title: Decreased hephaestin expression and activity leads to decreased iron efflux from differentiated Caco2 cells.
abstract: Iron is transported across intestinal brush border cells into the circulation in at least two distinct steps. Iron can enter the enterocyte via the apical surface through several paths. However, iron egress from the basolateral side of enterocytes converges on a single export pathway requiring the iron transporter, ferroportin1, and hephaestin, a ferroxidase. Copper deficiency leads to reduced hephaestin protein expression and activity in mouse enterocytes and intestinal cell lines. We tested the effect of copper deficiency on differentiated Caco2 cells grown in transwells and found decreased hephaestin protein expression and activity as well as reduced ferroportin1 protein levels. Furthermore, the decrease in hephaestin levels correlates with a decrease of (55)Fe release from the basolateral side of Caco2 cells. Presence of ceruloplasmin, apo-transferrin or holo-transferrin did not significantly alter the results observed. Repletion of copper in Caco2 cells leads to reconstitution of hephaestin protein expression, activity, and transepithelial iron transport.
authors.affiliation: Department of Nutritional Science and Toxicology, University of California, Berkeley, 94720-3104, USA. huijunchen@yahoo.com
authors.forename: Huijun
authors.initials: H
authors.lastname: Chen
authors.forename: Zouhair K
authors.initials: ZK
authors.lastname: Attieh
authors.forename: Thi
authors.initials: T
authors.lastname: Dang
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Regine M
authors.initials: RM
authors.lastname: van der Hee
authors.forename: Chris
authors.initials: C
authors.lastname: Vulpe
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000032:analysis; D002454:Cell Differentiation; D003300:Copper / Q000172:deficiency; D020895:Enterocytes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; C492164:HEPH protein, human; D008565:Membrane Proteins; D000098742:Ferroportin; D003300:Copper; D007501:Iron