Hepcidin directly inhibits transferrin receptor 1 expression in astrocytes via a cyclic AMP-protein kinase A pathway.
Glia
; 59(6): 936-45, 2011 Jun.
Article
em En
| MEDLINE
| ID: mdl-21438013
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores da Transferrina
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Transdução de Sinais
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Astrócitos
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Proteínas Quinases Dependentes de AMP Cíclico
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Peptídeos Catiônicos Antimicrobianos
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Ferro
Limite:
Animals
Idioma:
En
Revista:
Glia
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China