title: Effects of hyperoxia and iron on iron regulatory protein-1 activity and the ferritin synthesis in mouse peritoneal macrophages.
abstract: Ferritin is an intracellular iron storage protein and its translation is inhibited by binding of iron regulatory proteins (IRPs) to the iron-responsive element (IRE) located in the 5' untranslated region of its mRNA. In this paper, we have investigated the effect of hyperoxia and iron on the binding activity of IRP-1 and the ferritin synthesis in mouse peritoneal macrophages. The binding activity of IRP-1 was increased and the ferritin synthesis was suppressed when the macrophages were cultured under hyperoxia, and the reverse occurred under hypoxia. Iron diminished the IRP-1-binding activity and the enhanced synthesis of ferritin. However, this effect was arrested under hyperoxia. Consistently, hypoxia-induced loss of binding activity of IRP-1 and the enhanced synthesis of ferritin were blocked in the presence of an iron chelator deferoxamine. These alterations of the binding activity of IRP-1 in response to oxygen and iron were not reproduced in the cell-free extract. The data suggest that in the macrophages oxygen and iron inversely act on the binding activity of IRP-1 and the ferritin synthesis, and that intracellular mechanism(s) to sense iron and/or oxygen is required for these actions.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Tsukuba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kuriyama-Matsumura
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Bannai
mesh_terms: D000818:Animals; D005260:Female; D005293:Ferritins / Q000096:biosynthesis*; D018496:Hyperoxia / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D005293:Ferritins; D007501:Iron; D035941:Iron Regulatory Protein 1