title: Unexpected role of ceruloplasmin in intestinal iron absorption.
abstract: Ferroxidases are essential for normal iron homeostasis in most organisms. The paralogous vertebrate ferroxidases ceruloplasmin (Cp) and hephaestin (Heph) are considered to have nonidentical functions in iron transport: plasma Cp drives iron transport from tissue stores while intestinal Heph facilitates iron absorption from the intestinal lumen. To clarify the function of Cp, we acutely bled Cp-/- mice to stress iron homeostasis pathways. Red cell hemoglobin recovery was defective in stressed Cp-/- mice, consistent with low iron availability. Contrary to expectations, iron was freely released from spleen and liver stores in Cp-/- mice, but intestinal iron absorption was markedly impaired. Phlebotomy of wild-type mice caused a striking shift of Cp from the duodenal epithelium to the underlying lamina propria, suggesting a critical function of Cp in basolateral iron transport. Regulated relocalization of intestinal Cp may represent a fail-safe mechanism in which Cp shares with Heph responsibility for iron absorption under stress.
authors.affiliation: Department of Cell Biology, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Srujana
authors.initials: S
authors.lastname: Cherukuri
authors.forename: Ramesh
authors.initials: R
authors.lastname: Potla
authors.forename: Joydeep
authors.initials: J
authors.lastname: Sarkar
authors.forename: Saul
authors.initials: S
authors.lastname: Nurko
authors.forename: Z Leah
authors.initials: ZL
authors.lastname: Harris
authors.forename: Paul L
authors.initials: PL
authors.lastname: Fox
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D002570:Ceruloplasmin / Q000235:genetics* / Q000378:metabolism*; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007408:Intestinal Absorption; D007501:Iron / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D012333:RNA, Messenger; D014168:Transferrin; D000098742:Ferroportin; D007501:Iron; D002570:Ceruloplasmin