title: Duodenal cytochrome b and hephaestin expression in patients with iron deficiency and hemochromatosis.
abstract: OBJECTIVE
  An increased duodenal expression of the iron transporters, divalent-metal-transporter-1, and ferroportin is observed in patients with iron deficiency or hereditary hemochromatosis. Two oxidoreductases, termed duodenal cytochrome b and hephaestin, are proposed to co-operate with divalent-metal-transporter-1 and FPN1, respectively, to transfer iron from the duodenal lumen to the circulation.
  
  
  METHODS
  In the present study, we investigated the mRNA and protein expression of Dcytb and hephaestin in duodenal biopsies from patients with iron deficiency, HFE, and non-HFE-associated hemochromatosis and in control subjects by means of real-time polymerase chain reaction, Western blot, and immunofluorescence.
  
  
  RESULTS
  In iron deficiency a coordinated upregulation of the iron transporters divalent-metal-transporter-1 and ferroportin and of duodenal-cytochrome b and hephaestin was found, whereas in patients with HFE and non-HFE-associated hemochromatosis duodenal-cytochrome b and hephaestin protein and mRNA expression were not significantly different from control subjects. However, HFE but not non-HFE hemochromatosis patients presented with an increased duodenal ferric reductase activity. Spearman rank correlations showed that Dcytb, hephaestin, FPN1, and DMT1 mRNA expression are positively related to each other independently of the underlying disease, which ensures an efficient transepithelial transport of absorbed iron.
  
  
  CONCLUSIONS
  Our data show that duodenal-cytochrome b activity in iron deficiency is stimulated via enhanced protein expression, whereas in HFE hemochromatosis it is up-regulated post-translationally. This points to different kinetics of intestinal iron uptake between iron deficiency and HFE hemochromatosis and also indicates that duodenal iron accumulation in HFE and non-HFE hemochromatosis is pathophysiologically different.
authors.affiliation: Department of Medicine, University Hospital of Innsbruck, Innsbruck, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Zoller
authors.forename: Igor
authors.initials: I
authors.lastname: Theurl
authors.forename: Robert O
authors.initials: RO
authors.lastname: Koch
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McKie
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogel
authors.forename: Gü
authors.initials: G
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D003573:Cytochrome b Group / Q000032:analysis / Q000235:genetics*; D004386:Duodenum / Q000378:metabolism*; D038181:FMN Reductase / Q000378:metabolism; D005260:Female; D006432:Hemochromatosis / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000235:genetics
chemical_list: D003573:Cytochrome b Group; C492164:HEPH protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D007501:Iron; D038181:FMN Reductase; C023903:ferric citrate iron reductase