title: The iron regulatory hormone hepcidin inhibits expression of iron release as well as iron uptake proteins in J774 cells.
abstract: The mechanism by which hepcidin controls cellular iron release protein ferroportin 1 (Fpn1) in macrophages has been well established. However, little is known about the effects of hepcidin on cellular iron uptake proteins. Here, we demonstrated for the first time that hepcidin can significantly inhibit the expression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 in addition to Fpn1, and therefore reduce transferrin-bound iron and non-transferrin-bound iron uptake and also iron release in J774 macrophages. Analysis of mechanisms using the iron-depleted cells showed that hepcidin has a direct inhibitory effect on all iron transport proteins we examined. Further studies demonstrated that the down-regulation of TfR1 induced by hepcidin is associated with cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), probably being mediated by the cAMP-PKA pathway in J774 macrophages.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Fang
authors.initials: F
authors.lastname: Du
authors.forename: Zhong-ming
authors.initials: ZM
authors.lastname: Qian
authors.forename: Qi
authors.initials: Q
authors.lastname: Gong
authors.forename: Zhou Jin
authors.initials: ZJ
authors.lastname: Zhu
authors.forename: Lina
authors.initials: L
authors.lastname: Lu
authors.forename: Ya
authors.initials: Y
authors.lastname: Ke
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D064451:Hepcidins; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D008264:Macrophages / Q000378:metabolism*; D051381:Rats; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D064451:Hepcidins; D007501:Iron; D011990:Receptors, Transferrin; D000099236:Solute Carrier Family 11, Member 2; C578703:Hamp protein, rat; C545564:Tfrc protein, rat