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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian cellular iron is stored inside the multisubunit protein ferritin, normally taking the structure of a ferrihydrite-like mineral core. It has been suggested that biogenic magnetite, which has been detected in the brain and may be related to neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, could initially form in ferritin. Indeed, as ferritin is present in the brain, the ferrihydrite core could be a precursor for biogenic magnetite formation--particularly in cases where the normal functioning of the ferritin protein is disrupted. In this work, NMR relaxometry was used to detect magnetite inside samples of ferritin extracted from normal and Alzheimer-diseased brains. The method was first calibrated with different fractions of horse spleen ferritin and synthetic magnetite particles. The relaxometry results suggest that the proportion of iron contained in brain ferritin in the form of well-crystallized magnetite instead of ferrihydrite must be <1%, which is much less than that reported for 'magnetite-like' phase in recent transmission electron microscopy studies of similar samples. Consequently, the magnetization of this 'magnetite-like' phase must be very low compared with that of magnetite.
NMR Biomed 2005 Nov
PMID:Looking for biogenic magnetite in brain ferritin using NMR relaxometry. 1617 54

In an attempt to design a targeted drug delivery system to tumors' over-expressing H-ferritin specifically recognized by a monoclonal antibody, AMB8LK, a cationic emulsion - AMB8LK conjugate was prepared. A novel cross-linker molecule bearing maleimide group was synthesized and added to cationic emulsion formulation for AMB8LK Fab' fragment covalent coupling. NMR spectroscopy confirmed the cross-linker synthesis and the preservation of the active maleimide function. SDS gel-electrophoresis results corroborated the formation of the Fab' fragment. Different densities of Fab' fragments (10-200 Fab'/oil droplet) were conjugated to emulsion droplet interface and no changes in the physico-chemical properties were observed ( approximately 120 nm size and zeta potential of approximately +30 mV). The coupling efficiency ranged from 55% to 70% and was visualized by TEM showing gold particles attached to the droplet interface. Cell culture studies demonstrated specific binding to cells as confirmed by the occurrence of the marked reduction in binding when free AMB8LK Mab was incubated before adding the AMB8LK-emulsion conjugate to the cells. The coupling of AMB8LK Fab' fragment to the cationic emulsion increased the cells uptake by 50% as compared to non-conjugated respective cationic emulsion. Appropriate conditions were, thus, identified for coupling AMB8LK Fab' fragment to cationic emulsion without altering the specificity and affinity of the Mab fragment to the tumor antigen.
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PMID:The design and evaluation of a novel targeted drug delivery system using cationic emulsion-antibody conjugates. 1622 21

Ferritin, the iron-storing protein of mammals, is known to darken T2-weighted magnetic resonance images. This darkening can be used to noninvasively measure an organ's iron content. Significant discrepancies exist between T2 data obtained with ferritin-containing tissues and with aqueous solutions of horse spleen ferritin (HSF). The NMR properties of stable human ferritin have never been studied in aqueous solutions. Relaxometry results on human liver and spleen ferritin are reported here, showing that the relaxation induced in aqueous solutions by human ferritins is comparable to that induced by HSF. As a consequence, the differences between ferritin-containing human tissues and ferritin solutions cannot be attributed to different NMR properties of human and horse ferritins, but probably to a clustering of the protein in vivo.
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PMID:Relaxivities of human liver and spleen ferritin. 1637 84

Ferumoxides-protamine sulfate (FE-Pro) complexes are used for intracellular magnetic labeling of cells to non-invasively monitor cell trafficking by in vivo MRI. FE-Pro labeling is non-toxic to cells; however, the effects of FE-Pro labeling on cellular expression of transferrin receptor (TfR-1) and ferritin, proteins involved in iron transport and storage, has not been reported. FE-Pro-labeled human mesenchymal stem cells (MSCs), HeLa cells and primary macrophages were cultured from 1 week to 2 months and evaluated for TfR-1 and ferritin gene expression by RT-PCR and protein levels were determined using Western blots. MTT (proliferation assay) and reactive oxygen species (ROS) analysis were performed. FE-Pro labeling of HeLa and MSCs resulted in a transient decrease in TfR-1 mRNA and protein levels. In contrast, Fe-Pro labeling of primary macrophages resulted in an increase in TfR-1 mRNA but not in TfR-1 protein levels. Ferritin mRNA and protein levels increased transiently in labeled HeLa and macrophages but were sustained in MSCs. No changes in MTT and ROS analysis were noted. In conclusion, FE-Pro labeling elicited physiological changes of iron metabolism or storage, validating the safety of this procedure for cellular tracking by MRI.
NMR Biomed 2006 Aug
PMID:Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging. 1667 57

Ferritin catalyzes the oxidation of Fe2+ by O2 to form a reconstituted Fe3+ oxy-hydroxide mineral core, but extensive studies have shown that the Fe2+ to O2 stoichiometry changes with experimental conditions. At Fe2+ to horse spleen ferritin (HoSF) ratios greater than 200, an upper limit of Fe2+ to O2 of 4 is typically measured, indicating O2 is reduced to 2H2O. In contrast, a lower limit of Fe2+ to O2 of approximately 2 is measured at low Fe2+ to HoSF ratios, implicating H2O2 as a product of Fe2+ deposition. Stoichiometric amounts of H2O2 have not been measured, and H2O2 is proposed to react with an unknown system component. Evidence is presented that identifies this component as amine buffers, including 3-N-morpholinopropanesulfonic acid (MOPS), which is widely used in ferritin studies. In the presence of non-amine buffers, the Fe2+ to O2 stoichiometry was approximately 4.0, but at high concentrations of amine buffers (0.10 M) the Fe2+ to O2 stoichiometry is approximately 2.5 for iron loadings of eight to 30 Fe2+ per HoSF. Decreasing the concentration of amine buffer to zero resulted in an Fe2+ to O2 stoichiometry of approximately 4. Direct evidence for amine buffer modification during Fe2+ deposition was obtained by comparing authentic and modified buffers using mass spectrometry, NMR, and thin layer chromatography. Tris(hydroxymethyl)aminomethane, MOPS, and N-methylmorpholine (a MOPS analog) were all rapidly chemically modified during Fe2+ deposition to form N-oxides. Under identical conditions no modification was detected when amine buffer, H2O2, and O2 were combined with Fe2+ or ferritin separately. Thus, a short-lived ferritin intermediate is required for buffer modification by H2O2. Variation of the Fe2+ to O2 stoichiometry versus the Fe2+ to HoSF ratio and the amine buffer concentration are consistent with buffer modification.
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PMID:Ferritin-catalyzed consumption of hydrogen peroxide by amine buffers causes the variable Fe2+ to O2 stoichiometry of iron deposition in horse spleen ferritin. 1689 7

Ferritin, the iron-storing protein of mammals, is known to darken T(2)-weighted MR images. This darkening could be used for the non-invasive measurement of an organ's iron content. Unexplained discrepancies exist between T(2) data obtained in ferritin-containing tissues and aqueous solutions of ferritin. The clustering of the protein induced by trypsin is used to evaluate the effect of ferritin agglomeration on the relaxation rates. Although the longitudinal relaxation is not significantly influenced by clustering, T(2) depends greatly on the stage of agglomeration: the transverse relaxation rate is higher for a clustered sample than for an unclustered sample. Moreover, the field and inter-echo time dependences of the relaxation rate indicate that the relaxation mechanism may be different between small clusters -- where a linear dependence of 1/T(2) on B(0) is observed -- and large clusters -- where a quadratic dependence is observed. These results help to explain the relaxation induced by ferritin in tissues.
NMR Biomed 2007 Dec
PMID:Relaxation by clustered ferritin: a model for ferritin-induced relaxation in vivo. 1733 Sep 25

MR reporter genes have the potential to monitor transgene expression non-invasively in real time at high resolution. These genes can be applied to interrogate the efficacy of gene therapy, to assess cellular differentiation, cell trafficking, and specific metabolic activity, and also assess changes in the microenvironment. Efforts toward the development of MR reporter genes have been made for at least a decade, but, despite these efforts, the field is still in its early developmental stage. This reflects the fact that there are potential pitfalls, caused by the low sensitivity of detection, the need for substrates with their associated undesirable pharmacokinetics, and/or the difficult and, in some cases, delayed interpretation of signal changes. Nevertheless, significant progress has been made during the last few years. Whereas enzyme-based reporters were initially applied to NMR spectroscopic monitoring of changes in phosphor and fluorine metabolism, MRI-based approaches are now emerging that rely on: (1) enzyme-based cleavage of functional groups that block water (proton) exchange or protein binding of MR contrast agents; (2) expression of surface receptors that enable binding of specific MR contrast agents; (3) expression of para- and anti-ferromagnetic (metallo)proteins involved with iron metabolism, such as tyrosinase, transferrin receptor, and ferritin. After an introduction to the basic principles of designing promoters, expression vectors, and cloning of transgenes, a fresh look is provided on the use of reporter genes for optical (including bioluminescent) and nuclear imaging, with which MR reporter genes compete. Although progress in the use of MR reporter genes has been slow, newer strategies that use metalloproteins or alternative contrast mechanisms, with no need for substrates, promise rapid growth potential for this field.
NMR Biomed 2007 May
PMID:Developing MR reporter genes: promises and pitfalls. 1745 Nov 81

Molecular size has limited solution NMR analyses of proteins. We report (13)C-(13)C NOESY experiments on a 480 kDa protein, the multi-subunit ferritin nanocage with gated pores. By exploiting (13)C-resonance-specific chemical shifts and spin diffusion effects, we identified 75% of the amino acids, with intraresidue C-C connectivities between nuclei separated by 1-4 bonds. These results show the potential of (13)C-(13)C NOESY for solution studies of molecular assemblies >100 kDa.
J Biomol NMR 2007 Jul
PMID:13C- 13C NOESY spectra of a 480 kDa protein: solution NMR of ferritin. 1755 97

We have prepared water-soluble gadolinium oxide nanoparticles that show potential as MRI contrast agents. The particles were built into the apoferritin cavity and have an average size of 5 nm. After seven days a loss of 5% of Gd was detected compared with the as-prepared samples; after that the Gd remained constant and stabilized inside the apoferritin, indicating that the apoferritin capsid acts as a Gd store, avoiding metal delivery and consequent toxicity. The NMR longitudinal and transverse relaxivities resulted about 10 and 70 times higher than the ones of clinically approved paramagnetic Gd-chelates, thus indicating the possible route for synthesizing a novel class of MRI contrast agents.
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PMID:MRI relaxation properties of water-soluble apoferritin-encapsulated gadolinium oxide-hydroxide nanoparticles. 1915 73

Ferritin is a multimeric nanocage protein that directs the reversible biomineralization of iron. At the catalytic ferroxidase site two iron(II) ions react with dioxygen to form diferric species. In order to study the pathway of iron(III) from the ferroxidase site to the central cavity a new NMR strategy was developed to manage the investigation of a system composed of 24 monomers of 20 kDa each. The strategy is based on (13)C-(13)C solution NOESY experiments combined with solid-state proton-driven (13)C-(13)C spin diffusion and 3D coherence transfer experiments. In this way, 75% of amino acids were recognized and 35% sequence-specific assigned. Paramagnetic broadening, induced by iron(III) species in solution (13)C-(13)C NOESY spectra, localized the iron within each subunit and traced the progression to the central cavity. Eight iron ions fill the 20-A-long iron channel from the ferrous/dioxygen oxidoreductase site to the exit into the cavity, inside the four-helix bundle of each subunit, contrasting with short paths in models. Magnetic susceptibility data support the formation of ferric multimers in the iron channels. Multiple iron channel exits are near enough to facilitate high concentration of iron that can mineralize in the ferritin cavity, illustrating advantages of the multisubunit cage structure.
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PMID:NMR reveals pathway for ferric mineral precursors to the central cavity of ferritin. 2001 46


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