Hepcidin directly inhibits transferrin receptor 1 expression in astrocytes via a cyclic AMP‐protein kinase a pathway

@article{Du2011HepcidinDI,
  title={Hepcidin directly inhibits transferrin receptor 1 expression in astrocytes via a cyclic AMP‐protein kinase a pathway},
  author={Fang Du and Christopher Qian and Zhong Ming Qian and Xiao-mei Wu and Hui-Juan Xie and Wing-Ho Yung and Ya Ke},
  journal={Glia},
  year={2011},
  volume={59}
}
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… 
Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats
TLDR
It is concluded that, under iron-overload, hepcidin functions to reduce iron in the brain by downregulating iron transport proteins.
Regulating ferroportin‐1 and transferrin receptor‐1 expression: A novel function of hydrogen sulfide
TLDR
It is demonstrated that H 2S regulates the expression of TfR1 and Fpn1 in the spleen in vivo and in peritoneal macrophages in vitro predominantly via the IL‐6/pSTAT3/hepcidin pathway, under the conditions of inflammation induced by lipopolysaccharides.
Effects of aspirin on expression of iron transport and storage proteins in BV-2 microglial cells
Norcantharidin down-regulates iron contents in the liver and spleen of lipopolysaccharide-treated mice
TLDR
NCTD affects iron metabolism by modifying the expression of IL-6/JAK2/STAT3/hepcidin and IRP1 and the ability of NCTD to reduce tissue iron contents may be a novel mechanism associated with the anti-cancer effects of NCTd.
Angiotensin II Inhibits Iron Uptake and Release in Cultured Neurons
TLDR
It is demonstrated for the first time that ANGII significantly reduced transferrin-bound iron and non-transferrin bound iron uptake and iron release as well as expression of two major iron uptake proteins transferrin receptor 1 and divalent metal transporter 1 and the key iron exporter ferroportin 1 in cultured neurons.
Hepcidin-to-Ferritin Ratio Is Decreased in Astrocytes With Extracellular Alpha-Synuclein and Iron Exposure
TLDR
It is proposed that the hepcidin-to-ferritin ratio is indicative of a detrimental response in primary cultured astrocytes experiencing iron and extracellular α-syn, and ferritin protein levels were up-regulated or down-regulated with FAC or DFO treatment, respectively.
Interleukin-6 and Lipopolysaccharide Modulate Hepcidin mRNA Expression by Hepg2 Cells
TLDR
The results support the idea that Fe storage and inflammation act together to regulate Fe homeostasis and suggest a negative regulation in this hepatic cellular model to prevent excessive increases in Hpc.
...
...

References

SHOWING 1-10 OF 40 REFERENCES
Role of HIF-1 and NF-κB Transcription Factors in the Modulation of Transferrin Receptor by Inflammatory and Anti-inflammatory Signals*
TLDR
An interplay of the HIF-1 and NF-κB pathways controls TfR1 transcription in inflammation, which may be involved in modulating iron retention in inflammatory macrophages, thus possibly contributing to the development of hypoferremia in the early phases preceding the down-regulation of macrophage ferroportin by hepcidin.
Regulation of iron metabolism in murine J774 macrophages: role of nitric oxide-dependent and -independent pathways following activation with gamma interferon and lipopolysaccharide.
TLDR
It is demonstrated that the effect of IFN-gamma and/or LPS on macrophage iron metabolism is complex, and is not entirely due to either NO-or to IRP-mediated mechanisms.
Effects of Interferon-γ and Lipopolysaccharide on Macrophage Iron Metabolism Are Mediated by Nitric Oxide-induced Degradation of Iron Regulatory Protein 2*
TLDR
The results suggest that NO+-mediated degradation of IRP-2 plays a major role in iron metabolism during inflammation, and inhibitors of inducible nitric oxide synthase are prevented.
Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpression and down-regulated by hepcidin.
TLDR
FPN1 is directly involved in the export of iron during erythrocyte-iron recycling by macrophages, consistent with a role in the recycling of iron from senescent red cells.
Cytokine-mediated regulation of iron transport in human monocytic cells.
TLDR
The results demonstrate that the proinflammatory stimuli IFN-gamma and LPS increase the uptake of NTBI via stimulation of divalent metal transporter-1 expression and cause retention of the metal within monocytes by down-regulating ferroportin synthesis.
Regulation of iron metabolism by hepcidin.
TLDR
The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
Hepcidin inhibits apical iron uptake in intestinal cells.
TLDR
The results indicate that the effect of Hepc is cell dependent: in macrophages it inhibits iron export by inducing ferroportin degradation, whereas in enterocytes it inhibits apical iron uptake by inhibiting DMT1 transcription.
Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice
TLDR
A peculiar phenotype of Usf2−/− mice that progressively develop multivisceral iron overload is reported; plasma iron overcomes transferrin binding capacity, and nontransferrin-bound iron accumulates in various tissues including pancreas and heart.
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
TLDR
It is reported that hepcidin bound to ferroportin in tissue culture cells, leading to decreased export of cellular iron and the posttranslational regulation of ferroports by hePCidin may complete a homeostatic loop.
Inhibition of iron transport across human intestinal epithelial cells by hepcidin.
TLDR
The primary effect of this regulatory peptide is to modulate the apical membrane uptake machinery, thereby controlling the amount of iron absorbed from the diet.
...
...