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

Inhibition by 1,10-phenanthroline of cellular DNA strand scission induced by the antitumor antibiotic bleomycin in Ehrlich ascites tumor cells was studied. DNA alkaline elution was performed on cells after 1-hr bleomycin treatments. Pretreatment for 24 hr with initial 1,10-phenanthroline concentrations of 0.2 nmol/10(5) cells, which depletes cells of ferritin iron by 80%, had no consistent effect on bleomycin strand breakage. However, simultaneous treatment with 3.1 nmol of 1,10-phenanthroline/10(5) cells and with bleomycin concentrations from 5 to 25 microM decreased both apparent double-stranded breaks and random breakage. When cells were treated with both 3.1 nmol of 1,10-phenanthroline/10(5) cells and 25 microM bleomycin, washed free of both drugs, and incubated at 35 degrees for 1 hr, the resulting breakage was equivalent to that found in cells treated with bleomycin only. When the combination treatment was extended to 4 hr, cell washing and reincubation resulted in increased strand scission, as compared with strand scission in cells treated with bleomycin only. Growth inhibition by bleomycin was not affected appreciably by temporary suppression of DNA strand breakage activity.
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PMID:Inhibition of bleomycin-induced cellular DNA strand scission by 1,10-phenanthroline. 170 22

In a search for genes transcriptionally regulated by metal ions, we have isolated a Xenopus laevis ferritin cDNA clone, XL2-17, from cadmium-poisoned XL2 cells. The large size of the corresponding ferritin mRNA (1.4 kb) is due to the presence of a 629-nucleotide 5'-untranslated region. The Xenopus ferritin sequence is highly isologous with other vertebrate ferritins. In particular, there is a complete sequence identity for the iron-responsive element (IRE) located in the 5'-untranslated region in both XL2-17 and Rana catesbeiana ferritin mRNAs. The position of this IRE is unusual since it is located 489 nucleotides from the 5' end of the ferritin mRNA. Our analysis of phylogenetic relationships among ferritins indicates that all amphibian ferritins thus far sequenced would be more closely related to the mammalian H-type ferritin than to the L-type. The level of ferritin mRNA in XL2 cells rises 10- to 15-fold following exposure of cells to cadmium or copper. This increase is due to both transcriptional and translational regulation. A 10-fold increase was also found at the protein level. These results suggest that ferritin may be a primary detoxification response to heavy metals in Xenopus cells.
DNA Cell Biol 1991 Oct
PMID:Molecular cloning and expression of ferritin mRNA in heavy metal-poisoned Xenopus laevis cells. 171 17

Iron regulatory factor (IRF), also called iron responsive element-binding protein (IRE-BP), is a cytoplasmic RNA-binding protein which regulates post-transcriptionally transferrin receptor mRNA stability and ferritin mRNA translation. By using the polymerase chain reaction (PCR) and the sequence published by Rouault et al. (1990) a probe was derived which permitted the isolation of three human IRF cDNA clones. Hybridization to genomic DNA and mRNA, as well as sequencing data indicated a single copy gene of about 40 kb specifying a 4.0 kb mRNA that translates into a protein of 98,400 dalton. By in vitro transcription of a assembled IRF cDNA coupled to in vitro translation in a wheat germ extract, we obtained full sized IRF that bound specifically to a human ferritin IRE. In vitro translated IRF retained sensitivity to sulfhydryl oxidation by diamide and could be reactivated by beta-mercaptoethanol in the same way as native placental IRF. An IRF deletion mutant shortened by 132 amino acids at the COOH-terminus was no longer able to bind to an IRE, indicating that this region of the protein plays a role in RNA recognition. Placental IRF has previously been shown to migrate as a doublet on SDS-polyacrylamide gels. After V8 protease digestion the heterogeneity was located in a 65/70 kDa NH2-terminal doublet. The liberated 31 kDa COOH-terminal polypeptide was found to be homogeneous by amino acid sequencing supporting the conclusion of a single IRF gene.
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PMID:Expression of active iron regulatory factor from a full-length human cDNA by in vitro transcription/translation. 173 1

The aim of this study was to determine the crude prevalence of alpha-thalassemia traits in Taiwan. A total of 1435 healthy employees from a statewide company were randomly screened by complete blood count determination with indices. Subjects with mean corpuscular volume less than 80 fl were analyzed by hemoglobin electrophoresis on cellulose acetate to exclude beta-thalassemia and with serum ferritin to exclude iron deficiency. Modified hemoglobin H inclusion staining was performed to confirm the diagnosis of alpha-thalassemia traits, and DNA probe studies were used to confirm the validity of this test. The overall prevalence rate of alpha-thalassemia trait was 3.4% (48 out of 1435). In persons of mainland Chinese origin, prevalence was 0.4%, and among persons of Taiwanese origin, it was 4.0% (47 out of 1171). We conclude that alpha-thalassemia traits are common genetic disorders in Taiwan and that antenatal screening is advised to reduce the frequency of occurrence of hemoglobin Bart's hydrops fetalis. The methods we used proved to be reliable and inexpensive.
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PMID:Alpha-thalassemic traits are common in the Taiwanese population: usefulness of a modified hemoglobin H preparation for prevalence studies. 174 8

The reduction of ribonucleotides to deoxyribonucleotides, a rate-limiting step in DNA synthesis, is catalyzed by ribonucleotide reductase. This enzyme is composed of two components, M1 and M2. Recent work has shown that inhibition of ribonucleotide reductase by the antitumor drug hydroxyurea leads to a destabilized iron centre in protein M2. We have examined the relationship between the levels of ferritin, the iron storage protein, and the iron-containing M2 component of ribonucleotide reductase. These studies were carried out with hydroxyurea-sensitive, -resistant, and -revertant cell lines. Hydroxyurea-resistant mouse L cells contained M2 gene amplification and elevated levels of enzyme activity, M2 message, and total cellular M2 protein concentration. Hydroxyurea-revertant cells exhibited a wild-type M2 gene copy number, and approximately wild-type levels of enzyme activity, M2 message, and M2 protein concentration. In addition, we observed that the hydroxyurea-resistant cells possessed elevated levels of L-chain ferritin message and total cellular H-chain ferritin protein when compared to wild-type cells. In contrast, the revertant cell population contained approximately wild-type levels of ferritin mRNA and protein. In keeping with these observations, obtained with mouse L cells, was the finding that hydroxyurea-resistant Chinese hamster ovary cells with increased ribonucleotide reductase activity exhibited elevated expression of both ferritin and M2 genes, which declined in drug-sensitive revertant hamster cell lines with decreased levels of ribonucleotide reductase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correlation between levels of ferritin and the iron-containing component of ribonucleotide reductase in hydroxyurea-sensitive, -resistant, and -revertant cell lines. 179 65

We have isolated non-globin cDNA clones specific for erythroid differentiation from K562 human erythroleukemia cells and have identified those that may regulate globin gene transcription. A cDNA library was constructed from K562 cells induced by hemin for production of embryonic and fetal hemoglobins and screened against cDNA from uninduced K562 cells. Full-length clones specific for induced K562 cells were ligated into a eukaryotic expression vector and transfected into HeLa cells to allow for production of the corresponding coded polypeptide. The ability to increase epsilon- or gamma-globin promoter activity was identified using cotransfection with a second vector containing a globin gene promoter fused to a reporter gene. Six of the induced K562-specific clones exhibited the ability to increase the levels of the reporter genes, bacterial chloramphenicol acetyltransferase and human growth hormone. Sequencing analyses of these clones indicated that five were homologous to ferritin heavy and light chains and one had no homology with known DNA or protein sequences. The ferritin light chain cDNA had the greatest effect on globin gene promoter activation, increasing the gamma-globin promoter activity by 6-8-fold. The activation of the globin gene promoter in the absence of globin gene translation suggests that ferritin (or iron) may have a direct role in globin gene transcription. The subtractive library cloning strategy has enabled us to isolate cDNA clones that activate specific gene promoter without the requirement of direct DNA binding. This approach may allow further identification of the genes encoding proteins that are involved in the control of erythropoiesis.
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PMID:Activation of globin gene expression by cDNAs from induced K562 cells. Evidence for involvement of ferritin in globin gene expression. 184 May 94

Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.
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PMID:Iron and the liver. 184 76

The binding of Phaseolus vulgaris (PHA) isolectins L4 and E4 to the brush border membrane of differentiated Caco-2 cells was studied and the impact on cellular metabolism and microvilli was assessed. Computer analysis of the data based on binding experiments with peroxidase conjugated isolectins gave mean (SD) values for maximal binding of 2540 (151).10(-9) M for PHA-L4 and 2104 (140).10(-9) M for PHA-E4 per mg of brush border membrane protein. The dissociation constants for L4 and E4 binding were 4.3 (1.4).10(-6) M and 1.1 (0.8).10(-6) M, respectively. Incubation of differentiated Caco-2 cells for 30 minutes with ferritin conjugated PHA isolectins showed that, as indicated by the number of ferritin particles, PHA-E4 bound to the microvilli to a greater extent than PHA-L4. Ferritin particles were also localised intracellularly over endocytotic invaginations and vesicles. After incubation for 48 hours with PHA-L4 or PHA-E4, the relative incorporation of precursors for DNA, RNA, and (glyco)protein synthesis into the trichloroacetic acid insoluble fraction of the Caco-2 cells was determined. Both isolectins stimulated the incorporation of thymidine and glucosamine, but neither PHA-L4 nor PHA-E4 were able to influence the incorporation of uridine. With respect to fucose, methionine, and N-acetyl mannosamine, the stimulatory effect remained confined to PHA-E4. Since PHA-L4 and PHA-E4 were tested at the same concentrations, PHA-E4 is more effective than PHA-L4. The changes in the uptake of radioactive precursors were lost after heat inactivation of PHA-E4. Compared with control and PHA-L4 incubated Caco-2 cells, the microvilli of PHA-E4 incubated cells were shortened significantly (p less than 0.01).
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PMID:Binding of kidney bean (Phaseolus vulgaris) isolectins to differentiated human colon carcinoma Caco-2 cells and their effect on cellular metabolism. 186 41

A cDNA containing the entire coding region for the iron storage protein ferritin has been isolated from the French bean plant, Phaseolus vulgaris L. cv. Tendergreen. Ferritin protein was purified from young leaves and shoot meristem tissue and used to raise antisera in mice. A lambda gt11 cDNA library was constructed from seed-derived poly(A)+ RNA, and screened with the mouse anti-ferritin serum. A 1.2 kb immunopositive phage DNA insert was isolated and sequenced. The derived amino acid sequence shows substantial similarity with other ferritin sequences. The 5' untranslated region contains two out-of-frame AUG codons, a region of extreme pyrimidine composition bias and potentially stable secondary structure.
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PMID:The structure of a Phaseolus vulgaris cDNA encoding the iron storage protein ferritin. 188

Yersinia pestis is one of many microorganisms responding to environmental iron concentrations by regulating the synthesis of proteins and an iron transport system(s). In a number of bacteria, expression of iron uptake systems and other virulence determinants is controlled by the Fur regulatory protein. DNA hybridization analysis revealed that both pigmented and nonpigmented cells of Y. pestis possess a DNA locus homologous to the Escherichia coli fur gene. Introduction of a Fur-regulated beta-galactosidase reporter gene into Y. pestis KIM resulted in iron-responsive beta-galactosidase activity, indicating that Y. pestis KIM expresses a functional Fur regulatory protein. A cloned 1.9-kb ClaI fragment of Y. pestis chromosomal DNA hybridized specifically to the fur gene of E. coli. The coding region of the E. coli fur gene hybridized to a 1.1-kb region at one end of the cloned Y. pestis fragment. The failure of this clone to complement an E. coli fur mutant suggests that the 1.9-kb clone does not contain a functional promoter. Subcloning of this fragment into an inducible expression vector restored Fur regulation in an E. coli fur mutant. In addition, a larger 4.8-kb Y. pestis clone containing the putative promoter region complemented the Fur- phenotype. These results suggest that Y. pestis possesses a functional Fur regulatory protein capable of interacting with the E. coli Fur system. In Y. pestis Fur may regulate the expression of iron transport systems and other virulence factors in response to iron limitation in the environment. Possible candidates for Fur regulation in Y. pestis include genes involved in ferric iron transport as well as hemin, heme/hemopexin, heme/albumin, ferritin, hemoglobin, and hemoglobin/haptoglobin utilization.
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PMID:Identification and cloning of a fur regulatory gene in Yersinia pestis. 189 28


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