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Metallomics: Integrated Biometal Science

Katherine E Vest, Amanda L Paskavitz, Joseph B Lee, Teresita Padilla-Benavides
Copper (Cu) is an essential metal required for activity of a number of redox active enzymes that participate in critical cellular pathways such as metabolism and cell signaling. Because it is also a toxic metal, Cu must be tightly controlled by a series of transporters and chaperone proteins that regulate Cu homeostasis. The critical nature of Cu is highlighted by the fact that mutations in Cu homeostasis genes cause pathologic conditions such as Menkes and Wilson diseases. While Cu homeostasis in highly affected tissues like the liver and brain is well understood, no study has probed the role of Cu in development of skeletal muscle, another tissue that often shows pathology in these conditions...
January 15, 2018: Metallomics: Integrated Biometal Science
Belinda H Sørensen, Patrick Werth, Ian H Lambert, Patrick J Bednarski
The aim of this project is to gain insights into the uptake and cellular actions of the enantiomeric R- and S-1,1'-binaphthyl-2,2'-diaminodichlorido-Pt(ii) complexes (R- and S-[Pt(DABN)Cl2]) in the cisplatin-sensitive human Burkitt lymphoma cell line (Gumbus, IC50: 1.3 ± 0.2 μM) and its cisplatin-resistant sub-line (CDDPrGB, IC50: 6.6 ± 1.2 μM). The cellular uptakes of R- and S-[Pt(DABN)Cl2] are ca. 4-fold higher than cisplatin, and involve a transport mechanism independent of the volume-sensitive, organic anion-channel complex, which facilitates cisplatin accumulation...
January 15, 2018: Metallomics: Integrated Biometal Science
Antje Biesemeier, Oliver Eibl, Santhana Eswara, Jean-Nicolas Audinot, Tom Wirtz, Ulrich Schraermeyer
Understanding the localisation and abundance of structural elements, trace elements and especially transition metals like Cu and Zn in ocular tissue sections is important for physiology, and also for the characterisation of diseases related to oxidative stress like age-related macular degeneration. Transition metal abundances were investigated in an aged donor eye by nano-secondary ion mass spectrometry (nano-SIMS) elemental mapping using Cs+ and O- primary ions, respectively, and correlated to their respective mole fractions investigated by analytical electron microscopy (AEM)...
January 12, 2018: Metallomics: Integrated Biometal Science
Nan Jiang, Tianfan Cheng, Minji Wang, Godfrey Chi-Fung Chan, Lijian Jin, Hongyan Li, Hongzhe Sun
Porphyromonas gingivalis is a key oral anaerobic bacterium involved in human periodontitis, which may affect up to 15% adults worldwide. Using the membrane permeable fluorescent probe Fe-TRACER, we identified 17 iron-associated proteins in Porphyromonas gingivalis. We demonstrated the specific binding of the probe towards iron-associated proteins using transferrin as an example and provided an X-ray structure of the fluorescent probe-bound transferrin. Our study provides a basis for the understanding of iron homeostasis in pathogens, and our approach based on the integration of fluorescence imaging with proteomics and bioinformatics can be readily extended to mine other metalloproteomes in microbials...
January 11, 2018: Metallomics: Integrated Biometal Science
Nadiia Gumerova, Lukáš Krivosudský, Gil Fraqueza, Joscha Breibeck, Emir Al-Sayed, Elias Tanuhadi, Aleksandar Bijelic, Juan Fuentes, Manuel Aureliano, Annette Rompel
Polyoxometalates (POMs) are transition metal complexes that exhibit a broad diversity of structures and properties rendering them promising for biological purposes. POMs are able to inhibit a series of biologically important enzymes, including phosphatases, and thus are able to affect many biochemical processes. In the present study, we analyzed and compared the inhibitory effects of nine different polyoxotungstates (POTs) on two P-type ATPases, Ca2+-ATPase from skeletal muscle and Na+/K+-ATPase from basal membrane of skin epithelia...
January 9, 2018: Metallomics: Integrated Biometal Science
L Bütof, N Wiesemann, M Herzberg, M Altzschner, A Holleitner, F Reith, D H Nies
The bacterium Cupriavidus metallidurans is capable of reducing toxic Au(i/iii)-complexes into metallic gold (Au) nano-particles, thereby mediating the (trans)formation of Au nuggets in Earth surface environments. In this study we describe a novel detoxification pathway, which prevents synergistic copper (Cu)/Au-toxicity. Gold-complexes and Cu-ions exert cooperative toxicity, because cellular uptake of Au(i/iii)-complexes blocks Cu(i) export from the cytoplasm by the Cu-efflux pump CupA. Using a combination of micro-analytical and biochemical methods we show that inducible resistance to these Cu/Au mixtures is mediated by the periplasmic Cu(i)-oxidase CopA, which functions as an oxygen-consuming Au(i)-oxidase...
January 8, 2018: Metallomics: Integrated Biometal Science
Yinjie Liu, Ying Xiao, Jiaming Liu, Li Feng, Y James Kang
Trientine (TETA), a copper (Cu) chelator, is capable of replenishing Cu in the heart, and Cu repletion reduces cardiac fibrosis in a rodent model of cardiac hypertrophy. This study was undertaken to explore possible mechanisms by which Cu repletion diminishes cardiac fibrosis. Adult male Sprague-Dawley rats were subjected to ascending aortic constriction to induce cardiac hypertrophy. Four months after the operation, cardiac hypertrophy along with fibrosis was fully developed. TETA treatment was then followed at a dose of 21...
January 5, 2018: Metallomics: Integrated Biometal Science
Leo R Zacharski, Galina Shamayeva, Bruce K Chow
Iron-catalyzed oxygen-free radical-induced oxidative stress mediates the pathogenesis of diabetes and cardiovascular disease (CVD). Diabetics (n = 473) and non-diabetics (n = 804) with CVD entered into a randomized trial of iron (ferritin) reduction by calibrated phlebotomy (, Identifier NCT00032357) had comparable iron measures at entry but diabetics had a greater burden of CVD and comorbidities, lower hemoglobin and hematocrit levels, and higher glucose levels than non-diabetics. Entry iron measures were lower in diabetics on hypoglycemic therapy compared to previously untreated diabetics...
January 5, 2018: Metallomics: Integrated Biometal Science
Marie Laval, Chelsea Dumesny, Mal Eutick, Graham S Baldwin, Kathryn M Marshall
Immature forms of the peptide hormone gastrin have been implicated in the development of colorectal cancer (CRC). The biological activity of glycine-extended gastrin (Ggly) is dependent on the binding of Fe3+ ions in vitro and in vivo. The aim of the present study was to determine the effect of blocking Fe3+ ion binding to Ggly, using Bi3+, In3+ or Ru3+ ions, on the development of intestinal tumors in APCΔ14/+ mice. APCΔ14/+ mice were treated orally with Bi3+, In3+ or Ru3+ ions for up to 60 days, serum trace metals were analyzed by inductively coupled plasma mass spectrometry, and the incidence and size of intestinal tumors were assessed...
January 3, 2018: Metallomics: Integrated Biometal Science
Ruyue Xiao, Lan Yuan, Weijiang He, Xiaoda Yang
Zinc is an essential trace element presenting in particularly high concentration in the brain. In some regions, e.g. lateral amygdala, subiculum and hippocampus, rapidly-exchangeable zinc may transiently reach even up to 600 μM. To explore the possible roles of high-concentration Zn2+ in regulating the blood-brain barrier (BBB), we investigated the effects of Zn2+ on the functions and structures of the tight junction (TJ) with an in vitro model of a Madin-Darby canine kidney (MDCK) cell monolayer. The experimental results indicated that high concentrations (>200 μM) of Zn2+ can affect the TJ integrity in a polarized manner...
January 2, 2018: Metallomics: Integrated Biometal Science
Megan L Straw, Amanda K Chaplin, Michael A Hough, Jordi Paps, Vassiliy N Bavro, Michael T Wilson, Erik Vijgenboom, Jonathan A R Worrall
Streptomyces lividans has a distinct dependence on the bioavailability of copper for its morphological development. A cytosolic copper resistance system is operative in S. lividans that serves to preclude deleterious copper levels. This system comprises of several CopZ-like copper chaperones and P1-type ATPases, predominantly under the transcriptional control of a metalloregulator from the copper sensitive operon repressor (CsoR) family. In the present study, we discover a new layer of cytosolic copper resistance in S...
January 2, 2018: Metallomics: Integrated Biometal Science
S Meyer, A López-Serrano, H Mitze, N Jakubowski, T Schwerdtle
Single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) has become a powerful and fast tool to evaluate the elemental composition at a single-cell level. In this study, the cellular bioavailability of arsenite (incubation of 25 and 50 μM for 0-48 h) has been successfully assessed by SC-ICP-MS/MS for the first time directly after re-suspending the cells in water. This procedure avoids the normally arising cell membrane permeabilization caused by cell fixation methods (e.g. methanol fixation). The reliability and feasibility of this SC-ICP-MS/MS approach with a limit of detection of 0...
January 2, 2018: Metallomics: Integrated Biometal Science
A La, T Nguyen, K Tran, E Sauble, D Tu, A Gonzalez, T Z Kidane, C Soriano, J Morgan, M Doan, K Tran, C-Y Wang, M D Knutson, M C Linder
Much evidence indicates that iron stored in ferritin is mobilized through protein degradation in lysosomes, but concerns about this process have lingered, and the mechanistic details of its aspects are lacking. In the studies presented here, 59Fe-labeled ferritin was induced by preloading hepatic (HepG2) cells with radiolabeled Fe. Placing these cells in a medium containing desferrioxamine resulted in the loss of ferritin-59Fe, but adding high concentrations of reducing agents or modulating the internal GSH concentration failed to alter the rates of ferritin-59Fe release...
December 20, 2017: Metallomics: Integrated Biometal Science
Ronald A Glabonjat, Josef Ehgartner, Elliott G Duncan, Georg Raber, Kenneth B Jensen, Frank Krikowa, William A Maher, Kevin A Francesconi
The influence of arsenate and phosphate levels in water on the formation of arsenic-containing lipids (arsenolipids) and water-soluble arsenicals by a unicellular marine alga was investigated by exposing Dunaliella tertiolecta to five regimes of arsenic and phosphate, and determining the biosynthesized organoarsenicals with HPLC/mass spectrometry. Under all conditions, the major arsenolipid produced by D. tertiolecta was the novel phytyl 5-dimethylarsinoyl-2-O-methyl-ribofuranoside (AsSugPhytol546) representing ca...
December 18, 2017: Metallomics: Integrated Biometal Science
O Novakova, N P Farrell, V Brabec
Polynuclear platinum complexes represent a unique structural class of DNA-binding agents of biological significance. They contain at least two platinum coordinating units bridged by a linker, which means that the formation of double-base lesions (cross-links) in DNA is possible. Here, we show that the lead compound, bifunctional [{trans-PtCl(NH3)2}2μ-trans-Pt(NH3)2{H2N(CH2)6NH2}2]4+ (Triplatin or BBR3464), forms in DNA specific double-base lesions which affect the biophysical and biochemical properties of DNA in a way fundamentally different compared to the analogous double-base lesions formed by two adducts of monofunctional chlorodiethylenetriamineplatinum(ii) chloride (dienPt)...
December 15, 2017: Metallomics: Integrated Biometal Science
Anna Kocyła, Justyna Adamczyk, Artur Krężel
Cellular zinc (Zn(ii)) is bound with proteins that are part of the proteomes of all domains of life. It is mostly utilized as a catalytic or structural protein cofactor, which results in a vast number of binding architectures. The Zn(ii) ion is also important for the formation of transient protein complexes with a Zn(ii)-dependent quaternary structure that is formed upon cellular zinc signals. The mechanisms by which proteins associate with and dissociate from Zn(ii) and the connection with cellular Zn(ii) changes remain incompletely understood...
December 14, 2017: Metallomics: Integrated Biometal Science
Katarzyna Kluska, Justyna Adamczyk, Artur Krężel
Zinc fingers (ZFs) are among the most abundant motifs found in proteins, and are commonly known for their structural role. Classical ZFs (CCHH) are part of the transcription factors that participate in DNA binding. Although biochemical studies of classical ZFs have a long history, there is limited knowledge about the sequential and structural diversity of ZFs. We have found that classical ZFs, with metal binding sites consisting of amino acids other than conserved Cys or His residues, are frequently encoded in the human genome, and we refer to these peptides as ZFs with a naturally altered metal binding site...
December 12, 2017: Metallomics: Integrated Biometal Science
Simone Ciofi-Baffoni, Veronica Nasta, Lucia Banci
The biogenesis of iron-sulfur (Fe-S) proteins in humans is a multistage process occurring in different cellular compartments. The mitochondrial iron-sulfur cluster (ISC) assembly machinery composed of at least 17 proteins assembles mitochondrial Fe-S proteins. A cytosolic iron-sulfur assembly (CIA) machinery composed of at least 13 proteins has been more recently identified and shown to be responsible for the Fe-S cluster incorporation into cytosolic and nuclear Fe-S proteins. Cytosolic and nuclear Fe-S protein maturation requires not only the CIA machinery, but also the components of the mitochondrial ISC assembly machinery...
December 8, 2017: Metallomics: Integrated Biometal Science
Tessa R Young, Anthony G Wedd, Zhiguang Xiao
The extracellular domain E2 of the amyloid precursor protein (APP) features a His-rich metal-binding site (denoted as the M1 site). In conjunction with surrounding basic residues, the site participates in interactions with components of the extracellular matrix including heparins, a class of negatively charged polysaccharide molecules of varying length. This work studied the chemistry of Cu(i) binding to APP E2 with the probe ligands Bcs, Bca, Fz and Fs. APP E2 forms a stable Cu(i)-mediated ternary complex with each of these anionic ligands...
December 7, 2017: Metallomics: Integrated Biometal Science
Takahiro Furuta, Ayumi Mukai, Akihiro Ohishi, Kentaro Nishida, Kazuki Nagasawa
Neuron-glia communication mediated by neuro- and glio-transmitters such as ATP and zinc is crucial for the maintenance of brain homeostasis, and its dysregulation is found under pathological conditions. It is reported that under oxidative stress-loaded conditions, astrocytes exhibit increased intra- and extra-cellular labile zinc, the latter triggering microglial M1 activation, while the pathophysiological role of the former remains unrevealed. In this study, we examined whether the oxidative stress-induced increase of intracellular labile zinc is involved in the P2X7 receptor (P2X7R)-mediated regulation of astrocytic engulfing activity...
December 1, 2017: Metallomics: Integrated Biometal Science
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