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 ability of ferritin to catalyze rat liver microsomal chemiluminescence was determined in the absence and presence of the redox cycling agent paraquat, and with either NADPH or NADH as reductant. Microsomal chemiluminescence was used as a index of lipid peroxidation. In the absence of added ferritin, NADPH-dependent microsomal light emission was 4-fold greater than the NADH-dependent reaction, and was not sensitive to superoxide dismutase, catalase or DMSO. Ferritin stimulated NADPH-, but not NADH-dependent chemiluminescence in a time- and concentration-dependent manner. The stimulation by ferritin was completely sensitive to superoxide dismutase, but not to catalase or DMSO, suggesting the requirement for superoxide to mobilize iron from ferritin. An iron ligand was not required for the stimulation by ferritin; the addition of certain ligands such as EDTA, DETAPAC or desferrioxamine resulted in inhibition of the stimulation by ferritin. Paraquat potentiated the effect of ferritin on microsomal chemiluminescence with NADPH as cofactor and was weakly stimulatory with NADH. The potentiation by paraquat plus ferritin was prevented by superoxide dismutase and was further elevated by ligands such as ATP. Chemiluminescence proved to be a more sensitive parameter than production of thiobarbituric acid-reactive components to evaluate the stimulation of oxygen radical production by iron released from ferritin, in the absence or in the presence of paraquat.
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PMID:Stimulation of microsomal chemiluminescence by ferritin. 849 75

Many studies have shown that oxygen radicals can be produced during arsenic metabolism. We report here that in human fibroblasts (HFW cells) sodium arsenite exposure caused increased formation of fluorescent dichlorofluorescein (DCF) by oxidation of the nonfluorescent form. The enhanced DCF fluorescence was inhibited by a radical scavenger, butylated hydroxytoluene. The effects of sodium arsenite treatment on cellular antioxidant activities were then examined. Treatment of HFW cells with sodium arsenite resulted in a significant increase in heme oxygenase activity and ferritin level. Sodium arsenite-enhanced heme oxygenase synthesis was inhibited by co-treatment of cells with the antioxidants sodium azide and dimethyl sulfoxide. Furthermore, sodium arsenite treatment did not apparently affect glucose-6-phosphate dehydrogenase activity, but resulted in significantly increased glutathione levels and superoxide dismutase activity, slightly decreased glutathione peroxidase activity, and significantly decreased catalase activity. Sodium arsenite toxicity was partly reduced by addition of catalase to the culture medium. These results imply that arsenite can enhance oxidative stress in HFW cells.
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PMID:Modulation of cellular antioxidant defense activities by sodium arsenite in human fibroblasts. 852 46

Microsomes can remove iron from ferritin by a superoxide-dependent reaction. The released iron can then catalyse formation of a variety of reactive oxygen species. Experiments were carried out to evaluate the role of cytochrome P-450 in the release of iron from ferritin, and whether induction of certain P-450 isoforms alters ferritin-dependent reactive oxygen radical production. Rats were treated with phenobarbital, 3-methylcholanthrene, 4-methylpyrazole, or saline to produce microsomes with varying P-450 content and composition. Oxidation of 2,7'-dichlorofluorescein diacetate to a fluorescent product and chemiluminescence were used as indices of production of reactive oxygen species. The extreme sensitivity of these reactions to trolox, a potent chain-breaking oxidant, indicates the involvement of lipid peroxidation products in these reactions. In the absence of ferritin, formation of reactive oxygen species was higher in microsomes from the treated rats compared to saline controls when results were expressed on a per mg protein basis but not per nmol P-450, suggesting that the increased content of total P-450 (2-fold increases) rather than the population of isoforms was responsible for the increase. Superoxide dismutase had no effect on the non-ferritin catalyzed reactions. Ferritin increased production of reactive oxygen species with all the microsomal preparations; the increase by ferritin was completely prevented by superoxide dismutase. The net increase by ferritin was higher in microsomes from the treated rats compared to saline controls, but this, again, largely reflected the increased content, rather than the type of isoforms of P-450 present. Similar results were obtained with either NADPH or NADH as microsomal reductants, although NADPH was much more effective in supporting ferritin-dependent reactive oxygen formation. In microsomes from phenobarbital-treated rats, anti-CYP2B1/B2 IgG completely prevented the NADPH- and NADH-dependent increases in reactive oxygen formation produced by ferritin. Anti-cytochrome b5 IgG produced partial inhibition of the ferritin-stimulation. These results indicate that P-450, and to a lesser extent, cytochrome b5, play a role in the ferritin-dependent increase in formation of reactive oxygen species with either NADPH or NADH, most likely reflecting the requirement of these enzymes for microsomal production of superoxide anion.
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PMID:Role of cytochrome P-450 in the stimulation of microsomal production of reactive oxygen species by ferritin. 860 Sep 80

Ferritin is the major storage form of iron within cells, and iron released from ferritin has been shown to stimulate lipid peroxidation. Microsomes from rats chronically fed ethanol are more active in generating reactive oxygen intermediates than control microsomes. Since superoxide is one of the reductants capable of releasing iron from ferritin, and superoxide generation by microsomes is increased after chronic ethanol treatment, the ability of ferritin to stimulate lipid peroxidation of microsomes isolated from control rats and rats treated chronically with ethanol was evaluated. Ferritin was much more effective in stimulating lipid peroxidation of microsomes after ethanol treatment; net increases in thiobarbituric acid-reactive components by ferritin were 4-fold greater in the presence of NADPH with microsomes from the ethanol-treated rats compared to pair-fed controls and 10-fold greater with NADH as the microsomal reductant. Net increases in chemiluminescence by ferritin were about 10-fold greater with microsomes from the ethanol-treated rats. The NADPH- and NADH-dependent increases in lipid peroxidation produced by ferritin were prevented by superoxide dismutase, which lowered the rates found in the presence of ferritin to values found in the absence of ferritin. Catalase and hydroxyl radical scavengers had no effect on the stimulation by ferritin. Nonheme iron chelators prevented the ferritin stimulation as did glutathione, propylgallate, and trolox. Basal rates of lipid peroxidation were inhibited by anti-CYP2E1 IgG; the stimulation by ferritin was decreased by anti-CYP2E1 IgG. These results show that microsomes from ethanol-fed rats are more reactive than control microsomes in interacting with ferritin to produce oxidants capable of catalyzing lipid peroxidation. The inhibition of the ferritin-catalyzed lipid peroxidation by superoxide dismutase and anti-CYP2E1 IgG is consistent with a role for CYP2E1-generated superoxide radical in mobilizing iron from ferritin and in the subsequent catalysis of lipid peroxidation. Since ferritin is the major cellular storage form of iron, increased mobilization of iron from ferritin by CYP2E1-derived superoxide radical may play a role in the development of oxidative stress after ethanol treatment.
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PMID:Ferritin stimulation of lipid peroxidation by microsomes after chronic ethanol treatment: role of cytochrome P4502E1. 880 16

Cellular iron homeostasis is regulated by the cytoplasmic iron regulatory protein (IRP), which binds to iron-responsive elements (IRE) of mRNAs, modulating iron uptake and sequestration, respectively. When iron is scarce, IRP binds to IRE and coordinately increases the synthesis of transferrin receptor and decreases that of ferritin, thus providing the cell with readily available free iron. When iron is in excess, IRP does not bind and iron sequestration prevails over iron uptake. We have found that incubation of rat liver lysates with xanthine oxidase (XO), which generates superoxide (O2-.) and hydrogen peroxide (H2O2), caused a remarkable but reversible inhibition of IRP activity, as the formation of IRE-IRP decreased by 70-80% but returned to baseline values upon exposure to a reducing agent like 2-mercaptoethanol. IRP inhibition was prevented by separate or simultaneous addition of superoxide dismutase and catalase, showing that both O2-. and H2O2 were involved. By contrast, iron chelators and hydroxyl radical scavengers did not impede the inhibition of IRP, suggesting that O2-. and H2O2 acted independently of free iron sources. Ferritin enhanced IRP inhibition, but this process involved tightly bound iron centers that shunted reducing equivalents from XO and returned them to oxygen, thus increasing the formation of O2-. In agreement with the exclusive role of O2-. and H2O2, XO also inhibited recombinant human IRP in the absence of iron. These results demonstrate that O2-. and H2O2 can directly but reversibly down-regulate the RNA-binding activity of IRP, causing transient decrease of free iron that otherwise would convert them into more potent oxidants such as hydroxyl radicals or equally aggressive iron-peroxo complexes. This establishes a novel protective stratagem against oxidative injury under pathophysiologic conditions characterized by the excessive generation of O2-. and H2O2.
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PMID:Superoxide and hydrogen peroxide-dependent inhibition of iron regulatory protein activity: a protective stratagem against oxidative injury. 914 4

The in vivo production of HO- requires iron ions, H2O2 and O2- or other oxidants but probably does not occur through the Haber-Weiss reaction. Instead oxidants, such as O2-, increase free iron by releasing Fe(II) from the iron-sulfur clusters of dehydratases and by interfering with the iron-sulfur clusters reassembly. Fe(II) then reduces H2O2, and in turn Fe(III) and the oxidized cluster are re-reduced by cellular reductants such as NADPH and glutathione. In this way, SOD cooperates with cellular reductants in keeping the iron-sulfur clusters intact and the rate of HO. production to a minimum. O2- and other oxidants can release iron from Fe(II)-containing enzymes as well as copper from thionein. The released Fe(III) and Cu(II) are then reduced to Fe(II) and Cu(I) and can then participate in the Fenton reaction. In mammalian cells oxidants are able to convert cytosolic aconitase into active IRE-BP, which increases the "free" iron concentration intracellularly both by decreasing the biosynthesis of ferritin and increasing biosynthesis of transferrin receptors. The biological role of the soxRS regulon of Escherichia coli, which is involved in the adaptation toward oxidative stress, is presumably to counteract the oxidative inactivation of the iron clusters and the subsequent release of iron with consequent increased rate of production of HO.
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PMID:The role of iron-sulfur clusters in in vivo hydroxyl radical production. 890 35

The hypothesis that blood biochemical measurements of iron (Fe), copper (Cu), magnesium (Mg) and zinc (Zn) nutritional status and dietary intakes of these minerals are useful predictors of 100-yd free-style swimming performance during actual competition was examined in five female and five male collegiate swimmers. Dietary intakes of Fe, Cu, Mg, and Zn exceeded 70% of daily recommended or estimated safe and adequate intakes. Anemia was not present but body iron stores, assessed with serum ferritin concentration, were reduced in female swimmers who had significantly increased erythrocyte Mg and superoxide dismutase activity which suggest a biochemical adaptation to physical training. Actual 100-yd freestyle times (53.1 +/- 1.4 sec; mean +/- SE) measured during competition were similar to values (52.6 +/- 1.4 sec) predicted with models previously derived from other groups of swimmers. These findings indicate the important role of mineral nutritional status in facilitating the development of peak physical performance and support the hypothesis that mineral element nutritional status is one factor contributing to attainment of optimal human physiological function.
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PMID:Iron, copper, magnesium and zinc status as predictors of swimming performance. 891 70

Highly reactive oxyradicals can be generated in vitro by iron-catalyzed aerobic oxidation of synthetic and naturally occurring substances capable of enolization in aqueous medium. Of biological interest are alpha-hydroxy- and alpha-aminocarbonyls such as carbohydrates, 5-aminolevulinic acid, and aminoacetone which tautomerize to the corresponding enediols and enolamines and yield oxyradicals initiated by electron transfer to dioxygen. Free radicals have been implicated in several normal and pathological processes. We briefly review our hypothesis of an in vivo prooxidant role of 5-aminolevulinic acid (ALA), the heme precursor accumulated in several porphyric disorders (e.g., lead poisoning, acute intermittent porphyria (AIP), tyrosinosis). Accordingly, i) ALA undergoes transition metal-catalyzed oxidation to give O-2, H2O2 and HO.; ii) ALA induces iron release from ferritin, lipid peroxidation of cardiolipin-rich vesicles, single strand breaks in plasmid DNA, and guanosine oxidation in calf thymus DNA; iii) ALA causes Ca(2+)-mediated rat liver mitochondria permeabilization; iv) rats chronically treated with ALA exhibit increased glycolytic metabolism; v) brain extracts of ALA-treated rats reveal increased levels of thiobarbituric acid reactive substances, direct chemiluminescence intensity, carbonyl proteins, ferritin, and "free iron" and gamma-aminobutyric acid-receptor dissociation constant, and vi) patients with AIP and lead-exposed workers present augmented erythrocytic levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. These data indicate the involvement of ALA-generated reactive species in the clinical manifestations (neuropathy, mental changes, muscle weakness, hepatoma) shared by the aforementioned inherited and acquired porphyric diseases.
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PMID:Oxidative stress in acute intermittent porphyria and lead poisoning may be triggered by 5-aminolevulinic acid. 907 Mar 73

Nutritional assessments are frequently based on amounts of nutrients consumed. In the present paper the usefulness of nutrient intake data for assessing nutrient adequacy is examined in an elderly British population. Subjects were "free-living' elderly aged 68-90 years (sixty men, eighty-five women) in Norwich. Forty-two of forty-nine surviving males and sixty-seven of seventy-nine surviving females were reassessed after 2 years. With few exceptions, estimated micronutrient intake was not statistically predictive of biochemical measures of nutrient adequacy. Initial biochemical measures of nutritional adequacy were compared with those found 2 years later in an attempt to assess whether initial biochemical assessment was predictive of the "longer term' situation. Biochemical measurements at the start of the study were correlated to the same measurements made 2 years later for: serum ferritin, haemoglobin and erythrocyte count, whole-blood Se-glutathione peroxidase (EC 1.11.1.9; males only), plasma Cu, alkaline phosphatase (EC 3.1.3.1), ascorbic acid, vitamin B6 (pyridoxal-5-phosphate), folate and vitamin B12, total erythrocyte thiamin (males only), riboflavin (erythrocyte glutathione reductase (EC 1.6.4.1) activation coefficient): but not for: erythrocyte Cu-superoxide dismutase (EC 1.15.1.1) or plasma Zn. Either only small changes, or no changes, in mean values were seen over the 2 years for most of the biochemical measures. One exception was a large increase in plasma folate. The only important "negative' features seen at 2-year follow up were a large fall in serum ferritin concentration and a large increase in the activity of two antioxidant defence enzymes, superoxide dismutase and glutathione peroxidase. As judged by currently accepted biochemical deficiency threshold values, a small proportion of subjects were possibly at risk of Fe (3% men; 1% women), folate (7%, 3%), thiamin (12%; 3%) and vitamin C (15%; 17%) deficiency. Many more appeared to be at risk of vitamin B6 (42%; 47%) and riboflavin (77%; 79%) deficiency. It was concluded that the requirements of the elderly for vitamins B1, B2 and C, and the biochemical deficiency threshold values used to indicate vitamin B6 deficiency, need review.
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PMID:Relationships between micronutrient intake and biochemical indicators of nutrient adequacy in a "free-living' elderly UK population. 913 69

The objective of this prospective, cohort study was to compare the nutritional status of full-term infants who were fed human milk (BF, n = 29), formula (FF, n = 30) or evaporated milk formulae (EM, n = 30) for at least 3 months. Infants were seen at enrollment, 3 and 6 months, at which times a blood sample, diet record and anthropometric data were collected. Infants in the EM group received solids earlier (12 +/- 5 weeks) than did FF infants (15 +/- 4 weeks), and both were earlier than BF infants (19 +/- 4 weeks). Only 26% of the EM fed group received iron supplements as ferrous sulphate drops. Seven BF, 12 FF and 20 EM had abnormal ferritin values (< 10 ng ml-1) at 6 months. Copper intake was lower in the EM infants at 3 and 6 months. However, plasma copper and erythrocyte copper zinc superoxide dismutase (ZnCuSOD) levels did not differ between groups. Selenium intake was lower in the EM group (5 +/- 1 and 10 +/- 5 micrograms d-1; 3 and 6 months) than in the FF infants (13 +/- 4 and 19 +/- 7 micrograms d-1; 3 and 6 months). Erythrocyte SeGHSPx levels in EM infants were lower at 6 months (EM, 33.2 +/- 3.4; FF. 35.2 +/- 3.9: BF, 36.1 +/- 3.8 mU mg Hb-1). Thiamin intake (0.99 +/- 0.08 and 1.24 +/- 0.32; 3 and 6 months, mg 1000 kcal-1) was higher in the FF group than in EM infants (0.38 +/- 0.39 and 0.66 +/- 0.38; 3 and 6 months). There were more (13%) abnormal thiamin assays in the EM group at 6 months than in the BF and FF infants (0%). In conclusion, infants fed evaporated milk formula receive adequate copper but may not receive enough thiamin or selenium. Unless supplemented from birth with medicinal iron, intakes of iron will be inadequate.
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PMID:Evaluation of full-term infants fed an evaporated milk formula. 918 79


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