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 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

Glomerulonephritis in idiopatic mixed cryoglobulinemia represents perhaps a glomerular damage by immune complexes. In this study, a sigmoidal-like curve was obtained after addition of 13 different mixed cryoglobulins to both autologous and isologous platelet-rich plasma, tested in platelet aggregometer. The lag phase of the curve corresponds to platelet phagocytosis of cryoglobulin-binding ferritin, as shown in electron microscopy and the optical density decrease phase corresponds to the aggregation of platelets that shows the same ultrastructural characteristics of ADP-induced platelet aggregation. This platelet aggregation is inhibited by different drugs. Intraglomerular platelet aggregation by cryoglobulins might play a key role in determining the glomerular damage in cryoglobulinemia by the release of nucleotides and vasoactive amines.
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PMID:Human platelet aggregation by mixed cryoglobulins. 80 77

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

Sickle erythrocyte (RBC) membranes were previously shown to manifest increased Fenton activity (iron-dependent, peroxide-driven formation of hydroxyl radical [.OH]) compared with normal RBC membranes, but the nature of the catalytic iron was not defined. We now find that sickle membranes exposed to superoxide (.O2-) and hydrogen peroxide (H2O2) have three distinct iron compartments able to act as Fenton catalysts: preexisting free iron, free iron released during oxidant stress, and a component that cannot be chelated with deferoxamine (DF). In a model system, addition of iron compounds to normal ghosts showed that free heme, hemoglobin, Fe/adenosine diphosphate (ADP), and ferritin all catalyze .OH production; concurrent inhibition studies using DF documented that the unchelatable Fenton component is free heme or hemoglobin. During exposure to peroxide only, the iron in sickle membranes was unable to act as a Fenton catalyst without addition of a reducing agent. At physiologic concentrations, both ascorbate and glutathione restored Fenton activity. Lipid peroxidation studies showed that at physiologic levels ascorbate acts primarily as an antioxidant; however, as pharmacologic levels are reached, its pro-oxidant effects predominate. This study elucidates the catalytic ability of the iron compartments in the sickle cell membrane, the importance of which relates to the potential role of .OH in membrane damage. It also illustrates the potential participation of cytoplasmic reducing agents in this process, which may be especially relevant in the context of administration of supraphysiologic doses of ascorbate to sickle cell patients.
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PMID:Hydroxyl radical formation by sickle erythrocyte membranes: role of pathologic iron deposits and cytoplasmic reducing agents. 166 10

Anaesthetic drugs can induce reversible as well as irreversible changes in cell membranes and intracellular proteins as well as lipid peroxidation in the liver. Low molecular weight iron species (LMWI) can by their catalytic activity contribute to the generation of free radicals (hydroxyl radicals). Free radicals are a recognisable cause of intracellular damage. Impaired mitochondrial function is also a sign of intracellular damage, which is usually irreversible. Thus, an agent may be cytotoxic when it causes a significant increase in intracellular LMWI. Whether the LMWI arise from ferritin or is released from iron containing proteins, the same reaction occurs. As long as LMWI can undergo redox cycling, hydroxyl radicals can be formed. We investigated the effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on the intracellular LMWI content and mitochondrial function of the rat myocardium. Hearts isolated from rats anaesthetised with diethylether showed an increase in the cytosolic LMWI compared to the control group. No increase in mitochondrial LMWI was demonstrated. Subsequent perfusion of the isolated hearts showed a further increase in the LMWI. On perfusion the mitochondrial LMWI increased in comparison with controls. Mitochondrial function was significantly impaired as measured by the QO2 (state 3), ADP/O ratio and oxidative phosphorylation rate (OPR). Exposure of rats to 50% nitrous oxide for 15 minutes increased the myocardial LMWI, but had no effect on mitochondrial function. Exposure to room air for 30 minutes before isolating the hearts, still showed a significant increase in LMWI with no detectable change in mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of various mixtures of diethylether, halothane, nitrous oxide and oxygen on low molecular weight iron content and mitochondrial function of the rat myocardium. 177 41

ADR-529 [(+)-1,2-bis(3,5-dioxopiperazin-1-yl)propane], a nonpolar, cyclic analogue of EDTA, protects against anthracycline cardiotoxicity in vivo. The protective mechanism presumably involves chelation of iron by a hydrolysis product of ADR-529, thus preventing the formation of reactive iron/oxygen species which can damage membrane lipids. We investigated the effects of ADR-529 and its hydrolysis products (the tetraacid and the diacid diamide) on NADPH- and ADP-Fe(3+)-dependent lipid peroxidation of rat liver microsomes and liposomes in the presence of cytochrome P-450 reductase. Hydrolyzed ADR-529 products caused inhibition of lipid peroxidation when in excess of the iron concentration. However, no inhibition of lipid peroxidation was detected by similar concentrations of nonhydrolyzed ADR-529. Microsomes did not affect the inhibition of lipid peroxidation, suggesting that rat liver microsomes do not hydrolyze ADR-529. Similarly, the diacid diamide hydrolysis product of ADR-529 inhibited ferritin- and adriamycin-iron-dependent liposomal lipid peroxidation in a concentration-dependent manner. No correlation between partially reduced oxygen species (O2.- and .OH; as measured by electron spin resonance) and lipid peroxidation (as assayed by malondialdehyde formation) was observed, suggesting that liposomal lipid peroxidation was strictly an iron-dependent phenomenon. These results suggest that inhibition of lipid peroxidation by iron chelation may be related to the protective effects of ADR-529 on in vivo anthracycline toxicity.
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PMID:Effects of (+)-1,2-bis(3,5-dioxopiperazin-1-yl)propane (ADR-529) on iron-catalyzed lipid peroxidation. 196 87

Iron-catalyzed free radical reactions, such as the peroxidation of membrane lipids or the inactivation of critical enzymes, have been implicated in the cardiotoxicity of Adriamycin. Fe3+ reduction is an important step in both processes. The reduction of Fe3+, Fe3+ ADP, or Fe3(+)-ferritin by rabbit heart microsomes, Adriamycin, and NADPH was 10% inhibited by ICRF-187 (ADR-529) in N2 and 77% inhibited by ICRF-198, the hydrolysis product of ICRF-159 (the racemic form of ICRF-187). Lipid peroxidation and CaATPase inactivation catalyzed by Fe3+, Fe3+ ADP, or Fe3(+)-ferritin were substantially inhibited by ICRF-198 but only partially inhibited by ICRF-187. The cardioprotective action of ICRF-187 during Adriamycin treatment may be a result of its hydrolysis to the d isomer of ICRF-198 which inhibits reduction of Fe3+, thus limiting the role of iron in tissue damaging free radical reactions.
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PMID:dl-N,N'-dicarboxamidomethyl-N,N'-dicarboxymethyl-1,2-diaminopropane (ICRF-198) and d-1,2-bis(3,5-dioxopiperazine-1-yl)propane (ICRF-187) inhibition of Fe3+ reduction, lipid peroxidation, and CaATPase inactivation in heart microsomes exposed to adriamycin. 215 15

A monoclonal antibody named TM60, which inhibited both thrombin- and ristocetin-induced platelet aggregations, was obtained by hybridoma technique. TM60 inhibited binding of von Willebrand factor to platelets under the presence of ristocetin. The subclass of TM60 was IgG2a. TM60 did not inhibit ADP-, collagen-A-23187-, arachidonic acid- and PAF-induced platelet aggregations, but inhibited polylysine-, polybrene- and cationized ferritin-induced platelet aggregations. ATP-release from platelets induced by thrombin was also inhibited by TM60. Immunoprecipitation and SDS-PAGE experiments demonstrated that TM60 recognized an epitope on GPIb whose molecular weight was 165,000 under non-reduced and 145,000 under reduced conditions.
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PMID:Monoclonal antibody to glycoprotein Ib inhibits both thrombin- and ristocetin-induced platelet aggregations. 241 61

We used immunoelectron microscopic localization techniques to investigate whether platelets stimulated by ADP or ristocetin in the plasma milieu bind von Willebrand factor (vWF) to their surfaces. We found by both peroxidase- and ferritin-based methods that unstimulated platelets lack vWF on their surfaces, whereas platelets that are stimulated with ADP or ristocetin have vWF associated with their surfaces. The specificity of the findings was confirmed by absorption studies using severe von Willebrand disease (vWD) and hemophilic plasmas. The anti-vWF antibodies were blocked by incubation with hemophilic plasma but not by incubation with severe vWD plasma. Thus, in the plasma environment, in the presence of fibrinogen, vWF becomes associated with the platelet surface subsequent to stimulation with ADP or ristocetin.
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PMID:Localization of surface vWF on resting and stimulated platelets. 282 69

Reduction of iron is important in promoting xenobiotic-enhanced, microsomal lipid peroxidation, yet there is little evidence that Fe3+ chelates that promote lipid peroxidation can be reduced by the microsomal system. We have shown that rat liver microsomes catalyse NADPH-dependent reduction of Fe3+ without chelator, as well as Fe3+(ADP), Fe3+(ATP), Fe3+(citrate), Fe3+(EDTA), and ferrioxamine in N2. The NADPH oxidation that accompanied Fe3+ reduction was inhibited by CO for all chelates, except Fe3+ (EDTA). This implies that, except for Fe3+ (EDTA), cytochrome P450 was involved in reduction of the complexes. Adriamycin, paraquat, and anthraquinone 2-sulfonate (AQS) enhanced reduction of all the Fe3+ chelates, whereas menadione enhanced reduction only of Fe3+(ADP) and Fe3+(citrate). All the compounds enhanced oxidation of NADPH in the presence or absence of iron. This was not inhibited by CO, and the results are compatible with Fe3+ reduction occurring via the xenobiotic radicals produced by cytochrome P450 reductase. Microsomal reduction of the xenobiotics, except menadione, enabled the reduction and release of iron from ferritin. Fe3+ chelate reduction, both with and without xenobiotic, was inhibited by O2, although it still proceeded in air at 10-20% of the rate in N2. Iron-dependent lipid peroxidation was promoted by ADP and ATP, inhibited 50% by citrate, and completely inhibited by EDTA and desferrioxamine. Of the xenobiotics, only Adriamycin enhanced microsomal lipid peroxidation. These results indicate that the effects of chelators and xenobiotics on Fe3+ reduction do not correlate with lipid peroxidation and, although reduction is necessary, there must be other factors involved.
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PMID:Microsomal reduction of low-molecular-weight Fe3+ chelates and ferritin: enhancement by adriamycin, paraquat, menadione, and anthraquinone 2-sulfonate and inhibition by oxygen. 285 Jul 67


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