title: Limited iron export by hepatocytes contributes to hepatic iron-loading in the Hfe knockout mouse.
abstract: OBJECTIVE
  In hereditary hemochromatosis, iron-loading of hepatocytes is associated with increased iron uptake while little is known about iron release. This study aims to characterise iron release and ferroportin expression by Hfe knockout hepatocytes to determine if they contribute to iron overload in haemochromatosis.
  
  
  METHODS
  Iron release by hepatocytes from Hfe knockout, non-iron-loaded and iron-loaded wild-type mice was measured after incubation with nontransferrin-bound iron as iron-citrate.
  
  
  RESULTS
  Iron release and ferroportin expression by hepatocytes from Hfe knockout, non-iron-loaded and in vivo iron-loaded wild-type mice were similar although, nontransferrin-bound iron uptake was significantly increased in Hfe knockout hepatocytes and decreased in iron-loaded wild-type hepatocytes compared with non-iron-loaded wild-type cells. When expressed as a percentage of total iron uptake, iron release was decreased in Hfe knockout hepatocytes (4.6+/-0.7 versus 13.7+/-1.2%, P<0.0001) and increased in iron-loaded wild-type hepatocytes (29.5+/-0.5 versus 13.5+/-0.7%; P<0.0001) compared with wild-type hepatocytes. In contrast, in vitro iron-loading increased iron release and ferroportin expression by both Hfe knockout and wild-type hepatocytes.
  
  
  CONCLUSIONS
  Hfe knockout hepatocytes accumulate iron as a result of limited iron export and enhanced iron uptake. The correlation between iron release and ferroportin expression suggests that iron export in hepatocytes is mediated by ferroportin.
authors.affiliation: School of Medicine and Pharmacology, Fremantle Hospital, The University of Western Australia, Fremantle, WA 6160, Australia.
authors.forename: Anita C G
authors.initials: AC
authors.lastname: Chua
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Drake
authors.forename: Carly E
authors.initials: CE
authors.lastname: Herbison
authors.forename: John K
authors.initials: JK
authors.lastname: Olynyk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Leedman
authors.forename: Debbie
authors.initials: D
authors.lastname: Trinder
mesh_terms: D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006432:Hemochromatosis / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D007501:Iron / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000098742:Ferroportin; D007501:Iron