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

Hyperferritinemia, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression.
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PMID:Alcohol induction of ferritin expression in a human hepatoblastoma cell line (HEP G2). 198 98

We studied the mode of iron transport and storage in a human breast cancer cell line (HT-24) in comparison with a breast epithelial cell line (HBL-100). It was found that HT-24 cells incorporated over 18 h more 59Fe as compared to HBL-100 (24 vs. 16%). Yet, the number of surface transferrin-binding sites was less in cancer cells (6.2 x 10(5)) than in epithelial cells (8 x 10(5)). Moreover, the transferrin receptors in cancer cells were less affected by iron overloading as compared with epithelial cells. Following immunoprecipitation of isoferritins with specific monoclonal antibodies (MoAbs), it was found that the quantity of de novo synthesized normal ferritin immunoprecipitated with CM-G-8 MoAb was similar in both cancer and epithelial cells. However, the amount of 59Fe incorporated into the protein was significantly higher in HBL-100 cells. In contrast, HT-24 cells synthesized a high amount of placental-like isoferritin (PLF) immunoprecipitated with CM-H-9 MoAb which was significantly higher (p less than 0.001) than in epithelial cells. This isoferritin was characterized by its low iron incorporation. It is noteworthy that the ratio of PLF to normal ferritin was 2:1 in cancer cells and 0.7:1 in epithelial cells, indicating that PLF is a major type of isoferritin synthesized by HT-24 breast cancer cells. Furthermore, a significant amount of PLF was expressed on the surface of cancer cells as compared to epithelial cells. The results of this study suggest that iron supply and distribution in breast neoplastic cells are not controlled similarly to normal cells.
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PMID:Comparison of transferrin receptors, iron content and isoferritin profile in normal and malignant human breast cell lines. 204 66

The ultrastructural and immunohistochemical features of 19 hepatoblastomas were examined to evaluate the phenotypic expressivity of this solid embryonic neoplasm of childhood. Electron microscopy confirmed the embryonal and fetal characteristics of the neoplastic hepatocytes, but in addition, cells with features intermediate between these two cell types were identified. Dense bundles of collagen corresponding to the osteoid-like material by light microscopy surrounded nests of cells; the cells within this matrix stained for epithelial membrane antigen and vimentin and focally for cytokeratin, and they showed ultrastructural features of epithelial cells. The two cases of small cell hepatoblastoma reacted positively for vimentin and cytokeratin; the remaining 17 cases were immunoreactive for cytokeratin and alpha-fetoprotein, and some also for alpha 1-antitrypsin, ferritin, and vimentin. A histogenetic scheme based on our findings is proposed to explain the divergent morphologic features of this neoplasm.
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PMID:Hepatoblastoma: an immunohistochemical and ultrastructural study. 244 37

Hepatoblastoma, although rare, is the most common primary malignant neoplasm of the liver in children. In this paper we describe a case of hepatoblastoma with unusual cytologic features and present the histologic, immunocytochemical and ultrastructural features of this neoplasm. A 7-month-old girl presented with a large hepatic mass and metastatic nodules in both lungs. Intraoperative biopsy revealed a hepatoblastoma. Aspiration biopsy yielded a highly cellular aspirate with cords of pleomorphic cells embedded in a mucoid matrix. Histologic sections showed a diffusely infiltrative neoplasm composed of sheets and cords of highly pleomorphic cells. The neoplastic cells stained strongly positive for cytokeratin CAM 5.2 and AE1 and focally positive for alpha-fetoprotein, ferritin, carcinoembryonic antigen and vimentin. Ultrastructurally, the neoplastic cells had abundant intercellular junctions and intracytoplasmic aggregates of intermediate filaments. A mucoid matrix, to our knowledge, has not been reported as a finding on aspiration biopsy. This patient presented with pulmonary metastases, and thus we think the mucoid matrix may be a marker of a more aggressive variant of hepatoblastoma. This case illustrates additional cytologic features of hepatoblastoma and the usefulness of aspiration biopsy in the rapid diagnosis of this rare tumor.
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PMID:Hepatoblastoma. Report of a case with cytologic, histologic and ultrastructural findings. 751 34

In chronic inflammation it is reported that serum iron is depleted and hepatic iron is increased because of reticuloendothelial system iron blockade. However, recent studies indicate that hepatic parenchymal cells increase the uptake of transferrin-bound iron after in vivo stimulation with bacterial lipopolysaccharide, suggesting that endotoxemia itself or lipopolysaccharide-induced production of inflammation-related cytokines may also be responsible for this phenomenon. In this study the actions of inflammation-related cytokines on the synthesis of iron-binding proteins (transferrin and ferritin) and transferrin receptor and the uptake of transferrin-bound iron were investigated in a human hepatoblastoma cell line, HepG2, which is the most commonly used cell line for examining the regulation of hepatic protein synthesis by cytokines. The cells were exposed to interleukin-1 beta, interleukin-6 or tumor necrosis factor-alpha separately for 24 hr. In each cytokine treatment group, the level of transferrin, which is secreted into the conditioned medium, was found to be decreased compared with that of untreated cells. On the other hand, the biosynthesis of ferritin was markedly elevated after the same treatment. This increase in ferritin by cytokine treatment was diminished when deferoxamine was used concomitantly to deplete intracellular chelatable iron. After stimulation with interleukin-1 beta, interleukin-6 or tumor necrosis factor-alpha, 59Fe-labeled transferrin uptake into the cells was increased by 36%, 48%, or 18%, respectively, and this uptake was inhibited by the addition of excess unlabeled transferrin. A binding study with 125I-labeled diferric transferrin revealed that the three cytokines increased the number of transferrin receptors on the cell surface by 1.15-fold to 1.35-fold.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of iron metabolism in HepG2 cells: a possible role for cytokines in the hepatic deposition of iron. 840 63

Serum ferritin increases in chronic alcoholism, without clear explanation. We have previously shown that alcohol increases ferritin levels in a human hepatoblastoma cell line (HepG2). The aims of the present work were: 1) To extend our results in normal rat hepatocyte cultures, and 2) To determine the mechanism by which alcohol enhances ferritin levels. In HepG2 cells, high alcohol concentrations (300 mM) during long exposure (4 days) increased the synthesis of H and L ferritin subunits, in association with increased levels of ferritin mRNAs. In rat hepatocyte cultures, the synthesis of L ferritin increased after 24 h of exposure to lower alcohol concentrations (10 mM); alcohol had no effect on ferritin mRNAs levels. In both cell types, the alcohol effect was not related to an increase in iron intracellular incorporation. In HepG2 cells, desferrioxamine (Df), a potent iron chelator, abolished ferritin synthesis in the presence or absence of alcohol, and abolished the alcohol induction of ferritin mRNAs. In rat hepatocytes, Df decreased ferritin synthesis to a similar level in the presence or absence of alcohol. Alcohol increased ferritin synthesis differently in HepG2 cells and in normal rat hepatocyte cultures. In the latter case, the alcohol effect was observed at low concentration. Despite a striking inhibiting effect of Df on ferritin synthesis, in both cellular models a mechanism accounting for increased ferritin synthesis independently of iron is suggested. Globally, these data strongly suggest that hyperferritinemia in chronic alcoholism could be related to the induction of ferritin by alcohol.
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PMID:Regulation of ferritin expression by alcohol in a human hepatoblastoma cell line and in rat hepatocyte cultures. 865 61

The modulation of cellular iron metabolism depends on the expression of ferritin and transferrin receptor (TfR). These proteins are regulated post-transcriptionally by interaction of specific sequences, termed iron responsive elements (IRE) which are located in the 5' untranslated region (UTR) of ferritin mRNA and 3'UTR of TfR mRNA and a specific cytosolic protein, termed iron responsive element-binding protein (IRE-BP). The liver plays an important role in iron metabolism as a major organ of iron storage. In hepatocytes iron is taken up in the form of transferrin and intercellular iron levels are regulated by IRE/IRE-BP interaction. In spite of the important role of IRE/IRE-BP interaction, the role of it for proliferation and differentiational change in hepatoma cells is not well known. In this study, the author has investigated IRE/IRE-BP interaction and its target protein expression during proliferation and differentiational change of human hepatoblastoma cells (HepG2). This study revealed that the binding activity of IRE-BP to IRE was increased when HepG2 cells were cultured with an iron-chelating agent, deferoxamine (4.5 microM), and it was decreased when cultured with transferrin (100 micrograms/ml) during both proliferation and differentiational change induced by sodium butyrate. Also, the change of TfR expression was correlated with that of IRE-BP. These findings suggest that IRE/IRE-BP interaction may play an important role in the expression of TfR and cellular iron metabolism during proliferation and differentiational change of HepG2 cells.
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PMID:[Analysis of the iron-related proteins during proliferation and differentiational change of human hepatoblastoma cells (HepG2)]. 872 77

Subtractive hybridization was used to isolate genes expressed uniquely in the immortalized human breast epithelial cell (HBEC) line MCF-10F and not in the mortal HBEC line S-130, from which MCF-10F cells were derived. We identified a 233-bp cDNA that was expressed in MCF-10F cells and not in their mortal counterpart S-130 cells. Sequence comparison with the GenBank database revealed that the cDNA was identical to the gene encoding human ferritin heavy H chain. Northern blot analysis using the isolated cDNA as a probe showed a differentially expressed 1.1-kb transcript of ferritin H in total RNA from the immortal MCF-10F cells, MCF-10F cells treated with the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene, and the breast cancer cell lines MCF-7, HBL-100, T-47D, and BT-20. No ferritin H transcript was detected in the mortal line S-130 or in other primary HBEC cultures. Increased levels of mRNA transcript signals were also detected in total RNA from breast cancer tissue samples. Tissue with ductal hyperplasia had higher expression levels than normal adjacent mammary tissue. In situ hybridization showed high levels of ferritin H transcript in mammary tissue areas with ductal hyperplasia, carcinoma in situ, and infiltrating ductal carcinoma. This is the first report of the differential expression and upregulation of human ferritin H chain gene in immortal HBECs. It may be an important factor in the process of immortalization, possibly an early stage of malignant transformation of HBECs, providing cells with iron necessary for growth and clonal expansion. Also, ferritin iron, once released, may increase the level of reactive iron, leading to an increase in oxygen free-radical generation, oxidative DNA damage, and mutation.
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PMID:Differential expression of human ferritin H chain gene in immortal human breast epithelial MCF-10F cells. 943 77

Ferritin is a ubiquitous iron storage protein existing in multiple isoforms composed of 24 heavy and light chain subunits. We describe here a third ferritin-related subunit cloned from human placenta cDNA library and named PLIF (placental immunomodulatory ferritin). The PLIF coding region is composed of ferritin heavy chain (FTH) sequence lacking the 65 C-terminal amino acids, which are substituted with a novel 48 amino acid domain (C48). In contrast to FTH, PLIF mRNA does not include the iron response element in the 5'-untranslated region, suggesting that PLIF synthesis is not regulated by iron. The linkage between the FTH and C48 domains created a restriction site for EcoRI. PLIF protein was found to localize in syncytiotrophoblasts of placentas (8 weeks of gestation) at the fetal-maternal interface. Increased levels of PLIF transcript and protein were also detected in the breast carcinoma cell lines T47D and MCF-7 but not in the benign corresponding cell line HBL-100. In vitro, PLIF was shown to down-modulate mixed lymphocyte reactions and to inhibit the proliferation of peripheral blood mononuclear cells stimulated with OKT3. The accumulated data indicate that PLIF is an embryonic immune factor involved in down-modulating the maternal immune recognition of the embryo toward anergy. This mechanism may have been adapted by breast cancer cells over expressing PLIF.
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PMID:PLIF, a novel human ferritin subunit from placenta with immunosuppressive activity. 1182 35

Metal-based coordination compounds, including the well-known cytostatic drug cisplatin, are widely used in the anticancer therapy. Generally, they exhibit high cytotoxicity not only towards malignant cells, but also towards non-malignant cells, which represents main problem of their clinical use. Herein, we describe the synthesis, characterization and biological testing of three trinuclear nickel(II) coordination compounds. Central nickel atoms are bridged by trithiocyanurate anion and coordinated by triamine and bis-benzimidazoles, respectively. To delineate a potential usage in anticancer therapy, we encapsulated the most cytotoxic complex into biomacromolecular protein cage apoferritin (FRT), forming FRTNi. FRT encapsulation markedly decreased the hemotoxicity of free Ni compounds. Despite FRTNi can be internalized through passive targeting by enhanced permeability and retention effect, we further introduced active targeting utilizing folate receptor (FR) via folic acid (FA)-modified FRT (FRTNiFA). Using breast cancer cell lines T-47D (FR+), MCF-7 (FR-) and non-malignant mammary gland derived cell line HBL-100 (FR-), we show pronounced FR-dependent internalization of FRTNiFA. Overall, we demonstrate that the FRT macromolecular nanocarrier provides a very low off-target toxicity, which could enable the use of highly toxic Ni compounds in cancer nanomedicine.
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PMID:Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds. 3060 47


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