[Show abstract][Hide abstract] ABSTRACT: The mechanism by which hepcidin controls cellular iron release protein ferroportin 1 (Fpn1) in macrophages has been well established. However, little is known about the effects of hepcidin on cellular iron uptake proteins. Here, we demonstrated for the first time that hepcidin can significantly inhibit the expression of transferrin receptor 1 (TfR1) and divalent metal transporter 1 in addition to Fpn1, and therefore reduce transferrin-bound iron and non-transferrin-bound iron uptake and also iron release in J774 macrophages. Analysis of mechanisms using the iron-depleted cells showed that hepcidin has a direct inhibitory effect on all iron transport proteins we examined. Further studies demonstrated that the down-regulation of TfR1 induced by hepcidin is associated with cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), probably being mediated by the cAMP-PKA pathway in J774 macrophages.
No preview · Article · May 2012 · The Journal of nutritional biochemistry
[Show abstract][Hide abstract] ABSTRACT: The mechanisms of neuroprotection induced by hypoxic preconditioning (HP) and the effects of HP on iron metabolism proteins in the brain have not been fully elucidated. Based on the accumulated information, we hypothesized that HP would be able to affect the expression of iron metabolism proteins in the brain and that the changes in the expression of these proteins induced by HP might be partly associated with the HP-induced neuroprotection. Here, we demonstrated for the first time that HP could induce a significant increase in the expression of HIF-1alpha as well as iron uptake (TfR1 and DMT1) and release (Fpn1) proteins and thus increase transferrin-bound iron (Tf-Fe) and non-transferrin-bound iron (NTBI) uptake and iron release, and also a progressive increase in cellular iron content in the cultured neurons. We concluded that HP has the ability to speed iron transport rate and proposed that the increase in iron transport rate and cellular iron in neurons might be one of the mechanisms involved in neuroprotection in the HP neurons. We also demonstrated that Fpn1 expression was significantly affected by HIF-1alpha, implying that the gene encoding this iron efflux protein is hypoxia-inducible.
No preview · Article · Jan 2012 · Neurochemistry International