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)

The knowledge of the route through which iron can enter and leave the apoferritin shell is a prerequisite for the understanding of ferritin's function. The involvement of the hydrophilic 3-fold channels in the iron uptake process has been studied by taking advantage of the reactivity of specific residues that line such channels, i.e., glutamic acid-127 and aspartic acid-130, the major Cd(II) binding sites, and cysteine-126. 113Cd NMR experiments have provided direct evidence for the competition between Fe(II) and Cd(II) binding to major Cd(II) binding sites on the protein and or a higher affinity of Fe(II) for these sites, in line with the well-known inhibitory effect of Cd(II) on iron uptake. Further evidence for the use of the 3-fold channels in the iron entry process has been obtained by means of chemical modification of Cys-126 with different mercurials. In particular, the introduction of the additional carboxylate carried by p-(chloromercuri)benzoate near Asp-127 and Glu-130 increases the initial rate of iron uptake and affects the coordination geometry of the metal in the Fe(III)-apoferritin complex as indicated by optical absorption and EPR data. The assignment of these effects to the carboxylate moiety of p-(chloromercuri)benzoate is brought out by the observation that the introduction in the 3-fold channel of the benzene ring only by means of phenylmercuric acetate has no effect on the initial iron uptake kinetics and on the spectroscopic properties of the Fe(III)-apoferritin complex.
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PMID:Identification of the iron entry channels in apoferritin. Chemical modification and spectroscopic studies. 253 62

Ferritin was isolated from the spleen of sheep and found to contain an iron/protein content of 21 per cent. Electrophoretic behaviour on 6 per cent polyacrylamide gel revealed three protein bands of Rf values of 5.7, 19.3 and 76.1. Sheep ferritin has a molecular weight of about 475,000 daltons and is high in glutamic acid, leucine and aspartic acid and low in methionine and cysteine. Sheep ferritin is not crystallisable by 10 per cent cadmium sulphate and has an ultraviolet-visible spectrum similar to that of bovine ferritin. Anti (sheep) ferritin antibodies raised in rabbits showed a 57.1 per cent binding at a serum dilution of 1:800 and 30 per cent binding at a 1:12,800 dilution, in a titre determination using double antibody assay procedure.
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PMID:Isolation of sheep spleen ferritin. 647 7

The mechanisms involved and the potentially useful therapeutic strategies in the prevention of acute renal failure (ARF) are briefly reviewed. Factors mentioned are the role of calcium channel blockers, the antioxidant agents, heme oxygenase induction, and ferritin synthesis; and of substances with hemodynamic actions in ARF; such as endothelin, atrial natriuretic peptide, urodilatin, PAF antagonist, prostaglandins, diuretics, and dopamine. The loss of tubular epithelium polarity, the mechanisms involved in this process, and the usefulness of arginine-glycine-aspartic acid peptide and anti-ICAM antibodies in the prevention of tubular obstruction are also reviewed.
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PMID:Therapeutic strategies in the prevention of acute renal failure. 910 98

A novel extracellular mycobacterial enzyme was identified in the ruminant pathogen Mycobacterium paratuberculosis. The enzyme was capable of mobilizing iron from different sources such as ferric ammonium citrate, ferritin, and transferrin by reduction of the metal. The purified reductase had a calculated Mr of 17,000, was sensitive to proteinase K treatment, and had an isoelectric point of pH 9. Analysis of the amino acid composition revealed glycine, serine, asparagine (or aspartic acid), and glutamine (or glutamic acid) as the most frequently occurring residues. Enzymatic activity was highest at 37 degrees C and between pH 5 and 10. The calculated Km and Vmax for ferric ammonium citrate were 0.213 mM and 0.345 mM min(-1) mg(-1), respectively. Using a specific antireductase antibody in immunoelectron microscopy, we were able to detect the enzyme associated with intracellular mycobacteria in naturally M. paratuberculosis-infected bovine tissue. We prepose that the reductase of M. paratuberculosis represents an alternative strategy of mycobacteria to mobilize ferric iron and discuss its potential role in bacterial evasion of intracellular defense mechanisms.
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PMID:Identification and characterization of a novel extracellular ferric reductase from Mycobacterium paratuberculosis. 945 31

We describe a case of homozygosity due to the substitution of aspartic acid with histidine at position 63 of the protein encoded by the gene (known as HFE) associated with hereditary hemochromatosis. Liver biopsy did not disclose stainable iron accumulation; serum ferritin was elevated (639 ng/mL), while the transferrin saturation index was within the normal range (38.1%). As the patient was affected by chronic hepatitis C virus, the high serum ferritin could be attributed to this disease, a frequent occurrence. We also describe a case of heterozygosity for both the substitution of tyrosine with cysteine at position 282 and the substitution of histidine to aspartic acid at position 63 (so-called "compound heterozygosity"). The patient had the typical biochemical abnormalities of iron overload: transferrin saturation index of 53.1% and elevated serum ferritin (658 ng/mL). The removal of > 5 g of iron by phlebotomies did not precipitate iron deficiency. Although the patient refused to undergo liver biopsy, clinical evidence alone enabled a diagnosis of hemochromatosis. These two cases concord with the present scientific orientation, i.e.: 1) homozygosity for the major mutation is associated with the phenotypical (clinical) picture of hemochromatosis, but compound heterozygosity also determines significant iron metabolism abnormalities; 2) homozygosity for the minor mutation does not appear to determine important phenotypical abnormalities.
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PMID:[Significance of "minor" genetic mutations in hereditary hemochromatosis: 2 case reports]. 1105 64

In this paper, we proposed a naturally derived protein cage based pH-responsive delivery system for intracellular prodrug controlled release. The drug delivery system is based on apoferritin as delivery vehicles to encapsulate the anticancer drug daunomycin (DN) and alleviate the side effect. The hydrophobic drug DN was encapsulated into the interior of apoferritin by the hydrophobic channels of the cage with swelling at slight acidic pH and electrostatic adsorption. The negatively charged poly-l-aspartic acid (PLAA) was further introduced into the apoferritin to absorb the positively charged DN. The mixture of PLAA and DN easily flew into the apoferritin cage and was stably stored in the physiological fluids. PLAA protected the leakage of DN and encapsulated a sufficient amount of drug molecules in the cage. To specifically target the tumor cells, the surface of apoferritin was modified with hyaluronic acid (HA) which can easily bind to the HA-receptor CD44. Here, human embryonic lung MRC-5 cells and lung cancer A549 cells were used to observe the specific binding of HA and morphological changes in vitro and examine the antitumor activity. This unique protein based drug delivery platform using the apoferritin cage shows great potential in the therapeutic administration of the anti-cancer agents.
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PMID:Hyaluronic acid-conjugated apoferritin nanocages for lung cancer targeted drug delivery. 2630

Sustaining blood retention for theranostic nanoparticles is a big challenge. Various approaches have been attempted and have demonstrated some success but limitations remain. We hypothesized that peptides capable of increasing blood residence time for M13 bacteriophage, a rod-shaped nanoparticle self-assembled from proteins and nucleic acids, should also prolong blood circulation for engineered nanoparticles. Here we demonstrate the feasibility of this approach by identifying a series of blood circulation-prolonging (BCP) peptides through in vivo screening of an M13 peptide phage display library. Intriguingly, the majority of the identified BCP peptides contained an arginine-glycine-aspartic acid (RGD) motif, which was necessary but insufficient for the circulation-prolonging activity. We further demonstrated that the RGD-mediated specific binding to platelets was primarily responsible for the enhanced blood retention of BCP1. The utility of the BCP1 peptide was demonstrated by fusion of the peptide to human heavy-chain ferritin (HFn), leading to significantly improved pharmacokinetic profile, enhanced tumor cell uptake and optimum anticancer efficacy for doxorubicin encapsulated in the HFn nanocage. Our results provided a proof-of-concept for an innovative yet simple strategy, which utilizes phage display to discover novel peptides with the capability of substantially prolonging blood circulation for engineered theranostic nanoparticles.
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PMID:Blood Circulation-Prolonging Peptides for Engineered Nanoparticles Identified via Phage Display. 3073 Jan 45