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 identification of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as dopaminergic neurotoxins that can induce parkinsonism in humans and animals has contributed to a better understanding of Parkinson's disease (PD). Although the involvement of similar neurotoxins has been implicated in PD, the etiology of the disease remains obscure. However, the recently described pathology of PD supports the view for a state of oxidative stress in the substantia nigra (SN), resulting as a consequence of the selective accumulation of iron in SN zona compacta and within the melanized dopamine neurons. Whether iron is directly involved cannot be ascertained. Nevertheless, the biochemical changes due to oxidative stress resulting from tissue iron overload (siderosis) are similar to those now being identified in parkinsonian SN. These include the reduction of mitochondrial electron transport, complex I and III activities, glutathione peroxidase activity, glutathione (GSH) ascorbate, calcium-binding protein, and superoxide dismutase and increase of basal lipid peroxidation and deposition of iron. The participation of iron-induced oxygen free radicals in the process of nigrostriatal dopamine neuron degeneration is strengthened by recent studies in which the neurotoxicity of 6-OHDA has been linked to the release of iron from its binding sites in ferritin. This is further supported by experiments with the prototype iron chelator, desferrioxamine (Desferal), a free-radical inhibitor, which protects against 6-OHDA-induced lesions in the rat. Indeed, intranigral iron injection in rats produces a selective lesioning of dopamine neurons, resulting in a behavioral and biochemical parkinsonism.
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PMID:The possible role of iron in the etiopathology of Parkinson's disease. 841 92

Folic acid and other vitamin deficiencies may play a role in the etiology of neural tube defects. The Medical Research Council Vitamin Study confirmed the beneficial effect of folic acid supplementation on the prevention of neural tube defects. However, the concentrations of vitamins other than folate were not a common feature of any of the former studies. We measured the concentrations of vitamin A, riboflavin, riboflavine-5'-monophosphate, flavine-adenine-dinucleotide, vitamin B-6, vitamin B-12, vitamin C, vitamin E, folate and ferritin in the serum of women who had previously had a child with a neural tube defect and were planning a further pregnancy. Vitamin and folic acid supplements were supplied before conception to 44 high risk women before conception. Eighteen other high risk women not given supplements were the control group. We concluded that vitamin profiles do not form a suitable means for identifying women at risk for neural tube defects before pregnancy. This endorses the hypothesis that the beneficial effect of folic acid supplementation on the prevention of neural tube defects is possibly at least partly due to the fact that it overrides a relative folic acid shortage caused by a metabolic disorder.
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PMID:Periconceptional vitamin profiles are not suitable for identifying women at risk for neural tube defects. 842 68

Ferritins are iron-storage proteins that accumulate in plastids during seed formation, and also in leaves during senescence or iron overload. Iron release from ferritins occurs during growth of seedlings and greening of plastids. Depending on the concentration of the reducing agent ascorbate, either an overall iron release or uptake by ferritins from iron(III) citrate may occur. We have designed methods to measure these simultaneous and independent uptake and release fluxes. Each individual step of the exchange was studied using different iron chelates and an excess of ligand. It is shown that: (i) the chelated form of iron, and not ionic Fe3+, is the substrate for iron reduction, which controls the subsequent uptake by ferritin; (ii) iron uptake by ferritins is faster at pH 8.4 than at pH 7 or 6 and is inhibited by an excess of strongly binding free ligands; and (iii) strongly binding free ligands are inhibitory during iron release by ascorbate. When reactions are allowed to proceed simultaneously, the iron chelating power is shown to be a key factor in the overall exchange. The interactions of iron chelating power, reducing capacity and pH are discussed with regard to their influence on the biochemical mobilization of iron.
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PMID:Iron release and uptake by plant ferritin: effects of pH, reduction and chelation. 845 96

Dietary, anthropometric, and chronic disease risk factors (CDRF) including blood lipids and blood pressure (BP), were measured in 91 vitamin-mineral supplement users (SU) and nonusers (NU) representing a wide range of athletic interests. Supplements were used by 46 (51%) subjects; 100% of female athletes and 51% of male athletes used supplements while none of a group of 15 control female subjects currently used supplements. Both dietary intake and energy expenditure were measured using 7-day records. Adiposity was determined from body weight, body mass index, and skinfolds. Total cholesterol, high-density lipoprotein cholesterol, serum ferritin, hemoglobin, hematocrit, zinc, copper, and vitamin C were based on 12-hour fasting blood samples. Dietary intake (excluding supplements) for SU tended to be greater than NU for vitamin C, thiamin, riboflavin, niacin, B6, B12, folate, calcium, iron and magnesium. Plasma vitamin C levels were significantly higher among SU than NU of both gender groups (p < 0.05). Although SU may exhibit additional healthy lifestyle practices, lipid profiles for many of these athletes were unfavorable with regard to CDRF.
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PMID:Vitamin-mineral supplement use and nutritional status of athletes. 846 14

Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of vitamin C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.
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PMID:Resistance to erythropoietin in iron-overloaded haemodialysis patients can be overcome by ascorbic acid administration. 852 94

Duodenal biopsies from control subjects, patients with iron-deficiency anaemia and rheumatoid arthritic patients with anaemia of chronic disorders (ACD) were investigated for their ability to take up 59Fe from iron ascorbate. Additionally, duodenal tissues were analysed for iron and immunoreactive ferritin and transferrin. Biopsies from iron-deficient subjects showed a 2- to 3-fold increase in the apparent Vmax for 59Fe uptake, compared to control values. Uptake was inversely related to body iron stores. ACD patients showed similar rates of 59Fe uptake to controls; the rates were independent of the degree of anaemia or serum ferritin levels. Tissue analysis showed reductions in mucosal iron and ferritin levels in iron-deficient patients, whilst transferrin levels were within the normal range. ACD patients also exhibited lower mucosal iron levels, but had iron protein levels within the normal range. It is suggested that factors distant from the intestinal mucosa influence iron absorption in ACD.
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PMID:In vitro duodenal iron uptake and serum and mucosal iron protein levels, with special reference to rheumatoid arthritis. 854 5

A synthetic siderophore, O-Trensox (L), has been designed and synthesized to improve iron nutrition of plants. The affinity for iron of this ligand [pFe(III) = 29.5 and pFe(II) = 17.9] is very high compared with EDTA. In spite of its high and specific affinity for iron, O-Trensox was found to be able to prevent, and to reverse, iron chlorosis in several plant species grown in axenic conditions. It also allows the iron nutrition and growth of Acer pseudoplatanus L. cell suspensions. The rate of iron metabolization was monitored by 59Fe radioiron. Ferritins, the iron storage proteins, are shown to be the first iron-labelled proteins during iron metabolization and to be able to further dispatch the metal. Using Fe(III)-Trensox, the rate of iron incorporation into ferritin was found to be higher than when using Fe-EDTA, but slower than with Fe-citrate, the natural iron carrier in xylem. During a plant cell culture, the extracellular concentrations of iron complex and free ligand were measured; changes in their relative amounts showed that the iron complex is dissociated extracellularly and that only iron is internalized. This suggests a high affinity for iron of a putative carrier on the plasmalemma. In contrast with Fe-citrate and Fe-EDTA complexes, Fe(III)-Trensox is not photoreducible. Its ability to induce radical damage as a Fenton reagent was tested using supercoiled DNA as target molecule. Unlike Fe-citrate and Fe-EDTA, Fe(II)-Trensox and Fe(III)-Trensox were proven to be harmless even during ascorbate-driven reduction, while Fe-EDTA and Fe-citrate generate heavy damage to DNA.
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PMID:Metabolization of iron by plant cells using O-Trensox, a high-affinity abiotic iron-chelating agent. 855 34

The regulation of expression of hepatic iron-related proteins was examined during iron deficiency caused by scurvy in guinea pigs. Previous studies showed that some effects of scurvy, such as suppression of collagen gene expression, result from events associated with weight loss. During the initial phase of scurvy when vitamin C is depleted but animals grow normally, serum iron levels decreased to 50% of normal. During the second phase of scurvy when animals lose weight, there was a further decrease in iron levels to 10-15% of normal. Serum transferrin levels increased during scurvy, but this increase was related neither to the rate of weight loss nor to hepatic transferrin mRNA expression, which decreased. Serum ferritin levels of diminished early in scurvy with a preferential loss of the L subunit. In liver, however, both ferritin animals gaining weight. Ferritin gene expression during vitamin C deficiency was correlated with serum ferritin levels in that the level of mRNA for the H subunit remained relatively constant while that of the L subunit decreased early. Transferrin receptor mRNA expression in liver was induced as soon as iron levels decreased early in scurvy, which is similar to results reported for iron-depleted cultured cells. In contrast to results in cell culture, expression of iron regulatory protein 1 mRNA was decreased to approximately 50% of normal early in scurvy with a concomitant decrease in hepatic cytosolic aconitase activity. Our data indicate that iron deficiency occurs early during vitamin C deficiency and leads to changes in expression of iron-related proteins that differ in some aspects from regulation by iron in cell culture. Other events associated with weight loss in late scurvy may play a further role in this regulation.
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PMID:Gene expression of iron-related proteins during iron deficiency caused by scurvy in guinea pigs. 856 10

Twenty-eight strict vegetarians were given 500 mg ascorbic acid twice daily after lunch and dinner for two months. Hemoglobin and certain iron status parameters were measured before and after the treatment. Ascorbate treatment increased mean hemoglobin by 8%, serum iron by 17% and transferrin saturation by 23% and decreased total iron binding capacity by 7%. All these changes were statistically significant. The rise in serum ferritin was 12%. The serum protein or copper level did not indicate their dietary deficiency, while initial serum ascorbate level were low which rose by 60% on therapy. It is concluded that ascorbate supplementation is a better method of improving hematologic and iron status than iron salt administration.
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PMID:Correction of anemia and iron deficiency in vegetarians by administration of ascorbic acid. 858 55

The function of ferritins is to store and release ferrous iron. During oxidative iron uptake, ferritin tends to lower Fe2+ concentration, thus competing with Fenton reactions and limiting hydroxy radical generation. When ferritin functions as a releasing iron agent, the oxidative damage is stimulated. The antioxidant versus pro-oxidant functions of ferritin are studied here in the presence of Fe2+, oxygen and reducing agents. The Fe(2+)-dependent radical damage is measured using supercoiled DNA as a target molecule. The relaxation of supercoiled DNA is quantitatively correlated to the concentration of exogenous Fe2+, providing an indirect assay for free Fe2+. After addition of ferrous iron to ferritin, Fe2+ is actively taken up and asymptotically reaches a stable concentration of 1-5 microM. Comparable equilibrium concentrations are found with plant or horse spleen ferritins, or their apoferritins. After addition of ascorbate, iron release is observed using ferrozine as an iron scavenger. Rates of iron release are dependent on ascorbate concentration. They are about 10 times larger with pea ferritin than with horse ferritin. In the absence of ferrozine, the reaction of ascorbate with ferritins produces a wave of radical damage; its amplitude increases with increased ascorbate concentrations with plant ferritin; the damage is weaker with horse ferritin and less dependent on ascorbate concentrations.
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PMID:Dynamic equilibria in iron uptake and release by ferritin. 869 80


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