Publikationsdatum:
2009-08-15
Beschreibung:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923557/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923557/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vecchi, Chiara -- Montosi, Giuliana -- Zhang, Kezhong -- Lamberti, Igor -- Duncan, Stephen A -- Kaufman, Randal J -- Pietrangelo, Antonello -- DK42394/DK/NIDDK NIH HHS/ -- HL52173/HL/NHLBI NIH HHS/ -- P01 HL057346/HL/NHLBI NIH HHS/ -- P01 HL057346-11A18575/HL/NHLBI NIH HHS/ -- P01 HL057346-128575/HL/NHLBI NIH HHS/ -- R01 HL052173/HL/NHLBI NIH HHS/ -- R01 HL052173-11/HL/NHLBI NIH HHS/ -- R01 HL052173-12/HL/NHLBI NIH HHS/ -- R01 HL052173-12W1/HL/NHLBI NIH HHS/ -- R01 HL052173-13/HL/NHLBI NIH HHS/ -- R03 MH089782/MH/NIMH NIH HHS/ -- R03 MH089782-02/MH/NIMH NIH HHS/ -- R37 DK042394/DK/NIDDK NIH HHS/ -- R37 DK042394-12/DK/NIDDK NIH HHS/ -- R37 DK042394-12S1/DK/NIDDK NIH HHS/ -- R37 DK042394-13/DK/NIDDK NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2009 Aug 14;325(5942):877-80. doi: 10.1126/science.1176639.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Hemochromatosis, Department of Internal Medicine, University Hospital Policlinico di Modena, Modena, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19679815" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
3T3 Cells
;
Animals
;
Antimicrobial Cationic Peptides/*genetics/*metabolism
;
Cell Line, Tumor
;
Cyclic AMP Response Element-Binding Protein/*metabolism
;
Endoplasmic Reticulum/*physiology
;
Hepcidins
;
Homeostasis
;
Humans
;
Immunity, Innate
;
Iron/blood/*metabolism
;
Liver/metabolism
;
Mice
;
Mice, Knockout
;
Mutation
;
Promoter Regions, Genetic
;
Protein Folding
;
RNA Interference
;
Spleen/metabolism
;
*Stress, Physiological
;
Transcriptional Activation
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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