Do indicators of maternal iron status reflect placental iron status at delivery?

Indicators of maternal iron (Fe) status were studied in relation to placental Fe (Pl-Fe) status. Placental (Pl) and maternal (M) venous blood samples were obtained from primiparous women ($n=38$), with normal delivery at Paroissien Hospital, Argentina. Maternal hemoglobin (M Hb), soluble transferrin receptor (M sTfR) (ELISA) and serum ferritin (M S-Ft) were studied in relation to Pl-Fe, ferritin (Pl-Ft) and transferrin receptor (Pl-TfR). Pl-TfR was measured by dot blot assay, Pl-Ft and M S-Ft by immunoassay (IRMA) and Pl-Fe by atomic absorption spectrometry. Fe status indicators were, respectively, (mean±SD): M Hb 113±16 g/L; M S-Ft 36±42 μg/L; M sTfR 6.3±3.1 mg/L; Pl-Fe 170±56 μg/g placenta; Pl-Ft 33±18 μg/g placenta; Pl-TfR 18±18 (range 0–58) μg/g placenta. Pl-Fe, Pl-Ft and Pl-TfR did not correlate to M Hb, M S-Ft and M sTfR. Women with Pl- Fe, Pl-Ft and Pl-TfR above or below the corresponding median values did not show any statistical significant difference in M Hb, M sTfR or M S-Ft values. Pl-Ft concentration was lower in women with Hb<110 g/L than in women with normal values: 26±13 vs. 38±20 μg/g, respectively ($p=0.021$). When Pl-TfR, Pl-Ft and Pl-Fe were compared in women with M S-Ft above or below the cut-off point of 10 or 20 μg/L, no significant difference was found for Pl-TfR neither for Pl-Ft nor Pl-Fe. These results suggest that maternal indicators of Fe status, particularly M sTfR and M S-Ft, do not reflect Fe status of the placenta at delivery.     

Iron-activated iron uptake: A positive feedback loop mediated by iron regulatory protein 1

The love-hate relationship between iron and living matter has generated mechanisms to maintain iron concentration in a narrow range, above and below which deleterious effects occur. At the cellular level, iron homeostasis is accomplished by the activity of the IRP proteins, which, under conditions of iron depletion, up-regulate the expression of the iron acquisition proteins TfR and DMT1. It has been shown that hydrogen peroxide activates IRP1 and that this activation mediates a potentially harmful increase in cell iron uptake. Here we show that IRP1 activity is also induced by iron-mediated oxidative stress. When cells were incubated with up to 20 M of iron, a typical decrease in IRP1 and IRP2 activity was observed. Interestingly, when iron was further increased to 40 or 80 M, IRP1 was reactivated in three of the four different cell lines tested, i.e., Caco-2 cells, N2A cells and HepG2 cells. In the fourth cell line (K562) IRP1 activity did not increase, but neither did it decrease. This response to iron was largely abrogated when the antioxidant N-acetyl cysteine was added along with iron to the culture medium. Thus, the effect of iron was mediated by oxidative stress. Increases in IRP1 activity were accompanied by increases in cell iron uptake, an indication that the activated IRP1 was functional in the activation of iron uptake. Hence, this iron-induced iron uptake feedback loop results in the increase of intracellular iron and increased oxidative stress.     

Human MRCKα is regulated by cellular iron levels and interferes with transferrin iron uptake

Myotonic dystrophy kinase-related Cdc42-binding kinase α (MRCKα, formally known as CDC42BPA) is a serine/threonine kinase that can regulate actin/myosin assembly and activity. Recently, it has been shown that it possesses a functional iron responsive element (IRE) in the 3′-untranslated region (UTR) of its mRNA, suggesting that it may be involved in iron metabolism. Here we report that MRCKα protein expression is also regulated by iron levels; MRCKα colocalizes with transferrin (Tf)-loaded transferrin receptors (TfR), and attenuation of MRCKα expression by a short hairpin RNA silencing construct leads to a significant decrease in Tf-mediated iron uptake. Our results thus indicate that MRCKα takes part in Tf-iron uptake, probably via regulation of Tf-TfR endocytosis/endosome trafficking that is dependent on the cellular cytoskeleton. Regulation of the MRCKα activity by intracellular iron levels could thus represent another molecular feedback mechanism cells could use to finely tune iron uptake to actual needs.     

EGCG inhibit chemical reactivity of iron through forming an Ngal–EGCG–iron complex

Accumulated evidence indicates that the interconversion of iron between ferric (Fe³⁺) and ferrous (Fe²⁺) can be realized through interaction with reactive oxygen species in the Fenton and Haber–Weiss reactions and thereby physiologically effects redox cycling. The imbalance of iron and ROS may eventually cause tissue damage such as renal proximal tubule injury and necrosis. Many approaches were exploited to ameliorate the oxidative stress caused by the imbalance. (?)-Epigallocatechin-3-gallate, the most active and most abundant catechin in tea, was found to be involved in the protection of a spectrum of renal injuries caused by oxidative stress. Most of studies suggested that EGCG works as an antioxidant. In this paper, Multivariate analysis of the LC–MS data of tea extracts and binding assays showed that the tea polyphenol EGCG can form stable complex with iron through the protein Ngal, a biomarker of acute kidney injury. UV–Vis and Luminescence spectrum methods showed that Ngal can inhibit the chemical reactivity of iron and EGCG through forming an Ngal–EGCG–iron complex. In thinking of the interaction of iron and ROS, we proposed that EGCG may work as both antioxidant and Ngal binding siderphore in protection of kidney from injuries.     

Iron-sulfur clusters: why iron?

This communication addresses a simple question by means of density functional calculations: Why is iron used as the metal in iron-sulfur clusters? While there may be several answers to this question, it is shown here that one feature - the well-defined inner-sphere reorganization energy of self-exchange electron transfer - is very much favored in iron-sulfur clusters as opposed to metal substituted analogues of Mn, Co, Ni, and Cu. Furthermore, the conclusion holds for both 1Fe and 2Fe type iron-sulfur clusters. The results show that only iron provides a small inner-sphere reorganization energy of 21 kJ/mol in 1Fe (rubredoxin) and 46 kJ/mol in 2Fe (ferredoxin) models, whereas other metal ions exhibit values in the range 57-135 kJ/mol (1Fe) and 94-140 kJ/mol (2Fe). This simple result provides an important, although partial, explanation why iron alone is used in this type of clusters. The results can be explained by simple orbital rules of electron transfer, which state that the occupation of anti-bonding orbitals should not change during the redox reactions. This rule immediately suggests good and poor electron carriers.     

Phosphate aggravates iron chlorosis in sensitive plants grown on model calcium carbonate−iron oxide systems

Background and aims

The possible influence of phosphorus (P) on iron (Fe) deficiency chlorosis in susceptible plants needs elucidation. In this work, we tested the hypothesis that Fe chlorosis can be aggravated at high levels of P in the substrate.

Methods

Chickpea, lupin and peanut (in a preliminary experiment), and lupin and sorghum (in a second, factorial experiment) were successively grown on artificial substrates consisting of mixtures of Fe oxide-coated sand (FOCS), calcium carbonate (calcite) sand (CCS) and quartz sand to which phosphate was added at different doses.

Results

The proportion of FOCS in the substrate had a significant positive effect on leaf chlorophyll concentration (as estimated via SPAD) in all crops. In the factorial experiment, the SPAD value was negatively affected by the proportion of CCS in the dicot (lupin) but not in the monocot (sorghum). In the preliminary experiment, increasing the P dose generally had little effect on the SPAD of plants grown on the FOCS-rich substrate but a negative effect on those grown on the FOCS-poor substrate. In the factorial experiment, the P dose negatively affected SPAD in both lupin and sorghum.

Conclusions

Iron acquisition by the plant is negatively influenced by P probably because the solubility of the Fe oxides decreases with increasing coverage of their surfaces by sorbed phosphate.     

Metabolic regulation of citrate and iron by aconitases: role of iron–sulfur cluster biogenesis

Iron and citrate are essential for the metabolism of most organisms, and regulation of iron and citrate biology at both the cellular and systemic levels is critical for normal physiology and survival. Mitochondrial and cytosolic aconitases catalyze the interconversion of citrate and isocitrate, and aconitase activities are affected by iron levels, oxidative stress and by the status of the Fe–S cluster biogenesis apparatus. Assembly and disassembly of Fe–S clusters is a key process not only in regulating the enzymatic activity of mitochondrial aconitase in the citric acid cycle, but also in controlling the iron sensing and RNA binding activities of cytosolic aconitase (also known as iron regulatory protein IRP1). This review discusses the central role of aconitases in intermediary metabolism and explores how iron homeostasis and Fe–S cluster biogenesis regulate the Fe–S cluster switch and modulate intracellular citrate flux.     

The nitric oxide–iron interplay in mammalian cells: Transport and storage of dinitrosyl iron complexes

Nitrogen monoxide (NO) is a vital effector and messenger molecule that plays roles in a variety of biological processes. Many of the functions of NO are mediated by its high affinity for iron (Fe) in the active centres of proteins. Indeed, NO possesses a rich coordination chemistry with this metal and the formation of dinitrosyl–dithiolato–Fe complexes (DNICs) is well known to occur intracellularly. In mammals, NO produced by activated macrophages acts as a cytotoxic effector against tumour cells by binding and releasing cancer cell Fe that is vital for proliferation. Glucose metabolism and the subsequent generation of glutathione (GSH) are critical for NO-mediated Fe efflux and this process occurs by active transport. Our previous studies showed that GSH is required for Fe mobilisation from tumour cells and we hypothesized it was effluxed with Fe as a dinitrosyl–diglutathionyl–Fe complex (DNDGIC). It is well known that Fe and GSH release from cells induces apoptosis, a crucial property for a cytotoxic effector like NO. Furthermore, NO-mediated Fe release is mediated from cells expressing the GSH transporter, multi-drug resistance protein 1 (MRP1). Interestingly, the glutathione-S-transferase (GST) enzymes act to bind DNDGICs with high affinity and some members of the GST family act as storage intermediates for these complexes. Since the GST enzymes and MRP1 form a coordinated system for removing toxic substances from cells, it is possible to hypothesize these molecules regulate NO levels by binding and transporting DNDGICs.     

Do women with menorrhagia need iron?

Haematological indices of iron deficiency and serum ferritin concentrations were compared in 42 women complaining of menorrhagia and in 34 with normal menstrual loss. No significant differences in haemoglobin concentration, mean corpuscular volume, or mean corpuscular haemoglobin concentration were found between the two groups. Serum ferritin concentrations were significantly lower (p less than 0.001) in patients with menorrhagia. Though the iron stores in these women were significantly reduced, only a few were anaemic. Thus, women complaining of heavy menstrual loss do not require prophylactic iron supplements.     

Intracellular Leishmania: your iron or mine?

Iron is a co-factor for several essential enzymes and biochemical pathways, including those required for replication of pathogens such as Leishmania in macrophages. Iron acquisition is emerging as a key battleground in which the iron import systems of microbes are pitted against the iron withdrawal and sequestration systems of macrophages, with both competing for iron at the interface of host-pathogen interaction. The recent characterization of a ferrous iron transport system (LIT1) in Leishmania amazonensis that is induced intracellularly and is required for survival in macrophages and for virulence in vivo provides an elegant example of the adaptation of protozoa to the iron-poor phagosomal environment.     

Jarosite in cultures of iron‐oxidizing thiobacilli

Jarosite [KFe₃(SO₄)2(OH)₆] was precipitated in cultures of Thio‐bacillus ferrooxidans growing on ferrous sulfate. This basic ferric sulfate was characterized by x‐ray diffraction patterns and infrared spectra and was very similar to jarosite produced chemically from acidic ferric sulfate.     

Hyperfine structure of [57Fe]iron in the M?ssbauer spectrum of the high-potential iron protein from Chromatium

The magnetic hyperfine structure observed in the ⁵⁷Fe Mössbauer spectra of the high-potential iron protein from Chromatium shows that the iron atoms are inequivalent in pairs, with hyperfine fields of 121 and 90kG.     

Secreted ferritin: Mosquito defense against iron overload?

The yellow fever mosquito, Aedes aegypti, must blood feed in order to complete her life cycle. The blood meal provides a high level of iron that is required for egg development. We are interested in developing control strategies that interfere with this process. We show that A. aegypti larval cells synthesize and secrete ferritin in response to iron exposure. Cytoplasmic ferritin is maximal at low levels of iron, consists of both the light chain (LCH) and heavy chain (HCH) subunits and reflects cytoplasmic iron levels. Secreted ferritin increases in direct linear relationship to iron dose and consists primarily of HCH subunits. Although the messages for both subunits increase with iron treatment, our data indicate that mosquito HCH synthesis could be partially controlled at the translational level as well. Importantly, we show that exposure of mosquito cells to iron at low concentrations increases cytoplasmic iron, while higher iron levels results in a decline in cytoplasmic iron levels indicating that excess iron is removed from mosquito cells. Our work indicates that HCH synthesis and ferritin secretion are key factors in the response of mosquito cells to iron exposure and could be the primary mechanisms that allow these insects to defend against an intracellular iron overload.     

Sulfolobus aconitase,a regulator of iron metabolism?

The aconitase of Sulfolobus solfataricus, a hyperthermophilic crenarchaeon, was cloned and heterologously expressed in Escherichia coli. Enzymic analyses and EPR measurements indicated clearly that the iron-sulphur cluster of the thermophilic aconitase was already inserted in the mesophilic host. The enzyme was purified to a specific activity of approx. 44 units/mg and to 90% homogeneity. The enzymic parameters of the recombinant aconitase turned out to be in the same range as the respective values for the previously characterized native enzyme from the closely related S. acidocaldarius. Based on its primary sequence, the recombinant aconitase is closely related to bacterial A-like and to eukaryotic iron regulatory protein-like proteins. Specific aconitase activities in cytosolic extracts of S. acidocaldarius were found to be decreased markedly in iron-starved compared with iron-repleted cells. However, no differences in aconitase levels between iron-starved and iron-supplemented cells could be detected by immunostaining.     

Sub-lethal levels of amyloid β-peptide oligomers decrease non-transferrin-bound iron uptake and do not potentiate iron toxicity in primary hippocampal neurons

Two major lesions are pathological hallmarks in Alzheimer's disease (AD): the presence of neurofibrillary tangles formed by intracellular aggregates of the hyperphosphorylated form of the cytoskeletal tau protein, and of senile plaques composed of extracellular aggregates of amyloid beta (Aβ) peptide. Current hypotheses regard soluble amyloid beta oligomers (AβOs) as pathological causative agents in AD. These aggregates cause significant calcium deregulation and mediate neurotoxicity by disrupting synaptic activity. Additionally, the presence of high concentrations of metal ions such as copper, zinc, aluminum and iron in neurofibrillary tangles and senile plaques, plus the fact that they accelerate the rate of formation of Aβ fibrils and AβOs in vitro, suggests that accumulation of these metals in the brain is relevant to AD pathology. A common cellular response to AβOs and transition metals such as copper and iron is the generation of oxidative stress, with the ensuing damage to cellular components. Using hippocampal neurons in primary culture, we report here the effects of treatment with AβOs on the (+)IRE and (-)IRE mRNA levels of the divalent metal transporter DMT1. We found that non-lethal AβOs concentrations decreased DMT1 (-)IRE without affecting DMT1 (+)IRE mRNA levels, and inhibited non-transferrin bound iron uptake. In addition, since both iron and AβOs induce oxidative damage, we studied whether their neurotoxic effects are synergistic. In the range of concentrations and times used in this study, AβOs did not potentiate iron-induced cell death while iron chelation did not decrease AβOs-induced cell death. The lack of synergism between iron and AβOs suggests that these two neurotoxic agents converge in a common target, which initiates signaling processes that promote neurodegeneration.     

Is the iron an essential nutrient for enterococci?

Enterococci were considered as not requiring iron. The aim of study was evaluation of relationship between enterococci and iron. This study examined these relationships in a 71 strains belonging to two species--Enterococcus faecalis and Enterococcus faecium, which are often isolated from human infections. The iron is an essential nutrient for enterococci. Demonstrated that iron--regardless of the concentration in the medium--is collected during growth. Iron deficiency in the nutrient medium resulted in changes in the kinetics of growth of enterococci. Inhibiting the growth of enterococci by iron chelators and lack of inhibition are further proof of this demand for iron bacteria. Enterococci have the ability to acquire this important element of its connections with natural and synthetic chetators with different strength of chemical bonding and structure. Bacteria of the genus Enterococcus have a natural resistance to many antimicrobial agents. In the hospital environment can easily acquire resistance genes to many other classes of antimicrobial compounds. For these reasons, treatment of enterococal infections poses more difficulties. Inhibition of iron uptake in enterococci can be helpful in reducing and combating enterococal infections.