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Metallomics: Integrated Biometal Science

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https://www.readbyqxmd.com/read/28425536/cisplatin-resistance-in-cell-models-evaluation-of-metallomic-and-biological-predictive-biomarkers-to-address-early-therapy-failure
#1
Marta Espina, Mario Corte-Rodríguez, Leticia Aguado, María Montes-Bayón, Marta I Sierra, Pablo Martínez-Camblor, Elisa Blanco-González, L María Sierra
Cisplatin, one of the most extensively used metallodrugs in cancer treatment, presents the important drawback of patient resistance. This resistance is the consequence of different processes including those preventing the formation of DNA adducts and/or their quick removal. Thus, a tool for the accurate detection and quantitation of cisplatin-induced adducts might be valuable for predicting patient resistance. To prove the validity of such an assumption, highly sensitive plasma mass spectrometry (ICP-MS) strategies were applied to determine DNA adduct levels and intracellular Pt concentrations...
April 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28418062/flexible-aspartates-propel-iron-to-the-ferroxidation-sites-along-pathways-stabilized-by-a-conserved-arginine-in-dps-proteins-from-mycobacterium-smegmatis
#2
Sunanda Margrett Williams, Dipankar Chatterji
DNA-binding proteins under starvation (Dps) are dodecameric nano-compartments for iron oxidation and storage in bacterial cells. These proteins have roughly spherical structures with a hollow interior where iron is stored. Through mutational analysis of a conserved arginine residue in the second Dps protein from Mycobacterium smegmatis, we have identified residues which stabilize the interfaces between the iron entry and ferroxidation sites. Also, we have used X-ray crystallography to determine the structures of co-crystals of iron and Dps in varying proportions and compare the changes in these ligand-bound forms with respect to the apo-protein...
April 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28417130/iron-isotopic-composition-of-blood-serum-in-anemia-of-chronic-kidney-disease
#3
Yulia Anoshkina, Marta Costas-Rodríguez, Marijn Speeckaert, Wim Van Biesen, Joris Delanghe, Frank Vanhaecke
Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose...
April 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28401968/tight-binding-of-heme-to-staphylococcus-aureus-isdg-and-isdi-precludes-design-of-a-competitive-inhibitor
#4
Matthew A Conger, Deepika Pokhrel, Matthew D Liptak
The micromolar equilibrium constants for heme dissociation from IsdG and IsdI reported in the literature call into question whether these enzymes are actually members of the iron-regulated surface determinant system of Staphylococcus aureus, which harvests heme iron from a host during infection. In order to address this question, the heme dissociation constants for IsdG and IsdI were reevaluated using three approaches. The heme dissociation equilibrium constants were measured using a UV/Vis absorption-detected assay analyzed with an assumption-free model, and using a newly developed fluorescence-detected assay...
April 12, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28383086/platinum-transfer-from-hctr1-to-atox1-is-dependent-on-the-type-of-platinum-complex
#5
Xuelei Wu, Siming Yuan, Erqiong Wang, Yang Tong, Guolin Ma, Kaiju Wei, Yangzhong Liu
In spite of their wide application, the cellular uptake of platinum based anticancer drugs is still unclear. The copper transport protein, hCTR1, is proposed to facilitate the cellular uptake of cisplatin, whereas organic cation transport (OCT) is more important for oxaliplatin. It has been reported that both N-terminal and C-terminal metal binding motifs of hCTR1 are highly reactive to cisplatin, which is the initial step of protein assisted cellular uptake of cisplatin. It is still unknown how the platinum drugs in hCTR1 transfer to cytoplasmic media, and whether various platinum complexes possess different activities in this process...
April 6, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28374040/selenadiazole-derivatives-antagonize-hyperglycemia-induced-drug-resistance-in-breast-cancer-cells-by-activation-of-ampk-pathways
#6
Jianfu Zhao, Delong Zeng, Yuedan Liu, Yi Luo, Shengbin Ji, Xiaoling Li, Tianfeng Chen
Hyperglycemia is an important factor for chemoresistance of breast cancer patients with diabetes. In the present study, a novel selenadiazole derivative has been evaluated and found to be able to antagonize the doxorubicin (DOX) resistance of MCF-7 cells under simulated diabetes conditions. Hyperglycemia promotes the proliferation, invasion and migration of MCF-7 cells through activation of ERK and AKT pathways, which could be inhibited by the synthetic selenadiazole derivative. The antitumor effects of the selenadiazole derivative were attributed to its ability to activate AMPK pathways...
April 4, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28352890/high-affinity-metal-binding-by-the-escherichia-coli-nife-hydrogenase-accessory-protein-hypb-is-selectively-modulated-by-slyd
#7
Mozhgan Khorasani-Motlagh, Michael J Lacasse, Deborah B Zamble
[NiFe]-hydrogenase, which catalyzes the reversible conversion between hydrogen gas and protons, is a vital component of the metabolism of many pathogens. Maturation of [NiFe]-hydrogenase requires selective nickel insertion that is completed, in part, by the metallochaperones SlyD and HypB. Escherichia coli HypB binds nickel with sub-picomolar affinity, and the formation of the HypB-SlyD complex activates nickel release from the high-affinity site (HAS) of HypB. In this study, the metal selectivity of this process was investigated...
March 29, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28345104/biology-and-toxicology-of-tellurium-explored-by-speciation-analysis
#8
Yasumitsu Ogra
Tellurium (Te) is widely used in industry because it has unique physicochemical properties. Although Te is a non-essential element in animals and plants, it is expected to be metabolized to organometallic compounds having a carbon-Te bond in living organisms exposed to inorganic Te compounds. Thus, the speciation and identification of tellurometabolites are expected to contribute to the depiction of the metabolic chart of Te. Speciation by elemental mass spectrometry and identification by molecular mass spectrometry coupled with separation techniques have significantly contributed to the discovery of tellurometabolites in animals and plants...
March 27, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28318006/inhibiting-the-bfrb-bfd-interaction-in-pseudomonas-aeruginosa-causes-irreversible-iron-accumulation-in-bacterioferritin-and-iron-deficiency-in-the-bacterial-cytosol
#9
Kate Eshelman, Huili Yao, Achala N D Punchi Hewage, Jacqueline J Deay, Josephine R Chandler, Mario Rivera
Iron is an essential nutrient for bacteria but the reactivity of Fe(2+) and the insolubility of Fe(3+) present significant challenges to bacterial cells. Iron storage proteins contribute to ameliorating these challenges by oxidizing Fe(2+) using O2 and H2O2 as electron acceptors, and by compartmentalizing Fe(3+). Two types of iron-storage proteins coexist in bacteria, the ferritins (Ftn) and the heme-containing bacterioferritins (Bfr), but the reasons for their coexistence are largely unknown. P. aeruginosa cells harbor two iron storage proteins (FtnA and BfrB), but nothing is known about their relative contributions to iron homeostasis...
March 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28317950/in-vivo-identification-of-potential-uranium-protein-targets-in-zebrafish-ovaries-after-chronic-waterborne-exposure
#10
Y Eb-Levadoux, S Frelon, O Simon, C Arnaudguilhem, R Lobinski, S Mounicou
Ecotoxicological studies have indicated the reprotoxicity of uranium (U) in zebrafish, but its molecular mechanisms remain unclear. Due to the non-covalent nature of U-protein complexes, canonical proteomics approaches are often not relevant as they usually use denaturating reagents or solvents. In this study, non-denaturating (ND) methods were used to obtain insight into the nature of U potential targets in ovaries of reproduced and non-reproduced zebrafish after 20 days of exposure to an environmentally relevant U concentration (20 μg L(-1))...
March 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28252129/distinctive-hippocampal-zinc-distribution-patterns-following-stress-exposure-in-an-animal-model-of-ptsd
#11
Hagit Sela, Hagit Cohen, Zeev Karpas, Yehuda Zeiri
Emerging evidence suggests that zinc (Zn) deficiency is associated with depression and anxiety in both human and animal studies. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of Zn distribution. The work has focused on one case study, the association between an animal model of posttraumatic stress disorder (PTSD) and the Zn distribution in the rat hippocampus. Behaviors were assessed with the elevated plus-maze and acoustic startle response tests 7 days later...
March 2, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28217776/iron-acquisition-in-fungal-pathogens-of-humans
#12
Gaurav Bairwa, Won Hee Jung, James W Kronstad
The devastating infections that fungal pathogens cause in humans are underappreciated relative to viral, bacterial and parasitic diseases. In recent years, the contributions to virulence of reductive iron uptake, siderophore-mediated uptake and heme acquisition have been identified in the best studied and most life-threatening fungal pathogens: Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. In particular, exciting new work illustrates the importance of iron acquisition from heme and hemoglobin in the virulence of pathogenic yeasts...
February 20, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28205653/phosphorylation-of-zinc-channel-zip7-drives-mapk-pi3k-and-mtor-growth-and-proliferation-signalling
#13
T Nimmanon, S Ziliotto, S Morris, L Flanagan, K M Taylor
Zinc is an essential trace element participating in diverse biological processes. Cellular zinc levels are strictly controlled by two families of transport proteins: ZIP channels (SLC39A) and ZnT transporters (SLC30A). ZIP channels increase cytosolic zinc levels by importing zinc into cells or releasing zinc from intracellular stores such as the ER. Among all the 14 human members of the ZIP family, ZIP7 is a gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation on residues S275 and S276, resulting in activation of multiple downstream pathways...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28205649/comparative-studies-of-oxaliplatin-based-platinum-iv-complexes-in-different-in-vitro-and-in-vivo-tumor-models
#14
Simone Göschl, Ekaterina Schreiber-Brynzak, Verena Pichler, Klaudia Cseh, Petra Heffeter, Ute Jungwirth, Michael A Jakupec, Walter Berger, Bernhard K Keppler
Using platinum(iv) prodrugs of clinically established platinum(ii) compounds is a strategy to overcome side effects and acquired resistances. We studied four oxaliplatin-derived platinum(iv) complexes with varying axial ligands in various in vitro and in vivo settings. The ability to interfere with DNA (pUC19) in the presence and absence of a reducing agent (ascorbic acid) was investigated in cell-free experiments. Cytotoxicity was compared under normoxic and hypoxic conditions in monolayer cultures and multicellular spheroids of colon carcinoma cell lines...
February 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28194470/effect-of-vanadium-on-calcium-homeostasis-osteopontin-mrna-expression-and-bone-microarchitecture-in-diabetic-rats
#15
Cristina Sanchez-Gonzalez, Laura Moreno, Carlos Lopez-Chaves, Elena Nebot, Peter Pietschmann, Alba Rodriguez-Nogales, Julio Galvez, María Montes-Bayon, Alfredo Sanz-Medel, Juan Llopis
The aim of this study was to examine whether alterations caused by diabetes in calcium homeostasis, expression of osteopontin and the microarchitecture of bone are corrected by exposure to vanadium. Four study groups were examined over a period of five weeks: control (C), diabetic (DM), diabetic treated with 1 mg V per d (DMV), and diabetic treated with 3 mg V per d (DMVH). Vanadium was supplied in drinking water as bis(maltolato)oxovanadium(iv). Calcium was measured in the food, faeces, urine, serum, kidneys, liver, muscles, and femur...
February 14, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28194465/unravelling-the-role-of-protein-kinase-ck2-in-metal-toxicity-using-gene-deletion-mutants
#16
Adam J Johnson, Mohammad S Zaman, Filip Veljanoski, Alex A Phrakaysone, Suhua Li, Patrick J O'Doherty, Gayani Petersingham, Gabriel G Perrone, Mark P Molloy, Ming J Wu
Metal ions, biologically essential or toxic, are present in the surrounding environment of living organisms. Understanding their uptake, homeostasis or detoxification is critical in cell biology and human health. In this study, we investigated the role of protein kinase CK2 in metal toxicity using gene deletion strains of Saccharomyces cerevisiae against a panel of six metal ions. The deletion of CKA2, the yeast orthologue of mammalian CK2α', leads to a pronounced resistant phenotype against Zn(2+) and Al(3+), whilst the deletion of CKB1 or CKB2 results in tolerance to Cr(6+) and As(3+)...
February 14, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28184394/tracing-cytotoxic-effects-of-small-organic-se-species-in-human-liver-cells-back-to-total-cellular-se-and-se-metabolites
#17
T A Marschall, N Kroepfl, K B Jensen, J Bornhorst, B Meermann, D Kuehnelt, T Schwerdtle
Small selenium (Se) species play a major role in the metabolism, excretion and dietary supply of the essential trace element selenium. Human cells provide a valuable tool for investigating currently unresolved issues on the cellular mechanisms of Se toxicity and metabolism. In this study, we developed two isotope dilution inductively coupled plasma tandem-mass spectrometry based methods and applied them to human hepatoma cells (HepG2) in order to quantitatively elucidate total cellular Se concentrations and cellular Se species transformations in relation to the cytotoxic effects of four small organic Se species...
February 10, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28181616/na-k-atpase-as-a-target-for-anticancer-metal-based-drugs-insights-into-molecular-interactions-with-selected-gold-iii-complexes
#18
Aleksandra M Bondžić, Goran V Janjić, Miroslav D Dramićanin, Luigi Messori, Lara Massai, Tatjana N Parac Vogt, Vesna M Vasić
Na/K-ATPase is emerging as an important target for a variety of anticancer metal-based drugs. The interactions of Na/K-ATPase (in its E1 state) with three representative and structurally related cytotoxic gold(iii) complexes, i.e. [Au(bipy)(OH)2][PF6], bipy = 2,2'-bipyridine; [Au(py(dmb)-H)(CH3COO)2], py(dmb)-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine and [Au(bipy(dmb)-H)(OH)][PF6], bipy(c)-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2'-bipyridine, are investigated here in depth using a variety of spectroscopic methods, in combination with docking studies...
February 9, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28145544/copper-binding-and-redox-chemistry-of-the-a%C3%AE-16-peptide-and-its-variants-insights-into-determinants-of-copper-dependent-reactivity
#19
Nineveh Yako, Tessa R Young, Jade M Cottam Jones, Craig A Hutton, Anthony G Wedd, Zhiguang Xiao
The metal-binding sites of Aβ peptides are dictated primarily by the coordination preferences of the metal ion. Consequently, Cu(i) is typically bound with two His ligands in a linear mode while Cu(ii) forms a pseudo-square planar stereochemistry with the N-terminal amine nitrogen acting as an anchoring ligand. Several distinct combinations of other groups can act as co-ligands for Cu(ii). A population of multiple binding modes is possible with the equilibrium position shifting sensitively with solution pH and the nature of the residues in the N-terminal region...
February 1, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28128836/substrate-specificity-and-copper-loading-of-the-manganese-oxidizing-multicopper-oxidase-mnx-from-bacillus-sp-pl-12
#20
Cristina N Butterfield, Bradley M Tebo
Manganese(ii) oxidation in the environment is thought to be driven by bacteria because enzymatic catalysis is many orders of magnitude faster than the abiotic processes. The heterologously purified Mn oxidase (Mnx) from marine Bacillus sp. PL-12 is made up of the multicopper oxidase (MCO) MnxG and two small Cu and heme-binding proteins of unknown function, MnxE and MnxF. Mnx binds Cu and oxidizes both Mn(ii) and Mn(iii), generating Mn(iv) oxide minerals that resemble those found on the Bacillus spore surface...
January 27, 2017: Metallomics: Integrated Biometal Science
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