Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE‐expressing cells*

Roy, Cindy N.; Blemings, Kenneth P.; Deck, Kathryn M.; Davies, Paige S.; Anderson, Emily L.; Eisenstein, Richard S.; Enns, Caroline A.

doi:10.1002/jcp.10056

Cited by 34 publications

(26 citation statements)

References 52 publications

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“…49 It should be noted that this is the first study to report the effect of CS on IRP binding activity, and our results are consistent with existing data from cell culture studies, which showed a decline in IRP binding activity in the presence of an expanded LIP. [52][53][54] Given the decline in IRP activity during CS, ferritin synthesis increases in response to the expanded LIP and the lack of binding of IRP to ferritin mRNA. Our data are consistent with the notion that in the presence of an expanded LIP and decreased IRP binding, a corresponding induction of ferritin protein should occur.…”

Section: Discussionmentioning

confidence: 99%

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

Wyllie¹

2003

Liver Transplantation

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Very little is known about iron metabolism and the mediators of iron metabolism in liver subjected to cold storage before transplantation. Therefore, in this study, we investigated the effect of cold storage on iron homeostasis in the rat liver. When livers were stored at 4°C in University of Wisconsin solution for up to 6 and 24 hours, significant increases occurred in the labile iron pool, ferritin protein, and heme oxygenase activity. Significant decreases in heme content and iron regulatory protein 1 and 2 binding activities occurred by 24 hours. Liver injury indicated by significant increases in University of Wisconsin solution transaminase activity and liver lipid hydroperoxide levels occurred by 6 and 24 hours. Taken together, these results suggest that during pretransplantation cold storage of the liver, an aberrant iron homeostasis develops that contributes to preservation injury, and predisposes the liver to reperfusion injury by iron-dependent reactive oxygen species/Fenton reaction. (Liver Transpl 2003;9:401-410.)

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Section: Discussionmentioning

confidence: 99%

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

Wyllie¹

2003

Liver Transplantation

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“…TfR protein, whose expression is regulated by an IRE, is expressed on the membranes of cells and binds extracellular iron for transport into the cell. 40 When intracellular levels of iron increase, the IRE/IRP system decreases expression of TfR protein on the membrane of the cells to reduce transport of iron into cells. TfR levels thus respond to the iron level in cells.…”

Section: Measurement Of Intracellular Transferrin Receptor (Tfr) Exprmentioning

confidence: 99%

The contributions of metal impurities and tube structure to the toxicity of carbon nanotube materials

et al. 2012

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Due to the existence of considerable quantities of metallic and carbonaceous impurities, the key factor and mechanism for the reported toxicity of carbon nanotubes (CNTs) are unclear. Here, we first quantify the contribution of metal residues and fiber structure to the toxicity of CNTs. Significant quantities of metal particles could be mobilized from CNTs into surrounding fluids, depending on the properties and constituents of the biological microenvironment, as well as the properties of metal particles. Furthermore, electron spin resonance measurements confirm that hydroxyl radicals can be generated by both CNTs containing metal impurities and acid-leachable metals from CNTs. Several biomolecules facilitate the generation of free radicals, which might be due to the participation of these biomolecules in redox cycling influenced by pH. Among several major metal residues, Fe has a critical role in generating hydroxyl radicals, reducing cell viability and promoting intracellular reactive oxidative species. Cell viability is highly dependent on the amount of metal residues and iron in particular, but not tube structure, while the negative effect of CNTs themselves on cell viability is very limited in a certain concentration range below 80 lg ml À1 . It is crucial to systematically understand how these exogenous and endogenous factors influence the toxicity of CNTs to avoid their undesirable toxicity. Keywords: biological microenvironments; carbon nanotube; metal impurities; reactive oxygen species; toxicity INTRODUCTION Engineered nanomaterials possess novel properties and have been used worldwide in numerous consumer products, for example, food, clothes, pharmaceuticals and cleaning products. Estimates suggest that by 2015 nanotechnology will have a trillion-plus dollar global economic impact. 1 Therefore, ensuring the safety of nanomaterials is of great importance to the tremendous commercial applications of nanotechnology. Safety evaluation of nanomaterials should consider their behaviors in various aspects, including their interaction with proteins, DNA, lipids, membranes, organelles, cells, tissues, biological fluids and even the dissolution of metal constituents. [2][3][4] Carbon nanotubes (CNTs) have attracted great interest from both scientists and the industry because their high aspect ratios, strength and remarkable physical properties make them a unique material with a wide range of promising applications. Many applications of CNTs in biomedicine have been proposed, including nanoelectronics, 4 biosensors, 5 biomolecular recognition devices and molecular transporters, 6 artificial water channels, 7 cancer therapy 8,9 and photoacoustic molecular imaging. 10 Because transitional metals are often used as catalysts during CNT synthesis, 11 it is unavoidable that as-received CNTs are contaminated by catalyst residues. 12 The catalyst precursor (such as iron carbonyl) decomposes, and nanometer-sized metal particles form from the decomposition products. Therefore,

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“…Intracellular Fe levels regulate the binding of IRP1 and IRP2 to the IREs via different mechanisms [for reviews see 54 and 55]. It is generally accepted that IRPs are regulated by the concentration of Fe in the LIP [56][57][58][59]. High cellular Fe levels result in the synthesis of a [4Fe-4S] cluster in IRP1, with the loss of IRE-binding activity.…”

Section: Cellular Fe Metabolism In Health and Diseasementioning

confidence: 99%

“…Additionally, this chelator has very poor chelation efficacy in vitro, and its ability to cause significant 59 Fe efflux from prelabelled cells is highly dependent on both time and concentration [5]. In addition, in terms of preventing 59 Fe uptake from transferrin by cells, DFO also only shows significant activity after long incubations [5].…”

Section: Iron Chelators For Treatment Of Iron-loading Disorders 51 mentioning

confidence: 99%

Iron chelators for the treatment of iron overload disease: Relationship between structure, redox activity, and toxicity

Chaston¹,

Richardson²

2003

American J Hematol

152

120

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The success of the iron (Fe) chelator desferrioxamine (DFO) in the treatment of ␤-thalassemia is limited by its lack of bioavailability. The design and characterization of synthetic alternatives to DFO has attracted much scientific interest and has led to the discovery of orally active chelators that can remove pathological Fe deposits. However, chelators that access intracellular Fe pools can be toxic by either inhibiting Fe-containing enzymes or promoting Fe-mediated free radical damage. Interestingly, toxicity does not necessarily correlate with Fe-binding affinity or with chelation efficacy, suggesting that other factors may promote the cytopathic effects of chelators. In this review, we discuss the interactions of chelators and their Fe complexes with biomolecules that can lead to toxicity and tissue damage. Am.

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Increased IRP1 and IRP2 RNA binding activity accompanies a reduction of the labile iron pool in HFE‐expressing cells*

Cited by 34 publications

References 52 publications

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

Deregulation of iron homeostasis and cold-preservation injury to rat liver stored in University of Wisconsin solution

The contributions of metal impurities and tube structure to the toxicity of carbon nanotube materials

Iron chelators for the treatment of iron overload disease: Relationship between structure, redox activity, and toxicity

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