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)

The effect of succinylacetone (SA), a highly specific inhibitor of ALA-dehydratase and heme synthesis, on hemoglobin (Hb) production, transferrin receptor (TfR), and ferritin expression was analyzed in differentiating Friend leukemia cells (FLC). This compound exerted a pronounced inhibitory effect not only on heme and Hb synthesis, but also on all the remaining above-mentioned parameters. In particular, SA induced: (1) a reduction of the level of alpha-globin mRNA; (2) a decreased number of exposed TfR molecules, without modification of their affinity for the ligand; (3) a reduced level of TfR RNA, without significant change of TfR gene transcription rate; and (4) a lower ferritin content. The addition of exogenous hemin to differentiating FLC exerted opposite effects, and particularly induced an increase of both the number of TfRs and ferritin content. These findings suggest that in erythroid cells optimal heme synthesis is required to coordinately sustain globin chains synthesis and TfR/ferritin production; thus, the intracellular heme level may represent a key regulatory factor in the Hb synthesis pathway.
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PMID:Intracellular heme coordinately modulates globin chain synthesis, transferrin receptor number, and ferritin content in differentiating Friend erythroleukemia cells. 191 86

Hematological parameters and free eythrocyte protoporphyrin (FEP) on a capillary blood sample were measured in 175 apparently healthy children ranging from 6 months to six years of age. Thirty eight children had hematological parameters descended and/or FEP elevated were asked to return for blood counts, FEP, serum ferritin, serum iron, total iron binding, capacity, transferrin saturation and ALA-D activity, on a venous blood sample. Only 34 children returned. Twenty seven, 15.4%, had iron stores descended or iron deficiency, 18 of them with anemia. FEP had significant correlation coefficients with hematologic parameters (p less than 0.001), serum iron and transferrin saturation (p less than 0.01). On iron deficiency anemia detection, the FEP had a sensibility and specificity of 0.94 and 0.75 respectively.
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PMID:[Usefulness of the determination of free erythrocyte protoporphyrin in relation to other hematologic parameters in iron deficiency]. 227 93

The late events of erythroid differentiation in Friend erythroleukemic cells (FELC), stimulated by 5-amino levulinic acid (5-ALA), were studied. Cultivation of the cells in 5-ALA-enriched media triggered a chain reaction, beginning with an immediate and rapid accumulation of endogenous porphyrins, in particular protoporphyrin and hemin. Incorporation of 14C-ALA was rapid and independent of dimethylsulfoxide (DMSO) induction. In parallel, on the second day of growth, a marked decrease in cell volume was elucidated by flow cytometry. The total protein content was reduced, while Fe uptake and hemoglobin synthesis were increased. The combination of DMSO and 5-ALA produced the most effective induction of the FELC, and the differentiation criteria were the most advanced. The cells exposed to the combined stimulation became loaded with heme and hemoglobin and their generation time was prolonged up to 35 h. Transmission electron microscopy of these treated cells showed a morphological alteration to pearlike cells, associated with a typical nuclear translocation phenomenon and a regional segregation of sialoglycoproteins. An uneven distribution of organelles was revealed; one part of the cell contained numerous ribosomes and the nucleus, while the other part was hemoglobinized, contained mitochondria, and the outer membrane was heavily labeled with ferritin hydrazide, a marker for sialoglycoproteins. The enhanced stimulation of Friend cells by 5-ALA promoted an advanced step of erythroid maturation that has much in common with the late events of normal nuclear extrusion process.
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PMID:Stimulation of Friend erythroleukemic cell cytodifferentiation by 5-amino levulinic acid; porphyrins, cell size, segregation of sialoglycoproteins, and nuclear translocation. 316 53

Analysis of myoglobin levels in L6 cells (derived from rat skeletal muscle) by radioimmunoassay shows that myoglobin is not synthesized until after the cells differentiate to form multinucleated myotubes. Thereafter, myoglobin accumulates in a linear fashion for up to 20 days, the longest time for which the cultures may be reliably maintained. Treatment of cultures with hemin increased myoglobin levels in a dose-dependent manner resulting in a 70% increase in myoglobin with 20 microM hemin. Succinyl acetone, a heme synthesis inhibitor, reduced myoglobin levels by 40% while simultaneous treatment with hemin restored myoglobin levels to control values. Treatment of cultures with a variety of Fe(III) chelates known to enhance both iron accumulation and ferritin synthesis in L6 cells had no effect on myoglobin levels. delta-Aminolevulinic acid also had no effect on myoglobin levels. None of the treatments had any effect on either the total soluble protein or DNA content of the cultures, and, therefore, the observed effects appear to be specific for myoglobin. These results suggest that myoglobin is expressed as a function of differentiation and that intracellular heme exerts a regulatory effect on myoglobin levels.
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PMID:Myoglobin expression in L6 muscle cells. Role of differentiation and heme. 372 91

Acute iron loading of rats, by intraperitoneal administration of iron-dextran (500 mg Fe/kg body wt 18-20 h before killing) decreased by 30% the rate of conversion of 5-amino-[14C]levulinate ([14C]ALA) into heme as measured with a recently described procedure for liver homogenates (1981. Biochem. J. 198: 595-604). The decrease in conversion of labeled ALA into heme caused by iron loading was shown to be due to a 70-80% decrease in activity of ALA dehydrase. The decrease in activity of ALA dehydrase caused by iron loading was not associated with a decrease in hepatic concentrations of GSH, nor could it be reversed by addition of dithiothreitol, Zn2+ or chelators of Fe2+ and Fe3+. Addition of FeSO4, ferric citrate, or ferritin to homogenates of control liver had no effect of activity of ALA dehydrase. The decrease in activity of ALA dehydrase, caused by iron-dextran, was mirrored by a reciprocal increase in ALA synthase. Iron-dextran potentiated the induction of ALA synthase by allylisopropylacetamide. However, this potentiation could be dissociated from the decrease in ALA dehydrase caused by iron loading.
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PMID:Iron and the liver: acute effects of iron-loading on hepatic heme synthesis of rats. Role of decreased activity of 5-aminolevulinate dehydrase. 618 58

An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron-deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 ml) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070), including eicosapentenoic acid (EPA; p = 0.0034), docosapentenoic acid (DPA; p = 0.0048) and docosahexenoic acid (DHA; p = 0.0058), were observed in the ID group. The EMB phosphatidylethanol-amine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0.05) in the percentage of n-3 FAs in the EMB-PC and EMB-PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.
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PMID:The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron deficiency. 770 22

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.
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PMID:5-Aminolevulinic acid induces iron release from ferritin. 784 Jun 72

An intervention study was designed to evaluate the fatty acid (FA) status of children aged 6-11 years before and after iron fortification. Iron deficient (ID) and matched controls without ID (n = 30) were selected. All children received soup (160 mL) fortified with 20 mg iron and 100 mg vitamin C for 15 weeks on school days. Measurements before and after intervention included dietary intake, haematological and iron status and FA composition of plasma and erythrocyte membranes (EMBs). The prevalence of low plasma ferritin concentration and transferrin saturation decreased in the ID children by 40% and 56%, respectively, with intervention. Plasma FAs reflected dietary FA intake. In comparison with controls, the ID group presented with increased percentage total saturated FAs (SFAs; p = 0.0002) in their EMB phosphatidylcholine (PC) and reduced percentage total polyunsaturated FAs (PUFAs; p = 0.0037) before intervention. Lower total n-3 FAs (p = 0.0070) including eicosapentaenoic acid (EPA; p = 0.0034), docosapentaenoic acid (DPA; p = 0.0048) and docosahexaenoic acid (DHA; p = 0.0058) were observed in the ID group. The EMB phosphatidylethanolamine (PEA) of the ID children presented with lower percentages of alpha-linolenic acid (ALA; p = 0.0001), EPA (p = 0.0051) and DHA (p = 0.0084) compared to controls before intervention. Iron intervention was associated with an increase (p < 0,05) in the percentage of n-3 FAs in the EMB-PC and -PEA of the ID group to percentages comparable to that in the control group. It appears that iron status can influence FA metabolism of specific n-3 FAs in the EMBs of young children.
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PMID:The effect of iron fortification on the fatty acid composition of plasma and erythrocyte membranes in primary school children with and without iron-deficiency. 784 96

5-Aminolevulinic acid (ALA), a heme precursor accumulated during the clinical expression of acute intermittent porphyria, lead poisoning, and tyrosinosis, has been hypothesized to act as an endogenous source of oxyradicals. We now report oxidative effects on brain tissue of rats submitted to ALA treatment. Upon acute treatment (40 mg/kg body weight) increased total nonheme iron in the cortex (20%) was observed. After prolonged ALA administration (40 mg/kg body weight on alternate days during 2 weeks), the following indicators of oxidative stress were found to be significantly increased: CuZnSOD activity (67%) in total brain homogenate, total iron (68%) and ferritin (71%) in the cortex, ferritin in striatum (44%), protein carbonyls in homogenate of cerebral cortex (threefold) and 45Ca2+ uptake by cortical synaptosomes (45%). In addition, synaptic membranes prepared from whole brain assayed with the radioligand 3H-muscimol, revealed increased Kd values (twofold) of the high-affinity GABAergic receptor binding and formation of protein carbonyl groups, thiobarbituric acid reactive products, and conjugated dienes. In vitro, ALA produced similar effects upon the high affinity 3H-muscimol binding. No apparent alteration of either dopaminergic or serotonergic [3H]-ligand binding was observed. These results argue in favor of ALA-triggered oxidative stress in brain accompanied by iron metabolism alterations and GABAergic receptor damage, which may be implicated in the neuropsychiatric manifestations of the aforementioned porphyrias.
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PMID:The prooxidant effect of 5-aminolevulinic acid in the brain tissue of rats: implications in neuropsychiatric manifestations in porphyrias. 872 Aug 99

The effect of inhibitors and intermediates of heme synthesis, inhibitor of globin synthesis, and some iron proteins on in vitro iron uptake and haemoglobin synthesis by reticulocytes of iron deficient subjects was investigated in this study. Lead, INH, ALA, mesoprophyrin, ferritin and albumin substantially increased iron uptake by iron deficient reticulocytes, while cycloheximide and glycine depressed it. The results showed that it is possible to stimulate iron uptake and Hb synthesis in iron deficiency by substances other than iron; the most effective and remarkable of them was ferritin.
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PMID:Stimulation of iron uptake and Hb synthesis in iron deficient reticulocytes. 1084 42


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