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)

Polyclonal 131I rabbit anti-rat ferritin localizes in the H-4-II-E hepatoma model. The effect of tumor size, vascularity, and ferritin content on tumor localization was examined. The extravascular and intravascular quantity and location of 131I non-specific IgG and 131I-antiferritin IgG in tumors were determined by gamma counter analysis of tissue samples and autoradiography. Separate groups of 8-10 tumor bearing rats with 0.6-1 g, 1-3 g, 4-8 g, 8-14 g, and greater than 14 g tumors were injected with 500 microCi (200 micrograms) of 131I non-specific IgG or 131I-antiferritin. Tumor targeting with antiferritin occurred maximally in primary or metastatic lesions less than 1 g in size. Decreased localization occurred with increasing tumor size and no localization took place in tumors greater than 8 g in size. This finding is independent of administered dose because increasing the amount of injected antiferritin from 2- to 10-fold did not increase the antiferritin/normal IgG targeting ratio in any group of tumors greater than 4 g. The quantity and physical characteristics of the tumor vasculature may in part explain selective tumor localization. Tumor vascularity per gram as measured by 51Cr labeled erythrocytes decreased as tumor size increased. Decreased localization was evident in the necrotic portions of large tumors. Autoradiography of tumor sections revealed that most of the 125I-IgG activity is deposited perivascularly with decreased deposition of antibody in necrotic areas of tumors and at increasing distance from the lumen of vessels. These findings have clinical importance since this non-homogeneous distribution of antibody could result in the delivery of low doses of radiation to large necrotic areas of tumors. These results help to demonstrate some of the complex physiologic factors that affect tumor localization and antibody distribution.
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PMID:Distribution of and physiologic factors that affect 131I-antiferritin tumor localization in experimental hepatoma. 674 54

Iron, as ferric nitrilotriacetate or ferric ammonium citrate, was administered to rat hepatoma cells (H4AZC2) that were grown in serum-containing media or in hormone-supplemented defined media on collagen matrices. High levels of iron either retarded growth or were cytotoxic, so conditions were established for maximum iron loading where cells survived at near normal growth rates. In all cases, cells exposed to iron produced more ferritin than those grown in its absence, and elevated ferritin levels were paralleled by higher intracellular iron contents. Cells grown in serum-free media, however, took up iron more rapidly than corresponding cells in serum-supplemented media, and intracellular iron and ferritin also reached much higher levels. During exponential growth stages, for example, ferritin levels in iron-stimulated cells were 35-fold greater than those in control cells. These results indicate that transferrin is not required as an iron donor as the inorganic iron was taken up effectively and utilized to stimulate ferritin synthesis. Twenty-four hours after iron administration, endocytotic mechanisms were evident by the appearance of coated vesicles and pits and visible cytoskeletal structures. Subsequently, clusters of iron micelles appeared in the cell. Ferritin isolated from iron-overloaded cells were rich in L-type subunits, but newly synthesized ferritins in iron-stimulated or control cells had almost equivalent amounts of heavy and light subunit constituents.
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PMID:Iron uptake and regulation of ferritin synthesis by hepatoma cells in hormone-supplemented serum-free media. 683 99

A case of acquired dyserythropoiesis with inter-erythroblastic connections is reported in a patient with chronic myeloid leukaemia, developing a terminal acute hepatic failure related to hepatocarcinoma. The erythroblastic series was abundant but only made of clusters grouping 10 to 20 closely adherent cells. The cellular membranes showed linear junctions or were interdigitated and the intercellular space was occupied with electron dense ferritin granules. This non specific aspect of dyserythropoiesis may be related to the hepatic carcinoma, which was probably induced by busulfan therapy.
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PMID:Acquired dyserythropoiesis with abnormal intercellular contacts between erythroblasts. Report of a patient with chronic myeloid leukaemia and hepatocarcinoma. 693 42

Serum ferritin levels were measured in 72 normal subjects and in 214 cases with various diseases by an immunoradiometric assay. In normal subjects, the serum ferritin levels were 27-230 mg/ml. Elevated serum ferritins were observed in most cases with iron excess and acute hepatitis. Markedly elevated levels were found in the majority of cases with acute leukemia, malignant lymphoma, hepatoma, and pancreatic cancer. High ferritin levels were also found in other malignant diseases. However, the range overlapped broadly with that of nonmalignant diseases. The serum ferritin correlated significantly with serum iron in normals and in those with iron deficiency anemia. In most nonmalignant cases, the serum ferritin and iron levels distributed on a regression line obtained from levels in normals and those with iron deficiency anemia. However, 92% of the malignant cases showed a serum ferritin to iron ratio higher than that of normal subjects. The estimation of the serum ferritin to iron ratio is a useful means for screening patients or in the differential diagnosis of a suspected malignant lesion.
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PMID:Clinical evaluation of serum ferritin to iron ratio in malignant diseases. 725 Jan 41

23 descendents of a 74--year-old Englishman who had beta-thalassaemia trait, and died of hepatoma, were studied to discover whether thalassaemia minor alone could predispose to iron overload. Serum ferritin and HLA antigens were assessed in all members, and adults underwent radioiron investigations and liver biopsy. 2 members of the second generation and 1 of the third generation, all of whom had thalassaemia trait, had elevated liver iron concentration, indicating preclinical iron overload. This was not associated with any HLA type. None of the subjects had been treated with exogenous iron. The one member of the second generation who had thalassaemia minor but not iron overload was female, and the 5 members of the third generation with the trait, but with normal serum ferritin levels, were all under the age of 15 years. Members of the family without beta-thalassaemia minor had normal iron metabolism. It is possible that the development of iron overload in 4 members of this family was related to the presence of thalassaemia minor, and not to the inheritance of another abnormal gene causing idiopathic haemochromatosis.
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PMID:Iron overload in beta-thalassaemia minor. A family study. 734 95

We have cloned the functional gene coding for the L ferritin subunit by successive rounds of screening of a mouse genomic library using different oligonucleotides so as to avoid cloning the multiple pseudogenes of this rather complex multigene family. The L gene consists in 4 exons interrupted by 3 introns and spanning 1.8 kb. Quantitative measurements of H and L ferritin mRNA in various mouse tissues using a ribonuclease protection assay reveals important variations in the L/H ratio, the liver displaying the highest amount of L mRNA. Functional analysis of 1 kb of upstream sequence by transient transfections into the hepatoma cell line HepG2 shows that the mouse L gene transcription relies upon a minimal 130 bp promoter region containing 1 TATA box and 2 CCAAT motifs. Elements with an enhancing activity specific of hepatic tissue are likely to be located outside of this 1 kb fragment.
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PMID:[Cloning, characterization and expression of mouse ferritin L subunit gene]. 764 56

Ascorbate is an important cofactor in many cellular metabolic reactions and is intimately linked to iron homeostasis. Continuously cultured cells are ascorbate deficient due to the lability of the vitamin in solution and to the fact that daily supplementation of media with ascorbate is unusual. We found that ascorbate repletion alone did not alter ferritin synthesis. However, ascorbate-replete human hepatoma cells, Hep3B and HepG2, as well as K562 human leukemia cells achieved a substantially higher cellular ferritin content in response to a challenge with iron than did their ascorbate-deficient counterparts grown under standard culture conditions. Most of the elevation in ferritin content was due to an increase in de novo ferritin synthesis of greater than 50-fold, as shown by in vivo labeling with [35S]methionine and immunoprecipitation. RNA-blot analysis showed only minor changes in steady state levels of ferritin mRNA, suggesting that ascorbate enhances iron-induced ferritin synthesis primarily by post-transcriptional events. Transient gene expression experiments using chloramphenicol acetyltransferase reporter gene constructs showed that the ascorbate effect on ferritin translation is not mediated through the stem-loop near the translational start site that transduces ferritin synthesis in response to cytokines. The data suggest that ascorbate possibly modifies the action of the iron-responsive element on ferritin translation, although more precise structure-function studies are needed to clarify this issue. These data demonstrate a novel role of ascorbate as a signaling molecule in post-transcriptional gene regulation. The mechanism by which ascorbate modulates cellular iron metabolism is complex and requires additional detailed investigation.
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PMID:Ascorbic acid enhances iron-induced ferritin translation in human leukemia and hepatoma cells. 785 59

The erythrocyte (RBC) ferritin content was measured in patients with chronic liver diseases including alcoholic liver disease, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), and normal subjects as controls. The relationship between RBC ferritin content and iron deposition in hepatocytes was studied. The mean RBC ferritin content (MV +/- 1SD) from normal subjects was 20.7 +/- 9.7 ag/cell in male, 11.1 +/- 5.5 ag/cell in female (ag = 10(-18)g). RBC ferritin content from chronic liver disease was higher than that of normal subjects, especially in liver cirrhosis. It elevated to 71.0 +/- 52.2 ag/cell in male, and 41.6 +/- 35.0 ag/cell in female. The iron deposition in hepatocyte was observed mostly in patients with RBC ferritin content over 20 ag/cell. The microheterogeneities of RBC ferritin from liver cirrhosis was examined by isoelectric focusing (IEF) and compared with that of normal subjects. RBC ferritin from normal subjects was detected at pI range from 5.1 to 5.7 in most cases, while it was detected at pI range from about 5.0 to 6.0 in the liver cirrhosis. More basic ferritin was detected in the latter and the peaks of pI was also more basic than that of normal controls. Since patients with liver cirrhosis examined had iron deposition in hepatocytes, it is conceivable that the occurrence of basic ferritin reflects iron overload in the liver. Taking these results together, it was concluded that the presence of iron deposition in hepatocytes and the degree of iron overload can be assumed from the determination of RBC ferritin content, a noninvasive procedure.
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PMID:[The relationship between RBC ferritin content in chronic liver diseases and iron deposition in hepatocytes]. 786 62

Serum ferritin H and L subunit levels and H/L ratios were evaluated in normal subjects and patients with various diseases by means of enzyme-linked immunosorbent assay using monoclonal antibody against ferritin H or L subunits. In normal subjects, serum levels of H subunit were significantly lower than those of L subunit, as previously reported by Cazzola and coworkers. Although the serum levels of L subunit were elevated and the values of H/L ratios were decreased in inflammatory diseases, serum levels of H subunit were remarkably high in patients with infectious mononucleosis. In liver disease, elevation of mean values of L subunit was observed. However, in liver cirrhosis and severe acute hepatitis, the serum levels of H subunit were often elevated as well as those of L subunit, and so it was suggested that the elevation of H subunit was related to the degree of hepatocellular injury. In hepatocellular carcinoma and pancreatic cancer, since the levels of H/L ratio were higher than controls and no correlation was observed between H and L subunits, it was suggested that the production of H subunit was increased in these cancers. However, the result of H/L ratio determination in serum ferritin did not appear enough to be important for tumor marker, because of a few instances demonstrated over the cut off limit of H/L ratio in neoplastic diseases. The rate of the patients whose H or L subunit levels were over the cut off point was higher in leukemia than in solid cancer, and so it was likely that the measurement of H and L subunit at the same time was clinically useful in leukemic patients. In acute myeloblastic leukemia, relatively high levels of serum L subunits and low H/L ratio were shown. It was suggested that the measurement of H and L subunits in patients with neoplastic diseases would also be useful for monitoring the effect of the therapy.
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PMID:[Clinical significance of serum ferritin H and L subunit determination in various diseases--evaluation by enzyme-linked immunosorbent assay]. 795 82

Interleukin-1 beta (Il-1 beta), a key cytokine in the acute phase response, elevates hepatic expression of both the heavy (H) and light (L) ferritin subunits without influencing the steady-state levels of either ferritin transcript. Transfection experiments with human hepatoma cells reveal that sequences within the 5' untranslated region (5'UTR) of H-ferritin mRNA confer translational regulation to chimaeric chloramphenicol acetyl transferase (CAT) mRNAs in response to Il-1 beta in the absence of marked changes in CAT mRNA levels. Il-1 beta dependent translational enhancement is mediated by a distinct G + C rich RNA sequence within 70 nucleotides (nt) of the start codon. The upstream Iron Responsive Element RNA stemloop does not confer increased expression to CAT mRNA in Il-1 beta stimulated hepatoma transfectants. A 38 nucleotide consensus sequence within the 5'UTRs of the mRNAs encoding the hepatic acute phase proteins alpha 1-antitrypsin (alpha 1AT), alpha 1-acid glycoprotein (AGP) and haptoglobin (Dente et al., 1985) is similar to sequences in the G + C rich H-ferritin mRNA translational regulatory element. Deletion of three nucleotides from this region of the 61 nt G + C rich element in the H-ferritin mRNA 5' leader eliminates Il-1 beta translational enhancement of the CAT reporter transcripts.
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PMID:Translational enhancement of H-ferritin mRNA by interleukin-1 beta acts through 5' leader sequences distinct from the iron responsive element. 804 31


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