Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hematopoietic stem cells are capable of self-replication and differentiation to lineage-committed progenitor cells. The progenitors proliferate and differentiate to lineage-specific, morphologically recognizable precursors and, finally, to terminal circulating blood cells. These homeostatic mechanisms are regulated by a complex set of interacting growth stimulatory and inhibitory factors that are produced by, or in collaboration with, the tissue's regulatory microenvironment. A number of well-characterized cytokines have been implicated in the negative regulation of hematopoiesis: ferritin H-subunit (HF), lactoferrin (Lf), prostaglandin E (PGE), tumor necrosis factor (TNF), interferon (IFN), transforming growth factor-beta (TGF beta), acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) or thymosin-beta 4, pyroGlu-Glu-Asp-Cys-Lys (pEEDCK), macrophage inflammatory protein-1 alpha (MIP-1 alpha), inhibin, superoxide dismutase (SOD), glutathione (GSH) and others not well-known yet. The role of inhibitors in restraining stem cells from entering the cell cycle and protecting them from the toxic side effects of chemotherapeutic drugs is opening an alternate strategy for the treatment of cancer patients.
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PMID:[Biomolecules suppressing myelopoiesis]. 134 39

Blood cells develop in the bone marrow, controlled by a network of regulatory factors, some of which originate in the stroma. Previously, we found that most fibroblastoid (FB) cells growing in primary cultures of rat marrow bear surface antigens different from those found on FB of certain other tissues. As determined by two monoclonal antibodies ("ST3" and "ST4"), the "marrow type" is ST3+/ST4- and releases predominantly a colony-stimulating activity (CSA) into its culture media (CM), whereas the "peripheral type" (e.g. lung) is predominantly ST3-/ST4+ and produces inhibitory activity in excess of CSA. The studies described here show that this inhibitor also is active on rat leukemic myeloblasts (the BNML cell line), but not on eight other cell lines derived from rat tumors of various origins or on the human-derived leukemic cell lines tested. It was produced without exogenous stimulation, was labile to heat and acid, was not neutralized by antisera to transforming growth factor-beta, beta-interferon, or ferritin, and had an apparent mol wt in the range of 100-120 kD (peak of activity by gel filtration). From the results obtained at this time, we are not able to ascribe this fibroblast-derived activity to any known inhibitor molecule.
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PMID:Effects of a fibroblast-derived inhibitor on the growth of normal marrow and leukemic clonogenic cells. 163 84

We studied MDS-associated inhibitory activity, which inhibited colony formation in vitro of granulocyte-macrophage progenitors (CFU-GM). Macrophages obtained from MDS bone marrow mononuclear cells (BM-MNC) when pretreated with granulocyte-macrophage colony stimulating factor (GM-CSF) suppressed the growth of normal CFU-GM. These macrophages were designated as 'MDS-derived inhibitory macrophages'. Media conditioned by MDS-derived inhibitory macrophages (MDS-CM) also suppressed the growth of normal CFU-GM. In the MDS-CM, high levels of prostaglandin E2 (PGE2) and ferritin were found. However, MDS-CM did not contain detectable levels of tumour necrosis factor (TNF) or gamma-interferon (gamma-IFN). Antiserum against human placental ferritin and/or against PGE2 blocked the haemopoietic inhibitory activity to some extent. These results suggest that inhibitory macrophages may be responsible for the suppression of granulopoiesis in patients with MDS and that the suppression may be mediated by soluble factors including PGE2 and ferritin.
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PMID:Myelodysplastic syndrome (MDS)-associated inhibitory activity on haemopoietic progenitor cells. 218 Apr 70

Interleukin 1 alpha (IL-1) and tumor necrosis factor alpha (TNF) are two monokines which play a prominent role in the response to inflammation and injury. We recently observed that TNF leads to an increase in the synthesis of the heavy chain of ferritin, suggesting that TNF may be involved in iron homeostasis (Torti et al. (1988) J. Biol. Chem. 263, 12638-12644). The experiments reported here demonstrate that in cultured human muscle cells, IL-1 induces ferritin H mRNA and protein as effectively as TNF. TNF and IL-1 were additive in their effects on ferritin H expression, and IL-1 induction of ferritin H was not blocked by anti-TNF antibodies. Ferritin H induction was a specific response not observed with beta or gamma interferon, nor with transforming growth factor beta. Both differentiated myotubes as well as myoblasts responded to IL-1 with the induction of ferritin H. These results suggest that monokine-mediated alterations in the subunit composition of the ferritin molecule may be of biological relevance in the response to inflammation and injury.
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PMID:Interleukin 1 induces ferritin heavy chain in human muscle cells. 235 Mar 50

Highly purified murine granulocyte-macrophage progenitor cells (CFU-GM) were used as target cells to assess the possible direct effects of purified preparations of recombinant murine gamma-interferon, prostaglandin E, recombinant human heavy chain (acidic) ferritin, and recombinant human tumor necrosis factor alpha (TNF-alpha) on progenitor cells in vitro. Target CFU-GM, with cloning efficiencies of up to 84% and containing 0-3% morphologically recognizable accessory cells at the initiation of the culture period, were plated at a density of 100-150 cells/dish in the presence or absence of pure suppressor molecules. Colony formation was stimulated with either crude pokeweed mitogen-stimulated mouse spleen conditioned medium, pure natural murine macrophage colony-stimulating factor, or pure recombinant murine granulocyte-macrophage colony-stimulating factor. All four suppressor molecules were active in vitro against purified CFU-GM as assessed by their ability to inhibit colony or cluster formation. No apparent difference in the degree of responsiveness to prostaglandin E, gamma-interferon, or human heavy chain (acidic) ferritin was noted in the presence of pokeweed mitogen-stimulated mouse spleen conditioned medium, granulocyte-macrophage colony-stimulating factor, or macrophage colony-stimulating factor. In contrast, TNF-alpha in cultures containing macrophage colony-stimulating factor slightly, but significantly, potentiated colony formation. TNF-alpha also appeared more active at suppressing colony formation at lower concentrations in pokeweed mitogen-stimulated mouse spleen conditioned medium than in granulocyte-macrophage colony-stimulating factor-stimulated cultures of purified CFU-GM. The results suggest that TNF-alpha, human heavy chain (acidic) ferritin, gamma-interferon, and prostaglandin E can act directly at the progenitor cell level.
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PMID:Effects of hematopoietic suppressor molecules on the in vitro proliferation of purified murine granulocyte-macrophage progenitor cells. 244 53

Cancer grows in interaction with the host, that is, a host-tumor relationship exists. Investigations of host factors in patients receiving cancer chemotherapy are important, as they reveal the conditions in which a tumor response can develop. Furthermore, reliable host factors, if present, will be useful for quantitative evaluation of the effects of treatment. We have investigated the following three categories of host factors in relation to the effects of cancer chemotherapy and/or immunotherapy. CBC, and blood chemistries (44 parameters). Tumor markers; sialic acid, RNase, lysozyme, ferritin, IAP (immunosuppressive acidic protein), elastase I, AFP, CEA, POA, CA 19-9, CA 125, etc. Immunological parameters; lymphocyte, active T cell, T cell, B cell, IgG Fc receptor-positive T cell, lymphocyte blastogenesis stimulated by PHA, or concanavalin-A, ADCC activity, interferon production in vitro induced by poly I: C, or PHA, PPD skin test, immune complex, immunoglobulin G, A, and M, OKT series 3, 4, 8, 11, 4/8 ratio, antihuman HLA-DR, Leu 11, NK cell activity, etc. From our clinical observations, there were no significant differences in the pretreatment levels of these parameters between responders and non-responders. In responders, there was a tendency for the host factors to show greater degrees of improvement following treatment than in non-responders, but none proved to be reasonably reliable parameters for evaluating therapeutic effects. On the other hand, from our clinical observations on the advanced gastric cancer cases, life span showed a close correlation with tumor regression induced by cancer chemotherapy. Because of these facts, it is only natural that the clinical effects of chemotherapy are currently determined by definite tumor regression.
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PMID:[Host factors in cancer chemotherapy]. 372 33

The bindings sites for interferon (IFN) on the limiting cell membranes of human and mouse fibroblasts and erythrocytes were revealed by an indirect immunoferritin technique. Mouse IFN-beta and human IFN-beta of high specific activity were used with the corresponding purified antibodies. Species-specific IFN binding was demonstrated by ferritin deposition on human erythrocytes and fibroblast membranes treated with human IFN and on mouse erythrocytes and fibroblast membranes treated with mouse IFN, but not on human erythrocytes or fibroblast membranes treated with mouse IFN. IFN binding sites on fibroblasts were located on regions of membranes between microvilli, whereas diphtheria toxin receptors were demonstrated mainly on microvilli. IFN binding altered the diphtheria toxin after IFN treatment. This reduced toxicity correlated with a decrease in the quantity of receptors for diphtheria toxin on the cell membrane. Thus, the species-specific binding of IFN appears to depend on membrane receptors in discrete regions of the limiting membrane which are present not only on functionally responsive fibroblasts but also on erythrocytes.
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PMID:Ultrastructural localization of interferon receptors on the surfaces of cultured cells and erythrocytes. 617 39

Murine beta-interferon (IFN) receptors on L929 cells grown in suspension culture were visualized by indirect immunoferritin electron microscopy. Ferritin label on these cells was associated primarily with the coated areas and coated pits of the membrane, in contrast to previous observations with L929 cells grown in a monolayer, which did not reveal such coated areas or pits but showed ferritin label distributed randomly on the cell membrane (Kushnaryov et al., Infect. Immun. 36:811-821, 1982). On about 15% of the cell sections from suspension-grown cells, the ferritin label was found outside coated membrane areas. These findings suggest that different cell populations exist with respect to the localization and possibly the affinity of IFN receptors. In the same experiment, exogenously added gangliosides blocked the binding to cell surfaces not only of 125I-labeled IFN but also of unlabeled IFN as revealed by an immunospecific ferritin labeling technique, providing direct evidence that gangliosides interfere with the binding of IFN to specific receptor sites on the surface of mouse L929 cells. These studies establish that the binding of IFN to cell membranes, depending on cell growth conditions, can involve coated areas and coated pits, to which certain hormones and toxins have been shown to bind.
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PMID:Ultrastructural distribution of interferon receptor sites on mouse L fibroblasts grown in suspension: ganglioside blockade of ligand binding. 629 61

Iron-regulatory protein (IRP) is a master regulator of cellular iron homeostasis. Expression of several genes involved in iron uptake, storage, and utilization is regulated by binding of IRP to iron-responsive elements (IREs), structural motifs within the untranslated regions of their mRNAs. IRP-binding to IREs is controlled by cellular iron availability. Recent work revealed that nitric oxide (NO) can mimic the effect of iron chelation on IRP and on ferritin mRNA translation, whereas the stabilization of transferrin receptor mRNA following NO-mediated IRP activation could not be observed in gamma-interferon/lipopolysaccharide-stimulated murine macrophages. In this study, we establish the function of NO as a signaling molecule to IRP and as a regulator of mRNA translation and stabilization. Fibroblasts with undetectable levels of endogenous NO synthase activity were stably transfected with a cDNA encoding murine macrophage inducible NO synthase. Synthesis of NO activates IRE binding, which in turn represses ferritin mRNA translation and stabilizes transferrin receptor mRNA against targeted degradation. Furthermore, iron starvation and NO release are shown to be independent signals to IRP. The posttranscriptional control of iron metabolism is thus intimately connected with the NO pathways.
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PMID:Nitric oxide signaling to iron-regulatory protein: direct control of ferritin mRNA translation and transferrin receptor mRNA stability in transfected fibroblasts. 753 89

To date, there are no firm clinical, demographic, biochemical, serologic, or histologic features predicting which patients with chronic hepatitis C are more likely to respond to therapy with interferon-alpha. Serum iron, total iron-binding capacity, transferrin saturation, and ferritin were measured in the fasting state. The amount of stainable iron in liver biopsy specimens was evaluated histochemically as well. All patients received subcutaneous recombinant human IFN-alpha 2a three million units thrice weekly by self-administration. Eleven of 13 (84%) responders had low to normal serum iron levels as compared to one of 26 (4%) nonresponders (P < 0.001). The serum transferrin was similar in both groups, but iron saturation was significantly lower in responders (30 +/- 10%) than in nonresponders (53 +/- 12%) (P< 0.001). Serum ferritin and hepatic iron content were higher in nonresponders (NS). It is suggested that increased serum iron and transferrin saturation blunt the action of interferon, as they have opposite effects on the immune system. Iron overload can thus lead to a poor response to interferon. It remains to be seen whether reducing iron overload will improve the response to interferon therapy.
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PMID:Elevated serum iron predicts poor response to interferon treatment in patients with chronic HCV infection. 758 26


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