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

Embryonic chick and hamster aortas were examined in the electron microscope using ferritin-conjugated, elastin-specific antibodies after etching of the plastic, thin sections with a dilute solution of benzene, methanol and ethanol. Specific staining of intracellular vesicles was observed in both smooth muscle and endothelial cells in addition to extracellular elastin fibers. In the chick cells, these ferritin-stained vesicles had a lipid-laden appearance. In both species the vesicles appeared to fuse with the plasma membrane and discharge their contents into the extracellular space suggesting elastin is secreted via vesicular structures.
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PMID:Immuno electron microscopic studies on cells synthesizing elastin. 645 44

The control of cellular iron homeostasis involves the coordinate post-transcriptional regulation of ferritin mRNA translation and transferring receptor mRNA stability. These regulatory events are mediated by a soluble cytoplasmic protein, iron regulatory factor (IRF), which binds specifically to mRNA hairpin structures, termed iron-responsive elements (IREs), in the respective mRNAs. IRF is modulated by variations of cellular iron levels and exists as either an apo-protein or a [4Fe-4S]-cluster protein. The two conformations show distinct, mutually exclusive functions. High-affinity IRE binding is observed with the apo-form induced by iron deprivation, but is lost under high iron conditions when IRF is converted to the [4Fe-4S]-cluster form which shows cytoplasmic aconitase activity. Moreover, IRE binding is inactivated by the sulfhydryl-oxidizing agent diamide and fully activated in vitro by 2% 2-mercapto-ethanol, whereas alkylation of IRF inhibits IRE binding. In the present study, we analyzed each of the above features using site-directed mutants of recombinant human IRF. The results support the bifunctional nature of IRF. We conclude that cysteines 437, 503 and 506 anchor the [4Fe-4S]-cluster, and are essential to the aconitase activity. Mutagenesis changing any of the cysteines to serine leads to constitutive RNA binding in 0.02% 2-mercaptoethanol. Cysteine 437 is particularly critical to the RNA-protein interaction. The spontaneous or diamide-induced formation of disulfide bonds between cysteines 437 and 503 or 437 and 506, in apo-IRF, as well as its alkylation by N-ethylmaleimide, inhibit binding to the IRE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutational analysis of the [4Fe-4S]-cluster converting iron regulatory factor from its RNA-binding form to cytoplasmic aconitase. 750 61

Fetal alcohol syndrome produces defects that parallel abnormalities associated with early iron deficiency. Hence, we examined the effects of prenatal exposure to ethanol on iron, transferrin, and ferritin concentrations. The subjects were the offspring of pregnant rats fed an ethanol-containing diet (Et), pair-fed an isocaloric control diet (Ct), or fed chow and water. The amounts of iron, transferrin, and ferritin were assessed in three CNS regions (cerebral cortex, subcortical forebrain, and brainstem). In all three segments of the control rats, iron, transferrin, and ferritin levels decreased during the first 2 postnatal weeks, reached a minimum during week 3, and then rose to adult levels. This pattern was delayed by ethanol treatment, e.g., the minimal concentrations in iron, transferrin, and ferritin in the Et-treated rats were achieved later (3 days, 7 days, and 2 weeks, respectively) than they were in the Ct-treated rats. Ethanol-induced alterations in iron homeostasis persisted into adulthood; iron concentration was reduced, transferrin concentration was unaffected, and ferritin concentration was increased. The net result was that the timely delivery and bioavailability of iron were compromised by ethanol exposure. The defects in iron regulation are permanent and may underlie ethanol-induced abnormalities in iron-dependent growth processes such as myelination.
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PMID:Iron regulation in the developing rat brain: effect of in utero ethanol exposure. 779 Aug 82

The RRR-alpha-tocopherol (vitamin E) content in plasma from 46 patients with liver diseases and 23 healthy controls was determined by high performance liquid chromatography and electrochemical detection. Patients were divided into three groups: alcoholic liver diseases (n = 17; group A), hemochromatosis (n = 17; group B) and Wilson's disease (n = 12; group C). Lipid-standardized alpha-tocopherol levels were determined to neutralize differences due to hyperlipemia. The ratio of serum vitamin E to serum lipids (cholesterol, triglycerides, phospholipids) was highest in healthy controls and in patients in group A with cirrhosis and normal transaminases and bilirubin. Patients in group A with acute or chronic ethanol intoxication and high bilirubin levels had a 37% lower lipid-standardized vitamin E level than controls. Patients in group B with hemochromatosis, showing high serum iron (> 180 micrograms/dl), a low free iron binding capacity (< 8 mumol/l) and high ferritin-levels (< 450 micrograms/l), had a 34% lower vitamin E/lipid ratio than healthy controls. No significant lowering of the vitamin E/lipid ratio was observed in the other patients in group B. A significant decrease (37%) in the vitamin E/lipid ratio was only detectable in patients with Wilson's disease (group C) showing high free serum copper (> 10 micrograms/dl). The data support a role for free radicals in the pathogenesis of active liver diseases.
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PMID:Low vitamin E content in plasma of patients with alcoholic liver disease, hemochromatosis and Wilson's disease. 781 21

Iron mobilized from ferritin has been shown to catalyze production of potent reactive oxygen intermediates. Experiments were carried out to evaluate the ability of ferritin to catalyze nuclear generation of hydroxyl radical in the presence of either NADPH or NADH. In the absence of redox cycling agents, ferritin did not catalyze nuclear oxidation of hydroxyl radical scavenging agents (2-keto-4-thiomethylbutyric acid, dimethylsulfoxide, ethanol) even if EDTA was added to chelate any released iron. The addition of menadione or paraquat resulted in a ferritin-dependent oxidation of chemical scavengers; menadione promoted the catalysis by ferritin with either NADPH or NADH, whereas paraquat was much more reactive with NADPH as the nuclear reductant. The presence of an externally added iron chelator was required for elevated rates of scavenger oxidation, with EDTA and DTPA being more reactive than ATP or citrate and desferrioxamine being inhibitory. The ferritin-catalyzed hydroxyl radical scavenger oxidation was sensitive to superoxide dismutase, catalase, and competitive scavengers. In the absence or presence of ferritin, rates of NADPH- or NADH-dependent H2O2 production were low; menadione increased H2O2 production with both NADPH and NADH, whereas paraquat was mostly effective with NADPH. Depending on the nature of the added chelating agent (e.g., EDTA, ATP) and the reductant, rates of nuclear production of .OH in the presence of redox cycling agent plus ferritin were 10 to 70% as high as rates found with redox cycling agent plus ferric-chelate (e.g., ferric-EDTA, ferric-ATP). Since reactive oxygen intermediates such as the hydroxyl radical can alter the structural integrity of the nucleus and interact with DNA, the ability of ferritin to promote nuclear generation of hydroxyl radical may play a role in the toxicity associated with iron as well as redox cycling agents.
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PMID:Ferritin stimulation of hydroxyl radical production by rat liver nuclei. 831 76

The nonenzymatic reactions of dihydrolipoamide with a number of low-potential quinones, possessing either a fully or a partially substituted quinone ring at pH 7.0 were accompanied by consumption of oxygen in a significant excess of the quinone concentration, thus establishing their redox cycling. Contrary to this, only partially substituted quinones caused the consumption of oxygen in the presence of reduced glutathione due to reoxidation of reduced quinone-glutathione conjugates. Among compounds tested, 9,10-phenanthrene quinone catalyzed the most rapid consumption of oxygen in the presence of dihydrolipoamide with subsequent formation of lipoamide and H2O2. The rate constant of anaerobic reduction of phenanthrene quinone by dihydrolipoamide was 8.6 +/- 1.6 x 10(3) M-1 s-1 (pH 7.0, 0.1 M phosphate, 20% ethanol, 25 degrees C). The consumption of oxygen and formation of lipoamide were inhibited by superoxide dismutase, indicating that the redox cycling involves the autooxidation of 9,10-dihydroxy phenanthrene, mediated by superoxide. The reaction was accompanied by the reduction of added cytochrome c, which was insignificantly inhibited by superoxide dismutase, and the reductive mobilization of iron from ferritin, activated by superoxide dismutase. These data raise the possibility that dihydrolipoamide, usually regarded as an antioxidant, under certain conditions may exert moderate prooxidant activity, initiating the formation of radicals and activated forms of oxygen.
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PMID:Dihydrolipoamide-mediated redox cycling of quinones. 838 46

Alcohol abuse is known to cause disturbances to iron homeostasis in man and is associated with elevated serum ferritin levels. We have previously shown that ethanol metabolism in the rat hepatocyte is associated with an immediate reduction in ferritin uptake by this cell. In this study we have examined the effect of pair-feeding the Lieber-DeCarli liquid alcohol diet on ferritin uptake by rat hepatocytes. Rat liver ferritin was radiolabeled with 59Fe in vivo and isolated by conventional techniques. Rats were pair-fed the Lieber-DeCarli liquid alcoholic diet for 4-6 weeks. Hepatocytes, isolated from their livers by collagenase perfusion, were incubated with [59Fe]ferritin in L-15 medium at 37 degrees C and 4 degrees to measure ferritin uptake and binding. The in vitro effect of ethanol on these hepatocytes was also studied. Ferritin and iron parameters were measured in the sera and hepatocytes of these animals and a comparable group of normal chow-fed rats. The rate of ferritin uptake by hepatocytes from alcohol-fed rats was significantly faster than that of their pair-fed controls (0.743 +/- 0.061 vs. 0.540 +/- 0.042 ng/min/10(6) cells, p < 0.05). However, the rats on Lieber-DeCarli control diet exhibited a lower hepatocyte ferritin uptake rate than chow-fed animals (79.3 +/- 8.1% of the control values, p < 0.01). In vitro incubation of cells in 100 mM ethanol resulted in less inhibition of ferritin uptake by hepatocytes from alcoholic rats than from their pair-fed controls (11 +/- 7.1% inhibition vs. 43.6 +/- 10.7% for controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Clin Exp Res 1993 Apr
PMID:Effect of chronic alcohol feeding on hepatic iron status and ferritin uptake by rat hepatocytes. 848 84

Serum ferritin increases in chronic alcoholism, without clear explanation. We have previously shown that alcohol increases ferritin levels in a human hepatoblastoma cell line (HepG2). The aims of the present work were: 1) To extend our results in normal rat hepatocyte cultures, and 2) To determine the mechanism by which alcohol enhances ferritin levels. In HepG2 cells, high alcohol concentrations (300 mM) during long exposure (4 days) increased the synthesis of H and L ferritin subunits, in association with increased levels of ferritin mRNAs. In rat hepatocyte cultures, the synthesis of L ferritin increased after 24 h of exposure to lower alcohol concentrations (10 mM); alcohol had no effect on ferritin mRNAs levels. In both cell types, the alcohol effect was not related to an increase in iron intracellular incorporation. In HepG2 cells, desferrioxamine (Df), a potent iron chelator, abolished ferritin synthesis in the presence or absence of alcohol, and abolished the alcohol induction of ferritin mRNAs. In rat hepatocytes, Df decreased ferritin synthesis to a similar level in the presence or absence of alcohol. Alcohol increased ferritin synthesis differently in HepG2 cells and in normal rat hepatocyte cultures. In the latter case, the alcohol effect was observed at low concentration. Despite a striking inhibiting effect of Df on ferritin synthesis, in both cellular models a mechanism accounting for increased ferritin synthesis independently of iron is suggested. Globally, these data strongly suggest that hyperferritinemia in chronic alcoholism could be related to the induction of ferritin by alcohol.
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PMID:Regulation of ferritin expression by alcohol in a human hepatoblastoma cell line and in rat hepatocyte cultures. 865 61

The tetramethylbenzidine (TMB) oxidation kinetics dependent on spleen ferritin (FERR) has been studied in TMB-FERR-H2O2 (1) and TMB-FERR-O2 (2) systems at pH 4.2 and 6.0. At TMB concentrations below 6 mM, the dependencies of the initial rate for protein oxidation in system (1) on initial concentrations of TMB and H2O2 are described by the Michaelis-Menten kinetics. In terms of (kcat/K(m)), the maximum FERR efficiency during TMB oxidation is equal to 2.8-10(-1) s-1. Mannitol, urea, ethanol and sodium fluoride strongly inhibit TMB oxidation in system (1). Competitive type oxidation inhibition by urea is characterized by K(i) = 12.5 mM. At TMB concentrations above 6 mM in system (2) the autocatalytic oxidation of the amine is observed. In both systems the initial rate of TMB oxidation increases strongly with a decrease in pH from 9.3 down to 4.2. In system (1) the initiating role is played by Fe3+ ions interaction with H2O2, that in system (2)-by the interaction of the same ions with the amine proper. In both cases, TMB oxidation is a catalytic chain process including elementary ion radical stages. The main oxidizing agents in system (2) are HO radicals and Fe3+ ions. The TMB interaction with FERR may be the reason for the lipid peroxidation increase following administration of aromatic amines.
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PMID:[Ferritin--a biocatalyst of aromatic amine oxidation]. 871 97

The objective was to examine the relationships between serum ferritin, alcohol intake, and socioeconomic factors (school education, occupational education, occupation, income, marital status, cohabitation status, housing, social class) in a population survey performed in Copenhagen County during 1982-1984. The participants were selected at random from the census register and comprised 2235 healthy Danish individuals, non-blood donors (1044 men, 1191 women) in cohorts being 30, 40, 50, and 60 years old. The participants gave a detailed social and medical history and had a clinical examination including blood samples. In all age-groups, men had significantly higher serum ferritin and alcohol intake than women. In men, there was no relationship between serum ferritin and social class. Significant relationships were observed between ferritin and occupation (unemployed and self-employed men had higher ferritin than those with other occupations) and ferritin and income (in younger men, ferritin displayed a steady increase with income). None of the social variables were related to the prevalence of iron deficiency or iron overload. Alcohol intake was related to occupation and income, but not to social class. In women, none of the social variables showed any significant relationship to ferritin levels or iron overload. The prevalence of small iron stores (serum ferritin < or = 30 micrograms/l) was lower and the intake of alcohol was higher in women from high social classes. In both men and women, serum ferritin displayed highly significant positive correlations with alcohol intake. Likewise, the prevalence of iron overload (serum ferritin > 90th percentile) was closely correlated to alcohol intake. In conclusion, socioeconomic factors per se had a minor influence on serum ferritin levels and iron status in Danes. The distinct association between alcohol intake and serum ferritin levels should be considered in future iron status surveys.
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PMID:Relationship between serum ferritin, alcohol intake, and social status in 2235 Danish men and women. 876 57


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