DMT1, a physiologically relevant apical Cu1+transporter of intestinal cells

2003 ◽  
Vol 284 (6) ◽  
pp. C1525-C1530 ◽  
Author(s):  
Miguel Arredondo ◽  
Patricia Muñoz ◽  
Casilda V. Mura ◽  
Marco T. Núñez
Keyword(s):  
Iron Content ◽  
Antisense Oligonucleotide ◽  
Iron Uptake ◽  
Potential Role ◽  
Intestinal Cells ◽  
Copper Uptake ◽  
High Iron Content ◽  
Copper Transporter ◽  
Molecular Components

Despite important advances in the understanding of copper secretion and excretion, the molecular components of intestinal copper absorption remain a mystery. DMT1, also known as Nramp2 and DCT1, is the transporter responsible for intestinal iron uptake. Electrophysiological evidence suggests that DMT1 can also be a copper transporter. Thus we examined the potential role of DMT1 as a copper transporter in intestinal Caco-2 cells. Treatment of cells with a DMT1 antisense oligonucleotide resulted in 80 and 48% inhibition of iron and copper uptake, respectively. Cells incorporated considerable amounts of copper as Cu1+, whereas Cu2+ transport was about 10-fold lower. Cu1+inhibited apical Fe2+ transport. Fe2+, but not Fe3+, effectively inhibited Cu1+ uptake. The iron content of the cells influenced both copper and iron uptake. Cells with low iron content transported fourfold more iron and threefold more copper than cells with high iron content. These results demonstrate that DMT1 is a physiologically relevant Cu1+ transporter in intestinal cells, indicating that intestinal absorption of copper and iron are intertwined.

scholarly journals The role of thermal analysis in the development of high-iron-content kaolinite-based photocatalysts

2020 ◽  
Vol 142 (1) ◽  
pp. 289-299
Author(s):  
Veronika Vágvölgyi ◽  
Katalin Győrfi ◽  
Balázs Zsirka ◽  
Erzsébet Horváth ◽  
János Kristóf
Keyword(s):  
Iron Content ◽  
Adsorbed Water ◽  
Acid Base ◽  
High Iron Content ◽  
High Iron ◽  
Defect Sites ◽  
Heating Water ◽  
Coordinated Water

Abstract Dynamic and controlled-rate thermogravimetric analyses have been carried out on acid-treated (11 and 5.8 M HCl), high-iron-content kaolinites as potential photocatalysts. The mineral contaminants were determined by XRD, while the defect sites of reduced coordination number obtained by surface treatments were identified with 27Al MAS NMR spectroscopy. Upon heating, water is evolved from the surface-treated samples in three main stages: (1) removal of adsorbed water up to ~ 200 °C, (2) goethite dehydroxylation between 200 and 350 °C and (3) dehydroxylation of the clay in the 300–700 °C temperature range. Identification of water released from the above mass loss steps is difficult due to the significant overlap of steps 2 and 3, as well as to the presence of coordinated water at broken edges and defect sites (–OH2+ groups). As a result, the thermal behavior of surface-treated kaolinites should be taken into account both in the preparation of hybrids/composites and in the acid–base characterization of the catalytic surface.

The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

Microbiology ◽  
2004 ◽  
Vol 150 (7) ◽  
pp. 2197-2208 ◽  
Author(s):  
Marcus E. Marvin ◽  
Robert P. Mason ◽  
Annette M. Cashmore
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Iron Uptake ◽  
Invasive Growth ◽  
Hostile Environment ◽  
Null Mutant ◽  
Copper Uptake ◽  
Similar System ◽  
Copper Transporter ◽  
High Affinity ◽  
Null Strain

The ability of Candida albicans to acquire iron from the hostile environment of the host is known to be necessary for virulence and appears to be achieved using a similar system to that described for Saccharomyces cerevisiae. In S. cerevisiae, high-affinity iron uptake is dependent upon the acquisition of copper. The authors have previously identified a C. albicans gene (CaCTR1) that encodes a copper transporter. Deletion of this gene results in a mutant strain that grows predominantly as pseudohyphae and displays aberrant morphology in low-copper conditions. This paper demonstrates that invasive growth by C. albicans is induced by low-copper conditions and that this is augmented in a Cactr1-null strain. It also shows that deletion of CaCTR1 results in defective iron uptake. In S. cerevisiae, genes that facilitate high-affinity copper uptake are controlled by a copper-sensing transactivator, ScMac1p. The authors have now identified a C. albicans gene (CaMAC1) that encodes a copper-sensing transactivator. A Camac1-null mutant displays phenotypes similar to those of a Cactr1-null mutant and has no detectable CaCTR1 transcripts in low-copper conditions. It is proposed that high-affinity copper uptake by C. albicans is necessary for reductive iron uptake and is transcriptionally controlled by CaMac1p in a similar manner to that in S. cerevisiae.

scholarly journals Human copper transporter 2 is localized in late endosomes and lysosomes and facilitates cellular copper uptake

2007 ◽  
Vol 407 (1) ◽  
pp. 49-59 ◽  
Author(s):  
Peter V. E. van den Berghe ◽  
Dineke E. Folmer ◽  
Helga E. M. Malingré ◽  
Ellen van Beurden ◽  
Adriana E. M. Klomp ◽  
...  
Keyword(s):  
Molecular Mass ◽  
Fluorescent Protein ◽  
Copper Metabolism ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Copper Uptake ◽  
Copper Transporter ◽  
Late Endosomes ◽  
Cellular Copper

High-affinity cellular copper uptake is mediated by the CTR (copper transporter) 1 family of proteins. The highly homologous hCTR (human CTR) 2 protein has been identified, but its function in copper uptake is currently unknown. To characterize the role of hCTR2 in copper homoeostasis, epitope-tagged hCTR2 was transiently expressed in different cell lines. hCTR2–vsvG (vesicular-stomatitis-virus glycoprotein) predominantly migrated as a 17 kDa protein after imunoblot analysis, consistent with its predicted molecular mass. Chemical cross-linking resulted in the detection of higher-molecular-mass complexes containing hCTR2–vsvG. Furthermore, hCTR2–vsvG was co-immunoprecipitated with hCTR2–FLAG, suggesting that hCTR2 can form multimers, like hCTR1. Transiently transfected hCTR2–eGFP (enhanced green fluorescent protein) was localized exclusively to late endosomes and lysosomes, and was not detected at the plasma membrane. To functionally address the role of hCTR2 in copper metabolism, a novel transcription-based copper sensor was developed. This MRE (metal-responsive element)–luciferase reporter contained four MREs from the mouse metallothionein 1A promoter upstream of the firefly luciferase open reading frame. Thus the MRE–luciferase reporter measured bioavailable cytosolic copper. Expression of hCTR1 resulted in strong activation of the reporter, with maximal induction at 1 μM CuCl2, consistent with the Km of hCTR1. Interestingly, expression of hCTR2 significantly induced MRE–luciferase reporter activation in a copper-dependent manner at 40 and 100 μM CuCl2. Taken together, these results identify hCTR2 as an oligomeric membrane protein localized in lysosomes, which stimulates copper delivery to the cytosol of human cells at relatively high copper concentrations. This work suggests a role for endosomal and lysosomal copper pools in the maintenance of cellular copper homoeostasis.

scholarly journals Exosomes in Food: Health Benefits and Clinical Relevance in Diseases

2019 ◽  
Vol 11 (3) ◽  
pp. 687-696 ◽  
Author(s):  
Javaria Munir ◽  
Mihye Lee ◽  
Seongho Ryu
Keyword(s):  
Potential Role ◽  
Underlying Mechanism ◽  
Therapeutic Agents ◽  
Eukaryotic Cells ◽  
Intestinal Cells ◽  
Adult Health ◽  
Anti Cancer ◽  
Membrane Bound ◽  
Potential Use

ABSTRACT Exosomes are membrane-bound organelles generally secreted by eukaryotic cells that contain mRNAs, microRNAs, and/or proteins. However, recent studies have reported the isolation of these particles from foods such as lemon, ginger, and milk. Owing to their absorption by intestinal cells and further travel via the bloodstream, exosomes can reach distant organs and affect overall health in both infants and adults. The potential role of food-derived exosomes (FDEs) in alleviating diseases, as well as in modulating the gut microbiota has been shown, but the underlying mechanism is still unknown. Moreover, exosomes may provide biocompatible vehicles for the delivery of anti-cancer drugs, such as doxorubicin. Thus, exosomes may allow medical nutritionists and clinicians to develop safe and targeted therapies for the treatment of various pathologies. The present review introduces FDEs and their contents, highlights their role in disease and infant/adult health, and explores their potential use as therapeutic agents.

Transport and function of syntaxin 3 in human epithelial intestinal cells

2000 ◽  
Vol 279 (4) ◽  
pp. C1239-C1248 ◽  
Author(s):  
Lionel Breuza ◽  
Jack Fransen ◽  
André Le Bivic
Keyword(s):  
Potential Role ◽  
Apical Membrane ◽  
Transmembrane Protein ◽  
Intestinal Cells ◽  
Apical Surface ◽  
Human Transferrin Receptor ◽  
Efficient Delivery ◽  
And Function ◽  
Syntaxin 3

To follow the transport of human syntaxin (Syn) 3 to the apical surface of intestinal cells, we produced and expressed in Caco-2 cells a chimera made of the entire Syn3 coding sequence and the extracellular domain of the human transferrin receptor (TfR). This chimera (Syn3TfR) was localized to the apical membrane and was transported along the direct apical pathway, suggesting that this is also the case for endogenous Syn3. To test the potential role of Syn3 in apical transport, we overexpressed it in Caco-2 cells and measured the efficiency of apical and basolateral delivery of several endogenous markers. We observed a strong inhibition of apical delivery of sucrase-isomaltase (SI), an apical transmembrane protein, and of α-glucosidase, an apically secreted protein. No effect was observed on the basolateral delivery of Ag525, a basolateral antigen, strongly suggesting that Syn3 is necessary for efficient delivery of proteins to the apical surface of intestinal cells.

scholarly journals Iron Content Differs betweenFrancisella tularensisSubspeciestularensisand SubspeciesholarcticaStrains and Correlates to Their Susceptibility to H2O2-Induced Killing

2010 ◽  
Vol 79 (3) ◽  
pp. 1218-1224 ◽  
Author(s):  
Helena Lindgren ◽  
Marie Honn ◽  
Emelie Salomonsson ◽  
Kerstin Kuoppa ◽  
Åke Forsberg ◽  
...  
Keyword(s):  
Iron Content ◽  
Iron Uptake ◽  
Severe Form ◽  
Iron Starvation ◽  
High Iron Content ◽  
Phenotypic Differences ◽  
Gene Transcripts ◽  
Important Virulence Factor ◽  
Schu S4 ◽  
And Storage

ABSTRACTFrancisella tularensis, the causative agent of tularemia, is one of the most infectious bacterial pathogens known and is classified as a category A select agent and a facultative intracellular bacterium. WhyF. tularensissubsp.tularensiscauses a more severe form of tularemia thanF. tularensissubsp.holarcticadoes is not known. In this study, we have identified prominent phenotypic differences between the subspecies, since we found thatF. tularensissubsp.tularensisstrains contained less iron thanF. tularensissubsp.holarcticastrains. Moreover, strain SCHU S4 ofF. tularensissubsp.tularensiswas less susceptible than FSC200 and the live vaccine strain (LVS) ofF. tularensissubsp.holarcticato H2O2-induced killing. The activity of the H2O2-degrading enzyme catalase was similar between the strains, whereas the iron content affected their susceptibility to H2O2, since iron starvation renderedF. tularensissubsp.holarcticastrains more resistant to H2O2. Complementing LVS withfupA, which encodes an important virulence factor that regulates iron uptake, reduced its iron content and increased the resistance to H2O2-mediated killing. By real-time PCR, it was demonstrated that FSC200 and LVS expressed higher levels of gene transcripts related to iron uptake and storage than SCHU S4 did, and this likely explained their high iron content. Together, the results suggest thatF. tularensissubsp.tularensisstrains have restricted iron uptake and storage, which is beneficial for their resistance to H2O2-induced killing. This may be an important factor for the higher virulence of this subspecies ofF. tularensis, as reactive oxygen species, such as H2O2, are important bactericidal components during tularemia.

POPDC proteins and cardiac function

2019 ◽  
Vol 47 (5) ◽  
pp. 1393-1404 ◽  
Author(s):  
Thomas Brand
Keyword(s):  
Potential Role ◽  
Striated Muscle ◽  
Short Review ◽  
Effector Proteins ◽  
Muscle Disease ◽  
Disease Genes ◽  
Protein Protein Interaction ◽  
Interaction Partners ◽  
And Function

Abstract The Popeye domain-containing gene family encodes a novel class of cAMP effector proteins in striated muscle tissue. In this short review, we first introduce the protein family and discuss their structure and function with an emphasis on their role in cyclic AMP signalling. Another focus of this review is the recently discovered role of POPDC genes as striated muscle disease genes, which have been associated with cardiac arrhythmia and muscular dystrophy. The pathological phenotypes observed in patients will be compared with phenotypes present in null and knockin mutations in zebrafish and mouse. A number of protein–protein interaction partners have been discovered and the potential role of POPDC proteins to control the subcellular localization and function of these interacting proteins will be discussed. Finally, we outline several areas, where research is urgently needed.

The Effect of Path Length and Display Size on Memory for Spatial Information

2012 ◽  
Vol 59 (3) ◽  
pp. 147-152 ◽  
Author(s):  
Katherine Guérard ◽  
Sébastien Tremblay
Keyword(s):  
Path Length ◽  
Potential Role ◽  
Spatial Information ◽  
Recall Performance ◽  
Minor Role ◽  
Length Effect ◽  
Serial Memory ◽  
Fixed Reference ◽  
A Minor

In serial memory for spatial information, some studies showed that recall performance suffers when the distance between successive locations increases relatively to the size of the display in which they are presented (the path length effect; e.g., Parmentier et al., 2005) but not when distance is increased by enlarging the size of the display (e.g., Smyth & Scholey, 1994). In the present study, we examined the effect of varying the absolute and relative distance between to-be-remembered items on memory for spatial information. We manipulated path length using small (15″) and large (64″) screens within the same design. In two experiments, we showed that distance was disruptive mainly when it is varied relatively to a fixed reference frame, though increasing the size of the display also had a small deleterious effect on recall. The insertion of a retention interval did not influence these effects, suggesting that rehearsal plays a minor role in mediating the effects of distance on serial spatial memory. We discuss the potential role of perceptual organization in light of the pattern of results.

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