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

Ferritin was found to promote the peroxidation of phospholipid liposomes, as evidenced by malondialdehyde formation, when incubated with xanthine oxidase, xanthine, and ADP. Activity was inhibited by superoxide dismutase but markedly stimulated by the addition of catalase. Xanthine oxidase-dependent iron release from ferritin, measured spectrophotometrically using the ferrous iron chelator 2,2'-dipyridyl, was also inhibited by superoxide dismutase, suggesting that superoxide can mediate the reductive release of iron from ferritin. Potassium superoxide in crown ether also promoted superoxide dismutase-inhibitable release of iron from ferritin. Catalase had little effect on the rate of iron release from ferritin; thus hydrogen peroxide appears to inhibit lipid peroxidation by preventing the formation of an initiating species rather than by inhibiting iron release from ferritin. EPR spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide was used to observe free radical production in this system. Addition of ferritin to the xanthine oxidase system resulted in loss of the superoxide spin trap adduct suggesting an interaction between superoxide and ferritin. The resultant spectrum was that of a hydroxyl radical spin trap adduct which was abolished by the addition of catalase. These data suggest that ferritin may function in vivo as a source of iron for promotion of superoxide-dependent lipid peroxidation. Stimulation of lipid peroxidation but inhibition of hydroxyl radical formation by catalase suggests that, in this system, initiation is not via an iron-catalyzed Haber-Weiss reaction.
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PMID:Ferritin and superoxide-dependent lipid peroxidation. 298 54

Human polymorphonuclear leucocytes were found to promote peroxidation of phospholipid liposomes upon stimulation by phorbol myristate acetate. Peroxidation required the presence of either pyrophosphate-chelated or ADP-chelated iron, whereas iron chelated to EDTA or ATP had no effect. Peroxidation was also catalyzed by ferritin, but not by transferrin. Superoxide dismutase abolished the peroxidation, whereas catalase and apparently also the hydroxyl radical scavenger dimethyl sulphoxide were inactive, indicating that the peroxidation was mediated by superoxide radicals but not by hydrogen peroxide or hydroxyl radicals. Xanthine oxidase-promoted peroxidation was studied for comparison and showed similar characteristics except that transferrin catalyzed the peroxidation. Peroxidation of membrane lipids may be a mechanism whereby granulocytes cause tissue damage in inflammation. The drugs paracetamol, gentisic acid and 5-aminosalicylic acid inhibited lipid peroxidation, probably through their ability to react with the superoxide anion.
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PMID:Peroxidation of liposomes promoted by human polymorphonuclear leucocytes. 301 66

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.
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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

A deficiency of choline and methionine is hepatocarcinogenic and is associated with an apparent increase in lipid peroxidation. In this study the susceptibility of microsomes and nuclei to ferritin-dependent lipid peroxidation is examined together with the status of the peroxidation-protective systems. Choline-methionine deficiency caused an increase in Se-independent GSH peroxidases (GSH transferase subunit 2) and membrane vitamin E but a decrease in Se-dependent GSH peroxidase and microsomal GSH peroxidase activity. Choline-methionine deficient microsomes and nuclei were 4-fold more susceptible to lipid peroxidation induced in vitro by physiological concentrations of ferritin/ascorbate/ADP; and the peroxidation was less effectively inhibited by GSH and soluble GSH peroxidases than controls. The results indicate that a decreased level of Se-dependent and membrane GSH peroxidases is involved in the increase in lipid peroxidation observed in choline-methionine deficiency.
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PMID:Lipid peroxidation in choline-methionine deficiency. 350 37

In a comparative screening study of chelators intended for clinical use eleven iron chelators have been tested for their ability to mobilize (59Fe) iron from 59Fe-labelled ferritin and from hepatocytes of rats labelled with 59Fe-transferrin. The toxic effects of the chelators were also studied using microsomal lipid peroxidation induced by Fe3+/ADP and NADPH. From these tests it was shown that 1,2-dimethyl 3-hydroxypyrid-4-one (L1) and mimosine were the most effective iron chelators in iron mobilization and did not catalyse lipid peroxidation. In conclusion it can be stated that besides to investigate the iron binding capacity of new chelators also their ability to catalyse lipid peroxidation has to be ruled out.
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PMID:Free radical and cytotoxic effects of chelators and their iron complexes in the hepatocyte. 350 52

A lipid peroxidation system consisting of phospholipid liposomes, paraquat, ADP, and NADPH-cytochrome P450 reductase was constituted using ferritin as the sole source of iron. Lipid peroxidation was completely inhibited by superoxide dismutase, essentially not affected by mannitol, but markedly stimulated by catalase. Similar effects of these scavenging agents were observed in incubations void of ADP. These data suggest that O2-, produced by the redox cycling of paraquat, can release iron from ferritin and thereby promote lipid peroxidation. The effects of catalase and mannitol suggest that the initiation of peroxidation, in either the presence or absence of ADP, is not significantly dependent upon the hydroxyl radical produced via an iron-catalyzed Haber-Weiss reaction.
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PMID:Paraquat and ferritin-dependent lipid peroxidation. 393 39

We examined the effects of chronic dietary iron overload on hepatic mitochondrial oxidative metabolism. Experimental iron overload was produced by feeding rats a chow diet supplemented with carbonyl iron over a 7-week period. Biochemical and histologic evaluations of liver tissue confirmed moderate degrees of hepatic parenchymal iron overload. Electron microscopy showed no abnormalities in hepatic mitochondrial ultrastructure in blocks of tissue or in mitochondrial fractions from iron-loaded liver. Studies of mitochondrial oxidative metabolism revealed a consistent and progressive decrease in state 3 (ADP-stimulated) respiration and in respiratory control ratios at hepatic iron concentrations above 1,000 micrograms per gm for all three substrates studied, glutamate, beta-hydroxybutyrate and succinate. Changes in state 4 (ADP-limited) respiration and ADP/O ratios were not progressive with increasing hepatic iron concentrations. At hepatic iron concentrations at which there were decreases in state 3 respiration and respiratory control ratios, there was also evidence of lipid-conjugated diene formation, indicative of mitochondrial lipid peroxidation. There were no changes in mitochondrial function when iron as either ferritin or hemosiderin or as a combination of ferritin, hemosiderin and ferric nitrilotriacetate was added in vitro to normal liver homogenates. Use of density gradient centrifugation to reduce iron and lysosomal contamination of mitochondrial fractions failed to prevent the reduction in mitochondrial function. We conclude that moderate degrees of chronic hepatic iron overload in vivo result in an inhibitory defect in the mitochondrial electron transport chain as evidenced by a decrease in state 3 respiration and respiratory control ratios.
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PMID:Hepatic mitochondrial oxidative metabolism in rats with chronic dietary iron overload. 402 91

The fibrinogen distribution in platelet organelles after ADP-stimulation was investigated with anti-human fibrinogen using protein A-gold applied to serial sections. Fibrinogen was detected in the so-called alpha-granules of platelets and also in granule protrusions which were observed after ADP-stimulation. The ends of these protrusions were formed as coated membranes and the tips were often in apposition to the surface connected membranes or the plasmalemma. At such places fusion events and hence signs of an exocytosis could be demonstrated by means of cryofixation and cryosubstitution. Examination of serial sections revealed fibrinogen on all these granule profiles. Surface connected membranes, free surfaces and the characteristic structure of the contact zones of aggregated platelets were also labelled by gold particles but less than anticipated. On the platelet surfaces and surface connected membranes fibrinogen was rarely demonstrable with ferritin-labelled anti-human fibrinogen on washed or thrombin-stimulated, almost fibrinogen free platelets. After addition of human fibrinogen to the thrombin stimulated and disaggregated platelets a part of the platelets aggregated spontaneously and formed characteristic contact zones. Anti-human fibrinogen was observed on the free surfaces, in filamentous bridges between the contact spaces and in a tubular surface connected membrane system with involvement of coated membranes at the central ends of these structures. The results indicate the following: all alpha-granules contain fibrinogen; after ADP-stimulation secretion takes place with involvement of coated membranes; during aggregation fibrinogen binds to platelet surfaces and forms contact spaces; fibrinogen is taken up by the surface connected system with involvement of coated membranes.
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PMID:Fibrinogen distribution on surfaces and in organelles of ADP stimulated human blood platelets. 404 93

A ferritin-conjugated anti-fibrin/fibrinogen was localized by means of light and electron microscopy in artificial in vitro thrombi formed in the presence of the labeled antibody, and in preformed ADP-induced platelet aggregates. The ferritin was distributed throughout the central and peripheral regions of the columns of aggregated platelets in the thrombi. In the preformed ADP aggregates, ferritin was deposited only by infiltration from surrounding plasma and was confined to the periphery of the columns. The even distribution of ferritin in the central zone of the platelet columns of the thrombi indicated a specific reaction had occurred before or during thrombus formation unrelated to infiltration of plasma. In the artificial thrombi, the ferritin-labeled antibody was localized on the surface layer of platelets and on the bridging structures composed of the combined surface layers in the narrow spaces between cohesive platelets. Vesicles and alpha granules within the platelets also were tagged. The absence of obvious fibrin between narrow interspaces and within the platelets indicated that the antibody had reacted with fibrinogen or partly polymerized fibrin at these sites. Many invaginations of the platelet membrane containing dense fibrillar material were interpreted to be alpha granules discharging their contents during the "release reaction" at the time of aggregation. This material, which was tagged by the ferritin-conjugated antibody, merged with the interplatelet bridges to suggest that released fibrinogen from within the platelet contributed to the structural bond and strengthened it. A layer of dense fibrin and altered platelets in the periphery of the columns of aggregated platelets in the artificial thrombi contained the platelets and limited further growth of the aggregates. The fibrin was thought to be derived from infiltrated plasma as well as from released intraplatelet fibrinogen. Platelet fibrinogen thus appeared to take part both in the cohesion of aggregated platelets and in the stabilization of the aggregates formed.
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PMID:Localization of ferritin-conjugated anti-fibrin-fibrinogen in platelet aggregates produced in vitro. 506 May 78

We have studied iron transfer from transferrin to ferritin in the presence of ATP, GTP, ADP, AMP and 2,3-diphosphoglycerate. These compounds, with the exception of AMP, can release iron from transferrin at pH 7.4 and form a stable Fe(III)-phosphate complex. From these complexes, only a limited number of Fe(III) atoms can be incorporated into ferritin. Ascorbate enhances iron transfer from transferrin to ferritin at the beginning of the process but subsequently inhibits further iron deposition in ferritin.
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PMID:Iron transfer form transferrin to ferritin mediated by polyphosphate compounds. 627 Dec 55


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