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)

Iron regulatory proteins (IRPs) bind to specific RNA stem-loop structures known as iron-responsive elements (IREs) which mediate the post-transcriptional regulation of many genes of iron metabolism. Most studies have focused on the role of IRP1, which has previously been shown to bind with high affinity to IREs and mediate repression of in vitro translation of ferritin mRNAs. More recently, a second IRP has been identified that is expressed in all tissues and that binds IREs (Rouault, T. A., Haile, D. H., Downey, W. E., Philpott, C. C., Tang, C., Samaniego, F., Chin, J., Paul, I., Orloff, D., Harford, J. B., and Klausner, R. D. (1992) BioMetals 5, 131-140; Henderson, B. R., Seiser, C., and Kuhn, L. C. (1993) J. Biol. Chem. 268, 27327-27334; Guo, B., Yu, Y., and Leibold, E. A. (1994) J. Biol. Chem. 269, 24252-24260; Samaniego, F., Chin, J., Iwai, K., Rouault, T. A., and Klausner, R. D. (1994) J. Biol. Chem. 269, 30904-30910). Here we report that purified recombinant IRP2 inhibits translation of ferritin mRNAs with a molar efficacy equal to that of recombinant IRP1. There is a quantitative correlation between binding to isolated RNA target motifs, as judged by gel retardation assays, and translational repressor function as assayed in an in vitro translation system. In contrast to IRP1, IRP2 is not inactivated for RNA binding by alkylation with N-ethylmaleimide or phenylmaleimide, and as we would therefore predict, IRP2 treated with N-ethylmaleimide remains an effective repressor of ferritin translation. As IRP1 and IRP2 clearly have equal capability of mediating translational repression in vitro, the contributions of both IRPs to overall regulation must be considered in describing the pathways of iron regulated gene expression in individual cells.
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PMID:Translational repressor activity is equivalent and is quantitatively predicted by in vitro RNA binding for two iron-responsive element-binding proteins, IRP1 and IRP2. 789 Jun 3

Over a 9-year period, twelve patients (8 boys, 4 girls), from 3 to 14 years old, were diagnosed as having Still's disease. Intermittent spiking high fever, poly- or pauci- articular arthritis, and typical evanescent skin rash were the most prominent clinical features. Hemogram examinations showed that 36% of the patients had anemia, ninety-two percent had neutrophilic leukocytosis and 78% had thrombocytosis. Serologically, none had positive results of rheumatoid factor and anti-nuclear antibody. Serum ferritin level was obtained from six patients and all revealed marked elevation during active disease. C-reactive protein and erythrocyte sedimentation rate were both invariably elevated. Immunologically, elevated serum concentrations of IgG, IgA, and complements (C3, C4) were found in 33%, 20%, and 17%, respectively. Furthermore, eighty percent of patients showed an increased serum level of circulating immune complexes. Aspirin (ASA) was used in all patients, but 92% of them required non-steroid antiinflammatory drugs (NSAIDs) in combination to get a better response. Sixty-seven percent of patients needed corticosteroids to control the acute systemic manifestations. Other disease-modifying agents were also used in 33% of our patients. ASA-induced liver function impairment was found in two cases. In addition, one patient experienced an episode of upper gastrointestinal bleeding. Generally speaking, the overall prognosis was good. One patient (8%) died of internal bleeding after a needle liver biopsy.
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi
PMID:Still's disease: experience in 12 children. 823 59

We have reported previously that the heavy chain of ferritin is required for iron incorporation by ceruloplasmin (J.-H. Guo, M. Abedi, and S. D. Aust (1996) Arch. Biochem. Biophys. 335(1)). The purpose of this study was to determine how many heavy chains were required for ceruloplasmin to interact with ferritin such that iron loading occurred. The cDNA sequences encoding the heavy and light chains of rat liver ferritin were cloned into the baculovirus transfer vector pA-cUW51 under the control of polyhedrin and p10 promoters, respectively, which was then incorporated by homologous recombination into the infections Autographa californica nuclear polyhedrosis virus genome. Both ferritin chains were expressed and assembled into two heteropolymers following the infection of insect cells by recombinant virus, which were separated by DEAE-Sepharose chromatography. The percentage of heavy (H) and light (L) chains making up the two heteropolymers, determined by gel scanning following the resolution of chains on SDS-PAGE, were equivalent to 1 H and 23 L chains and 2 H and 22 L chains. The maximal extent of iron loading was observed using 1 mol of rat ceruloplasmin per mole of H chain in the two heteropolymers. The extent of iron incorporation decreased with additional ceruloplasmin. Iron incorporation into rat liver ferritin, found to contain 10 H chains, increased as the molar ratio of ceruloplasmin to ferritin increased to 4:1 and remained the same up to 8:1. Iron loading into horse spleen ferritin, found to have one H chain, appeared similar to that for recombinant ferritin, having only one H chain. Therefore, we propose that the optimal molar ratio of ceruloplasmin to ferritin depends upon the numbers of H chain making up the ferritin molecule for the maximal incorporation of iron into ferritin. These results also suggest that the iron loading channel is contained within a single H chain subunit.
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PMID:Loading of iron into recombinant rat liver ferritin heteropolymers by ceruloplasmin. 916 16

We previously reported that the heavy chain of ferritin was required for loading it with iron using ceruloplasmin as a ferroxidase [J.-H. Guo, M. Abedi, and S. D. Aust (1996) Arch. Biochem. Biophys. 335, 197-204]. Site-directed mutagenesis, K58E and G61H, on recombinant rat liver L chain ferritin (rL-Ft) was performed to construct a proposed iron-loading channel in the alpha-helix bundle similar to rat liver H chain ferritin (rH-Ft). Conversely, the channel in rH-Ft was closed by mutations E62K and H65G to form a K62 to E107 salt bridge, which is believed to exist in the L chain. Both variants were expressed in insect cells and were soluble and able to form multi-subunit homopolymers. The rH-Ft mutant homopolymer could not be loaded, whereas the rL-Ft mutant homopolymer could be loaded with iron by ceruloplasmin. However, we found that the initial rate of iron loading into the rL-Ft mutant homopolymer by ceruloplasmin was less than that into the rH-Ft homopolymer. When 500 atoms of iron per ferritin were used for loading, 98% was loaded into the rH-Ft homopolymer by ceruloplasmin in 15 min, but only 30% was loaded into the rL-Ft mutant homopolymer in the same time. Moreover, the ferroxidase activity of ceruloplasmin was enhanced in the presence of the rH-Ft and the rH-Ft mutant homopolymers, but not in the presence of the rL-Ft or the rL-Ft mutant homopolymers. These observations suggested that the four alpha-helix bundle channel of ferritin is required for iron loading, but an additional factor, i.e. , a site which stimulate the ferroxidase activity of ceruloplasmin, is also essential.
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PMID:Mutational analysis of the four alpha-helix bundle iron-loading channel of rat liver ferritin. 952 17

We are interested in learning how iron is safely inserted and stored in ferritin. Recombinant DNA technology has considerable potential in determining the functional roles of the two ferritin subunits (H and L). In previous studies, we have observed that recombinant rat H ferritin was repressive to cell growth in both prokaryotic and eukaryotic expression systems (Guo et al., Biochem. Biophys. Res. Commun. 242, 39-45 (1998)). This results in the protein being expressed at very low levels. This problem was partially bypassed by the use of an inducible expression system, which utilizes T7 RNA polymerase dependent expression of the gene, induced by isopropyl beta-D-thiogalactopyranoside (IPTG). Simultaneously expressing the H and L ferritin genes in this system resulted in only a narrow range of ferritin heteromers, which predominantly consisted of the L subunit. Addition of rifampicin to cultures, 1 h following the induction of protein synthesis by IPTG, increased the production of the H subunit and thus increased the range of ferritin H:L subunit ratios. Simultaneous expression of the H and L ferritin genes in Escherichia coli grown in a deficient medium with minimal iron and with the addition of rifampicin resulted in the production of a range of recombinant human apoferritin heteromers that could be separated based on their subunit composition.
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PMID:Production of recombinant human apoferritin heteromers. 1114 22