Physiological implications of mammalian ferritin-binding proteins interacting with circulating ferritin and a new aspect of ferritin- and zinc-binding proteins

Orino, Koichi

doi:10.1007/s10534-015-9897-x

Cited by 14 publications

(15 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study suggests that IgG and fibrinogen interact with each other and/or bind zinc ions with different mechanisms. Zinc ions are taken up intracellularly by transporters but may also be indirectly taken up by receptors for zinc-binding proteins [22]. Further research is required to elucidate how important variables such as body condition, aging, species specificity and various zinc-binding proteins affect zinc availability.…”

Section: Resultsmentioning

confidence: 99%

Binding Analysis of Human Immunoglobulin G as a Zinc-Binding Protein

et al. 2016

Self Cite

View full text Add to dashboard Cite

Human immunoglobulin G (IgG) binding with zinc ions was examined using zinc ions immobilized on chelating Sepharose beads (Zn-beads). Human IgG bound to Zn-beads but not to Sepharose beads (control beads). Mouse, rat, bovine and equine IgGs also bound to Zn-beads, similar to human IgG. The human IgG F(c) fragment showed zinc ion–binding activity whereas the Fab fragment did not. Ethylenediaminetetraacetic acid (EDTA)-treated Zn-beads no longer bound human IgG; however, washing the beads, followed by the addition of zinc ions, restored the binding activity towards human IgG. Zn-beads saturated with human fibrinogen could bind human IgG, and Zn-beads saturated with human IgG could bind fibrinogen. These results suggest that animal IgGs, including human, specifically bind zinc ions, probably through a zinc-binding site in the F(c) fragment and not in the Fab fragment. In addition, IgG and fibrinogen interact with each other and/or bind zinc ions through different mechanisms.

show abstract

Section: Resultsmentioning

confidence: 99%

Binding Analysis of Human Immunoglobulin G as a Zinc-Binding Protein

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, further study needs to clarify the effect of PPIX-binding IgG on the antibody-antigen reaction due to the different affinities of antibodies to their respective antigen. In humans, fibrinogen and albumin are also known as a PPIX and/or heme-binding protein in addition to IgG [16], and these proteins may play a protective role against oxidative stress caused by PPIX itself and/or iron as radical scavenger [15,16]. On the other hand, albumin shows stronger binding to PPIX than IgG [8].…”

Section: Resultsmentioning

confidence: 99%

Binding of Immunoglobulin G to Protoporphyrin IX and Its Derivatives: Evidence the Fab Domain Recognizes the Protoporphyrin Ring

Orino

2019

Antibodies

Self Cite

View full text Add to dashboard Cite

Immunoglobulin G (IgG) is known to bind zinc via the Fc domain. In this study, biotinylated protoporphyrin IX (PPIX) was incubated with human IgG and then zinc-immobilized Sepharose beads (Zn-beads) were added to the mixture. After washing the beads, the binding of biotinylated PPIX with IgG trapped on Zn-beads was detected using alkaline phosphatase (ALP)-labeled avidin. Human IgG and its Fab domain coated on microtiter plate wells recognized biotin-labeled PPIX and its derivatives, Fe-PPIX and Zn-PPIX, whereas the Fc domain showed some extent of reaction only with Zn-PPIX. When rabbit anti-bovine transferrin (Tf) antibodies were incubated with biotinylated PPIX, the binding of anti-Tf antibodies with apo-Tf was indirectly detected using ALP-labeled avidin, suggesting that even if the antibody is modified with PPIX, the antibody-antigen reaction occurs. These results suggest that the IgG Fab domain recognizes PPIX and its derivatives, probably via the recognition of the PPIX ring. It is unlikely that binding between the Fab domain and PPIX affects the Fc domain-zinc interaction or antigen-antibody reaction.

show abstract

“…First, stabilin-1 may have a role as a scavenger receptor for serum ferritin at the surface of macrophages and/or liver sinusoidal endothelial cells. There is general agreement that cells uptake ferritin through two routes: direct uptake by ferritin receptors and indirect uptake by ferritin-binding proteins 14 . It was shown that SCARA5, which belongs to scavenger receptor class A, mediates the uptake of ferritin iron in specific cell types in the developing kidney in mice 16 , and that SCARA5-transfected cells can bind or internalize human L-ferritin and H-ferritin 35 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, tissue of origin, secretory pathway, receptor interactions, clearance, and functions remain topics of active debate [11][12][13] . It has been hypothesized that ferritin clearance occurs through two different routes: direct uptake by specific ferritin receptors and indirect uptake by ferritin-binding proteins 14 . So far, studies have led to the identification of ferritin receptors such as TIM2, SCARA5, and TFR1 [15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

BiallelicSTAB1pathogenic variants cause hereditary hyperferritinemia

Monfrini

Pelucchi

Hollmén

et al. 2022

Preprint

View full text Add to dashboard Cite

Serum ferritin measurement is a routine laboratory test to indirectly evaluate body iron content. However, many additional factors may elevate serum ferritin levels disproportionally to iron stores. Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. Despite the long history of clinical use, fundamental aspects of the biology of serum ferritin are still unclear. We studied eleven healthy subjects from eight different families presenting unexplained hyperferritinemia without iron overload. To detect the genetic cause of hyperferritinemia we carried out whole-exome sequencing. Immunohistochemistry and flow cytometry assays were performed on patient liver biopsies and monocyte-macrophages to confirm the pathogenic role of the identified candidate variants. Through a combined approach of whole-exome sequencing and homozygosity mapping, we found biallelic candidate STAB1 variants in ten subjects from seven families. STAB1 encodes the multifunctional scavenger receptor stabilin-1. Immunohistochemical studies and flow cytometry analyses showed absent or markedly reduced stabilin-1 in patient liver samples, monocytes and monocyte-derived macrophages. We present biallelic STAB1 mutations as a new cause of inherited hyperferritinemia without iron overload suggesting the existence of new and unexpected function of stabilin-1 in ferritin metabolism. In conclusion, our findings strongly support biallelic STAB1 mutations as a novel genetic cause of inherited hyperferritinemia without iron overload and suggest the existence of a new and unexpected function of stabilin-1 in ferritin metabolism.

show abstract

Physiological implications of mammalian ferritin-binding proteins interacting with circulating ferritin and a new aspect of ferritin- and zinc-binding proteins

Cited by 14 publications

References 66 publications

Binding Analysis of Human Immunoglobulin G as a Zinc-Binding Protein

Binding Analysis of Human Immunoglobulin G as a Zinc-Binding Protein

Binding of Immunoglobulin G to Protoporphyrin IX and Its Derivatives: Evidence the Fab Domain Recognizes the Protoporphyrin Ring

BiallelicSTAB1pathogenic variants cause hereditary hyperferritinemia

Contact Info

Product

Resources

About