermore, the expression in oligodendrocytes is restricted to mature but not immature cells. In addition, we show that the iron exporter FPN1 is also expressed in oligodendrocytes and microglia.
Conclusions: The co-expression of Hp and FPN1 in oligodendrocytes and microglia suggests that Hp may play a role in exporting iron from these cells through its interaction with FPN1. Functional studies are currently underway to examine this effect. These data show that different ferroxidases are expressed in different CNS glial cells – ceruloplasmin in astrocytes and hephaestin in oligodendrocytes, while microglia express both. The latter may reflect the important role macrophages play in iron recycling.
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