title: Human hephaestin expression is not limited to enterocytes of the gastrointestinal tract but is also found in the antrum, the enteric nervous system, and pancreatic {beta}-cells.
abstract: Hephaestin (Hp) is a membrane protein with ferroxidase activity that converts Fe(II) to Fe(III) during the absorption of nutritional iron in the gut. Using anti-peptide antibodies to predicted immunogenic regions of rodent Hp, previous immunocytochemical studies in rat, mouse, and human gut tissues localized Hp to the basolateral membranes of the duodenal enterocytes where the Hp was predicted to aid in the transfer of Fe(III) to transferrin in the blood. We used a recombinant soluble form of human Hp to obtain a high-titer polyclonal antibody to Hp. This antibody was used to identify the intracellular location of Hp in human gut tissue. Our immunocytochemical studies confirmed the previous localization of Hp in human enterocytes. However, we also localized Hp to the entire length of the gastrointestinal tract, the antral portion of the stomach, and to the enteric nervous system (both the myenteric and submucous plexi). Hp was also localized to human pancreatic beta-cells. In addition to its expression in the same cells as Hp, ferroportin was also localized to the ductal cells of the exocrine pancreas. The localization of the ferroxidase Hp to the neuronal plexi and the pancreatic beta cells suggests a role for the enzymatic function of Hp in the protection of these specialized cell types from oxidative damage.
authors.affiliation: Centre for Blood Research and Department of Biochemistry, University of British Columbia, Vancouver, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Hudson
authors.forename: Susan B
authors.initials: SB
authors.lastname: Curtis
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Smith
authors.forename: Tanya A M
authors.initials: TA
authors.lastname: Griffiths
authors.forename: Ann Y K
authors.initials: AY
authors.lastname: Wong
authors.forename: Charles H
authors.initials: CH
authors.lastname: Scudamore
authors.forename: Alison M J
authors.initials: AM
authors.lastname: Buchan
authors.forename: Ross T A
authors.initials: RT
authors.lastname: MacGillivray
mesh_terms: D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D002011:Brunner Glands / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002570:Ceruloplasmin / Q000276:immunology; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D017615:Enteric Nervous System / Q000166:cytology / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007082:Ileum / Q000166:cytology / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007583:Jejunum / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009197:Myenteric Plexus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D011706:Pyloric Antrum / Q000166:cytology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013368:Submucous Plexus / Q000166:cytology / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D000906:Antibodies; D027682:Cation Transport Proteins; C492164:HEPH protein, human; D007328:Insulin; D008565:Membrane Proteins; D011994:Recombinant Proteins; D000098742:Ferroportin; D002570:Ceruloplasmin