2017
DOI: 10.3389/fphys.2017.00332
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Hepcidin Protects Neuron from Hemin-Mediated Injury by Reducing Iron

Abstract: Hemin plays a key role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH) and the cell toxicity of hemin is thought to be due to iron that is liberated when hemin is degraded. In a recent study, we demonstrated the iron regulatory hormone hepcidin reduces brain iron in iron-overloaded rats. Therefore, we hypothesized that hepcidin might be able to reduce iron and then protect neurons from hemin or iron-mediated neurotoxicity in hemin-treated neuronal cells. Here, we tested the hypothes… Show more

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Cited by 33 publications
(31 citation statements)
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“…This occurs because during brain inflammation, cytokines, and hepcidin have agonistic effects in suppressing cellular iron efflux ( Urrutia et al, 2013 ; Xiong et al, 2016 ; Zhao Y. et al, 2018 ). In addition, inflammatory signaling overrides the blocking effect of hepcidin on cellular iron uptake which creates an ideal environment that promotes brain iron overload by both, inflammatory signals and hepcidin ( Urrutia et al, 2013 ; Du et al, 2015 ; Gong et al, 2016 ; Xiong et al, 2016 ; Zhou et al, 2017 ; Zhao Y. et al, 2018 ).…”
Section: Role Of Systemic Hepcidin In Brain Homeostasismentioning
confidence: 99%
See 1 more Smart Citation
“…This occurs because during brain inflammation, cytokines, and hepcidin have agonistic effects in suppressing cellular iron efflux ( Urrutia et al, 2013 ; Xiong et al, 2016 ; Zhao Y. et al, 2018 ). In addition, inflammatory signaling overrides the blocking effect of hepcidin on cellular iron uptake which creates an ideal environment that promotes brain iron overload by both, inflammatory signals and hepcidin ( Urrutia et al, 2013 ; Du et al, 2015 ; Gong et al, 2016 ; Xiong et al, 2016 ; Zhou et al, 2017 ; Zhao Y. et al, 2018 ).…”
Section: Role Of Systemic Hepcidin In Brain Homeostasismentioning
confidence: 99%
“…Furthermore, iron dysregulation has been proposed as a pathogenic factor in neurodegenerative diseases as well ( Ward et al, 2014 ). Recent research suggests that brain iron dysmetabolism can be tackled via hepcidin manipulation, since local hepcidin production in the brain has been shown to affect cellular iron transport ( Urrutia et al, 2013 ; Du et al, 2015 ; Gong et al, 2016 ; Xiong et al, 2016 ; Zhou et al, 2017 ). But, it seems that the presence or absence of inflammation dictates the deleterious vs. beneficial effects of hepcidin in the brain.…”
Section: Introductionmentioning
confidence: 99%
“…NIPAM-hemin did not decrease cell viability, even though hemin is known to be toxic to several cell types. 16,17 One of the causes of hemin-induced cytotoxicity is the hydrophobicity of the heme group, which interacts with lipids and leads to peroxidation. 16 NIPAM is soluble and binds to the non-soluble hemin to form a soluble copolymer.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to iron release protein Fpn1, hepcidin was also found to significantly inhibit the expression of iron uptake proteins TfR1 and DMT1 in cultured microvascular endothelial cells, neurons, and astrocytes . The inhibitory effect of hepcidin on iron uptake proteins was also observed in iron‐depleted astrocytes, indicating that the inhibition effect of iron uptake proteins by hepcidin is a direct rather than an indirect effect by the increased cellular iron induced by the hepcidin‐induced reduction in Fpn1.…”
Section: Hepcidin and The Treatment Of Neurodegenerative Disordersmentioning
confidence: 93%