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)

1. Infant rats and rabbits received intraperitonal aluminium (Al) chloride (5, 10 or 20 mg Al/kg body weight) every third day from one to four weeks of age. 2. When the polysomal fraction was tested in a protein synthesizing system, a significant increase in the incorporation of [14C] leucine, [14C] phenylalanine, or [35S] methionine into proteins in vitro was observed at the higher doses in rats but not rabbits. 3. The incorporation of [35S]methionine into brain ferritin was measured using polysomal mRNA or mRNA "stored" in the ribonucleoprotein (RNP) particle fraction. 4. The results suggest that Al exposure causes the mobilization of ferritin mRNA from the latter fraction to the polysomal fraction for increased ferritin synthesis.
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PMID:Some effects of aluminium on rat brain protein synthesis. 136 9

Mammalian brains contain low levels of the Alzheimer amyloid precursor variants (AAPPs) and the normal form of the scrapie agent protease-resistant protein (PrPc); however, their mRNAs are readily detectable. To understand these discrepancies we have investigated some aspects of the translational regulation of these mRNAs. An accurate blot-hybridization procedure was developed to measure absolute amounts of mRNA. Rat brain contains the following mRNA levels (ng/g tissue) AAPP(695), 170; AAPP(751/770), 63; PrPc, 144; actin, 615; glyceraldehyde-3-phosphate dehydrogenase (G3PDH), 359; ferritin, 148. The method was also used to determine the distribution of mRNAs between translationally active polysomes and translationally inactive ribonucleoprotein protein particles (mRNPs). More than 90% of G3PDH and actin mRNAs were associated with polysomal RNA; whereas, ferritin light chain mRNA was predominantly (90%) in mRNP RNA. The degree of cross-contamination of mRNPs with polysomes was less than 10%. Probes specific for the scrapie PrP protein and the AAPP(695) splice junction revealed that 70% of these mRNAs were associated with polysomes. One-half of AAPP(751/770) mRNAs (which comprise 20-30% of all AAPP mRNA in brain) were found in polysomes. We conclude therefore that both scrapie and AAPP mRNAs are subject to translational regulation in rat brain. Evidence from in vitro translational experiments confirm the message distribution determined by blot hybridization and corroborate the hypothesis that AAPP is subject to partial post-transcriptional regulation. Nevertheless, the low tissue levels of AAPP and PrPc must result primarily from their relatively rapid turnover.
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PMID:Distribution and activity of alternatively spliced Alzheimer amyloid peptide precursor and scrapie PrP mRNAs on rat brain polysomes. 168 Mar 10

Estrogen causes the cytoplasmic destabilization of albumin and gamma-fibrinogen mRNA in Xenopus laevis liver. The purpose of the present study was to determine whether mRNA destabilization is a generalized phenomenon in response to estrogen, or whether this process is restricted to a particular class of mRNAs. To address this, we have expanded our bank of serum protein-coding cDNA clones to include transferrin, the second protein of inter-alpha-trypsin inhibitor and clone 12B, for which there is no mammalian homolog. Together with albumin and gamma-fibrinogen, these represent more than 85% of the mRNAs encoding liver secreted proteins. Estrogen administration to male Xenopus or to liver explant cultures causes the generalized disappearance of all of these mRNAs. In contrast, estrogen has no effect on actin, ferritin, or poly(A)-binding protein mRNA, all of which encode intracellular proteins. We have previously demonstrated that albumin mRNA is degraded in both messenger ribonucleoprotein and polysome fractions. Sucrose gradient analysis demonstrates the same pattern for degradation of all other serum protein-coding mRNAs. Estrogen has no effect on the amounts or gradient distribution of actin, ferritin, or poly(A)-binding protein mRNA. We conclude that regulated destabilization of mRNAs encoding secreted proteins is a generalized phenomenon in response to estrogen stimulation of Xenopus liver.
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PMID:Coordinate estrogen-regulated instability of serum protein-coding messenger RNAs in Xenopus laevis. 192 78

Ferritin messenger RNA has been shown to be translationally inactivated by the binding of a cytosolic protein to a 28-nucleotide iron-responsive element (IRE) located in the 5'-untranslated region of the mRNA. This interaction has been studied using quantitative receptor-ligand binding methods with gel retardation and nitrocellulose filter binding assays for the separation of bound complex from free RNA. In competition assays the entire 5'-untranslated region and the isolated IRE bound identically. The specificity of the RNA binding was studied using IRE variants. Two IREs from transferrin receptor mRNA and several variants with single base substitutions in the stem or loop had similar affinities. RNAs which could not form a stem-loop structure bound 1000-fold less well. These studies demonstrate the importance of the RNA conformation and the relative insensitivity of binding to much of the primary sequence. Saturation assays with increasing concentrations of 32P-IRE resulted in a binding hyperbola characteristic of mass action binding to a single class of sites with a KD = 0.09 nM. At 37 degrees C the dissociation rate is 0.04 min-1 (t 1/2 = 17 min). This rate is fast enough to account for the shift of ferritin RNA from the ribonucleoprotein pool to polysomes after rats are injected with iron. Determination of the concentration of the repressor requires accounting for three interconverting pools: free active repressor, mRNA-bound protein, and inactive (low affinity) repressor. Rat liver cytosol has a concentration of free active repressor of about 1 pmol/mg protein. Protein bound to endogenous mRNA can be measured by pretreatment with micrococcal nuclease or by separation with DEAE-Sepharose chromatography; it is present at a level similar to that of the free active protein. Inclusion of high levels of thiol reductants in the binding incubations reduces the inactive or low affinity repressor, forming unstably activated protein which has the same KD as the endogenous active protein; this inactive or low affinity protein is 2-4 times more abundant. A mechanism for iron regulation is proposed which accounts for the kinetics, the multiple protein pools, and the characteristics of the protein in these pools.
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PMID:Determinants of the interaction between the iron-responsive element-binding protein and its binding site in rat L-ferritin mRNA. 232 9

Translational control of ferritin synthesis was studied in rat spleen, and compared with that for liver, heart and brain, in response to iron and inflammation. Spleen concentrations of total RNA in the ribonucleoprotein (mRNP) fraction was comparable to that for liver, while polyribosomal RNA was less. Both fractions were ten-fold lower in heart and brain. In untreated animals, the mRNP fraction of all tissues had the largest portion of the ferritin mRNA, as determined by slot blot hybridization with 32P-labeled cDNA for the L subunit. Acute treatment with ferric ammonium citrate shifted the spleen ferritin mRNA to the polyribosome fraction. This was also so in liver but not in the heart and brain which took up much less iron. The findings were confirmed by hybridization studies of mRNPs and polyribosomes separated in sucrose gradients. Turpentine-induced inflammation also caused a shift in ferritin mRNA from the mRNP to the polyribosome fraction of spleen and liver, over 12 h. We conclude that as in liver, spleen ferritin synthesis is under translational control by iron, and that both tissues also respond to inflammation by shifting of ferritin mRNA to the polyribosomes.
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PMID:Translational regulation of ferritin synthesis in rat spleen: effects of iron and inflammation. 247 Mar 68

In rats with chronic dietary iron overload, a higher amount of liver ferritin L-subunit mRNA was found mainly engaged on polysomes, whereas in control rats ferritin L-subunit mRNA molecules were largely stored in ribonucleoprotein particles. On the other hand, ferritin H-subunit mRNA was unchanged by chronic iron load and remained in the inactive cytoplasmic pool. In agreement with previous reports, in rats acutely treated with parenteral iron, only the ferritin L-subunit mRNA increased in amount, whereas both ferritin subunit mRNAs shifted to polysomes. This may indicate that, whereas in acute iron overload the hepatocyte operates a translation shift of both ferritin mRNAs to confront rapidly the abrupt entry of iron into the cell, during chronic iron overload it responds to the slow iron influx by translating a greater amount of L-subunit mRNA to synthesize isoferritins more suitable for long-term iron storage.
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PMID:Translational regulation of ferritin synthesis in rat liver. Effects of chronic dietary iron overload. 261 20

The mRNAs for the heavy and light subunits of the iron-storage protein ferritin occur in cells largely as inactive ribonucleoprotein particles, which are recruited for translation when iron enters the cell. Cytoplasmic extracts from rat tissues and hepatoma cells were shown by an electrophoretic separation procedure to form RNA-protein complexes involving a highly conserved sequence in the 5' untranslated region of both ferritin heavy- and light-subunit mRNAs. The pattern of complex formation was affected by pretreatment of rats or cells with iron. Crosslinking by UV irradiation showed that the complexes contained an 87-kDa protein interacting with the conserved sequence of the ferritin mRNA. We propose that intracellular iron levels regulate ferritin synthesis by causing changes in specific protein binding to the conserved sequence in the ferritin heavy- and light-subunit mRNAs.
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PMID:Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs. 312 26

Synthesis of the iron storage protein ferritin is induced in rat liver by iron administration, the ferritin L subunit being preferentially stimulated over the H subunit. To examine the basis for this differential regulation of the two subunits, the transcription rates of the L and H genes, the total cellular levels of L and H subunit mRNA, and the distribution of the mRNAs between a stored ribonucleoprotein form and the polysomes were examined in rat liver at several times after iron injection. Iron caused a rapid increase in transcription of the L subunit gene, followed by a rise in L mRNA levels, whereas H subunit gene transcription and H mRNA levels did not increase significantly. Differential transcriptional regulation of ferritin L and H mRNA levels by iron contrasted with the coordinate control of the two subunit mRNAs at the translational level. On giving iron, there was a rapid and synchronous shift of both mRNAs from the ribonucleoprotein fraction onto the polysomes, the same proportion of each mRNA being mobilized. Thus, regulation of ferritin subunit synthesis at these two levels allows both a rapid translational response and a specific transcriptional response to increased intracellular iron levels.
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PMID:Induction of ferritin subunit synthesis by iron is regulated at both the transcriptional and translational levels. 337 54

The translation of a small number of mRNAs in mouse SC-1 fibroblasts can be stimulated by cycloheximide, under conditions where the synthesis of most proteins is inhibited. These mRNAs are ordinarily present in small polyribosomes or messenger ribonucleoprotein particles, although the addition of cycloheximide drives them into large (greater than or equal to 5) polysomes. These mRNAs cannot be translated in vitro unless they are extracted with phenol. With such treatment, however, they are translated with normal competitive efficiencies. In iron-poor media, the mRNA for ferritin exhibits several of the distinctive kinetic properties of this class of mRNAs. With iron supplementation, however, ferritin translation appears normal. These observations are consistent with the existence of translational induction/repression systems in eukaryotes. Several types of evidence suggest that repressors may act by interfering with the interaction between mRNAs and limiting translational initiation components.
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PMID:Translational control of gene expression in a normal fibroblast. Characterization of a subclass of mRNAs with unusual kinetic properties. 370 30

The development of type 2 parainfluenza virus in HeLa and stable human amnion cells was examined by use of antisera labeled with fluorescein and ferritin. Serum containing antibody predominantly to soluble viral antigen gave specific fluorescence which was first detectable in small cytoplasmic foci 8 to 10 hr after initiation of infection. By 20 to 24 hr, when the production of infective virus and hemagglutinin was maximal, large perinuclear aggregates of fluorescence were observed which corresponded in distribution and time of appearance to the eosinophilic inclusions seen in similar preparations stained with azure eosin. The inclusions, examined by electron microscopy, were composed of fibrils, presumably viral ribonucleoprotein, which specifically bound the antibody labeled with ferritin. With antiserum to concentrated virus, on the other hand, specific fluorescence was most marked at the surface of infected cells. Foci of fluorescence at the surface represented segments of membrane which had become differentiated morphologically and antigenically to resemble the viral envelope. These were the sites where mature virions appeared. The latter exhibited marked pleomorphism; in some instances, particles were formed which lacked recognizable internal fibrils but which possessed an enclosing membrane bearing viral antigen. Filamentous forms showing an organized internal structure were also observed at the cell surface, but were never encountered in negatively stained preparations. No clear relationship between these filaments and the spherical or oval forms could be established. In negatively stained preparations, nucleocapsid released by rupture of viral particles was similar in appearance to that reported for other paramyxoviruses. It seems probable that this component has a helical configuration.
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PMID:Morphogenesis of type 2 parainfluenza virus examined by light and electron microscopy. 431 44


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