title: Hepcidin directly inhibits transferrin receptor 1 expression in astrocytes via a cyclic AMP-protein kinase A pathway.
abstract: Hepcidin, an iron-regulatory hormone, plays a central role in iron homeostasis in peripheral tissues. The widespread distribution of hepcidin in the brain implies that the hormone may be essential for brain iron homeostasis. Here, we investigated the effects of hepcidin on the expression of iron uptake proteins, including transferrin receptor 1 (TfR1) and divalent metal transporter1 (DMT1) and the release protein ferroportin1 (Fpn1) in the cultured astrocytes. The effects of hepcidin on iron uptake, including transferrin-bound iron (Tf-Fe) and non-transferrin-bound iron (NTBI), and iron release were also studied. Our results demonstrated that astrocytes, when treated with hepcidin peptide or infected with hepcidin expression adenovirus (ad-hepcidin), showed a significant ability in reducing iron uptake (both Tf-Fe and NTBI), and iron release, which were accompanied by decreased expressions of TfR1, DMT1, and Fpn1. Moreover, we found that the effect of hepcidin in reducing TfR1 expression, which is dependent on the cyclic AMP-protein kinase A pathway, was the primary and dominant event. In conclusion, our results demonstrated that hepcidin controlled iron uptake and release by regulating expression of iron transport proteins. The findings also implied the existence of a novel hepcidin-receptor on the membrane of astrocytes.
authors: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
authors: Fang
authors: F
authors: Du
authors: Christopher
authors: C
authors: Qian
authors: Zhong Ming
authors: ZM
authors: Qian
authors: Xiao-Mei
authors: XM
authors: Wu
authors: Hui
authors: H
authors: Xie
authors: Wing-Ho
authors: WH
authors: Yung
authors: Ya
authors: Y
authors: Ke
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000502:physiology*; D001253:Astrocytes / Q000201:enzymology* / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology / Q000235:genetics; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology*; D064451:Hepcidins; D006706:Homeostasis / Q000235:genetics; D007501:Iron / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; C578703:Hamp protein, rat; D064451:Hepcidins; D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D007501:Iron; D017868:Cyclic AMP-Dependent Protein Kinases