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)

Lipid peroxidation has been invoked as a mechanism of alcoholic liver injury but its role has been controversial and the mechanism by which it occurs is unclear. Catalytic iron is known to play an important role in cellular injury and is produced during mobilization of ferritin iron. In vivo administration of a large acute dose of ethanol (5 g/kg) which produces hepatic lipid peroxidation in chow-fed rats resulted in mobilization of non-heme iron. The generation of NADH from alcohol metabolism via ADH or superoxide from acetaldehyde-xanthine oxidase mobilized iron from horse spleen ferritin in vitro. Chronic feeding of alcohol as 36% of energy for 6 weeks does not itself produce peroxidation in the rat but potentiates acute effects of ethanol. It produced microsomal induction which enhanced iron-stimulated lipid peroxidation and increased hepatic non-heme iron. Carbon monoxide increased rather than decreased accumulation of microsomal peroxidation products in vitro suggesting that cytochrome P-450 reductase mediates peroxidation but cytochrome P-450 may metabolize products. Incubation at lowered oxygen tensions equivalent to those observed in the perivenular zone (pO2 = 24 mmHg) enhanced in vitro iron mobilization but decreased peroxidation. Lipid peroxidation and its stimulation by iron mobilization and microsomal induction may be an important contributory mechanism of alcohol-induced liver injury.
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PMID:Lipid peroxidation as a mechanism of alcoholic liver injury: role of iron mobilization and microsomal induction. 313 9

Rabbit muscle phosphoglucomutase was irreversibly inactivated upon preincubation with vitamin C (Vit C). Fe(III), NADH.NADH oxidase.Fe(III), or ferritin.Vit C. Substrate, glucose 1-phosphate and Mg2+ afforded partial protection. No altered amino acid could be detected in the inactive enzyme. Enzyme so inactivated was more susceptible to trypsin. More importantly, during inactivation, the enzyme lost up to 70% of its enzyme-bound phosphate; the completely inactivated enzyme retained the remainder of the bound phosphate which was isolatable as phosphoserine residing in the 22-amino acid long tryptic peptide. Free phosphoserine as well as those in phosphorylase alpha and phosphocasein were resistant to the oxidizing system, suggesting that the phosphoserine of phosphoglucomutase is uniquely vulnerable to these treatments. Alternatively, a fraction of the total 1 mol of phosphate in the phosphoform of phosphoglucomutase may not be associated with phosphoserine. Phosphoglyceromutase, which has phosphohistidine at its active site, was also inactivated by the oxidizing system. However, it did not release any of the bound phosphate.
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PMID:Vit C.Fe(III) induced loss of the covalently bound phosphate and enzyme activity of phosphoglucomutase. 315 31

It is not known which message and mechanism triggers the cell to mobilize iron from ferritin. In this paper we present the results of incubation experiments with 59Fe-labelled hepatocytes. Anemic serum gives a significant higher rate of iron mobilization than normal serum. The involvement of apo-transferrin is ruled out because it did not increase iron mobilization. Citrate increased iron mobilization which is not the result of an increase in NADH/NAD+-ratio because addition of ethanol did not stimulate iron mobilization. Desferrioxamine is used clinically in iron overloaded patients and it is known that iron removal is a very slow process. Although desferrioxamine can mobilize iron from ferritin in hepatocytes, a considerable amount remains inside the cell as a low molecular weight fraction. This fraction represents chelator bound iron and is slowly released into the circulation.
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PMID:Iron mobilization from isolated hepatocytes. 380 97

A newborn female, the second child of consanguineous parents, exhibited general muscle hypotonia, apathy, hepatomegaly and failure to thrive from birth and signs of craniofacial dysmorphia were present. Pipecolic and trihydroxicoprostanoic acid were excreted in the urine and serum transferrin, ferritin and iron were markedly elevated. At the age of 7 weeks the baby died of respiratory insufficiency. Besides malformations of the brain, renal cysts, liver damage with hypoplastic intrahepatic bile ducts and cholestasis, increased storage of iron and cytochemically proven deficiency of peroxisomes in liver and kidney, morphological studied provided evidence of a mitochondrial myopathy in striated muscle with the accumulation of enlarged bizarre mitochondria, showing only minor structural abnormalities. No defects of NADH-reductase, succinate-dehydrogenase or cytochrome-c-oxidase were demonstrated histochemically. Cytochemical-ultrastructural investigation of mitochondrial ATPase revealed activation of the ATP-synthesising enzyme even before the addition of an uncoupler, this indicating loosely coupled oxidative phosphorylation. In addition a high rate of subcellular autophagy with segregation of mitochondria and focal loss of fibrils was present. Muscle damage in Zellweger syndrome appears to be the consequence of complex, interacting metabolic processes. The mitochondrial myopathy thereby induced allows a better understanding of general muscle hypotonia, one of the leading symptoms of this disorder.
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PMID:Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. A cytochemical-ultrastructural study. 614 41

Yeast plasma membranes have been isolated from homogenized yeast cells, identified as pure plasma membrane vesicles which were used as antigens. By crossed immunoelectrophoresis with anti-membrane immunoglobulins, 17 discrete antigens have been detected in Triton X-100 extracts from plasma membranes. Three different immunoabsorption experiments were performed with : a) isolated membranes exposing the cytoplasmic surfaces (PS) and the external surfaces (ES), b) yeast protoplasts exposing only antigenic determinants on the ES, c) lysed protoplasts which had been saturated on the ES with antibodies prior to lysis. These absorption experiments demonstrated that seven of the antigens are expressed on the ES while eight immunogens expose antigenic determinants on the PS. Four of the principal immunoprecipitates are not affected by absorption with surface antigens whereas two of the antigens indicate transmembrane characteristics. Of these 17 immunoprecipitates four were shown by zymograms to possess enzymatic activities: ATPase (EC 3.6.1.3) and NADH-dehydrogenase (EC 1.8.99.3) (three separate components). Three of these enzymes are expressed on the PS, and one NADH-dehydrogenase exposes determinants on the ES of the protoplasts. The presence of antigens on the PS of the plasma membrane could also be demonstrated on micrographs by the indirect ferritin-antibody labeling technique followed by freeze-etching and shadowing of the membranes.
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PMID:Immunochemical analysis of the plasma membrane from baker's yeast Saccharomyces cerevisiae. 616 18

Nonheme iron is synergistic with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in producing hepatotoxicity in mice. Fe2+ rather than Fe3+ is the probable toxin and we speculated that TCDD, an inducer of microsomal electron transport, might favour reduction of iron. We have defined a system which will release Fe2+ from ferritin (Fe3+) under anaerobic conditions and in the presence of added flavin mononucleotide (FMN). The rate of reduction iron was proportional (a) to microsomal protein from 0.5 to greater than 3 mg/mL, (b) to the activity of NADPH-cytochrome c reductase over 0.1 U/mL, (c) to ferritin at concentrations exceeding iron concentrations greater than 200 mumol/L, and (d) to the concentration of FMN when it was less than 125 mumol/L. The system was approximately twice as active with NADPH as with NADH as electron donor. The linear phase of iron release did not commence immediately, but followed a delay (+/- 0.5 min) after adding FMN to an anaerobic mixture containing microsomes, ferritin, an NADPH-generating system, and an oxygen-scavenging system. When microsomes from untreated, phenobarbital-treated (3 days), or TCDD-treated (1 or 3 weeks) rats were compared, iron release correlated most closely with the cytochrome P-450 concentration. However, when the microsomal proteins were solubilized and the NADPH-cytochrome c reductase and cytochrome P-450 activities were separated, reduction of ferritin iron was shown to be a function only of the reductase fraction, except that the delay in initiating release of Fe2+ was increased with purified reductase and decreased when a monooxygenase system was reconstituted with cytochrome (phenobarbital or TCDD induced) and lipid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release of ferrous iron from ferritin by liver microsomes: a possible role in the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 644 9

Glucose-6-phosphatase (G6Pase) is a microsomal enzyme which is very sensitive to inactivation by lipid peroxidation. Experiments were carried out to evaluate whether ferritin, which is the major storage form of iron within cells, could catalyze inactivation of G6Pase and to determine the mechanism responsible for this effect of ferritin. Incubation of microsomes with NADPH in the absence of ferritin led to decreased activity of G6Pase. Ferritin stimulated this inactivation of G6Pase in a time- and concentration-dependent manner. Ferritin did not stimulate G6Pase inactivation when NADH replaced NADPH as the microsomal reductant. Superoxide dismutase but not catalase or DMSO prevented the ferritin-stimulated inactivation of G6Pase suggesting a role for superoxide, but not H2O2 or hydroxyl radical, in the overall mechanism. Trolox, at concentrations which prevent lipid peroxidation, also prevented the ferritin-catalyzed inactivation of G6Pase. Inhibition of G6Pase by ferritin was further enhanced in the presence of ATP but was inhibited in the presence of EDTA or desferrioxamine; ferric-ATP stimulates, whereas ferric-EDTA inhibits microsomal lipid peroxidation. The redox cycling agent paraquat increased the ability of ferritin to inactivate G6Pase by a reaction prevented by superoxide dismutase, trolox, EDTA, and desferrioxamine, but not by catalase or DMSO. Ferritin stimulated microsomal light emission, a reaction reflecting lipid peroxidation, with time and concentration dependence, and sensitivity to scavengers (trolox, superoxide dismutase), iron chelators and paraquat, identical to the inactivation of G6Pase. These results indicate that one possible toxicological consequence of ferritin-catalyzed lipid peroxidation is inhibition of microsomal enzymes such as G6Pase.
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PMID:Ferritin-dependent inactivation of microsomal glucose-6-phosphatase. 818 31

Iron mobilized from ferritin has been shown to catalyze production of potent reactive oxygen intermediates. Experiments were carried out to evaluate the ability of ferritin to catalyze nuclear generation of hydroxyl radical in the presence of either NADPH or NADH. In the absence of redox cycling agents, ferritin did not catalyze nuclear oxidation of hydroxyl radical scavenging agents (2-keto-4-thiomethylbutyric acid, dimethylsulfoxide, ethanol) even if EDTA was added to chelate any released iron. The addition of menadione or paraquat resulted in a ferritin-dependent oxidation of chemical scavengers; menadione promoted the catalysis by ferritin with either NADPH or NADH, whereas paraquat was much more reactive with NADPH as the nuclear reductant. The presence of an externally added iron chelator was required for elevated rates of scavenger oxidation, with EDTA and DTPA being more reactive than ATP or citrate and desferrioxamine being inhibitory. The ferritin-catalyzed hydroxyl radical scavenger oxidation was sensitive to superoxide dismutase, catalase, and competitive scavengers. In the absence or presence of ferritin, rates of NADPH- or NADH-dependent H2O2 production were low; menadione increased H2O2 production with both NADPH and NADH, whereas paraquat was mostly effective with NADPH. Depending on the nature of the added chelating agent (e.g., EDTA, ATP) and the reductant, rates of nuclear production of .OH in the presence of redox cycling agent plus ferritin were 10 to 70% as high as rates found with redox cycling agent plus ferric-chelate (e.g., ferric-EDTA, ferric-ATP). Since reactive oxygen intermediates such as the hydroxyl radical can alter the structural integrity of the nucleus and interact with DNA, the ability of ferritin to promote nuclear generation of hydroxyl radical may play a role in the toxicity associated with iron as well as redox cycling agents.
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PMID:Ferritin stimulation of hydroxyl radical production by rat liver nuclei. 831 76

One mechanism by which Listeria monocytogenes is thought to obtain iron required for growth is through the extracellular reduction of a ferric iron source to the ferrous form. To better characterize this reductase activity we have developed a simple plate assay that allows detection of colonies of Listeria species able to reduce ferric iron. Cells are plated on an agar base medium containing a ferric iron source and ethylenediamine dihydroxyphenylacetic acid. Colonies are then overlain with soft agarose containing NADH, flavin mononucleotide, and Ferrozine, a chelator of ferrous iron. Colonies able to reduce the ferric iron source form a red-purple color as the ferrous iron is complexed with ferrozine. Using this qualitative assay we have shown that all species of Listeria are able to reduce ferric iron when presented as ferric ammonium citrate whereas most other species of Gram-positive and Gram-negative bacteria are not. Only Clostridium perfringens was able to reduce ferric iron to the same extent as Listeria. Listeria monocytogenes was further shown to be capable of reducing various ferric iron salts as well as iron bound to ferritin, transferrin, and 2,3-dihydroxybenzoic acid in the agar plate assay. The utility of this assay was demonstrated by using it to screen a bank of Tn916-derived mutants of L. monocytogenes for clones unable to reduce ferric iron. Four such mutants were identified and all were shown to have greatly decreased ferric reductase activity.
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PMID:Reduction of ferric iron by Listeria monocytogenes and other species of Listeria. 833 Feb 59

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


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