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Metallomics: Integrated Biometal Science

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https://www.readbyqxmd.com/read/28217776/iron-acquisition-in-fungal-pathogens-of-humans
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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/28170006/age-modulates-the-injury-induced-metallomic-profile-in-the-brain
#8
Stuart D Portbury, Dominic J Hare, Charlotte J Sgambelloni, David P Bishop, David I Finkelstein, Philip A Doble, Paul A Adlard
The biological transition metals iron (Fe), copper (Cu) and zinc (Zn) are thought to contribute to the neuronal pathologies that occur following traumatic brain injury (TBI), and indeed our previously published work in young (3 month-old) mice clearly demonstrates a significant spatiotemporal modulation of metals following TBI. Of note, however, is the literature observation that there is both an apparent detrimental effect of aging on TBI outcomes and an alteration in metals and their various transporters with normal advancing age...
February 7, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28168254/the-effect-of-metalloprotein-inhibitors-on-cellular-metal-ion-content-and-distribution
#9
Yao Chen, Barry Lai, Zhenjie Zhang, Seth M Cohen
With metalloproteins garnering increased interest as therapeutic targets, designing target-specific metalloprotein inhibitors (MPi) is of substantial importance. However, in many respects, the development and evaluation of MPi lags behind that of conventional small molecule therapeutics. Core concerns around MPi, such as target selectivity and potential disruption of metal ion homeostasis linger. Herein, we used a suite of analytical methods, including energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma atomic emission spectroscopy (ICP-OES), and synchrotron X-ray fluorescence microscopy (SXRF) to investigate the effect of several MPi on cellular metal ion distribution and homeostasis...
February 7, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28164202/a-ubiquitous-metal-difficult-to-track-towards-an-understanding-of-the-regulation-of-titanium-iv-in-humans
#10
Sergio A Loza-Rosas, Manoj Saxena, Yamixa Delgado, Kavita Gaur, Mallesh Pandrala, Arthur D Tinoco
Despite the ubiquitous nature of titanium(iv) and several examples of its beneficial behavior in different organisms, the metal remains underappreciated in biology. There is little understanding of how the metal might play an important function in the human body. Nonetheless, a new insight is obtained regarding the molecular mechanisms that regulate the blood speciation of the metal to maintain it in a nontoxic and potentially bioavailable form for use in the body. This review surveys the literature on Ti(iv) application in prosthetics and in the development of anticancer therapeutics to gain an insight into soluble Ti(iv) influx in the body and its long-term impact...
February 6, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28154861/application-of-imaging-mass-spectrometry-approaches-to-facilitate-metal-based-anticancer-drug-research
#11
Ronald F S Lee, Sarah Theiner, Anders Meibom, Gunda Koellensperger, Bernhard K Keppler, Paul J Dyson
Mass spectrometry imaging is being increasingly used in metal-based anticancer drug development to study elemental and/or molecular drug distributions in different biological systems. The main analytical tools employed are SIMS (especially nanoSIMS), LA-ICP-MSI and MALDI-MSI as well as a combination of complementary imaging techniques. Main challenges are appropriate sample preparation methods, reliable and validated quantification strategies and a trade-off between sensitivity and spatial resolution. So far, research has mostly focused on the development of analytical methods for imaging with the long term goal to study drug uptake into tumor tissue and toxicity affected organs and to identify cellular targets of metal-based drugs...
February 3, 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
#12
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/28133682/uhplc-q-tof-ms-based-plasma-metabolomics-reveals-the-metabolic-perturbations-by-manganese-exposure-in-rat-models
#13
Hui Wang, Zhiqi Liu, Shengyi Wang, Dongan Cui, Xinke Zhang, Yongming Liu, Yihua Zhang
Although manganese (Mn) is an essential metal ion biological cofactor, high concentrations could potentially induce an accumulation in the brain and lead to manganism. However, there is no "gold standard" for manganism assessment due to a lack of objective biomarkers. We hypothesized that Mn-induced alterations are associated with metabolic responses to manganism. Here we use an untargeted metabolomics approach by performing ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) on control and Mn-treated rat plasma, to identify metabolic disruptions under high Mn exposure conditions...
January 30, 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
#14
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
https://www.readbyqxmd.com/read/28128390/transcriptome-profile-of-yeast-reveals-the-essential-role-of-pma2-and-uncharacterized-gene-ybr056w-a-mnc1-in-adaptation-to-toxic-manganese-concentration
#15
N Andreeva, E Kulakovskaya, A Zvonarev, A Penin, I Eliseeva, A Teterina, A Lando, I V Kulakovskiy, T Kulakovskaya
Adaptation of S. cerevisiae to toxic concentrations of manganese provides a physiological model of heavy metal homeostasis. Transcriptome analysis of adapted yeast cells reveals upregulation of cell wall and plasma membrane proteins including membrane transporters. The gene expression in adapted cells differs from that of cells under short-term toxic metal stress. Among the most significantly upregulated genes are PMA2, encoding an ortholog of Pma1 H(+)-ATPase of the plasma membrane, and YBR056W-A, encoding a putative membrane protein Mnc1 that belongs to the CYSTM family and presumably chelates manganese at the cell surface...
January 27, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28124054/metal-maps-of-sclerotic-hippocampi-of-patients-with-mesial-temporal-lobe-epilepsy
#16
Miloš Opačić, Aleksandar J Ristić, Danijela Savić, Vid Simon Šelih, Marko Živin, Dragoslav Sokić, Savo Raičević, Vladimir Baščarević, Ivan Spasojević
The loss of metal homeostasis has been implicated in the pathophysiology of mesial temporal lobe epilepsy associated with hippocampal sclerosis (mTLE-HS). Here we applied laser ablation inductively coupled plasma mass spectrometry imaging to establish the spatial distribution of Zn, Fe, Cu and Mn in coronal sections of hippocampi of four patients with drug-resistant mTLE-HS who underwent amygdalohippocampectomy. Detailed maps of the metal concentrations in the different morphological areas/layers were built and analyzed...
January 26, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28091665/trace-element-protein-interactions-in-endolymph-from-the-inner-ear-of-fish-implications-for-environmental-reconstructions-using-fish-otolith-chemistry
#17
Oliver R B Thomas, Katherine Ganio, Blaine R Roberts, Stephen E Swearer
Otoliths, the biomineralised hearing "ear stones" from the inner ear of fish, grow throughout the lifespan of an individual, with deposition of alternating calciferous and proteinaceous bands occurring daily. Trace element : calcium ratios within daily increments measured by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) are often used in fisheries science to reconstruct environmental histories. There is, however, considerable uncertainty as to which elements are interacting with either the proteinaceous or calciferous zones of the otolith, and thus their utility as indicators of environmental change...
January 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28091661/biochemical-characterization-of-the-selenoproteome-in-gallus-gallus-via-bioinformatics-analysis-structure-function-relationships-and-interactions-of-binding-molecules
#18
Shi-Yong Zhu, Xue-Nan Li, Xiao-Chen Sun, Jia Lin, Wei Li, Cong Zhang, Jin-Long Li
Knowledge about mammalian selenoproteins is increasing. However, the selenoproteome of birds remains considerably less understood, especially concerning its biochemical characterization, structure-function relationships and the interactions of binding molecules. In this work, the SECIS elements, subcellular localization, protein domains and interactions of binding molecules of the selenoproteome in Gallus gallus were analyzed using bioinformatics tools. We carried out comprehensive analyses of the structure-function relationships and interactions of the binding molecules of selenoproteins, to provide biochemical characterization of the selenoproteome in Gallus gallus...
January 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28091657/zinc-transport-and-the-inhibition-of-the-l-type-calcium-channel-are-two-separable-functions-of-znt-1
#19
Eden Shusterman, Ofer Beharier, Shiri Levy, Raz Zarivach, Yoram Etzion, Craig R Campbell, Il-Ha Lee, Anuwat Dinudom, David I Cook, Asher Peretz, Amos Katz, Daniel Gitler, Arie Moran
Traditionally, proteins are considered to perform a single role, be it as an enzyme, a channel, a transporter or as a structural scaffold. However, recent studies have described moonlighting proteins that perform distinct and independent functions; for example, TRPM7 is both an ion channel and a kinase. ZnT-1 is a member of the Carrier Diffusion Facilitator family that is expressed throughout the phylogenetic tree from bacteria to humans. Since its cloning in 1995, ZnT-1 is considered a major extruder of Zn(2+) based on its capability to protect cells against zinc toxicity...
January 16, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28067393/longitudinal-assessment-of-metal-concentrations-and-copper-isotope-ratios-in-the-g93a-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#20
T Gabriel Enge, Heath Ecroyd, Dianne F Jolley, Justin J Yerbury, Anthony Dosseto
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease, which involves progressive motor neuron degeneration in the central nervous system (CNS). The G93A SOD1 mouse model simulates one of the most common causes of familial ALS through the overexpression of a mutated form of the human gene encoding copper/zinc superoxide dismutase (SOD1). Transition metals, particularly Cu and Zn, have been shown to behave abnormally in the disease context and have been hypothesized to contribute to and potentially trigger the disease...
January 9, 2017: Metallomics: Integrated Biometal Science
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