Journal articles: 'Human ferritin'

1

Ghosh, Sharmistha, Sarah Hevi, and Steven L. Chuck. "Regulated secretion of glycosylated human ferritin from hepatocytes." Blood 103, no. 6 (March 15, 2004): 2369–76. http://dx.doi.org/10.1182/blood-2003-09-3050.

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Abstract Serum ferritin has been used widely in clinical medicine chiefly as an indicator of iron stores and inflammation. Circulating ferritin also can have paracrine effects. Despite the clinical significance of serum ferritin, its secretion remains an enigma. The consensus view is that serum ferritin arises from tissue ferritins— principally ferritin light—which can be glycosylated. Ferritin heavy and light chains are cytosolic proteins that form cages of 24 subunits to store intracellular iron. We show that ferritin light is secreted when its expression is increased in stable, transfected HepG2 cells or adenovirus-infected HepG2 cells. Export occurs through the classical secretory pathway and some chains are N-glycosylated. Ferritins do not need to form cages prior to secretion. Secretion is blocked specifically, effectively, and rapidly by a factor in serum. The timing of this inhibition of ferritin secretion suggests that normally cytosolic ferritin L is targeted to the secretory pathway during translation despite the absence of a conventional signal sequence. Thus, secretion of glycosylated and unglycosylated ferritin is a regulated and not a stochastic process.

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CORSI, Barbara, Federica PERRONE, Monique BOURGEOIS, Carole BEAUMONT, C. Maria PANZERI, Anna COZZI, Romina SANGREGORIO, et al. "Transient overexpression of human H- and L-ferritin chains in COS cells." Biochemical Journal 330, no. 1 (February 15, 1998): 315–20. http://dx.doi.org/10.1042/bj3300315.

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The understanding of the in vitro mechanisms of ferritin iron incorporation has greatly increased in recent years with the studies of recombinant and mutant ferritins. However, little is known about how this protein functions in vivo, mainly because of the lack of cellular models in which ferritin expression can be modulated independently from iron. To this aim, primate fibroblastoid COS-7 cells were transiently transfected with cDNAs for human ferritin H- and L-chains under simian virus 40 promoter and analysed within 66 h. Ferritin accumulation reached levels 300-500-fold higher than background, with about 40% of the cells being transfected. Thus ferritin concentration in individual cells was increased up to 1000-fold over controls with no evident signs of toxicity. The exogenous ferritin subunits were correctly assembled into homopolymers, but did not affect either the size or the subunit composition of the endogenous heteropolymeric fraction of ferritin, which remained essentially unchanged in the transfected and non-transfected cells. After 18 h of incubation with [59Fe]ferric-nitrilotriacetate, cellular iron incorporation was similar in the transfected and non-transfected cells and most of the protein-bound radioactivity was associated with ferritin heteropolymers, while H- and L-homopolymers remained iron-free. Cell co-transfection with cDNAs for H- and L-chains produced ferritin heteropolymers that also did not increase cellular iron incorporation. It is concluded that transient transfection of COS cells induces a high level of expression of ferritin subunits that do not co-assemble with the endogenous ferritins and have no evident activity in iron incorporation/metabolism.

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Lobreaux, S., S. J. Yewdall, J. F. Briat, and P. M. Harrison. "Amino-acid sequence and predicted three-dimensional structure of pea seed (Pisum sativum) ferritin." Biochemical Journal 288, no. 3 (December 15, 1992): 931–39. http://dx.doi.org/10.1042/bj2880931.

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The iron storage protein, ferritin, is widely distributed in the living kingdom. Here the complete cDNA and derived amino-acid sequence of pea seed ferritin are described, together with its predicted secondary structure, namely a four-helix-bundle fold similar to those of mammalian ferritins, with a fifth short helix at the C-terminus. An N-terminal extension of 71 residues contains a transit peptide (first 47 residues) responsible for plastid targetting as in other plant ferritins, and this is cleaved before assembly. The second part of the extension (24 residues) belongs to the mature subunit; it is cleaved during germination. The amino-acid sequence of pea seed ferritin is aligned with those of other ferritins (49% amino-acid identity with H-chains and 40% with L-chains of human liver ferritin in the aligned region). A three-dimensional model has been constructed by fitting the aligned sequence to the coordinates of human H-chains, with appropriate modifications. A folded conformation with an 11-residue helix is predicted for the N-terminal extension. As in mammalian ferritins, 24 subunits assemble into a hollow shell. In pea seed ferritin, its N-terminal extension is exposed on the outside surface of the shell. Within each pea subunit is a ferroxidase centre resembling those of human ferritin H-chains except for a replacement of Glu-62 by His. The channel at the 4-fold-symmetry axes defined by E-helices, is predicted to be hydrophilic in plant ferritins, whereas it is hydrophobic in mammalian ferritins.

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Ebrahimi, Kourosh Honarmand, Eckhard Bill, Peter-Leon Hagedoorn, and Wilfred R. Hagen. "Spectroscopic evidence for the role of a site of the di-iron catalytic center of ferritins in tuning the kinetics of Fe(ii) oxidation." Molecular BioSystems 12, no. 12 (2016): 3576–88. http://dx.doi.org/10.1039/c6mb00235h.

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Spectroscopic studies of human H-type ferritin in comparison with an archaeal ferritin from Pyrococcus furiosus reveal how kinetics of a common mechanism of Fe(ii) oxidation is tuned differently in these two ferritins.

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Pozzi, Cecilia, Flavio Di Pisa, Caterina Bernacchioni, Silvia Ciambellotti, Paola Turano, and Stefano Mangani. "Iron binding to human heavy-chain ferritin." Acta Crystallographica Section D Biological Crystallography 71, no. 9 (August 25, 2015): 1909–20. http://dx.doi.org/10.1107/s1399004715013073.

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Maxi-ferritins are ubiquitous iron-storage proteins with a common cage architecture made up of 24 identical subunits of five α-helices that drive iron biomineralization through catalytic iron(II) oxidation occurring at oxidoreductase sites (OS). Structures of iron-bound human H ferritin were solved at high resolution by freezing ferritin crystals at different time intervals after exposure to a ferrous salt. Multiple binding sites were identified that define the iron path from the entry ion channels to the oxidoreductase sites. Similar data are available for another vertebrate ferritin: the M protein fromRana catesbeiana. A comparative analysis of the iron sites in the two proteins identifies new reaction intermediates and underlines clear differences in the pattern of ligands that define the additional iron sites that precede the oxidoreductase binding sites along this path. Stopped-flow kinetics assays revealed that human H ferritin has different levels of activity compared with itsR. catesbeianacounterpart. The role of the different pattern of transient iron-binding sites in the OS is discussed with respect to the observed differences in activity across the species.

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6

Fargion, S., AL Fracanzani, B. Brando, P. Arosio, S. Levi, and G. Fiorelli. "Specific binding sites for H-ferritin on human lymphocytes: modulation during cellular proliferation and potential implication in cell growth control." Blood 78, no. 4 (August 15, 1991): 1056–61. http://dx.doi.org/10.1182/blood.v78.4.1056.1056.

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Abstract Interactions between human recombinant H- and L-ferritins and human lymphocytes were studied in vitro by direct binding assays and by flow cytometry. L-ferritin did not cause detectable specific binding, whereas H-ferritin showed a specific and saturable binding that increased markedly in phytohemagglutinin (PHA)-stimulated cells. This ferritin bound up to 30% of CD4+ and CD8+ T-lymphocytes and most B cells, indicating that expression of ferritin binding sites is not related to cell lineage or function. Dual-color flow cytometry experiments showed that ferritin binding sites were present on cells expressing the proliferation markers HLA-DR, MLR3, interleukin 2 (IL- 2), and transferrin receptors (Tf-R). In addition, after PHA induction, the time course of the expression of H-ferritin binding sites was similar to those of the above proliferation markers. Ferritin binding sites were observed in lymphocytes at all cell cycle phases, including the early S-phase. H-Ferritin at nanomolar and picomolar concentrations had an inhibitory effect on PHA-induced blastogenesis. We propose that H-ferritin binding sites behave like proliferation markers, with the unusual function of downregulating proliferation.

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Fargion, S., AL Fracanzani, B. Brando, P. Arosio, S. Levi, and G. Fiorelli. "Specific binding sites for H-ferritin on human lymphocytes: modulation during cellular proliferation and potential implication in cell growth control." Blood 78, no. 4 (August 15, 1991): 1056–61. http://dx.doi.org/10.1182/blood.v78.4.1056.bloodjournal7841056.

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Interactions between human recombinant H- and L-ferritins and human lymphocytes were studied in vitro by direct binding assays and by flow cytometry. L-ferritin did not cause detectable specific binding, whereas H-ferritin showed a specific and saturable binding that increased markedly in phytohemagglutinin (PHA)-stimulated cells. This ferritin bound up to 30% of CD4+ and CD8+ T-lymphocytes and most B cells, indicating that expression of ferritin binding sites is not related to cell lineage or function. Dual-color flow cytometry experiments showed that ferritin binding sites were present on cells expressing the proliferation markers HLA-DR, MLR3, interleukin 2 (IL- 2), and transferrin receptors (Tf-R). In addition, after PHA induction, the time course of the expression of H-ferritin binding sites was similar to those of the above proliferation markers. Ferritin binding sites were observed in lymphocytes at all cell cycle phases, including the early S-phase. H-Ferritin at nanomolar and picomolar concentrations had an inhibitory effect on PHA-induced blastogenesis. We propose that H-ferritin binding sites behave like proliferation markers, with the unusual function of downregulating proliferation.

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8

Morikawa, K., F. Oseko, and S. Morikawa. "H- and L-rich ferritins suppress antibody production, but not proliferation, of human B lymphocytes in vitro." Blood 83, no. 3 (February 1, 1994): 737–43. http://dx.doi.org/10.1182/blood.v83.3.737.737.

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Abstract The effect of human spleen(L-rich) and heart(H-rich) ferritins on the proliferation and differentiation of human B lymphocytes was studied in comparison with that of holo- and apo-transferrins. Ferritins rich in H and L chain, as well as the transferrins, did not inhibit the proliferative response of resting and activated B cells stimulated with polyclonal B-cell mitogen, Staphylococcus aureus Cowan strain I. In contrast, the ferritins, but not the transferrins, clearly suppressed the antibody production by B blasts in T-cell-independent as well as T- cell-dependent system. Kinetic study showed that inhibitory action of ferritins on immunoglobulin (Ig) production was caused at an early stage of B-cell differentiation. The cytoplasmic Ig-containing cells decreased in proportion to the reduction of Ig secretion. The evidence that ferritin inhibited Ig synthesis of Epstein-Barr virus-transformed human B-lymphoblastoid cell line also supported the idea that the effect of ferritin was directed toward the antibody-producing B lymphocytes. The molecular analysis showed that the inhibitory effect of ferritin was regulated at the transcriptional level of the Ig generation signal. Our results suggest that H- and L-rich ferritins exert their inhibitory action on the differentiation of B cells maturing into Ig-producing cells.

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9

Morikawa, K., F. Oseko, and S. Morikawa. "H- and L-rich ferritins suppress antibody production, but not proliferation, of human B lymphocytes in vitro." Blood 83, no. 3 (February 1, 1994): 737–43. http://dx.doi.org/10.1182/blood.v83.3.737.bloodjournal833737.

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The effect of human spleen(L-rich) and heart(H-rich) ferritins on the proliferation and differentiation of human B lymphocytes was studied in comparison with that of holo- and apo-transferrins. Ferritins rich in H and L chain, as well as the transferrins, did not inhibit the proliferative response of resting and activated B cells stimulated with polyclonal B-cell mitogen, Staphylococcus aureus Cowan strain I. In contrast, the ferritins, but not the transferrins, clearly suppressed the antibody production by B blasts in T-cell-independent as well as T- cell-dependent system. Kinetic study showed that inhibitory action of ferritins on immunoglobulin (Ig) production was caused at an early stage of B-cell differentiation. The cytoplasmic Ig-containing cells decreased in proportion to the reduction of Ig secretion. The evidence that ferritin inhibited Ig synthesis of Epstein-Barr virus-transformed human B-lymphoblastoid cell line also supported the idea that the effect of ferritin was directed toward the antibody-producing B lymphocytes. The molecular analysis showed that the inhibitory effect of ferritin was regulated at the transcriptional level of the Ig generation signal. Our results suggest that H- and L-rich ferritins exert their inhibitory action on the differentiation of B cells maturing into Ig-producing cells.

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10

Bauminger, E. R., A. Treffry, A. J. Hudson, D. Hechel, N. W. Hodson, S. C. Andrews, S. Levi, et al. "Iron incorporation into ferritins: evidence for the transfer of monomeric Fe(III) between ferritin molecules and for the formation of an unusual mineral in the ferritin of Escherichia coli." Biochemical Journal 302, no. 3 (September 15, 1994): 813–20. http://dx.doi.org/10.1042/bj3020813.

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Iron that has been oxidized by H-chain ferritin can be transferred into other ferritin molecules before it is incorporated into mature ferrihydrite iron cores. Iron(III) dimers are formed at the ferroxidase centres of ferritin H chains at an early stage of Fe(II) oxidation. Mössbauer spectroscopic data now show that the iron is transferred as monomeric species arising from dimer dissociation and that it binds to the iron core of the acceptor ferritin. Human H-chain ferritin variants containing altered threefold channels can act as acceptors, as can the ferritin of Escherichia coli (Ec-FTN). A human H-chain ferritin variant with a substituted tyrosine (rHuHF-Y34F) can act as a donor of Fe(III). Since an Fe(III)-tyrosinate (first identified in bullfrog H-chain ferritin) is absent from variant rHuHF-Y34F, the Fe(III) transferred is not derived from this tyrosinate complex. Mössbauer parameters of the small iron cores formed within Ec-FTN are significantly different from those of mammalian ferritins. Analysis of the spectra suggests that they are derived from both ferrihydrite and non-ferrihydrite components. This provides further evidence that the ferritin protein shell can influence the structure of its iron core.

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Takami, Masao, Kenji Mizumoto, Izumi Kasuya, Kohsuke Kino, Howard H. Sussman, and Hajime Tsunoo. "Human placental ferritin receptor." Biochimica et Biophysica Acta (BBA) - General Subjects 884, no. 1 (October 1986): 31–38. http://dx.doi.org/10.1016/0304-4165(86)90223-0.

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12

Fargion, S., P. Arosio, AL Fracanzani, V. Cislaghi, S. Levi, A. Cozzi, A. Piperno, and G. Fiorelli. "Characteristics and expression of binding sites specific for ferritin H- chain on human cell lines." Blood 71, no. 3 (March 1, 1988): 753–57. http://dx.doi.org/10.1182/blood.v71.3.753.753.

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Abstract Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.

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Fargion, S., P. Arosio, AL Fracanzani, V. Cislaghi, S. Levi, A. Cozzi, A. Piperno, and G. Fiorelli. "Characteristics and expression of binding sites specific for ferritin H- chain on human cell lines." Blood 71, no. 3 (March 1, 1988): 753–57. http://dx.doi.org/10.1182/blood.v71.3.753.bloodjournal713753.

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Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.

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Cozzi, Anna, Paolo Santambrogio, Daniela Privitera, Vania Broccoli, Luisa Ida Rotundo, Barbara Garavaglia, Rudolf Benz, et al. "Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome." Journal of Experimental Medicine 210, no. 9 (August 12, 2013): 1779–91. http://dx.doi.org/10.1084/jem.20130315.

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The ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient’s fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS.

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Van Wuytswinkel, O., G. Savino, and J. F. Briat. "Purification and characterization of recombinant pea-seed ferritins expressed in Escherichia coli: influence of N-terminus deletions on protein solubility and core formation in vitro." Biochemical Journal 305, no. 1 (January 1, 1995): 253–61. http://dx.doi.org/10.1042/bj3050253.

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Plant ferritin subunits are synthesized as precursor molecules; the transit peptide (TP) in their NH2 extremity, responsible for plastid targeting, is cleaved during translocation to this compartment. In addition, the N-terminus of the mature subunit contains a plant-specific sequence named extension peptide (EP) [Ragland, Briat, Gagnon, Laulhère, Massenet, and Theil, E.C. (1990) J. Biol. Chem. 265, 18339-18344], the function of which is unknown. A novel pea-seed ferritin cDNA, with a consensus ferroxidase centre conserved within H-type animal ferritins has been characterized. This pea-seed ferritin cDNA has been engineered using oligonucleotide-directed mutagenesis to produce DNA fragments (1) corresponding to the wild-type (WT) ferritin precursor, (2) with the TP deleted, (3) with both the TP and the plant specific EP sequences deleted and (4) containing the TP but with the EP deleted. These four DNA fragments have been cloned in an Escherichia coli expression vector to produce the corresponding recombinant pea-seed ferritins. Expression at 37 degrees C led to the accumulation of recombinant pea-seed ferritins in inclusion bodies, whatever the construct introduced in E. coli. Expression at 25 degrees C in the presence of sorbitol and betaine allowed soluble proteins to accumulate when constructs with the TP deleted were used; under this condition, E. coli cells transformed with constructs containing the TP were unable to accumulate recombinant protein. Recombinant ferritins purified from inclusion bodies were found to be assembled only when the TP was deleted; however assembled ferritin under this condition had a ferroxidase activity undetectable at acid pH. On the other hand, soluble recombinant ferritins with the TP deleted and expressed at 25 degrees C were purified as 24-mers containing an average of 40-50 iron atoms per molecule. Despite the conservation in the plant ferritin subunit of a consensus ferroxidase centre, the iron uptake activity in vitro at pH 6.8 was found to be lower than that of the recombinant human H-ferritin, though it was much more active than the recombinant human L-ferritin. The recombinant ferritin with both the TP and the EP deleted (r delta TP/EP) assembled correctly as a 24-mer; it has slightly higher ferroxidase activity and decreased solubility compared with the wild-type protein with the TP deleted (r delta TP). In addition, on denaturation by urea followed by renaturation by dialysis the r delta TP/EP protein showed a 25% increase in core-formation in vitro compared with the r delta TP protein.(ABSTRACT TRUNCATED AT 400 WORDS)

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SANTAMBROGIO, Paolo, Patrizia PINTO, Sonia LEVI, Anna COZZI, Ermanna ROVIDA, Alberto ALBERTINI, Peter ARTYMIUK, Pauline M. HARRISON, and Paolo AROSIO. "Effects of modifications near the 2-, 3- and 4-fold symmetry axes on human ferritin renaturation." Biochemical Journal 322, no. 2 (March 1, 1997): 461–68. http://dx.doi.org/10.1042/bj3220461.

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Ferritin is a protein of 24 subunits which assemble into a shell with 432 point symmetry. It can be denatured reversibly in acidic guanidine hydrochloride, with the formation of poorly populated renaturation intermediates. In order to increase the accumulation of intermediates and to study the mechanism of ferritin renaturation, we analysed variants of the human ferritin H-chain altered at the N-terminus (Δ1–13), near the 4-fold axis (Leu-169→Arg), the 3-fold axis (Asp-131→Ile+Glu-134→Phe) or the 2-fold axis (Ile-85→Cys). We also carried out specific chemical modifications of Cys-130 (near the 3-fold axis) and Cys-85 (near the 2-fold axis). Renaturation of the modified ferritins yielded assembly intermediates that differed in size and physical properties. Alterations of residues around the 2-, 4- and 3-fold axes produced subunit monomers, dimers and higher oligomers respectively. All these intermediates could be induced to assemble into ferritin 24-mers by concentrating them or by co-renaturing them with wild-type H-ferritin. The results support the hypothesis that the symmetric subunit dimers are the building blocks of ferritin assembly, and are consistent with a reassembly pathway involving the coalescence of dimers, probably around the 4-fold axis, followed by stepwise addition of dimers until the 24-mer cage is completed. In addition they show that assembly interactions are responsible for the large hysteresis of folding and unfolding plots. The implications of the studies for in vivoheteropolymer formation in vertebrates, which have two types of ferritin chain (H and L), are discussed.

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Pozzi, Cecilia, Silvia Ciambellotti, Caterina Bernacchioni, Flavio Di Pisa, Stefano Mangani, and Paola Turano. "Chemistry at the protein–mineral interface in L-ferritin assists the assembly of a functional (μ3-oxo)Tris[(μ2-peroxo)] triiron(III) cluster." Proceedings of the National Academy of Sciences 114, no. 10 (February 15, 2017): 2580–85. http://dx.doi.org/10.1073/pnas.1614302114.

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X-ray structures of homopolymeric L-ferritin obtained by freezing protein crystals at increasing exposure times to a ferrous solution showed the progressive formation of a triiron cluster on the inner cage surface of each subunit. After 60 min exposure, a fully assembled (μ3-oxo)Tris[(μ2-peroxo)(μ2-glutamato-κO:κO′)](glutamato-κO)(diaquo)triiron(III) anionic cluster appears in human L-ferritin. Glu60, Glu61, and Glu64 provide the anchoring of the cluster to the protein cage. Glu57 shuttles incoming iron ions toward the cluster. We observed a similar metallocluster in horse spleen L-ferritin, indicating that it represents a common feature of mammalian L-ferritins. The structures suggest a mechanism for iron mineral formation at the protein interface. The functional significance of the observed patch of carboxylate side chains and resulting metallocluster for biomineralization emerges from the lower iron oxidation rate measured in the E60AE61AE64A variant of human L-ferritin, leading to the proposal that the observed metallocluster corresponds to the suggested, but yet unobserved, nucleation site of L-ferritin.

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O'Connell, M., B. Halliwell, C. P. Moorhouse, O. I. Aruoma, H. Baum, and T. J. Peters. "Formation of hydroxyl radicals in the presence of ferritin and haemosiderin. Is haemosiderin formation a biological protective mechanism?" Biochemical Journal 234, no. 3 (March 15, 1986): 727–31. http://dx.doi.org/10.1042/bj2340727.

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Horse spleen and human spleen ferritins increase the formation of hydroxyl radicals (OH) at both pH 4.5 and pH 7.4 in reaction mixtures containing ascorbic acid and H2O2. The generation of OH is inhibited by the chelator desferrioxamine. Human spleen haemosiderin also accelerates OH generation in identical reaction mixtures, but is far less effective (on a unit iron basis) than ferritin under all reaction conditions. It is proposed that conversion of ferritin into haemosiderin in iron overload is biologically advantageous in that it decreases the ability of iron to promote oxygen-radical reactions.

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Wiwanitkit, Viroj. "Radiofrequency Radiation and Human Ferritin." Journal of Medical Signals & Sensors 3, no. 1 (2013): 61. http://dx.doi.org/10.4103/2228-7477.114330.

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Dempster, W. S., H. De V. Heese, F. H. Pocock, G. Kirsten, and S. Watermeyer. "Ferritin levels in human milk." Annals of Tropical Paediatrics 6, no. 3 (September 1986): 209–12. http://dx.doi.org/10.1080/02724936.1986.11748441.

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RADISKY, Derek C., and Jerry KAPLAN. "Iron in cytosolic ferritin can be recycled through lysosomal degradation in human fibroblasts." Biochemical Journal 336, no. 1 (November 15, 1998): 201–5. http://dx.doi.org/10.1042/bj3360201.

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Examination of the mechanism of intracellular iron recovery from lysosomally-degraded ferritin in vivo has been complicated by the continuous flux of cellular iron through ferritin molecules. Here we incubated human fibroblasts with cationic ferritin, a derivative of horse spleen ferritin, as a technique for delivering immunologically distinct ferritin molecules directly to lysosomes. Using this method, we found increased endogenous ferritin levels after the cellular degradation of cationic ferritin, demonstrating that cells can utilize lysosomal ferritin to produce increased cytosolic ferritin levels. Further, using an in vitro assay, we showed that isolated lysosomes degrade endogenous ferritin in a time- and temperature-dependent manner. These results are consistent with a model in which cytosolic ferritin is taken into the lysosomes and degraded. The solubilized iron from the ferric core could then be transported across the lysosomal membrane back into the cytosol.

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Moglia, Italo, Margarita Santiago, Simon Guerrero, Mónica Soler, Alvaro Olivera-Nappa, and Marcelo J. Kogan. "Enhanced Cellular Uptake of H-Chain Human Ferritin Containing Gold Nanoparticles." Pharmaceutics 13, no. 11 (November 19, 2021): 1966. http://dx.doi.org/10.3390/pharmaceutics13111966.

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Gold nanoparticles (AuNP) capped with biocompatible layers have functional optical, chemical, and biological properties as theranostic agents in biomedicine. The ferritin protein containing in situ synthesized AuNPs has been successfully used as an effective and completely biocompatible nanocarrier for AuNPs in human cell lines and animal experiments in vivo. Ferritin can be uptaken by different cell types through receptor-mediated endocytosis. Despite these advantages, few efforts have been made to evaluate the toxicity and cellular internalization of AuNP-containing ferritin nanocages. In this work, we study the potential of human heavy-chain (H) and light-chain (L) ferritin homopolymers as nanoreactors to synthesize AuNPs and their cytotoxicity and cellular uptake in different cell lines. The results show very low toxicity of ferritin-encapsulated AuNPs on different human cell lines and demonstrate that efficient cellular ferritin uptake depends on the specific H or L protein chains forming the ferritin protein cage and the presence or absence of metallic cargo. Cargo-devoid apoferritin is poorly internalized in all cell lines, and the highest ferritin uptake was achieved with AuNP-loaded H-ferritin homopolymers in transferrin-receptor-rich cell lines, showing more than seven times more uptake than apoferritin.

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Briat, Jean-François. "Plant ferritin and human iron deficiency." Nature Biotechnology 17, no. 7 (July 1999): 621. http://dx.doi.org/10.1038/10797.

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Wang, Zhongmin, Chester Li, Melanie Ellenburg, Elizabeth Soistman, John Ruble, Brenda Wright, Joseph X. Ho, and Daniel C. Carter. "Structure of human ferritin L chain." Acta Crystallographica Section D Biological Crystallography 62, no. 7 (June 20, 2006): 800–806. http://dx.doi.org/10.1107/s0907444906018294.

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Gelvan, D., E. Fibach, EG Meyron-Holtz, and AM Konijn. "Ferritin uptake by human erythroid precursors is a regulated iron uptake pathway." Blood 88, no. 8 (October 15, 1996): 3200–3207. http://dx.doi.org/10.1182/blood.v88.8.3200.bloodjournal8883200.

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Iron delivery to mammalian cells is traditionally ascribed to diferric transferrin (Tf). We recently reported that human erythroid precursor cells possess specific membranes receptors that bind and internalize acid isoferritin. Here we show that ferritin uptake by these cells is highly regulated and that the internalized ferritin-iron is used for home synthesis and thus, this process could constitute a physiological pathway for iron assimilation. Ferritin was internalized by a specific, saturable process, distinct from the uptake of iron associated with albumin. Ferritin uptake downregulated transferrin-receptor expression, indicating that internalized ferritin-iron was recognized as an integral part of the cellular iron content. Ferritin receptor expression was coordinated to cell development and was tightly regulated by cellular iron status. Receptor abundance was increased by iron-depletion and decreased by iron-loading, while the affinity of the ferritin receptor for acid isoferritin remained nearly constant (kd = 4.1 +/- 0.5 x 10(-6) mol/L). Under all experimental conditions, ferritin- and transferrin-receptor expression was closely coordinated, suggesting that these pathways possess a common regulatory element. It is concluded that ferritin uptake by erythroid cells constitutes an iron uptake pathway in addition to the classical transferrin uptake pathway.

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Asakawa, Hideo, Keiko Yamaguchi, Masashi Kurimoto, Ryuichi Motoda, Makoto Takeuchi, and Wataru Mori. "A comparative study on K562 cell ferritin and normal human liver ferritin." SEIBUTSU BUTSURI KAGAKU 39, no. 2 (1995): 91–93. http://dx.doi.org/10.2198/sbk.39.91.

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Lucignano, Rosanna, Alessandro Pratesi, Paola Imbimbo, Daria Maria Monti, Delia Picone, Luigi Messori, Giarita Ferraro, and Antonello Merlino. "Evaluation of Auranofin Loading within Ferritin Nanocages." International Journal of Molecular Sciences 23, no. 22 (November 16, 2022): 14162. http://dx.doi.org/10.3390/ijms232214162.

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Auranofin (AF), a gold(I) compound that is currently used for the treatment of rheumatoid arthritis and is in clinical trials for its promising anticancer activity, was encapsulated within the human H-chain and the horse spleen ferritin nanocages using the alkaline disassembly/reassembly protocol. The aim of the work was to highlight possible differences in their drug loading capacity and efficacy. The drug-loaded ferritins were characterized via UV-vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy to assess AF encapsulation and to define the exact amount of gold atoms trapped in the Ft cavity. The crystal structures allowed us to define the nature of AF interaction with both ferritins and to identify the gold binding sites. Moreover, the biological characterization let us to obtain preliminary information on the cytotoxic effect of AF when bound to the human H-chain.

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Hodgetts, J., S. W. Peters, T. G. Hoy, and A. Jacobs. "The ferritin content of normoblasts and megaloblasts from human bone marrow." Clinical Science 70, no. 1 (January 1, 1986): 47–51. http://dx.doi.org/10.1042/cs0700047.

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1. Erythroblasts were enriched from human bone marrow samples and fractionated on Percoll gradients according to maturity. 2. Heart-type and spleen-type ferritin was measured in each fraction by an immunoradiometric assay. 3. In normal marrow, heart-type ferritin content was higher in the early erythroblast fractions and fell with maturation. Spleen-type ferritin content showed no such consistent change. 4. Megaloblastic erythroblasts had a significantly higher ferritin content.

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29

Cazzola, Mario, Paolo Arosio, Vittorio Bellotti, Gaetano Bergamaschi, Laura Dezza, Carmelo Iacobello, and Giuseppina Ruggeri. "Use of a monoclonal antibody against human heart ferritin for evaluating acidic ferritin concentration in human serum." British Journal of Haematology 61, no. 3 (November 1985): 445–53. http://dx.doi.org/10.1111/j.1365-2141.1985.tb02848.x.

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30

PARTHASARATHY, Narayanan, Suzy V. TORTI, and Frank M. TORTI. "Ferritin binds to light chain of human H-kininogen and inhibits kallikrein-mediated bradykinin release." Biochemical Journal 365, no. 1 (July 1, 2002): 279–86. http://dx.doi.org/10.1042/bj20011637.

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Ferritin is an iron-storage protein that exists in both intracellular and extracellular compartments. We have previously identified H-kininogen (high-molecular-weight kininogen) as a ferritin-binding protein [Torti and Torti (1998) J. Biol. Chem. 273, 13630–13635]. H-Kininogen is a precursor of the potent pro-inflammatory peptide bradykinin, which is released from H-kininogen following cleavage of H-kininogen by the serine protease kallikrein. In this report, we demonstrate that binding of ferritin to H-kininogen occurs via the modified light chain of H-kininogen, and that ferritin binds preferentially to activated H-kininogen. We further demonstrate that binding of ferritin to H-kininogen retards the proteolytic cleavage of H-kininogen by kallikrein and its subsequent release of bradykinin fromH-kininogen. Ferritin does not interfere with the ability of kallikrein to digest a synthetic substrate, suggesting that ferritin specifically impedes the ability of kallikrein to digest H-kininogen, perhaps by steric hindrance. Based on these results, we propose a model of sequential H-kininogen cleavage and ferritin binding. These results are consistent with the hypothesis that the binding of ferritin to H-kininogen may serve to modulate bradykinin release.

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31

Levi, Sonia, Maddalena Ripamonti, Marko Dardi, Anna Cozzi, and Paolo Santambrogio. "Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions." Cells 10, no. 8 (August 3, 2021): 1969. http://dx.doi.org/10.3390/cells10081969.

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In 2001, a new type of human ferritin was identified by searching for homologous sequences to H-ferritin in the human genome. After the demonstration that this ferritin is located specifically in the mitochondrion, it was called mitochondrial ferritin. Studies on the properties of this new type of ferritin have been limited by its very high homology with the cytosolic H-ferritin, which is expressed at higher levels in cells. This great similarity made it difficult to obtain specific antibodies against the mitochondrial ferritin devoid of cross-reactivity with cytosolic ferritin. Thus, the knowledge of the physiological role of mitochondrial ferritin is still incomplete despite 20 years of research. In this review, we summarize the literature on mitochondrial ferritin expression regulation and its physical and biochemical properties, with particular attention paid to the differences with cytosolic ferritin and its role in physiological condition. Until now, there has been no evidence that the alteration of the mitochondrial ferritin gene is causative of any disorder; however, the identified association of the mitochondrial ferritin with some disorders is discussed.

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32

Percy, Maire E., Sharon J. Bauer, Susan Rainey, Donald R. C. McLachlan, Madhu S. Dhar, and Jayant G. Joshi. "Localization of a new ferritin heavy chain sequence present in human brain mRNA to chromosome 11." Genome 38, no. 3 (June 1, 1995): 450–57. http://dx.doi.org/10.1139/g95-059.

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Two types of ferritin heavy (H) chain clones have been isolated from cDNA libraries of human fetal and adult brain: one corresponds to the ferritin H chain mRNA that is abundant in liver and is called "liver-like" brain cDNA; the other contains an additional 279 nucleotide (nt) sequence in the 3′untranslated region and is called brain ferritin H chain cDNA. To map the 279-nt sequence, polymerase chain reaction (PCR) amplification was carried out using DNA from rodent × human hybrid cell lines containing single human chromosomes as templates, and oligomeric primers homologous to the 3′end of the 279-nt sequence (primer A) and to a coding sequence just 5′ to the 279-nt sequence. Significant PCR product of the size expected from analysis of the brain ferritin H chain cDNA clones and a genomic ferritin H chain clone (487 bp) was generated only from hybrid-cell DNA containing human chromosome 11. This PCR product and the "liver-like" brain cDNA (lacking the 279-nt sequence) both hybridized to chromosome 11 fragments that are known to define the well-characterized functional liver ferritin H chain gene and a putative pseudogene. Preliminary data indicate that primer A (and thus the 279-nt sequence) maps to the functional ferritin H chain gene fragments, but binding to the pseudogene has not been ruled out.Key words: gene mapping, human brain ferritin, chromosome 11.

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33

Lönnerdal. "The Importance and Bioavailability of Phytoferritin-Bound Iron in Cereals and Legume Foods." International Journal for Vitamin and Nutrition Research 77, no. 3 (May 1, 2007): 152–57. http://dx.doi.org/10.1024/0300-9831.77.3.152.

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Ferritin is present in several types of plants in low concentrations, but it is possible to enhance this content by plant breeding, or by inserting the gene for ferritin into staple foods. Since each ferritin molecule can bind thousands of iron atoms, this may be a sustainable means to increase the iron content of plants. Before launching such efforts it is important to determine whether ferritin-bound iron is bioavailable. We assessed this in vitro using Caco-2 cells and in vivo using radiolabeled ferritin and whole body counting in human subjects. In Caco-2 cells, we found that dietary factors affecting iron absorption, such as ascorbic acid, phytate, and calcium, had very limited effect on iron uptake from intact ferritin, suggesting that ferritin-bound iron is absorbed via a mechanism different from that of non-heme iron. Using in vitro digestion, we found that ferritin was relatively resistant against proteolytic enzymes. Binding of ferritin to Caco-2 cells was found to be saturable and the kinetics for binding characteristic for a receptor-mediated process. In human subjects, we found that iron absorption from animal ferritin was similar to that from ferrous sulfate, suggesting that iron is well absorbed from ferritin. We did not find any significant difference between iron absorption from ferritin reconstituted with high-phosphate (plant-type) and low-phosphate (animal-type) ferritin mineral, suggesting that plant ferritin-iron is bioavailable. In a subsequent human study we also found that iron from purified soybean ferritin given in a meal was as well absorbed as ferrous iron. In conclusion, iron is well absorbed from phytoferritin and may represent a means of biofortification of staple foods.

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34

Treffry, A., E. R. Bauminger, D. Hechel, N. W. Hodson, I. Nowik, S. J. Yewdall, and P. M. Harrison. "Defining the roles of the threefold channels in iron uptake, iron oxidation and iron-core formation in ferritin: a study aided by site-directed mutagenesis." Biochemical Journal 296, no. 3 (December 15, 1993): 721–28. http://dx.doi.org/10.1042/bj2960721.

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This paper aims to define the role of the threefold intersubunit channels in iron uptake and sequestration processes in the iron-storage protein, ferritin. Iron uptake, measured as loss of availability of Fe(II) to ferrozine (due to oxidation), has been studied in recombinant human H-chain ferritins bearing amino acid substitutions in the threefold channels or ferroxidase centres. Similar measurements with recombinant horse L-chain ferritin are compared. It is concluded that significant Fe(II) oxidation occurs only at the H-chain ferroxidase centres and not in the threefold channels, although this route is used by Fe(II) for entry. Investigations by Mössbauer and u.v.-difference spectroscopy show that part of the iron oxidized by H-chain ferritin returns to the threefold channels as Fe(III). This monomeric Fe(III) can be displaced by addition of Tb(III). Fe(III) also moves into the cavity for formation of the iron-core mineral, ferrihydrite. Iron incorporated into ferrihydrite becomes kinetically inert.

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35

KAKHLON, Or, Yosef GRUENBAUM, and Z. Ioav CABANTCHIK. "Repression of the heavy ferritin chain increases the labile iron pool of human K562 cells." Biochemical Journal 356, no. 2 (May 24, 2001): 311–16. http://dx.doi.org/10.1042/bj3560311.

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The role of ferritin in the modulation of the labile iron pool was examined by repressing the heavy subunit of ferritin in K562 cells transfected with an antisense construct. Repression of the heavy ferritin subunit evoked an increase in the chemical levels and pro-oxidant activity of the labile iron pool and, in turn, caused a reduced expression of transferrin receptors and increased expression of the light ferritin subunit

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36

Higashi, Shusaku, Kosei Nagasawa, Yasunaga Yoshikawa, Kiyotaka Watanabe, and Koichi Orino. "Characterization Analysis of Human Anti-Ferritin Autoantibodies." Antibodies 3, no. 1 (March 21, 2014): 169–81. http://dx.doi.org/10.3390/antib3010169.

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37

Leyland, M. J., P. C. Ganguli, D. Blower, and I. W. DELAMORE. "Immunoradiometric Assay for Ferritin in Human Serum." Scandinavian Journal of Haematology 14, no. 5 (April 24, 2009): 385–92. http://dx.doi.org/10.1111/j.1600-0609.1975.tb02711.x.

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38

Whittaker, D., J. D. Torrance, and M. C. Kew. "Isolation of ferritin from human hepatocellular carcinoma." Scandinavian Journal of Haematology 33, no. 5 (April 24, 2009): 432–39. http://dx.doi.org/10.1111/j.1600-0609.1984.tb00721.x.

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39

Gossuin, Yves, Robert N. Muller, Pierre Gillis, and Lionel Bartel. "Relaxivities of human liver and spleen ferritin." Magnetic Resonance Imaging 23, no. 10 (December 2005): 1001–4. http://dx.doi.org/10.1016/j.mri.2005.10.009.

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40

Klockars, M., T. Weber, P. Tanner, P. E. Hellstrom, and T. Pettersson. "Pleural fluid ferritin concentrations in human disease." Journal of Clinical Pathology 38, no. 7 (July 1, 1985): 818–24. http://dx.doi.org/10.1136/jcp.38.7.818.

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41

Adams, Paul C., Lawrie W. Powell, and June W. Halliday. "Isolation of a human hepatic ferritin receptor." Hepatology 8, no. 4 (July 1988): 719–21. http://dx.doi.org/10.1002/hep.1840080402.

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42

Fan, Kelong, Lizeng Gao, and Xiyun Yan. "Human ferritin for tumor detection and therapy." Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 5, no. 4 (April 18, 2013): 287–98. http://dx.doi.org/10.1002/wnan.1221.

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43

Terashima, Masahiro, Masaki Uchida, Hisanori Kosuge, Philip S. Tsao, Mark J. Young, Steven M. Conolly, Trevor Douglas, and Michael V. McConnell. "Human ferritin cages for imaging vascular macrophages." Biomaterials 32, no. 5 (February 2011): 1430–37. http://dx.doi.org/10.1016/j.biomaterials.2010.09.029.

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44

Bou-Abdallah, Fadi, Paolo Santambrogio, Sonia Levi, Paolo Arosio, and N. Dennis Chasteen. "Unique Iron Binding and Oxidation Properties of Human Mitochondrial Ferritin: A Comparative Analysis with Human H-chain Ferritin." Journal of Molecular Biology 347, no. 3 (April 2005): 543–54. http://dx.doi.org/10.1016/j.jmb.2005.01.007.

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45

Boerner, P., R. Lafond, W. Z. Lu, P. Brams, and I. Royston. "Production of antigen-specific human monoclonal antibodies from in vitro-primed human splenocytes." Journal of Immunology 147, no. 1 (July 1, 1991): 86–95. http://dx.doi.org/10.4049/jimmunol.147.1.86.

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Abstract We have developed culture conditions for human lymphocytes that support primary in vitro immune responses to protein Ag of either human or nonhuman origin. We now show that these primed B cells can be efficiently immortalized by fusion with a heterohybrid fusion partner to generate human, Ag-specific IgM or IgG antibody-producing heterohybridomas at a rate of 17 to 50 hybrids/10(6) lymphocytes fused. Approximately 50% of the Ig-secreting clones were stable with respect to Ig secretion. Levels of secretion attained with terminal cultures ranged from less than 1 to 100 micrograms/ml. Fusions of cells between 2 and 5 days after initiation of in vitro exposure to Ag produced more Ag-reactive and Ag-specific antibodies than fusions at 1 day or fusions performed after 5 days. Ag-reactive hybrids could be isolated at frequencies of 3 to 10%, depending on antigenicity of the immunogen. Foreign proteins, horse spleen ferritin, and a murine monoclonal Ig, induced higher percentages of Ag-reactive mAb than immunization with the human-derived ferritin. Ag-reactive IgG mAb were produced at relatively high frequency, depending on immunization conditions and the nature of the Ag. The strategy for identification of the best hybrids included early elimination of unstable hybridomas and of hybridomas producing broadly cross-reactive antibody, followed by evaluation of units of Ag reactivity/micrograms Ig. Ferritin-specific mAb selected according to these criteria showed immunocytochemical reactivity with ferritin-containing tissues and apparent affinities in the range of 10(7) to 10(8)/mol.

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46

Meyron-Holtz, E. G., B. Vaisman, Z. I. Cabantchik, E. Fibach, T. A. Rouault, C. Hershko, and A. M. Konijn. "Regulation of Intracellular Iron Metabolism in Human Erythroid Precursors by Internalized Extracellular Ferritin." Blood 94, no. 9 (November 1, 1999): 3205–11. http://dx.doi.org/10.1182/blood.v94.9.3205.

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Abstract Human erythroid precursors grown in culture possess membrane receptors that bind and internalize acid isoferritin. These receptors are regulated by the iron status of the cell, implying that ferritin iron uptake may represent a normal physiologic pathway. The present studies describe the fate of internalized ferritin, the mechanisms involved in the release of its iron, and the recognition of this iron by the cell. Normal human erythroid precursors were grown in a 2-phase liquid culture that supports the proliferation, differentiation, and maturation of erythroid precursors. At the stage of polychromatic normoblasts, cells were briefly incubated with 59Fe- and/or125I-labeled acid isoferritin and chased. The125I-labeled ferritin protein was rapidly degraded and only 50% of the label remained in intact ferritin protein after 3 to 4 hours. In parallel, 59Fe decreased in ferritin and increased in hemoglobin. Extracellular holoferritin uptake elevated the cellular labile iron pool (LIP) and reduced iron regulatory protein (IRP) activity; this was inhibited by leupeptin or chloroquine. Extracellular apoferritin taken up by the cell functioned as an iron scavenger: it decreased the level of cellular LIP and increased IRP activity. We suggest that the iron from extracellular is metabolized in a similar fashion by developing erythroid cells as is intracellular ferritin. Following its uptake, extracellular ferritin iron is released by proteolytic degradation of the protein shell in an acid compartment. The released iron induces an increase in the cellular LIP and participates in heme synthesis and in intracellular iron regulatory pathways.

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47

Meyron-Holtz, E. G., B. Vaisman, Z. I. Cabantchik, E. Fibach, T. A. Rouault, C. Hershko, and A. M. Konijn. "Regulation of Intracellular Iron Metabolism in Human Erythroid Precursors by Internalized Extracellular Ferritin." Blood 94, no. 9 (November 1, 1999): 3205–11. http://dx.doi.org/10.1182/blood.v94.9.3205.421k25_3205_3211.

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Human erythroid precursors grown in culture possess membrane receptors that bind and internalize acid isoferritin. These receptors are regulated by the iron status of the cell, implying that ferritin iron uptake may represent a normal physiologic pathway. The present studies describe the fate of internalized ferritin, the mechanisms involved in the release of its iron, and the recognition of this iron by the cell. Normal human erythroid precursors were grown in a 2-phase liquid culture that supports the proliferation, differentiation, and maturation of erythroid precursors. At the stage of polychromatic normoblasts, cells were briefly incubated with 59Fe- and/or125I-labeled acid isoferritin and chased. The125I-labeled ferritin protein was rapidly degraded and only 50% of the label remained in intact ferritin protein after 3 to 4 hours. In parallel, 59Fe decreased in ferritin and increased in hemoglobin. Extracellular holoferritin uptake elevated the cellular labile iron pool (LIP) and reduced iron regulatory protein (IRP) activity; this was inhibited by leupeptin or chloroquine. Extracellular apoferritin taken up by the cell functioned as an iron scavenger: it decreased the level of cellular LIP and increased IRP activity. We suggest that the iron from extracellular is metabolized in a similar fashion by developing erythroid cells as is intracellular ferritin. Following its uptake, extracellular ferritin iron is released by proteolytic degradation of the protein shell in an acid compartment. The released iron induces an increase in the cellular LIP and participates in heme synthesis and in intracellular iron regulatory pathways.

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48

Dezza, L., M. Cazzola, W. Piacibello, P. Arosio, S. Levi, and M. Aglietta. "Effect of acidic and basic isoferritins on in vitro growth of human granulocyte-monocyte progenitors." Blood 67, no. 3 (March 1, 1986): 789–95. http://dx.doi.org/10.1182/blood.v67.3.789.789.

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Abstract Acidic isoferritins have been previously found to be highly potent inhibitors of hematopoietic progenitors at concentrations of 10(-16) to 10(-18) mol/L, and it has been suggested that acidic isoferritin inhibitory activity plays a role in the regulation of normal hematopoiesis and also in the pathogenesis of leukemia. To characterize the ferritin species that affect the in vitro growth of human colony- forming unit-granulocyte-macrophage (CFU-GM), we tested different preparations of basic (L-subunit-rich) and acidic (H-subunit-rich) isoferritins. Three preparations of human liver (basic) ferritin did not show any effects on CFU-GM growth at concentrations up to 10(-9) mol/L, irrespective of the degree of glycosylation. Acidic isoferritins were purified both from HeLa cells and human heart. HeLa cell ferritin did not affect in vitro colony formation. One of two preparations of human heart ferritin, containing 5% glycosylated ferritin, showed a mean inhibition of 26% +/- 8% of the control at 10(-9) mol/L (P less than .02), whereas the other preparation, which contained no glycosylated ferritin, did not show any effect of CFU-GM growth. A preparation enriched for glycosylated acidic isoferritins from human heart was found to produce a mean inhibition of 32% +/- 11% of the control at 10(-9) mol/L (P less than .01), whereas another one was ineffective. A significant part of the inhibitory activity was removed by preincubation with the monoclonal antibody 2A4 directed against human heart ferritin. The present findings indicate that basic isoferritins, ie, the predominant ferritin type in human blood, have no effect on the growth of human CFU-GM, and this is in keeping with indirect clinical evidence. Inhibition of colony formation may be obtained by some preparations of acidic isoferritins that are rich in H subunits and bind to concanavalin A. The mechanism(s) responsible for this are not clear, but the effective concentrations are higher than those found in human blood both under normal conditions and in leukemia. At present, the physiologic significance of the observed inhibitory activity is uncertain.

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49

Dezza, L., M. Cazzola, W. Piacibello, P. Arosio, S. Levi, and M. Aglietta. "Effect of acidic and basic isoferritins on in vitro growth of human granulocyte-monocyte progenitors." Blood 67, no. 3 (March 1, 1986): 789–95. http://dx.doi.org/10.1182/blood.v67.3.789.bloodjournal673789.

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Acidic isoferritins have been previously found to be highly potent inhibitors of hematopoietic progenitors at concentrations of 10(-16) to 10(-18) mol/L, and it has been suggested that acidic isoferritin inhibitory activity plays a role in the regulation of normal hematopoiesis and also in the pathogenesis of leukemia. To characterize the ferritin species that affect the in vitro growth of human colony- forming unit-granulocyte-macrophage (CFU-GM), we tested different preparations of basic (L-subunit-rich) and acidic (H-subunit-rich) isoferritins. Three preparations of human liver (basic) ferritin did not show any effects on CFU-GM growth at concentrations up to 10(-9) mol/L, irrespective of the degree of glycosylation. Acidic isoferritins were purified both from HeLa cells and human heart. HeLa cell ferritin did not affect in vitro colony formation. One of two preparations of human heart ferritin, containing 5% glycosylated ferritin, showed a mean inhibition of 26% +/- 8% of the control at 10(-9) mol/L (P less than .02), whereas the other preparation, which contained no glycosylated ferritin, did not show any effect of CFU-GM growth. A preparation enriched for glycosylated acidic isoferritins from human heart was found to produce a mean inhibition of 32% +/- 11% of the control at 10(-9) mol/L (P less than .01), whereas another one was ineffective. A significant part of the inhibitory activity was removed by preincubation with the monoclonal antibody 2A4 directed against human heart ferritin. The present findings indicate that basic isoferritins, ie, the predominant ferritin type in human blood, have no effect on the growth of human CFU-GM, and this is in keeping with indirect clinical evidence. Inhibition of colony formation may be obtained by some preparations of acidic isoferritins that are rich in H subunits and bind to concanavalin A. The mechanism(s) responsible for this are not clear, but the effective concentrations are higher than those found in human blood both under normal conditions and in leukemia. At present, the physiologic significance of the observed inhibitory activity is uncertain.

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50

Kopřivová, H., F. Novák, P. Poučková, P. Dvořák, J. Šeblová, P. Švihovcová, J. Dušková, J. Pospíšil, and Z. Dienstbier. "Antiferritin Antibodies in Immunoscintigraphic Detection of Human Tumor Xenografts." International Journal of Biological Markers 3, no. 3 (July 1988): 159–64. http://dx.doi.org/10.1177/172460088800300303.

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Affinity-purified antibodies against human placental ferritin and their F(ab) 2 fragments labeled with 131I were examined for suitability for radioimmunodetection of ferritin-containing tumors. The nude mouse model (BALB/c, nu/nu) with xenografts of HeLa cell tumors and human adenocarcinoma of the rectum (with proven ferritin content) was used. Gamma-camera imaging and tissue distribution studies revealed that both kinds of tumor selectively accumulate antiferritin antibodies and their fragments. In large necrotic tumors nonspecific uptake of radiolabeled normal IgG occurred, but otherwise there was no tumor localisation. This study, in accordance with the literature, confirms the utility of antiferritin antibodies for the detection of human tumors in an animal model.

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Journal articles on the topic 'Human ferritin'

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