Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NADPH- and iron-dependent lipid peroxidation of rat heart and liver microsomes was measured in the presence and absence of adriamycin. Lipid peroxidation was enhanced by adriamycin when incubated in air and was increased as the pO2 was lowered, to a maximum of 3-4 times the aerobic level at a pO2 of approx. 4 mm Hg. Fe-ADP, Fe-ATP and ferritin were able to catalyse adriamycin-dependent peroxidation of microsomes under low pO2. Superoxide dismutase and catalase had minimal effect. These results indicate that adriamycin-dependent lipid peroxidation is favoured by the low O2 concentration that exist in active muscle cells and suggest that ferritin could provide the iron catalyst for the reaction.
 ...
PMID:Adriamycin-dependent peroxidation of rat liver and heart microsomes catalysed by iron chelates and ferritin. Maximum peroxidation at low oxygen partial pressures. 339 66

Oxygen free radicals are probably involved in the pathogenesis of rheumatoid arthritis (RA). The enzymes involved in protection against oxygen free radicals and H2O2 (superoxide dismutase, catalase, and glutathione peroxidase) were measured. Superoxide dismutase was not increased, glutathione peroxidase was slightly and catalase was strongly elevated in RA synovial fluid (SF) compared with control SF. Although these enzymes are present in SF, the activities are insufficient to protect against oxygen free radicals and H2O2. In contrast to transferrin, ferritin was increased in RA synovial fluid. Ceruloplasmin was also elevated. When rat liver microsomes were used as a target for oxygen free radicals, serum and SF were both protective. Gel filtration experiments showed that the fraction pattern in which there was maximal protective potential against lipid peroxidation corresponded closely to the level of ceruloplasmin. After removal of ceruloplasmin from serum or SF, about 70% of the protective capacity disappeared. It is concluded that ceruloplasmin is an important protector against oxygen free radicals.
 ...
PMID:Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid. 674 61

5-Aminolevulinic acid (ALA), a heme precursor accumulated in acute intermittent porphyria (AIP) and lead poisoning, undergoes metal-catalyzed oxidation in air-equilibrated solutions buffered at neutral pH, yielding free radicals (O2, HO. and ALA.). The capacity of ALA to release iron from horse spleen and rat liver ferritin in vitro and to concomitantly initiate liposome lipid peroxidation was characterized. ALA induced iron release from ferritin in normally aerated solutions, in a dose (0.05-1 mM)- and time (0-120 min)-dependent manner; no reaction occurs under nitrogen. Superoxide dismutase partially inhibited (50% at 100 U/ml) iron release by 0.5 mM ALA, whereas the addition of catalase (50 U/ml) had no effect under these conditions. In phosphatidylcholine: cardiolipin (80:20) liposomes, and in the presence of 2 microM EDTA, ALA (0.025-1 mM) per se had a subtle effect on lipid peroxidation, while after addition of ferritin (0.25 mg/ml) there was a significant increase in lipid peroxidation as evaluated by dose-dependent formation of 2-thiobarbituric-reactive substances and diene conjugation. In vivo, iron accumulation in the liver of ALA-treated rats was observed. Altogether, these data demonstrate the ability of ALA-generated free radicals to release iron from ferritin and to affect iron metabolism in vivo. ALA-mediated iron release from ferritin, therefore, may aggravate oxidative damage to cell components and contribute to the pathology observed in AIP (eg., primary liver cancer) and lead poisoning.
 ...
PMID:5-Aminolevulinic acid induces iron release from ferritin. 784 Jun 72

Numerous mechanisms have been invoked to explain the cardiotoxicity of Adriamycin, most of which share a requirement for iron. Adriamycin is chemically reactive with iron loosely associated with subcellular membranes as well as with ferritin and the heme iron of hemoglobin. The present investigation examined whether Adriamycin also reacts with myoglobin, an abundant source of iron in cardiac muscle. Adriamycin caused a 4-fold stimulation of the autoxidation of oxymyoglobin to metmyoglobin. Hydrogen peroxide is an obligatory intermediate as catalase completely inhibited the reaction. Superoxide dismutase, however, was without effect. This interaction of Adriamycin with myoglobin may impose significant restrictions on oxygen storage and delivery in vivo. In light of the abundance of myoglobin and the deficiency of catalase in the heart, this interaction with myoglobin may be an important determinant of the cardioselective toxicity of Adriamycin.
 ...
PMID:Adriamycin-induced oxidation of myoglobin. 794 75

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.
 ...
PMID:Ferritin-dependent inactivation of microsomal glucose-6-phosphatase. 818 31

When erythrocyte membranes were incubated with adriamycin (ADM) in the presence of ferritin, lipid peroxidation occurred with release of iron from the ferritin. In the presence of apoferritin, ADM did not cause lipid peroxidation. Deferoxamine inhibited the ADM-induced lipid peroxidation in the presence of ferritin. These results indicate that lipid peroxidation depends upon the release of iron from ferritin. Even when the iron content in ferritin was very low, ADM could induce lipid peroxidation. Superoxide dismutase, catalase and hydroxyl radical scavengers did not substantially affect lipid peroxidation, indicating that the peroxidation reaction was independent of superoxide, H2O2 and hydroxyl radicals. Ceruloplasmin, a ferroxidase, markedly inhibited lipid peroxidation but did not affect the release of iron from ferritin. ADM-Fe(3+)-binding erythrocyte membranes were readily formed during the incubation of erythrocyte membranes with ADM in the presence of ferritin, and deferoxamine removed iron from the ADM-Fe(3+)-binding membranes, indicating that the iron moiety of the ADM-Fe(3+) complex is exposed at the membrane surface. These results may suggest that the peroxidation reaction occurs in a site-specific manner.
 ...
PMID:Adriamycin-induced lipid peroxidation of erythrocyte membranes in the presence of ferritin and the inhibitory effect of ceruloplasmin. 840 98

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.
 ...
PMID:Role of cytochrome P-450 in the stimulation of microsomal production of reactive oxygen species by ferritin. 860 Sep 80

Superoxide dismutase exerted a pronounced inhibitory effect upon xanthine oxidase-mediated reduction of iron in ferritin, ferric chloride, or ferric ADP. Maximal inhibition was observed when the superoxide dismutase concentration was only about 1% of that found in normal porcine liver. These observations indicate that superoxide anion radical is an intermediate in the reduction of iron by xanthine oxidase in vitro but not in vivo.
 ...
PMID:The role of superoxide anion radical in the reduction of ferritin iron by xanthine oxidase. 1134 83

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.
 ...
PMID:Aminoacetone induces loss of ferritin ferroxidase and iron uptake activities. 1470 1

Release of iron from ferritin requires reduction of ferric to ferrous iron. The iron can participate in the diabetogenic action of alloxan. We investigated the ability of ascorbate to catalyze the release of iron from ferritin in the presence of alloxan. Incubation of ferritin with ascorbate alone elicited iron release (33 nmol/10 min) and the generation of ascorbate free radical, suggesting a direct role for ascorbate in iron reduction. Iron release by ascorbate significantly increased in the presence of alloxan, but alloxan alone was unable to release measurable amounts of iron from ferritin. Superoxide dismutase significantly inhibited ascorbate-mediated iron release in the presence of alloxan, whereas catalase did not. The amount of alloxan radical (A.(-)) generated in reaction systems containing both ascorbate and alloxan decreased significantly upon addition of ferritin, suggesting that A.(-) is directly involved in iron reduction. Although release of iron from ferritin and generation of A.(-) were also observed in reactions containing GSH and alloxan, the amount of iron released in these reactions was not totally dependent on the amount of A.(-) present, suggesting that other reductants in addition to A.(-) (such as dialuric acid) may be involved in iron release mediated by GSH and alloxan. These results suggest that A.(-) is the main reductant involved in ascorbate-mediated iron release from ferritin in the presence of alloxan and that both dialuric acid and A.(-) contribute to GSH/alloxan-mediated iron release.
 ...
PMID:Ascorbate-mediated iron release from ferritin in the presence of alloxan. 1679 70


<< Previous 1 2 3 Next >>