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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid peroxide formation was initiated by the addition of either ADP-complexed Fe3+ or cumene hydroperoxide to a suspension of isolated hepatocytes. The reaction was monitored by malonaldehyde measurements. Upon the addition of iron, malonaldehyde production in the cells started immediately but ceased within 30-60 min, and the response was dose-related with iron concentrations ranging from 19 to 187 muM. Malonaldehyde formation was associated with increased oxygen uptake and conjugated diene production. The addition in vitro of N,N,N',N'-tetramethyl-p-phenylenediamine, menadione or p-benzoquinone inhibited the iron-induced malonaldehyde production. It was also possible to demonstrate an apparent disappearance of malonaldehyde from fresh cells by addition of adequate amounts of N,N,N',N'-tetramethyl-p-phenylenediamine (100 muM). The attenuation of the iron-induced malonaldehyde production was found to be correlated with an increased binding of iron to an intracellular ferritin fraction. Further, malonaldehyde formation was also associated with a conversion of reduced glutathione to the oxidized form which, in turn, revealed a faster permeation out of the cells into the surrounding medium of the oxidized than of the reduced thiol. So, concomitant with the redox alterations, there was also an overall loss of glutathione from the cells. Cumene hydroperoxide-induced malonaldehyde production could be initiated by the addition of this peroxide in concentrations ranging from 150 muM to the liver cell incubate. With concentrations below 150 muM, a lag phase was present which seemed to be glutathione-dependent. It is concluded that iron enters the cell, then is probably reduced inside the cell by NADPH via the NADPH-cytochrome P-450 reductase, and in the reduced state initiates lipid peroxidation. The reaction is inhibited by intracellular mechanisms, the glutathione redox system being of principal importance, and possibly terminated by the iron-apoferritin complex formation.
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PMID:Further studies on lipid-peroxide formation in isolated hepatocytes. 0 Dec 55

Ionic iron at physiological pH hydrolyzes into insoluble aggregates, which disperse on slight acidification. Uncontrolled ionic iron promotes autoxidation, which crosslinks biomolecules and produces destructive activated oxygen. Defenses against autoxidative crosslinking include: 1. ferritin, the macromolecular scavenger of iron; 2. metabolic turnover, which prevents irreversible crosslinking through early catabolic degradation and replacement; and 3. enzymatic deactivation of oxygen. I am proposing that the anticrosslinking defenses are defeated by transient actions of metabolic perturbations, toxicants, oxidants and "foreign bodies", which cause oxidative crosslinking of proteins and lipids into irreversible tissue imprint: indigestible bodies containing porous limited-access spaces (LASs). The pores exclude the macromolecular ferritin and the digestive and antiautoxidation enzymes but admit ionic iron which, sheltered from ferritin, accumulates into decontrolled-iron pathogen (DIP). DIP utilizes the energy of ambient pH fluctuations to erupt from the LAS, swamp the available ferritin, poison the surroundings, catalyze autoxidation and crosslink cell components into additional LAS carriers. With time and sufficient promotion by pH fluctuations or metal-complexing agents, DIP and LAS expand. DIP injures through heavy-metal inhibition of life processes and catalysis of autoxidation. Typically, carcinogenic initiators are protein denaturants, cell poisons, "foreign bodies" and autoxidation catalysts. These are DIP-initiating properties, and DIP may be a preneoplastic stage of carcinogenesis. A DIP-model interpretation is given for the growth of asbestos bodies. DIP is an inorganic parasite. It may envelope and attack phagocytized particles.
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PMID:Biological autoxidation. I. Decontrolled iron: an ultimate carcinogen and toxicant: an hypothesis. 3 81

On account of its easy access in aqueous solution to the two states ferrous (FeII) and ferric (FeIII), iron is ideally suited for the activation of molecular oxygen. It is, therefore, logical to seek links between the normal and pathological metabolism of iron and oxygen activation. The pathways of intracellular iron metabolism require changes in the oxidation state of iron both in its deposition in the storage form, ferritin, and in its mobilization from the storage form and use in the cell. Evidence is presented which shows that iron oxidation and deposition in ferritin involves activation of molecular oxygen with formation of a stable peroxo-complex as an intermediate in which the oxygen is bound between two iron atoms attached to adjacent polypeptide chains. The release of iron from ferritin is thought to involve reduction by a flavin, which is associated with the protein, and serves as a cofactor being alternately reduced by NADH or NADPH and oxidized by iron(III). The nature of the low-molecular-weight iron complex which serves to transfer storage iron to transferrin and to supply iron for intracellular use remains to be established. The consequence of excessive iron overload can be rationalized on the basis of oxidative free-radical reactions which provoke lesions typical of deregulated oxygen activation. In some cases these pathological defects can be reversed by iron chelators. Progress in the development of chelation therapy for iron overload are reviewed.
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PMID:Interactions between iron metabolism and oxygen activation. 25 65

Hyperbaric oxygen therapy (HBO) has been used in the treatment of cerebral edema with variable results. Two different actions of HBO, one decreasing and the other increasing cerebral edema, have been postulated. We examined the permeability of the blood-brain barrier (BBB) in rats and cats. Animals of each species were treated for 90 min/d with 100% oxygen at a pressure of 2.5 atm for 5 consecutive days. Following treatment, cadmium-free ferritin was injected intravenously. Sections of the brain were prepared for electron microscopic evaluation of the capillaries and their neighboring structures. Perivascular edematous zones were observed. Ferritin particles penetrated through the capillary endothelium and into the pericapillary structures. Hyperbaric oxygenation appears to increase the permeability of cerebral vessel walls in normal animals. Further work on this phenomenon may provide a more rational basis for the treatment of cerebral edema with HBO.
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PMID:Changes in the permeability of the blood-brain barrier under hyperbaric conditions. 66 82

Renal erythropoietin production is dependent on local oxygen content of blood which activates so called "oxygen sensors". Taking into consideration altered local renal blood supply in patients with arterial hypertension in the course of arteritis (HA) and from the other side contribution of the renin-angiotensin system in both pathogenesis of hypertension and regulation of erythropoietin production it seemed plausible to undertake this study. The aim of the study was to determine whether and in what extent patients with HA and healthy subjects differ in EPO secretion and whether EPO serum level is related in this patients to renin response to dietary sodium restriction and upright position of the body. 18 patients with HA and 12 healthy subjects were investigated. In all subjects haematocrit value, haemoglobin concentration, erythrocyte count, sodium, potassium, creatinine, iron, ferritin serum levels, total iron binding capacity, plasma renin activity (PRA), erythropoietin serum level and mean arterial blood pressure (MAP) were measured in basic conditions (normal sodium diet). Additionally PRA, EPO and MAP were measured after dietary sodium restriction to 10-20 mmol Na/24 hrs for three days and upright position of the body for three hours. Patients with HA had insignificantly lower serum EPO concentrations than healthy subjects and both studied groups did not differ in haematocrit value and determinants of iron metabolism except of significantly higher ferritin concentration in HA. After dietary sodium restriction and upright position of the body significant rise in PRA and no significant changes in EPO level were found in studied groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of erythropoietin in blood pressure regulation in patients with arteritis]. 130 May 62

The generation of deleterious activated oxygen species capable of damaging DNA, lipids, and proteins requires a catalyst such as iron. Once released, ferritin iron is capable of catalyzing these reactions. Thus, agents that promote iron release may lead to increased oxidative damage. The superoxide anion formed enzymatically, radiolytically, via metal-catalyzed oxidations, or by redox cycling xenobiotics reductively mobilizes ferritin iron and promotes oxidative damage. In addition, a growing list of compounds capable of undergoing single electron oxidation/reduction reactions exemplified by paraquat, adriamycin, and alloxan have been reported to release iron from ferritin. Because the rapid removal of iron from ferritin requires reduction of the iron core, it is not surprising that the reduction potential of a compound is a primary factor that determines whether a compound will mobilize ferritin iron. The reduction potential does not, however, predict the rate of iron release. Therefore, ferritin-dependent oxidative damage may be involved in the pathogenesis of diseases where increased superoxide formation occurs and the toxicity of chemicals that increase superoxide production or have an adequate reduction potential to mobilize ferritin iron.
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PMID:Ferritin as a source of iron for oxidative damage. 145 89

Apo horse spleen ferritin undergoes a 6.3 +/- 0.5 electron redox reaction at -310 mV at pH 6.0-8.5 and 25 degrees C to form reduced apoferritin (apoMFred). Reconstituted ferritin containing up to 50 ferric ions undergoes reduction at the same potential, taking up one electron per ferric ion and six additional electrons by the protein. We propose that apo mammalian ferritin (apoMF) contains six redox centers that can be fully oxidized forming oxidized apoferritin (apoMFox) or fully reduced forming apoMFred. ApoMFred can be prepared conveniently by dithionite or methyl viologen reduction. ApoMFred is slowly oxidized by molecular oxygen but more rapidly by Fe(CN)6(3-) to apoMFox. Fe(III)-cytochrome c readily oxidizes apoMFred to apoMFox with a stoichiometry of 6 Fe(III)-cytochrome c per apoMFred, demonstrating a rapid interprotein electron-transfer reaction. Both redox states of apoMF react with added Fe3+ and Fe2+. Addition of eight Fe2+ to apoMFox under anaerobic conditions produced apoMFred and Fe3+, as evidenced by the presence of a strong g = 4.3 EPR signal. Subsequent addition of bipyridyl produced at least six Fe(bipyd)3(2+) per MF, establishing the reversibility of this internal electron-transfer process between the redox centers of apoMF and bound iron. Incubation of apoMFred with the Fe(3+)-ATP complex under anaerobic conditions resulted in the formation and binding of two Fe2+ and four Fe3+ by the protein. The various redox states formed by the binding of Fe2+ and Fe3+ to apoMFox and apoMFred are proposed and discussed. The yellow color of apoMF appears to be an integral characteristic of the apoMF and is possibly associated with its redox activity.
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PMID:Redox reactions of apo mammalian ferritin. 132 25

Little is known about changes in the amount of iron in the intracellular low molecular weight pool, which catalyzes the Fenton reactions during reperfusion after ischemia. In this study a new approach is presented to measure low molecular weight iron and it is applied to normal hearts during ischemia and to iron-loaded hearts during anoxia and reoxygenation. The results of this study show that (a) during ischemia in normal hearts a progressive 30-fold increase occurs in low molecular weight iron after 45 min of ischemia, whereas (b) during 45 min of anoxic perfusion the low molecular weight iron does not increase. This means that the reductive release from the storage protein ferritin is greatly enhanced by the acidification that occurs during ischemia. (c) Anoxic perfusion of iron-loaded hearts does increase low molecular weight iron and there is a further increase upon reoxygenation, which is prevented by (+)-cyanidanol-3. Based on these findings it is concluded that oxygen deprivation enhances the susceptibility of rat hearts to oxygen radicals by increasing the amount of catalytic, ferrous iron in the low molecular weight pool.
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PMID:Low molecular weight iron and the oxygen paradox in isolated rat hearts. 143 Feb 27

In the past, antioxidant and chelator studies have implicated a role for iron-dependent oxidative damage in tissues subjected to ischaemia followed by reperfusion. As ferritin is a major source of iron in non-muscular organs and therefore a potential source of the iron required for oxygen radical chemistry, we have determined conditions under which ferritin iron reduction leads to the formation of a pool of iron which is capable of catalysing lipid peroxidation. Under anaerobic conditions and in the presence of rat liver microsomes, flavin mononucleotide (FMN) catalysed the reduction of ferritin iron as shown by both continuous spectrophotometric measurements of tris ferrozine-Fe(II) complex formation and post-reaction Fe(II) determination. The presence of either ferrozine or citrate was not found to alter the time course or extent of ferritin reduction. In contrast, the addition of air to the reactants after a 20 min period of anaerobic reduction resulted in peroxidation of the microsome suspension (as determined with the 2-thiobarbituric acid test) only in the presence of a chelator such as citrate, ADP or nitrilotriacetic acid. These results support the concept that reduced ferritin iron can mediate oxidative damage during reperfusion of previously ischaemic tissues, provided that chelating agents such as citrate or ADP are present.
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PMID:A chelator is required for microsomal lipid peroxidation following reductive ferritin-iron mobilisation. 145 90

The effect of intravenously infused iron-dextran (Imferon) on the progression of antigen induced monarticular arthritis in rabbits was studied. A rapid deposition of iron and apoferritin in the synovia of arthritis joints occurred after infusion of iron-dextran during either the acute or chronic phases of the disease. This coincided with the appearance of catalytic (bleomycin reactive) iron in the synovial fluid. There was no evidence, however, for an exacerbation of the antigen induced arthritis as a result of the iron-dextran, and synovial and bleomycin reactive iron concentrations decreased with time after administration, indicating a redistribution of the synovial iron load. Thus although intravenously infused iron-dextran appears to 'prime' the rabbit arthritic joint transiently with the potential for iron stimulated oxygen free radical damage, other factors may determine its occurrence.
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PMID:Effect of intravenous iron-dextran (Imferon) infusion on antigen induced monarticular arthritis in rabbits. 146


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