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

Azotobacter vinelandii bacterioferritin (AvBF) containing 800-1500 Co or Mn atoms as Co(III) and Mn(III) oxyhydroxide cores (Co-AvBF, Mn-AvBF) was synthesized by the same procedure used previously for horse spleen ferritin (HoSF). The kinetics of reduction of Co-AvBF and Mn-AvBF by ascorbic acid are first-order in each reactant. The rate constant for the reduction of Mn-AvBF (8.52 M(-1) min(-1)) is approximately 12 times larger than that for Co-AvBF (0.72 M(-1) min(-1)), which is consistent with a previous observation that Mn-HoSF is reduced approximately 10-fold faster than Co-HoSF [Zhang, B. et al. (2005) Inorg. Chem. 44, 3738-3745]. The rates of reduction of M-AvBF (M = Co and Mn) are more than twice that for the reduction of the corresponding M-HoSF. HoSF containing reduced Fe(II) cores (Fe(II)-HoSF), prepared by methyl viologen and CO, also reduces M-HoSF and M-AvBF species, with both cores remaining within ferritin, suggesting that electrons transfer through the ferritin shell. Electron transfer from Fe(II)-HoSF to Co-AvBF occurs at a rate approximately 3 times faster than that to Co-HoSF, indicating that the Co cores in AvBF are more accessible to reduction than the Co cores in HoSF. The presence of nonconductive (SiO2) or conductive (gold) surfaces known to bind ferritins enhances the rate of electron transfer. A more than approximately 4-fold increase in the apparent reaction rate is observed in the presence of gold. Although both surfaces (SiO2 and gold) enhance reaction by providing binding sites for molecular interaction, results show that ferritins with different mineral cores bound to a gold surface transfer electrons through the gold substrate so that direct contact of the reacting molecules is not required.
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PMID:Electron exchange between Fe(II)-horse spleen ferritin and Co(III)/Mn(III) reconstituted horse spleen and Azotobacter vinelandii ferritins. 1666 20

Concern over the neurotoxic effects of chronic moderate exposures to manganese has arisen due to increased awareness of occupational exposures and to the use of methylcyclopentadienyl manganese tricarbonyl, a manganese-containing gasoline antiknock additive. Little data exist on how the oxidation state of manganese exposure affects toxicity. The objective of this study was to better understand how the oxidation state of manganese exposure affects accumulation and subsequent toxicity of manganese. This study utilized a rat model of manganese neurotoxicity to investigate how ip exposure to Mn(II)-chloride or Mn(III)-pyrophosphate at total cumulative doses of 0, 30, or 90 mg Mn/kg body weight affected the brain region distribution and neurotoxicity of manganese. Results indicate that Mn(III) exposures produced significantly higher blood manganese levels than equimolar exposures to Mn(II). Brain manganese concentrations increased in a dose-dependent manner, with Mn(III) exposures producing significantly higher (> 25%) levels than exposures to Mn(II) but with no measurable differences in the accumulation of manganese across different brain regions. Gamma amino butyric acid concentrations were increased in the globus pallidus (GP) with manganese exposure. Dopamine (DA) levels were altered in the GP, with the highest Mn(II) and Mn(III) exposures producing significantly different DA levels. In addition, transferrin receptor and H-ferritin protein expression increased in the GP with manganese exposure. These data substantiate the heightened susceptibility of the GP to manganese, and they indicate that the oxidation state of manganese exposure may be an important determinant of tissue toxicodynamics and subsequent neurotoxicity.
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PMID:Brain accumulation and toxicity of Mn(II) and Mn(III) exposures. 1674 Jun 17

Studies suggest that disturbances of amino acid metabolism and cellular iron regulation are important mechanisms underlying manganese (Mn) neurotoxicity, although the targets underlying these disturbances are poorly defined. Using the AF5 neural-derived cell line, which displays GABAergic properties, we showed that Mn significantly increased glutamate release to 174%-214% of that of the control and that the effects of Mn exposure on the metabolism of glutamate, glutamine, alanine, and GABA resembled the effects of fluorocitrate, an inhibitor of aconitase, but not the effects of other toxicants including paraquat, rotenone, or 3-nitropropionic acid. Consistent with this, Mn inhibited aconitase activity in AF5 cells, resulting in a 90% increase in intracellular citrate; an in vitro assay revealed that m-aconitase was significantly more sensitive to inhibition by Mn than was c-aconitase. RNA mobility shift assay and Western blot showed that Mn treatment caused c-aconitase to be converted to iron regulatory protein 1 (IRP1) and increased the abundance of IRP2, leading to reduced H-ferritin expression, increased transferrin receptor expression, and increased uptake of transferrin. To determine the relative contributions of IRP1 and IRP2 in mediating the effects of Mn on iron homeostasis, we exposed transgenic fibroblasts lacking either c-aconitase/IRP1 or IRP2 to Mn. Manganese exposure minimally altered ferritin levels in cells possessing only c-aconitase/IRP1, whereas cells possessing only IRP2 showed a robust decrease in ferritin, indicating a dominant role of IRP2 in Mn-induced alteration of iron homeostasis. Together, these results demonstrate that m-aconitase is an important target of Mn and thatMn-induced alteration of iron homeostasis is mediated predominantly through IRP2.
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PMID:Manganese targets m-aconitase and activates iron regulatory protein 2 in AF5 GABAergic cells. 1746 37

Although the concentrations of the toxic metal cadmium in breast milk are generally low (< 1 microg/L), experimental studies indicated neurobehavioral and endocrine effects in the suckling offspring. The aim of the present study was to elucidate how cadmium is transported to breast milk by assessing interactions with essential micronutrients. The study is nested into a food and micronutrient supplementation trial conducted among pregnant women in Matlab, a rural area in Bangladesh, where malnutrition is prevalent and the cadmium exposure is relatively high. We measured cadmium in breast milk (BM-Cd; median 0.14 microg/kg; range <0.050-1.0 microg/kg), in erythrocytes (Ery-Cd; median 1.5 microg/kg; range 0.46-4.8 microg/kg) and in urine (U-Cd; median 0.63 microg/L; range 0.050-4.5 microg/L), using inductively coupled plasma mass spectrometry (ICPMS). We found a significant positive association between Ery-Cd and BM-Cd and a breast milk-plasma ratio of approximately 3-4, indicating no barrier against cadmium transport from plasma to breast milk. BM-Cd was positively associated with manganese (r(s)=0.56; p<0.01) and iron (r(s)=0.55; p<0.01) in breast milk, but not with plasma ferritin. On the other hand, BM-Cd was negatively associated with BM-Ca (r(s)=-0.17; p=0.05), indicating that cadmium inhibits the transport of calcium to breast milk. In conclusion, the present study may indicate that cadmium shares common transporters with iron and manganese for transfer to breast milk, but inhibits secretion of calcium to breast milk.
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PMID:Cadmium interacts with the transport of essential micronutrients in the mammary gland - a study in rural Bangladeshi women. 1912 24

Experimental studies indicate that zinc (Zn) and calcium (Ca) status, in addition to iron (Fe) status, affect gastrointestinal absorption of cadmium (Cd), an environmental pollutant that is toxic to kidneys, bone and endocrine systems. The aim of this study was to evaluate how various nutritional factors influence the uptake of Cd in women, particularly during pregnancy. The study was carried out in a rural area of Bangladesh, where malnutrition is prevalent and exposure to Cd via food appears elevated. The uptake of Cd was evaluated by associations between erythrocyte Cd concentrations (Ery-Cd), a marker of ongoing Cd exposure, and concentrations of nutritional markers. Blood samples, collected in early pregnancy and 6 months postpartum, were analyzed by inductively coupled plasma mass spectrometry (ICPMS). Ery-Cd varied considerably (range: 0.31-5.4microg/kg) with a median of 1.1microg/kg (approximately 0.5microg/L in whole blood) in early pregnancy. Ery-Cd was associated with erythrocyte manganese (Ery-Mn; positively), plasma ferritin (p-Ft; negatively), and erythrocyte Ca (Ery-Ca; negatively) in decreasing order, indicating common transporters for Cd, Fe and Mn. There was no evidence of Cd uptake via Zn transporters, but the association between Ery-Cd and p-Ft seemed to be dependent on adequate Zn status. On average, Ery-Cd increased significantly by 0.2microg/kg from early pregnancy to 6 months postpartum, apparently due to up-regulated divalent metal transporter 1 (DMT1). In conclusion, intestinal uptake of Cd appears to be influenced either directly or indirectly by several micronutrients, in particular Fe, Mn and Zn. The negative association with Ca may suggest that Cd inhibits the transport of Ca to blood.
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PMID:Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women--a prospective cohort study. 1964 88

Microorganisms control the redox cycling of manganese in the natural environment. Although the homogeneous oxidation of Mn(II) to form manganese oxide minerals is slow, solid MnO(2) is the stable form of manganese in the oxygenated portion of the biosphere. Diverse bacteria and fungi have evolved the ability to catalyze this process, producing the manganese oxides found in soils and sediments. Other bacteria have evolved to utilize MnO(2) as a terminal electron acceptor in respiration. This Account summarizes the properties of Mn oxides produced by bacteria (bacteriogenic MnO(2)) and our current thinking about the biochemical mechanisms of bacterial Mn(II) oxidation. According to X-ray absorption spectroscopy and X-ray scattering studies, the MnO(2) produced by bacteria consists of stacked hexagonal sheets of MnO(6) octahedra, but these particles are extremely small and have numerous structural defects, particularly cation vacancies. The defects provide coordination sites for binding exogenous metal ions, which can be adsorbed to a high loading. As a result, bacterial production of MnO(2) influences the bioavailability of these metals in the natural environment. Because of its high surface area and oxidizing power, bacteriogenic MnO(2) efficiently degrades biologically recalcitrant organic molecules to lower-molecular-mass compounds, spurring interest in using these properties in the bioremediation of xenobiotic organic compounds. Finally, bacteriogenic MnO(2) is reduced to soluble Mn(II) rapidly in the presence of exogenous ligands or sunlight. It can therefore help to regulate the bioavailability of Mn(II), which is known to protect organisms from superoxide radicals and is required to assemble the water-splitting complex in photosynthetic organisms. Bioinorganic chemists and microbiologists have long been interested in the biochemical mechanism of Mn(IV) oxide production. The reaction requires a two-electron oxidation of Mn(II), but genetic and biochemical evidence for several bacteria implicate multicopper oxidases (MCOs), which are only known to engage one-electron transfers from substrate to O(2). In experiments with the exosporium of a Mn(II)-oxidizing Bacillus species, we could trap the one-electron oxidation product, Mn(III), as a pyrophosphate complex in an oxygen-dependent reaction inhibited by azide, consistent with MCO catalysis. The Mn(III) pyrophosphate complex can further act as a substrate, reacting in the presence of the exosporium to produce Mn(IV) oxide. Although this process appears to be unprecedented in biology, it is reminiscent of the oxidation of Fe(II) to form Fe(2)O(3) in the ferritin iron storage protein. However, it includes a critical additional step of Mn(III) oxidation or disproportionation. We shall continue to investigate this biochemically unique process with purified enzymes.
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PMID:Bacteriogenic manganese oxides. 1977 36

Exposure to arsenic (As), cadmium (Cd), and lead (Pb) may generate oxidative stress, which can be assessed by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine, a sensitive marker of oxidatively damaged DNA. We have evaluated oxidative stress induced by chronic mixed exposure to As, Cd, and Pb, as well as the influence of As metabolism and nutritional status, i.e., levels of ferritin (Ft), selenium (Se), zinc (Zn), and manganese (Mn) and body weight. 8-OxodG was measured in urine from 212 women in early pregnancy from Matlab, in rural Bangladesh, using LC-MS/MS. Cd and Pb were analyzed in urine and erythrocytes, and Se, Mn, and Zn were analyzed in erythrocytes, all by ICPMS. As and As metabolites were analyzed in urine by HPLC-ICPMS. Ferritin was analyzed in plasma by radioimmunoassay. The median concentration of 8-oxodG was 8.3 nmol/L (adjusted for specific gravity), range 1.2-43, corresponding to a median of 4.7 microg/g creatinine, range 1.8-32. 8-OxodG was positively associated with urinary Cd (beta=0.32, p< 0.001), urinary As (beta=0.0007, p=0.001), the fraction of the monomethylated arsenic metabolite in urine (beta=0.0026, p=0.004), and plasma Ft (beta=0.20, p< 0.001). A joint effect was seen for urinary Cd and As, but whether this effect was additive or multiplicative was difficult to discern.
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PMID:Chronic exposure to cadmium and arsenic strongly influences concentrations of 8-oxo-7,8-dihydro-2'-deoxyguanosine in urine. 2015 23

Low iron (Fe) stores may influence absorption or transport of divalent metals in blood. To obtain more knowledge about such associations, the divalent metal ions cadmium (Cd), manganese (Mn), cobalt (Co), copper (Cu), zinc (Zn) and lead (Pb) and parameters of Fe metabolism (serum ferritin, haemoglobin (Hb) and transferrin) were investigated in 448 healthy, menstruating non-smoking women, age 20-55 years (mean 38 years), participating in the Norwegian HUNT 2 study. The study population was stratified for serum ferritin: 257 were iron-depleted (serum ferritin < 12 microg/L) and 84 had iron deficiency anaemia (serum ferritin < 12 microg/L and Hb < 120 g/L). The low ferritin group had increased blood concentrations of Mn, Co and Cd but normal concentrations of Cu, Zn and Pb. In multiple regression models, ferritin emerged as the main determinant of Mn, Co and Cd (p < 0.001), while no significant associations with Cu, Zn and Pb were found. Adjusted r(2) for the models were 0.28, 0.48 and 0.34, respectively. Strong positive associations between blood concentrations of Mn, Co and Cd were observed, also when controlled for their common association with ferritin. Apart from these associations, the models showed no significant interactions between the six divalent metals studied. Very mild anaemia (110 < or = Hb < 120 g/L) did not seem to have any effect independent of low ferritin. Approximately 26% of the women with iron deficiency anaemia had high concentrations of all of Mn, Co and Cd as opposed to 2.3% of iron-replete subjects. The results confirm that low serum ferritin may have an impact on body kinetics of certain divalent metal ions, but not all. Only a fraction of women with low iron status exhibited an increased blood concentration of divalent metals, providing indication of complexities in the body's handling of these metals.
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PMID:Low iron stores are related to higher blood concentrations of manganese, cobalt and cadmium in non-smoking, Norwegian women in the HUNT 2 study. 2038 Oct 26

A new MRI method is proposed for separately quantifying the two principal forms of tissue storage (nonheme) iron: ferritin iron, a dispersed, soluble fraction that can be rapidly mobilized, and hemosiderin iron, an aggregated, insoluble fraction that serves as a long-term reserve. The method utilizes multiple spin echo sequences, exploiting the fact that aggregated iron can induce nonmonoexponential signal decay for multiple spin echo sequences. The method is validated in vitro for agarose phantoms, simulating dispersed iron with manganese chloride, and aggregated iron with iron oxide microspheres. To demonstrate feasibility for human studies, preliminary in vivo data from two healthy controls and six patients with transfusional iron overload are presented. For both phantoms and human subjects, conventional R(2) and R(2)* relaxation rates are also measured in order to contrast the proposed method with established MRI iron quantification techniques. Quantification of dispersed (ferritin-like) iron may provide a new means of monitoring the risk of iron-induced toxicity in patients with iron overload and, together with quantification of aggregated (hemosiderin-like) iron, improve the accuracy of estimates for total storage iron.
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PMID:Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron. 2043 91

Chronic manganese (Mn) exposure produces neurological deficits including a form of parkinsonism that is different from Parkinson's disease (PD). In chronic Mn exposure, dopamine neurons in the substantia nigra (SN) do not degenerate but they appear to be dysfunctional. Further, previous studies have suggested that the substantia nigra pars reticulata (SNr) is affected by Mn. In the present study, we investigated whether chronic Mn exposure induces microglia activation in the substantia nigra pars compacta (SNc) and SNr in Cynomolgus macaques. Animals were exposed to different weekly doses of Mn (3.3-5.0, 5.0-6.7, 8.3-10 mg Mn/kg body weight) and microglia were examined in the substantia nigra using LN3 immunohistochemistry. We observed that in control animals, LN3 labeled microglia were characterized by a resting phenotype. However, in Mn-treated animals, microglia increased in number and displayed reactive changes with increasing Mn exposure. This effect was more prominent in the SNr than in the SNc. In the SNr of animals administered the highest Mn dose, microglia activation was the most advanced and included dystrophic changes. Reactive microglia expressed increased iNOS, L-ferritin, and intracellular ferric iron which were particularly prominent in dystrophic compartments. Our observations indicate that moderate Mn exposure produces structural changes on microglia, which may have significant consequences on their function.
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PMID:Manganese exposure induces microglia activation and dystrophy in the substantia nigra of non-human primates. 2111 53


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