title: Lack of Plasma Protein Hemopexin Results in Increased Duodenal Iron Uptake.
abstract: The body concentration of iron is regulated by a fine equilibrium between absorption and losses of iron. Iron can be absorbed from diet as inorganic iron or as heme. Hemopexin is an acute phase protein that limits iron access to microorganisms. Moreover, it is the plasma protein with the highest binding affinity for heme and thus it mediates heme-iron recycling. Considering its involvement in iron homeostasis, it was postulated that hemopexin may play a role in the physiological absorption of inorganic iron.
  
  
  
  Hemopexin-null mice showed elevated iron deposits in enterocytes, associated with higher duodenal H-Ferritin levels and a significant increase in duodenal expression and activity of heme oxygenase. The expression of heme-iron and inorganic iron transporters was normal. The rate of iron absorption was assessed by measuring the amount of (57)Fe retained in tissues from hemopexin-null and wild-type animals after administration of an oral dose of (57)FeSO4 or of (57)Fe-labelled heme. Higher iron retention in the duodenum of hemopexin-null mice was observed as compared with normal mice. Conversely, iron transfer from enterocytes to liver and bone marrow was unaffected in hemopexin-null mice.
  
  
  
  The increased iron level in hemopexin-null duodenum can be accounted for by an increased iron uptake by enterocytes and storage in ferritins. These data indicate that the lack of hemopexin under physiological conditions leads to an enhanced duodenal iron uptake thus providing new insights to our understanding of body iron homeostasis.
authors.affiliation: Molecular Biotechnology Center, University of Torino, Torino, Italy ; Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Fiorito
authors.forename: Simonetta
authors.initials: S
authors.lastname: Geninatti Crich
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Silengo
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Fiorella
authors.initials: F
authors.lastname: Altruda
authors.forename: Emanuela
authors.initials: E
authors.lastname: Tolosano
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006466:Hemopexin / Q000172:deficiency* / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D007503:Iron Isotopes; D008099:Liver / Q000378:metabolism; D057507:Mice, 129 Strain; D018345:Mice, Knockout
chemical_list: D007503:Iron Isotopes; D006418:Heme; D001052:Apoferritins; D006466:Hemopexin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)