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)

Twenty-five premature infants (mean gestational age+/-SD, 31.4+/-1.9 weeks) were administered subcutaneously recombinant human erythropoietin (rHuEpo) at a dose of 300 u/kg of body weight three times a week beginning on the third day of life and continuing for 6 weeks. The controls (n=23) were premature infants with a mean gestational age of 32.2+/-2.3 weeks who did not receive rHuEpo. Haematological indices, haemoglobin and serum phosphate (Pi), and red blood cell (RBC) phosphate metabolites (ATP, 2,3-DPG, RBCPi) were tested monthly until the 6th month and thereafter at the 9th and 12th months of life. The level of serum soluble transferrin receptors (sTfR) correlated significantly with rHuEpo (p<0.05). The ratio of sTfR to log (ferritin) was significantly higher (p<0.001) in the infants treated with rHuEpo than the controls. Intracellular organic and inorganic Pi changes were not affected by the Epo administration. The RBC 2,3-DPG seemed adequate in infants receiving rHuEpo.
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PMID:Effect of recombinant human erythropoietin in preterm infants. 1048 Feb 85

Gout affects mostly males over 40 years old and, occasionally, postmenopausal women. This pattern coincides with the pattern of iron accumulation. On the other hand, menstruating women are seldom afflicted by gout, because the monthly blood loss causes them to accumulate iron to a much lesser degree. Gout involves seven aspects: (1) uric acid overproduction from increased purines in the diet; (2) uric acid overproduction from ATP degradation; (3) uric acid overproduction from increased de novo synthesis of purines; (4) uric acid overproduction from increased DNA breakdown from cell damage; (5) decreased uric acid elimination, caused by molybdenum and sulfur binding to copper in the kidneys; (6) precipitation of sodium urate-iron crystals in the joints due to high ferritin and saturated transferrin and low CuZn-SOD and Cu-thionein in the joint; (7) development of inflammation, triggered by tyrosine bonding to the sodium-urate-iron crystals and being transformed by tyrosine kinase. Alcohol and iron greatly affect most of these aspects. Therefore, phlebotomy is suggested as therapy for gout patients, in order to eliminate the accumulated Fe. Furthermore, yearly blood donation is recommended for males with a family history of gout, so as to prevent Fe accumulation and avoid gout.
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PMID:Effect of gradual accumulation of iron, molybdenum and sulfur, slow depletion of zinc and copper, ethanol or fructose ingestion and phlebotomy in gout. 1061 42

Chlorella protothecoides cultures grown in a nitrogen-free bleaching medium (BM-N) in the dark rapidly degraded chlorophyll (Chl) to red catabolites. This degreening process was investigated under different growth conditions. Supply of nitrogen to the culture medium (BM+N) inhibited bleaching and the synthesis of catabolites as did the addition to BM-N of cycloheximide or a chelator, 2,2'-bipyridyl. In contrast, chloramphenicol or the protease inhibitor E64 had no effect. During bleaching, Chl breakdown was accompanied by the degradation of cellular proteins such as light-harvesting complex II, cytochrome f and protochlorophyllide oxido-reductase. During growth in BM-N, protease activity increased and proteins immunologically detectable with an antibody against a senescence-enhanced cysteine protease accumulated. cDNAs from BM-N and BM+N cells were used for differential and subtractive screening to isolate cDNAs representing genes with degreening-enhanced expression (dee) in C. protothecoides. Several different dees were identified with different patterns of expression during Chlorella growth but which were all expressed at higher levels during bleaching. Among these, dee4 was most abundant and its expression was exclusive in BM-N cultures. Analysis of the dee sequences showed that they encode different proteins including a novel amino acid carrier (dee4), ferritin, ATP-dependent citrate lyase, a Ca2+-binding protein, MO25, ubiquinone-cytochrome c-reductase and several new proteins.
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PMID:Chlorophyll breakdown in Chlorella protothecoides: characterization of degreening and cloning of degreening-related genes. 1079 14

We previously demonstrated ferritin binding is specific to white matter in mouse and human brain tissue and is not found within Multiple Sclerotic plaques. These results suggest that ferritin receptors are selectively expressed on oligodendrocytes. The present studies were designed to test the hypothesis that oligodendrocyte progenitor cells selectively bind ferritin and internalize it by methods consistent with receptor-mediated endocytosis. Using a cell culture system enriched for oligodendrocyte progenitor cells, we determined, that oligodendrocyte progenitor cells bind ferritin in a saturable and competitive manner with a K(d) of 5 nM and a receptor density of 0.06 fmol bound/20,000 cells. FITC tagged ferritin is internalized by A2B5, O4 or CNPase expressing cells in the culture, but not by GFAP+ cells. The uptake of ferritin into the oligodendrocyte progenitors was inhibited by treating the cells with inhibitors of receptor mediated endocytosis (hypertonic medium, potassium deficient medium, ATP depletion, sulfhydryl reagents). In addition exogenous ferritin decreased iron responsive element/iron regulatory protein binding indicating that the iron within the internalized ferritin is released and contributes to the intracellular iron pool. Given the relatively high amount of iron that can be delivered via ferritin, and the selective distribution of ferritin receptors in the white matter tracts in vivo, we propose that ferritin is a major source of iron for oligodendrocytes.
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PMID:Oligodendrocyte progenitor cells internalize ferritin via clathrin-dependent receptor mediated endocytosis. 1086 99

5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria (AIP) and lead poisoning, undergoes enolization and subsequent iron-catalyzed oxidation at neutral pH. Iron is released from horse spleen ferritin (HoSF) by both ALA-generated O(2)(.-) and enoyl radical (ALA(z.rad)), which amplifies the chain of ALA oxidation (autocatalysis). Iron chelators such as EDTA, ATP, but not citrate, and phosphate accelerate this process and ALA-promoted iron release from HoSF is faster in horse spleen isoferritins containing larger amounts of phosphate in the core. ALA (+0.377 V versus standard hydrogen electrode) is less effective in releasing iron from ferritin than are thioglycollic acid, 6-hydroxydopamine, and N,N,N', N'-tetramethyl-p-phenylenediamine. During electrochemical one electron oxidation of ALA in a nitrogen atmosphere, spin trapping experiments with 3,5-dibromo-4-nitrosobenzenesulfonic acid demonstrated the formation of a spin adduct characterized by a six line signal, indicating a secondary carbon-centered radical and attributed to a resonant ALA&z.rad; radical. Iron is also released in such anaerobic electrochemical oxidations of ALA in the presence of ferritin, suggesting that, in addition to O(2)(*-), ALA&z.rad; can promote iron mobilization from ferritin. Hence, ALA&z.rad; may amplify the metal-catalyzed oxidation of ALA, damaging ALA-accumulating cells and possibly contributing to the symptoms of porphyria.
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PMID:Roles of phosphate and an enoyl radical in ferritin iron mobilization by 5-aminolevulinic acid. 1111 17

Free radicals and other so-called 'reactive species' are constantly produced in the brain in vivo. Some arise by 'accidents of chemistry', an example of which may be the leakage of electrons from the mitochondrial electron transport chain to generate superoxide radical (O2*-). Others are generated for useful purposes, such as the role of nitric oxide in neurotransmission and the production of O2*- by activated microglia. Because of its high ATP demand, the brain consumes O2 rapidly, and is thus susceptible to interference with mitochondrial function, which can in turn lead to increased O2*- formation. The brain contains multiple antioxidant defences, of which the mitochondrial manganese-containing superoxide dismutase and reduced glutathione seem especially important. Iron is a powerful promoter of free radical damage, able to catalyse generation of highly reactive hydroxyl, alkoxyl and peroxyl radicals from hydrogen peroxide and lipid peroxides, respectively. Although most iron in the brain is stored in ferritin, 'catalytic' iron is readily mobilised from injured brain tissue. Increased levels of oxidative damage to DNA, lipids and proteins have been detected by a range of assays in post-mortem tissues from patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis, and at least some of these changes may occur early in disease progression. The accumulation and precipitation of proteins that occur in these diseases may be aggravated by oxidative damage, and may in turn cause more oxidative damage by interfering with the function of the proteasome. Indeed, it has been shown that proteasomal inhibition increases levels of oxidative damage not only to proteins but also to other biomolecules. Hence, there are many attempts to develop antioxidants that can cross the blood-brain barrier and decrease oxidative damage. Natural antioxidants such as vitamin E (tocopherol), carotenoids and flavonoids do not readily enter the brain in the adult, and the lazaroid antioxidant tirilazad (U-74006F) appears to localise in the blood-brain barrier. Other antioxidants under development include modified spin traps and low molecular mass scavengers of O2*-. One possible source of lead compounds is the use of traditional remedies claimed to improve brain function. Little is known about the impact of dietary antioxidants upon the development and progression of neurodegenerative diseases, especially Alzheimer's disease. Several agents already in therapeutic use might exert some of their effects by antioxidant action, including selegiline (deprenyl), apomorphine and nitecapone.
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PMID:Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. 1159 35

Oxidatively modified proteins that accumulate in aging and many diseases can form large aggregates because of covalent cross-linking or increased surface hydrophobicity. Unless repaired or removed from cells, these oxidized proteins are often toxic, and threaten cell viability. Most oxidatively damaged proteins appear to undergo selective proteolysis, primarily by the proteasome. Previous work from our laboratory has shown that purified 20 S proteasome degrades oxidized proteins without ATP or ubiquitin in vitro, but there have been no studies to test this mechanism in vivo. The aim of this study was to determine whether ubiquitin conjugation is necessary for the degradation of oxidized proteins in intact cells. We now show that cells with compromised ubiquitin-conjugating activity still preferentially degrade oxidized intracellular proteins, at near normal rates, and this degradation is still inhibited by proteasome inhibitors. We also show that progressive oxidation of proteins such as lysozyme and ferritin does not increase their ubiquitinylation, yet the oxidized forms of both proteins are preferentially degraded by proteasome. Furthermore, rates of oxidized protein degradation by cell lysates are not significantly altered by addition of ATP, excluding the possibility of an energy requirement for this pathway. Contrary to earlier popular belief that most proteasomal degradation is conducted by the 26 S proteasome with ubiquitinylated substrates, our work suggests that oxidized proteins are degraded without ubiquitin conjugation (or ATP hydrolysis) possibly by the 20 S proteasome, or the immunoproteasome, or both.
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PMID:Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasome. 1240 7

Citric acid is produced industrially by depriving Aspergillus niger of iron. The lack of Fe deactivates mitochondrial aconitase and interrupts the krebs cycle, causing the mitochondria to release citric acid as a siderophore (an Fe getter). When the mitochondrion has plenty of Fe and the cell has enough ATP, aerobic phosphorylation stops and fatty acid or haem synthesis take place, when the cell has plenty of haem, haem synthesis stops. Since most of the Fe activity in the cell is related to the mitochondria, I hypothesise that in the animal cell when the mitochondria are low in Fe, citric acid acts as a signal that triggers the production of transferrin receptor messenger RNA (TrR mRNA) in the nucleus, which in the absence of Fe causes the expression of transferrin receptor. When the cell has plenty of Fe, cytosolic aconitase detaches itself from the transferrin receptor and ferritin mRNA stopping expression of the former and initiating expression of the latter. The detached cytosolic aconitase transforms the citric acid, blocking the production of the transferrin receptor mRNA.
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PMID:Do mitochondria regulate cellular iron homeostasis through citric acid and haem production? Implications for cancer and other diseases. 1245 Jul 75

Aminoacetone (AA) is a threonine and glycine metabolite overproduced and recently implicated as a contributing source of methylglyoxal (MG) in conditions of ketosis. Oxidation of AA to MG, NH4+, and H2O2 has been reported to be catalyzed by a copper-dependent semicarbazide sensitive amine oxidase (SSAO) as well as by copper- and iron ion-catalyzed reactions with oxygen. We previously demonstrated that AA-generated O2*-. and enoyl radical (AA*) induce dose-dependent Fe(II) release from horse spleen ferritin (HoSF); no reaction occurs under nitrogen. In the present study we further explored the mechanism of iron release and the effect of AA on the ferritin apoprotein. Iron chelators such as EDTA, ATP and citrate, and phosphate accelerated AA-promoted iron release from HoSF, which was faster in horse spleen isoferritins containing larger amounts of phosphate in the core. Incubation of apoferritin with AA (2.5-50 mM, after 6 h) changes the apoprotein electrophoretic behavior, suggesting a structural modification of the apoprotein by AA-generated ROS. Superoxide dismutase (SOD) was able to partially protect apoferritin from structural modification whereas catalase, ethanol, and mannitol were ineffective in protection. Incubation of apoferritin with AA (1-10 mM) produced a dose-dependent decrease in tryptophan fluorescence (13-30%, after 5 h), and a partial depletion of protein thiols (29% after 24 h). The AA promoted damage to apoferritin produced a 40% decrease in apoprotein ferroxidase activity and an 80% decrease in its iron uptake ability. The current findings of changes in ferritin and apoferritin may contribute to intracellular iron-induced oxidative stress during AA formation in ketosis and diabetes mellitus.
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PMID:Aminoacetone induces loss of ferritin ferroxidase and iron uptake activities. 1470 1

Both nitrogen monoxide (NO) and carbon monoxide (CO) are biologically relevant diatomic effector molecules that mediate a variety of biological functions through their avid binding to iron (Fe). Previous studies showed that NO can inhibit Fe uptake from transferrin (Tf) and increase Fe mobilisation from cells [J. Biol. Chem. 276 (2001) 4724]. We used CO gas, a CO-generating agent ([Ru(CO)3Cl2]2), and cells stably transfected with the CO-producing enzyme, haem oxygenase 1 (HO1), to assess the effect of CO on Fe metabolism. These results were compared to the effects of NO produced by a variety of NO-generating agents, including S-nitrosoglutathione (GSNO), spermine-NONOate (SperNO) and S-nitroso-N-acetylpenicillamine (SNAP). Incubation of cells with CO inhibited 59Fe uptake from 59Fe-Tf by cells, and like NO, reduced ATP levels. Hence, the ability of both agents to inhibit 59Fe uptake may be partially mediated by inhibition of energy-dependent processes. These results showing a CO-mediated decrease in 59Fe uptake from 59Fe-Tf using exogenous CO were in agreement with studies implementing cells transfected with HO1. Like NO, CO markedly prevented 59Fe uptake into ferritin. In comparison to the avid ability of exogenous CO to inhibit 59Fe uptake, it had less effect on cellular 59Fe mobilisation. Experiments with HO1-transfected cells compared to control cells showed that 59Fe mobilisation was slightly enhanced. In contrast to NO, CO did not affect the RNA-binding activity of the iron regulatory protein 1 that plays an important role in Fe homeostasis. Our studies demonstrate that subtle differences in the chemistry of NO and CO results in divergence of their ability to affect Fe metabolism.
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PMID:Differential effects on cellular iron metabolism of the physiologically relevant diatomic effector molecules, NO and CO, that bind iron. 1515 59


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