ER stress controls iron metabolism through induction of hepcidin.
Science
; 325(5942): 877-80, 2009 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-19679815
ABSTRACT
Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin overproduction causes anemia of inflammation, whereas its deficiency leads to hemochromatosis. Inflammation and iron are known extracellular stimuli for hepcidin expression. We found that endoplasmic reticulum (ER) stress also induces hepcidin expression and causes hypoferremia and spleen iron sequestration in mice. CREBH (cyclic AMP response element-binding protein H), an ER stress-activated transcription factor, binds to and transactivates the hepcidin promoter. Hepcidin induction in response to exogenously administered toxins or accumulation of unfolded protein in the ER is defective in CREBH knockout mice, indicating a role for CREBH in ER stress-regulated hepcidin expression. The regulation of hepcidin by ER stress links the intracellular response involved in protein quality control to innate immunity and iron homeostasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
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Peptídeos Catiônicos Antimicrobianos
/
Retículo Endoplasmático
/
Ferro
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Itália