title: Pathways for the regulation of body iron homeostasis in response to experimental iron overload.
abstract: OBJECTIVE
  Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions.
  
  
  METHODS
  To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days.
  
  
  RESULTS
  Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced.
  
  
  CONCLUSIONS
  Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation.
authors.affiliation: Department of General Internal Medicine, Clinical Immunology and Infectious Diseases, Medical University, Anichstr. 35, A-6020 Innsbruck, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Theurl
authors.forename: Susanne
authors.initials: S
authors.lastname: Ludwiczek
authors.forename: Philipp
authors.initials: P
authors.lastname: Eller
authors.forename: Markus
authors.initials: M
authors.lastname: Seifert
authors.forename: Erika
authors.initials: E
authors.lastname: Artner
authors.forename: Peter
authors.initials: P
authors.lastname: Brunner
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
mesh_terms: D000818:Animals; D017931:DNA Primers; D004195:Disease Models, Animal; D018450:Disease Progression; D004386:Duodenum / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification
chemical_list: D017931:DNA Primers; D012313:RNA; D007501:Iron