Non-transferrin iron uptake by trophoblast cells in culture. Significance of a NADH-dependent ferrireductase

Verrijt, C.E.H.; Kroos, M.J.; Huijskes-Heins, M.I.E.; Eijk, H.G. Van; Dijk, J.P. van

doi:10.1016/s0143-4004(98)91046-3

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…6A). In support of this conclusion, numerous cell types are able to reduce a variety of NTBI ferric chelates in the absence of exogenous reductants (8,10,23). However, strong experimental support for exclusive involvement of "enzyme-mediated" ferrireduction is lacking.…”

Section: Discussionmentioning

confidence: 99%

“…divalent metal transporter, isoform 1 (21)). Although the requirement for ferrireduction in NTBI uptake is clear (9,10,22,23), the mechanism of reduction remains ill-defined. Most models propose a membrane-bound ferrireductase activity (16) in analogy with the plasma membrane ferrireductase activity of yeast (16) and the recently identified endosomal membrane ferrireductase of the transferrinmediated pathway (24).…”

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confidence: 99%

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Non-transferrin Iron Reduction and Uptake Are Regulated by Transmembrane Ascorbate Cycling in K562 Cells

Lane

Lawen

2008

Journal of Biological Chemistry

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K562 erythroleukemia cells import non-transferrin-bound iron (NTBI) by an incompletely understood process that requires initial iron reduction. The mechanism of NTBI ferrireduction remains unknown but probably involves transplasma membrane electron transport. We here provide evidence for a novel mechanism of NTBI reduction and uptake by K562 cells that utilizes transplasma membrane ascorbate cycling. Incubation of cells with dehydroascorbic acid, but not ascorbate, resulted in (i) accumulation of intracellular ascorbate that was blocked by the glucose transporter inhibitor, cytochalasin B, and (ii) subsequent release of micromolar concentrations of ascorbate into the external medium via a route that was sensitive to the anion channel inhibitor, 4,4-diisothiocyanatostilbene-2,2-disulfonate. Ascorbate-deficient control cells demonstrated low levels of ferric citrate reduction. However, incubation of the cells with dehydroascorbic acid resulted in a dose-dependent stimulation of both iron reduction and uptake from radiolabeled [ 55 Fe]ferric citrate. This stimulation was abrogated by ascorbate oxidase treatment, suggesting dependence on direct chemical reduction by ascorbate. These results support a novel model of NTBI reduction and uptake by K562 cells in which uptake is preceded by reduction of iron by extracellular ascorbate, the latter of which is subsequently regenerated by transplasma membrane ascorbate cycling.Iron, the most abundant transition metal in mammalian systems, is required for normal metabolic processes spanning molecular oxygen transport, respiratory electron transfer, DNA synthesis, and drug metabolism (1). The tendency of free ferric iron to form insoluble polynuclear aggregates under physiological conditions is typically counteracted through iron sequestration by both proteinaceous and non-proteinaceous chelators in human plasma (1, 2). In addition to the cellular acquisition of iron by the classic transferrin-dependent pathway (2, 3), uptake of non-transferrin-bound iron (NTBI) 2 is well documented (4 -13). NTBI uptake may be particularly relevant in the face of iron overload diseases such as hereditary hemochromatosis, hypotransferrinemia, and thalassemia (14 -17), in which plasma iron presents in excess of transferrin-binding capacity (18). Under such conditions, NTBI uptake by tissues (e.g. liver, heart, and pancreas (16), but not brain (19)) may serve to "clear" potentially toxic levels of iron from the plasma before damage due to iron-catalyzed oxygen radicals can accumulate (5,15,20). However, such iron scavenging may also contribute to the pathophysiology of iron overload disorders (14, 16).Mechanistically, NTBI uptake depends on (i) iron reduction and (ii) consequent cellular import of ferrous iron (9, 16) by divalent metal ion transporters (e.g. divalent metal transporter, isoform 1 (21)). Although the requirement for ferrireduction in NTBI uptake is clear (9,10,22,23), the mechanism of reduction remains ill-defined. Most models propose a membrane-bound ferrireductase activity (16) i...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Non-transferrin Iron Reduction and Uptake Are Regulated by Transmembrane Ascorbate Cycling in K562 Cells

Lane

Lawen

2008

Journal of Biological Chemistry

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“…Whether one or more other ferric reductases exist remains to be determined. A mammalian iron reductase is also found in the placenta [109]. Thus, the functional linking of an oxidoreductase to an iron transporter is a common theme in iron metabolism.…”

Section: Ferric Reductases and Cellular Iron Uptakementioning

confidence: 99%

Mammalian iron transport

Anderson

Vulpe

2009

Cell. Mol. Life Sci.

257

265

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Iron is essential for basic cellular processes but is toxic when present in excess. Consequently, iron transport into and out of cells is tightly regulated. Most iron is delivered to cells bound to plasma transferrin via a process that involves transferrin receptor 1, divalent metal-ion transporter 1 and several other proteins. Non-transferrin-bound iron can also be taken up efficiently by cells, although the mechanism is poorly understood. Cells can divest themselves of iron via the iron export protein ferroportin in conjunction with an iron oxidase. The linking of an oxidoreductase to a membrane permease is a common theme in membrane iron transport. At the systemic level, iron transport is regulated by the liver-derived peptide hepcidin which acts on ferroportin to control iron release to the plasma.

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“…Another strong reprogramming blocker that we found, especially for iTSC reprogramming, is USF2, a known tumor suppressor and MYC inhibitor 49 . USF2 is a strong regulator of iron metabolism and oxidative stress response 50 , 51 , possibly explaining its stronger effect on iTSC reprogramming (Fig. 6e–h ).…”

Section: Resultsmentioning

confidence: 99%

Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states

Jaber¹,

Radwan²,

Loyfer

et al. 2022

Nat Commun

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Following fertilization, it is only at the 32-64-cell stage when a clear segregation between cells of the inner cell mass and trophectoderm is observed, suggesting a ‘T’-shaped model of specification. Here, we examine whether the acquisition of these two states in vitro, by nuclear reprogramming, share similar dynamics/trajectories. Using a comparative parallel multi-omics analysis (i.e., bulk RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, RRBS and CNVs) on cells undergoing reprogramming to pluripotency and TSC state we show that each reprogramming system exhibits specific trajectories from the onset of the process, suggesting ‘V’-shaped model. We describe in detail the various trajectories toward the two states and illuminate reprogramming stage-specific markers, blockers, facilitators and TSC subpopulations. Finally, we show that while the acquisition of the TSC state involves the silencing of embryonic programs by DNA methylation, during the acquisition of pluripotency these regions are initially defined but retain inactive by the elimination of H3K27ac.

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Non-transferrin iron uptake by trophoblast cells in culture. Significance of a NADH-dependent ferrireductase

Cited by 6 publications

References 27 publications

Non-transferrin Iron Reduction and Uptake Are Regulated by Transmembrane Ascorbate Cycling in K562 Cells

Non-transferrin Iron Reduction and Uptake Are Regulated by Transmembrane Ascorbate Cycling in K562 Cells

Mammalian iron transport

Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states

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