Effect of iron chelators on placental uptake and transfer of iron in rat

1987 ◽  
Vol 252 (5) ◽  
pp. C477-C482 ◽  
Author(s):  
C. T. Wong ◽  
H. J. McArdle ◽  
E. H. Morgan
Keyword(s):  
Ferrous Iron ◽  
Iron Uptake ◽  
Iron Transport ◽  
Ferric Iron ◽  
Cultured Cells ◽  
Iron Chelator ◽  
Cell Matrix ◽  
Intracellular Vesicles ◽  
Iron Excretion ◽  
Cycling Time

The uptake of radiolabelled transferrin and iron by the rat placenta has been studied using two approaches. The first involved injection of a ferrous or ferric iron chelator followed by injection of label. Neither chelator decreased the amount of labelled transferrin in the placenta after 2-h incubation and only bipyridine, a ferrous iron chelator, inhibited iron transport to the fetus. Deferoxamine (DFO), a ferric iron chelator, had no effect on iron transport to the fetus but reduced iron uptake by the liver. Both bipyridine and DFO increased iron excretion into the gut and by the urinary tract to the same degree into the gut, but there was a 10-fold greater urinary excretion with bipyridine than with DFO. Injection of iron attached to the chelators showed that neither bipyridine nor DFO could donate iron to the fetus as efficiently as transferrin. The mechanism involved was further investigated by studying the effect of the chelators on uptake of transferrin-bound iron by placental cells in culture. DFO inhibited iron accumulation more effectively than bipyridine in the cultured cells. The effect was not due to a decrease in the cycling time of the receptor. The results can be explained if the iron is released from the transferrin in intracellular vesicles in the ferrous form, where it may be chelated by bipyridine and prevented from passing to the fetus or converted to the ferric form once it is inside the cell matrix.

scholarly journals Secreted Pyomelanin of Legionella pneumophila Promotes Bacterial Iron Uptake and Growth under Iron-Limiting Conditions

2013 ◽  
Vol 81 (11) ◽  
pp. 4182-4191 ◽  
Author(s):  
Huaixin Zheng ◽  
Christa H. Chatfield ◽  
Mark R. Liles ◽  
Nicholas P. Cianciotto
Keyword(s):  
Legionella Pneumophila ◽  
Ferrous Iron ◽  
Iron Uptake ◽  
Iron Transport ◽  
Ferric Iron ◽  
Iron Acquisition ◽  
Ferric Hydroxide ◽  
Supernatant Fraction ◽  
Content Type ◽  
Ferrous Iron Transport

ABSTRACTIron acquisition is critical to the growth and virulence ofLegionella pneumophila. Previously, we found thatL. pneumophilauses both a ferrisiderophore pathway and ferrous iron transport to obtain iron. We now report that two molecules secreted byL. pneumophila, homogentisic acid (HGA) and its polymerized variant (HGA-melanin, a pyomelanin), are able to directly mediate the reduction of various ferric iron salts. Furthermore, HGA, synthetic HGA-melanin, and HGA-melanin derived from bacterial supernatants enhanced the ability ofL. pneumophilaand other species ofLegionellato take up radiolabeled iron. Enhanced iron uptake was not observed with a ferrous iron transport mutant. Thus, HGA and HGA-melanin mediate ferric iron reduction, with the resulting ferrous iron being available to the bacterium for uptake. Upon further testing ofL. pneumophilaculture supernatants, we found that significant amounts of ferric and ferrous iron were associated with secreted HGA-melanin. Importantly, a pyomelanin-containing fraction obtained from a wild-type culture supernatant was able to stimulate the growth of iron-starved legionellae. That the corresponding supernatant fraction obtained from a nonpigmented mutant culture did not stimulate growth demonstrated that HGA-melanin is able to both promote iron uptake and enhance growth under iron-limiting conditions. Indicative of a complementary role in iron acquisition, HGA-melanin levels were inversely related to the levels of siderophore activity. Compatible with a role in the ecology and pathogenesis ofL. pneumophila, HGA and HGA-melanin were effective at reducing and releasing iron from both insoluble ferric hydroxide and the mammalian iron chelates ferritin and transferrin.

scholarly journals Characterization and partial purification of a ferrireductase from human duodenal microvillus membranes

1995 ◽  
Vol 309 (3) ◽  
pp. 745-748 ◽  
Author(s):  
H D Riedel ◽  
A J Remus ◽  
B A Fitscher ◽  
W Stremmel
Keyword(s):  
Ferrous Iron ◽  
Iron Uptake ◽  
Plasma Membranes ◽  
Ferric Iron ◽  
Reductase Activity ◽  
Nitrilotriacetic Acid ◽  
Iron Chelator ◽  
Partial Purification ◽  
Uptake System ◽  
Ammonium Sulphate Precipitation

Reduction of ferric iron in the presence of HuTu 80 cells or duodenal microvillus membranes (MVMs) was investigated. With both systems, NADH-dependent reduction of Fe3+/NTA (nitrilotriacetic acid) was demonstrated, using the ferrous iron chelator ferrozine. Uptake of Fe3+ from Fe3+/NTA by HuTu 80 cells was strongly inhibited by addition of ferrozine, indicating that Fe2+ is the substrate for the iron uptake system. With isolated plasma membranes it is shown that the reductase activity is sensitive to trypsin and incubation at 65 degrees C. The reductase activity could be extracted from the plasma membrane and partially purified by ammonium sulphate precipitation and isoelectric focusing. From the purification and inhibition characteristics we conclude that reduction of ferric iron on the surface of duodenal plasma membranes is catalysed by a membrane protein.

scholarly journals Genes Essential to Iron Transport in the Cyanobacterium Synechocystis sp. Strain PCC 6803

2001 ◽  
Vol 183 (9) ◽  
pp. 2779-2784 ◽  
Author(s):  
Hirokazu Katoh ◽  
Natsu Hagino ◽  
Arthur R. Grossman ◽  
Teruo Ogawa
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Ferric Iron ◽  
Iron Acquisition ◽  
Complete Medium ◽  
Iron Starvation ◽  
Transporter Family ◽  
Genes Encoding ◽  
In Cells ◽  
Pcc 6803

ABSTRACT Genes encoding polypeptides of an ATP binding cassette (ABC)-type ferric iron transporter that plays a major role in iron acquisition inSynechocystis sp. strain PCC 6803 were identified. These genes are slr1295, slr0513, slr0327, and recently reportedsll1878 (Katoh et al., J. Bacteriol. 182:6523–6524, 2000) and were designated futA1, futA2, futB, andfutC, respectively, for their involvement in ferric iron uptake. Inactivation of these genes individually or futA1and futA2 together greatly reduced the activity of ferric iron uptake in cells grown in complete medium or iron-deprived medium. All the fut genes are expressed in cells grown in complete medium, and expression was enhanced by iron starvation. ThefutA1 and futA2 genes appear to encode periplasmic proteins that play a redundant role in iron binding. The deduced products of futB and futC genes contain nucleotide-binding motifs and belong to the ABC transporter family of inner-membrane-bound and membrane-associated proteins, respectively. These results and sequence similarities among the four genes suggest that the Fut system is related to the Sfu/Fbp family of iron transporters. Inactivation of slr1392, a homologue offeoB in Escherichia coli, greatly reduced the activity of ferrous iron transport. This system is induced by intracellular low iron concentrations that are achieved in cells exposed to iron-free medium or in the fut-less mutants grown in complete medium.

scholarly journals Toward a mechanistic understanding of Feo-mediated ferrous iron uptake

Metallomics ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 887-898 ◽  
Author(s):  
Alexandrea E. Sestok ◽  
Richard O. Linkous ◽  
Aaron T. Smith
Keyword(s):  
Ferrous Iron ◽  
Iron Uptake ◽  
Iron Transport ◽  
Structure And Function ◽  
Ferrous Iron Transport ◽  
Mechanistic Understanding ◽  
And Function

The ferrous iron transport (Feo) system is the predominant mode of bacterial Fe2+import. Advancements in the structure and function of FeoB provide glimpses into the mechanism of Fe2+uptake.

scholarly journals Vibrio cholerae VciB Mediates Iron Reduction

2017 ◽  
Vol 199 (12) ◽  
Author(s):  
Eric D. Peng ◽  
Shelley M. Payne
Keyword(s):  
Electron Transport ◽  
Vibrio Cholerae ◽  
Ferrous Iron ◽  
Electron Transport Chain ◽  
Iron Reduction ◽  
Iron Transport ◽  
Ferric Iron ◽  
Transport Systems ◽  
Content Type ◽  
Transport Chain

ABSTRACT Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. V. cholerae thrives within the human host, where it replicates to high numbers, but it also persists within the aquatic environments of ocean and brackish water. To survive within these nutritionally diverse environments, V. cholerae must encode the necessary tools to acquire the essential nutrient iron in all forms it may encounter. A prior study of systems involved in iron transport in V. cholerae revealed the existence of vciB, which, while unable to directly transport iron, stimulates the transport of iron through ferrous (Fe2+) iron transport systems. We demonstrate here a role for VciB in V. cholerae in which VciB stimulates the reduction of Fe3+ to Fe2+, which can be subsequently transported into the cell with the ferrous iron transporter Feo. Iron reduction is independent of functional iron transport but is associated with the electron transport chain. Comparative analysis of VciB orthologs suggests a similar role for other proteins in the VciB family. Our data indicate that VciB is a dimer located in the inner membrane with three transmembrane segments and a large periplasmic loop. Directed mutagenesis of the protein reveals two highly conserved histidine residues required for function. Taken together, our results support a model whereby VciB reduces ferric iron using energy from the electron transport chain. IMPORTANCE Vibrio cholerae is a prolific human pathogen and environmental organism. The acquisition of essential nutrients such as iron is critical for replication, and V. cholerae encodes a number of mechanisms to use iron from diverse environments. Here, we describe the V. cholerae protein VciB that increases the reduction of oxidized ferric iron (Fe3+) to the ferrous form (Fe2+), thus promoting iron acquisition through ferrous iron transporters. Analysis of VciB orthologs in Burkholderia and Aeromonas spp. suggest that they have a similar activity, allowing a functional assignment for this previously uncharacterized protein family. This study builds upon our understanding of proteins known to mediate iron reduction in bacteria.

scholarly journals Characterization of a Nucleotide-Binding Domain Associated with Neisserial Iron Transport

2004 ◽  
Vol 186 (10) ◽  
pp. 3266-3269 ◽  
Author(s):  
Gloria H. Y. Lau ◽  
Ross T. A. MacGillivray ◽  
Michael E. P. Murphy
Keyword(s):  
Iron Uptake ◽  
Iron Transport ◽  
Ferric Iron ◽  
Specific Activity ◽  
Nucleotide Binding ◽  
Binding Domain ◽  
Nucleotide Binding Domain ◽  
Atp Binding Cassette Transporter ◽  
Fold Reduction

ABSTRACT The fbpABC operon in Neisseria gonorrhoeae encodes an ATP-binding cassette transporter required for iron uptake from the host ferric binding proteins. The gene for the nucleotide-binding domain (fbpC) expressed in Escherichia coli has intrinsic ATPase activity (0.5 mmol/min/mg) uncoupled from the iron transport process. The FbpC E164D mutant is found to have a 10-fold reduction in specific activity. FbpC is covalently modified by 8-azido-[γ32P]ATP, indicating that FbpC is a functional ATPase that likely combines with FbpB to form a ferric iron transporter.

scholarly journals Role of copper in mitochondrial iron metabolism

Blood ◽  
1976 ◽  
Vol 48 (1) ◽  
pp. 77-85 ◽  
Author(s):  
DM Williams ◽  
D Loukopoulos ◽  
GR Lee ◽  
GE Cartwright
Keyword(s):  
Cytochrome Oxidase ◽  
Iron Metabolism ◽  
Oxidase Activity ◽  
Ferrous Iron ◽  
Iron Uptake ◽  
Ferric Iron ◽  
Intracellular Iron ◽  
Cytochrome Oxidase Activity ◽  
Heme Synthesis

Abstract Heme synthesis by copper-deficient cells was investigated to elucidate the nature of the defect in intracellular iron metabolism. Iron uptake from transferrin by copper-deficient reticulocytes was 52% of normal, and the rate of heme synthesis was 33% of normal. Hepatic mitochondria isolated from copper-deficient animals were deficient in cytochrome oxidase activity and failed to synthesize heme from ferric iron (Fe III) and protoporphyrin at the normal rate. The rate of heme synthesis correlated with the cytochrome oxidase activity. Heme synthesis from Fe(III) and protoporphyrin by normal mitochondria was enhanced by succinate and inhibited by malonate, antimycin A, azide, and cyanide. It is proposed that an intact electron transport system is required for the reduction of Fe(III), thereby providing a pool of ferrous iron (Fe II) for protoheme and heme a synthesis.

scholarly journals Vibrio cholerae VciB Promotes Iron Uptake via Ferrous Iron Transporters

2008 ◽  
Vol 190 (17) ◽  
pp. 5953-5962 ◽  
Author(s):  
Alexandra R. Mey ◽  
Elizabeth E. Wyckoff ◽  
Lindsey A. Hoover ◽  
Carolyn R. Fisher ◽  
Shelley M. Payne
Keyword(s):  
Vibrio Cholerae ◽  
Transport System ◽  
Ferrous Iron ◽  
Iron Uptake ◽  
Iron Transport ◽  
Growth Enhancement ◽  
Outer Membrane Receptor ◽  
E Coli

ABSTRACT Vibrio cholerae uses a variety of strategies for obtaining iron in its diverse environments. In this study we report the identification of a novel iron utilization protein in V. cholerae, VciB. The vciB gene and its linked gene, vciA, were isolated in a screen for V. cholerae genes that permitted growth of an Escherichia coli siderophore mutant in low-iron medium. The vciAB operon encodes a predicted TonB-dependent outer membrane receptor, VciA, and a putative inner membrane protein, VciB. VciB, but not VciA, was required for growth stimulation of E. coli and Shigella flexneri strains in low-iron medium. Consistent with these findings, TonB was not needed for VciB-mediated growth. No growth enhancement was seen when vciB was expressed in an E. coli or S. flexneri strain defective for the ferrous iron transporter Feo. Supplying the E. coli feo mutant with a plasmid encoding either E. coli or V. cholerae Feo, or the S. flexneri ferrous iron transport system Sit, restored VciB-mediated growth; however, no stimulation was seen when either of the ferric uptake systems V. cholerae Fbp and Haemophilus influenzae Hit was expressed. These data indicate that VciB functions by promoting iron uptake via a ferrous, but not ferric, iron transport system. VciB-dependent iron accumulation via Feo was demonstrated directly in iron transport assays using radiolabeled iron. A V. cholerae vciB mutant did not exhibit any growth defects in either in vitro or in vivo assays, possibly due to the presence of other systems with overlapping functions in this pathogen.

Separate pathways for cellular uptake of ferric and ferrous iron

2000 ◽  
Vol 279 (4) ◽  
pp. G767-G774 ◽  
Author(s):  
Marcel E. Conrad ◽  
Jay N. Umbreit ◽  
Elizabeth G. Moore ◽  
Lucille N. Hainsworth ◽  
Michael Porubcin ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Cellular Uptake ◽  
Ferrous Iron ◽  
Ferric Iron ◽  
Cultured Cells ◽  
Competitive Inhibition ◽  
Culture Media ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Iron And Manganese

Separate pathways for transport of nontransferrin ferric and ferrous iron into tissue cultured cells were demonstrated. Neither the ferric nor ferrous pathway was shared with either zinc or copper. Manganese shared the ferrous pathway but had no effect on cellular uptake of ferric iron. We postulate that ferric iron was transported into cells via β3-integrin and mobilferrin (IMP), whereas ferrous iron uptake was facilitated by divalent metal transporter-1 (DMT-1; Nramp-2). These conclusions were documented by competitive inhibition studies, utilization of a β3-integrin antibody that blocked uptake of ferric but not ferrous iron, development of an anti-DMT-1 antibody that blocked ferrous iron and manganese uptake but not ferric iron, transfection of DMT-1 DNA into tissue culture cells that showed enhanced uptake of ferrous iron and manganese but neither ferric iron nor zinc, hepatic metal concentrations in mk mice showing decreased iron and manganese but not zinc or copper, and data showing that the addition of reducing agents to tissue culture media altered iron binding to proteins of the IMP and DMT-1 pathways. Although these experiments show ferric and ferrous iron can enter cells via different pathways, they do not indicate which pathway is dominant in humans.

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