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

Rat-liver microsomes and NADPH could reduce Adriamycin, epirubicin and daunorubicin to their free radical forms, which enhanced peroxidation of microsomal lipids less than 2-fold in air but 3- to 5-fold at a pO2 of 4 mmHg. Mitoxantrone was not reduced by microsomes and had no effect on microsomal peroxidation. Daunorubicin caused more lipid peroxidation than similar concentrations of either Adriamycin or epirubicin, which were equally efficient. In each case peroxidation was iron-dependent and could be catalysed by ferritin. The antioxidants beta-carotene and alpha-tocopherol inhibited lipid peroxidation at low or high pO2. The dose-for-dose difference in the cardiotoxicity of epirubicin compared with Adriamycin is not explained by its effect on microsomal lipid peroxidation. However, the lower incidence of cardiotoxicity with mitoxantrone may be a consequence of its inability to form free radical species and promote lipid peroxidation.
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PMID:Microsomal lipid peroxidation induced by adriamycin, epirubicin, daunorubicin and mitoxantrone: a comparative study. 254 12

A distinct pool of liver ferritin has been described in man, guinea pigs and rats [Cham, Roeser, Nikles & Ridgway (1986) Clin. Chim. Acta 158, 71-79]. This ferritin accounts for approx. 30% of total intracellular ferritin. It differs from previously described cytosolic and 'microsomal-fraction' ferritin by its firm association with lipid and by the absence of heat-stability at 75 degrees C. The present study demonstrates that cytosolic ferritin and lipid-associated ferritin in guinea-pig livers have distinctly different rates of turnover. Cytosolic ferritin has a rate of turnover approx. 3.5 times as high as lipid-associated ferritin. The apparent metabolic heterogeneity suggests that the two forms of ferritin may have different functional roles.
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PMID:Cytosolic ferritin and lipid-associated ferritin are metabolically different in guinea-pig livers. 268 41

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

The role of Ca2+-ATPase as the driving force for active calcium uptake, involved in the relaxation of smooth muscle, was studied. It was shown by immunocytochemistry that Ca2+-ATPase activity was localized at the plasma membrane level of longitudinal smooth muscle of pregnant rat uteri (18-20 days). To study calcium regulation in uterine longitudinal smooth muscle, 2 microsomal fractions (F1 and F2) were obtained, enriched in plasma membrane material (Lalanne et al., 1984, in: Calcium Regulation in Smooth Muscles. INSERM series, 124, pp. 283-292). In the present paper this material is characterized at both morphologic and cytochemical levels. Both fractions are ultrastructurally heterogeneous: (a) thin sections clearly show 2 populations that differ in vesicular shape and size; (b) negative staining also shows differences in membrane structure, which could be related to biochemical differences and/or to the well known heterogeneity of the plasma membrane. Two reactions (PATAg and concanavalin A-biotin-avidin-ferritin), allowing visualization of cell coat glycans, were performed on F1 and F2 and on thin sections of longitudinal smooth muscle. Plasma membrane and almost all the vesicles of F1 and F2 are reactive. It is concluded that these 2 fractions are characteristic enough for studying, at the molecular level, the ability of plasma membrane to control calcium circulation in uterine smooth muscle.
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PMID:Ultrastructural and cytochemical characterization of subcellular fraction of plasmalemmal origin obtained from uterine longitudinal smooth muscle. 296 82

Microsomes prepared by the usual method of differential centrifugation were found to contain ferritin, superoxide dismutase (SOD), and catalase which could be removed by chromatography on Sepharose CL-2B. Addition of purified rat liver ferritin to chromatographed microsomes resulted in a significant stimulation of NADPH-dependent lipid peroxidation which was inhibited by exogenously added SOD. Iron release from ferritin by these microsomes was also inhibited by SOD. Ferritin did not promote NADPH-dependent microsomal lipid peroxidation when added to microsomes isolated in the usual manner, presumably due to the endogenous SOD present in the microsomes. Accordingly, only very low rates of iron release from ferritin were observed with these microsomes. Paraquat (PQ), which generates superoxide O2-. via redox cycling, greatly stimulated iron release from ferritin and lipid peroxidation in chromatographed microsomes. Paraquat had no effect on iron release from ferritin or lipid peroxidation in microsomes. which were not chromatographed unless they were first treated with CN- to inhibit endogenous SOD. These studies indicate that the majority of microsomal iron is contained within ferritin and that following release by O2-. this iron serves to promote the peroxidation of microsomal lipids.
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PMID:Rat liver microsomal NADPH-dependent release of iron from ferritin and lipid peroxidation. 301 80

We have investigated the degradation in rat liver of two typical endoplasmic reticulum (ER) membrane proteins, phenobarbital (PB)-inducible cytochrome P-450 (P-450[PB]) and NADPH-cytochrome P-450 reductase (FP2). Autolysosomes, almost completely free from contamination by the other organelles such as ER, were prepared from leupeptin-treated rat livers according to the method of Furuno et al. (Furuno, K., T. Ishikawa, and K. Kato, 1982, J. Biochem., 91:1943-1950). Quantitative immunoblot analysis showed that these two proteins were found in large amounts in the autolysosomes regardless of PB treatment. The specific content of P-450 (PB) in the autolysosomes changed along with that in the microsomes during and after PB treatment, whereas hardly any P-450(PB) was detected in the cytosol fraction throughout the experiment. We also found a marked increase in the autolysosomal proteins 3 d after cessation of PB treatment when microsomal proteins are degraded most rapidly. Ferritin immunoelectron microscopy revealed directly that when the limiting membranes of the premature autolysosomes were partially broken the smooth vesicles segregated within the autolysosomes were heavily stained with ferritin anti-P-450(PB) conjugates. Thus, for the first time, we could present convincing evidence that P-450(PB) and FP2 are segregated to be degraded in the autolysosomes.
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PMID:Cytochrome P-450 and NADPH-cytochrome P-450 reductase are degraded in the autolysosomes in rat liver. 310 62

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

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

Chrysotile asbestos fibers impair the activities of rat liver microsomal aryl hydrocarbon hydroxylase (AHH), aminopyrine (AP) N-demethylase and dimethylnitrosamine (DMN) demethylase in vitro. This inhibition is concentration-dependent. Preincubation of 3-methylcholanthrene (3-MC)-pretreated rat liver microsomes with chrysotile depresses the overall metabolism of [G-3H]benzo[a]pyrene (BaP). Various forms of asbestos employed inhibit AHH activity to the same extent. However, other types of asbestos are not as effective as chrysotile in diminishing AP demethylase activity. Chrysotile and crocidolite fibers are not found to significantly change the apparent Km of AHH activity, from 3-MC-pretreated rat liver microsomes, for BaP. Increasing the microsomal protein concentration partially abolishes the inhibition of AHH activity caused by chrysotile fibers. Inhibition of AP demethylase and AHH activities is attenuated by bovine serum albumin (BSA) or ferritin. Depression of AHH activity by crocidolite is significantly reversed by ferritin. Since polymers such as ferritin override enzyme inhibition by chrysotile as well as crocidolite, surface chemical groups of the fibers may be involved in enzyme modification.
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PMID:Effect of asbestos fibers on aryl hydrocarbon hydroxylase and aminopyrine N-demethylase activities of rat liver microsomes. 394 7


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