title: Control of cellular iron homeostasis by iron-responsive elements in vivo.
abstract: It has recently been proposed that cellular iron homeostasis in mammalian cells is regulated at the post-transcriptional level by the reciprocal control of transferrin receptor and ferritin mRNA expression via an iron-regulatory factor. This iron-regulatory factor has been shown to be a cytoplasmic aconitase which can bind to iron-responsive elements in the corresponding mRNAs with greater or lesser affinity as a function of the iron status of the cell. In the present study, we show that in vivo the affinity of iron-regulatory factor for iron-responsive elements in liver reflects the long-term iron status of the tissue in animal models for iron overloading and iron deficiency, when combined with altered transferrin saturation and serum iron levels. In contrast hepatic iron overload achieved without altering such haematopoeitic indices, had a less pronounced effect. In both spleen and heart, the affinities of iron-regulatory factor changed in parallel with both altered iron status and haematological markers. In brain and duodenum, there were no consistent changes in iron-regulatory-factor activity with iron loading or depletion. Iron-regulatory-factor activity in kidney responded in an as yet unexplained manner.
authors.affiliation: Department of Clinical Biochemistry, King's College Hospital, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Ward
authors.forename: L C
authors.initials: LC
authors.lastname: Kühn
authors.forename: P
authors.initials: P
authors.lastname: Kaldy
authors.forename: A
authors.initials: A
authors.lastname: Florence
authors.forename: T J
authors.initials: TJ
authors.lastname: Peters
authors.forename: R R
authors.initials: RR
authors.lastname: Crichton
mesh_terms: D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D003911:Dextrans; D005296:Ferrous Compounds / Q000378:metabolism; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins; D000075163:Metallocenes; D009942:Organometallic Compounds / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats
chemical_list: D003911:Dextrans; D005296:Ferrous Compounds; D035925:Iron-Regulatory Proteins; D000075163:Metallocenes; D009942:Organometallic Compounds; D016601:RNA-Binding Proteins; D007501:Iron; C004998:ferrocene