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Metallomics: Integrated Biometal Science

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https://www.readbyqxmd.com/read/29139524/computational-modelling-of-the-redistribution-of-copper-isotopes-by-proteins-in-the-liver
#1
Alexander Tennant, Arvi Rauk, Michael E Wieser
Changes in the stable isotope composition of copper in blood serum as a result of biological processes in the liver were quantified as coupled equilibrium fractionation processes. The model used calculated reduced partition function ratios corresponding to interactions involving individual proteins using Density Functional Theory. This quantified the effect that each process had on the redistribution of copper isotopes in the liver. It was not possible to calculate the reduced partition function of CTR1 as a high resolution crystal structure of its copper binding domains are unavailable at the time of writing, and an optimization process was used to estimate the reduced partition function of CTR1 and constrain the possible isotopic fractionation associated with interactions involving CTR1 independent of direct DFT calculations and assumptions of its structure...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29131211/pharmaco-genomic-investigations-of-organo-iridium-anticancer-complexes-reveal-novel-mechanism-of-action
#2
Jessica M Hearn, George M Hughes, Isolda Romero-Canelón, Alison F Munro, Belén Rubio-Ruiz, Zhe Liu, Neil O Carragher, Peter J Sadler
Resistance to platinum drugs (used in >50% of cancer chemotherapies) is a clinical problem. Other precious metal complexes with distinct mechanisms of action might overcome this. Half-sandwich organometallic complexes containing arene or cyclopentadienyl (Cp) ligands show promise. We screened two iridium(iii) complexes [Ir(Cp(Xbiph))(ppy)Cl] (ZL49, 1, ppy = phenylpyridine) and [Ir(Cp(Xph))(azpyNMe2)Cl]PF6 (ZL109, 2, azpyNMe2 = N,N-dimethylphenylazopyridine) in 916 cancer cell lines from 28 tissue types. On average, complex 2 was 78× more potent than 1, 36× more active than cisplatin (CDDP), and strongly active (nanomolar) in patient-derived ovarian cancer cell lines...
November 13, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29120476/linking-iron-deficiency-with-allergy-role-of-molecular-allergens-and-the-microbiome
#3
REVIEW
Franziska Roth-Walter, Luis F Pacios, Rodolfo Bianchini, Erika Jensen-Jarolim
Atopic individuals tend to develop a Th2 dominant immune response, resulting in hyperresponsiveness to harmless antigens, termed allergens. In the last decade, epidemiological studies have emerged that connected allergy with a deficient iron-status. Immune activation under iron-deficient conditions results in the expansion of Th2-, but not Th1 cells, can induce class-switching in B-cells and hampers the proper activation of M2, but not M1 macrophages. Moreover, many allergens, in particular with the lipocalin and lipocalin-like folds, seem to be capable of binding iron indirectly via siderophores harboring catechol moieties...
November 9, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29119175/protective-effect-of-selenium-supplementation-following-oxidative-stress-mediated-by-glucose-on-retinal-pigment-epithelium
#4
Raquel González de Vega, Montserrat García, María Luisa Fernández-Sánchez, Héctor González-Iglesias, Alfredo Sanz-Medel
There are many conditions that affect the retina. However, diabetic retinopathy (RD) as a complication of Diabetes Mellitus continues to be the leading cause of blindness in working people globally. Diabetic retinopathy is an ocular complication of diabetes that is caused by the deterioration of the blood vessels that supply the retina, which has the consequence that the vision deteriorates irreversibly. The retina, and specifically the retinal pigment epithelium (RPE) is the only neural tissue that is exposed directly and frequently to light, which favors the oxidation of lipids that become extremely toxic to the cells of the retina...
November 9, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29115324/calcium-isotope-signature-new-proxy-for-net-change-in-bone-volume-for-chronic-kidney-disease-and-diabetic-rats
#5
Yu-Ki Tanaka, Nobuyuki Yajima, Yusuke Higuchi, Hideyuki Yamato, Takafumi Hirata
Herein, we measure the Ca isotope ratios ((44)Ca/(42)Ca and (43)Ca/(42)Ca) in serum and bone samples collected from rats with chronic kidney disease (CKD) or diabetes mellitus (DM). For the serum samples, the isotope ratios are lower for the CKD (δ(44)Ca/(42)Caserum = 0.16 ± 0.11‰; 2SD, n = 6) and the DM (δ(44)Ca/(42)Caserum = -0.11 ± 0.25‰; 2SD, n = 7) rats than that for the control rats (δ(44)Ca/(42)Caserum = 0.25 ± 0.04‰; 2SD, n = 7). Bone samples from two distinct positions of 20 rats in total, namely, the center and proximal parts of the tibial diaphysis, are subject to Ca isotope analysis...
November 8, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29114686/modulation-of-xpc-peptide-on-binding-tb-3-to-euplotes-octocarinatus-centrin
#6
Enxian Shi, Wenlong Zhang, Yaqin Zhao, Binsheng Yang
Centrins are Ca(2+)-binding proteins found throughout eukaryotic organisms. Xeroderma pigmentosum group C protein (XPC), a dominant component of the nuclear excision repair (NER) pathway, is a critical target protein of centrins. A 22-residue peptide (K842-R863) from XPC was used to investigate the effect of metal ions (Ca(2+) and Tb(3+)) on the peptide binding of Euplotes octocarinatus centrin (EoCen) by isothermal titration calorimetry (ITC) and fluorescence spectroscopy. ITC and tryptophan spectrofluorimetric titrations revealed that metal ions (Ca(2+) and Tb(3+)) could enhance the affinity between EoCen and the XPC peptide, and the enhanced effects were closely related to the ion potential of metal ions...
November 8, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29104982/on-the-toxicity-and-transport-mechanisms-of-cisplatin-in-kidney-tissues-in-comparison-to-a-gold-based-cytotoxic-agent
#7
Sarah Spreckelmeyer, Natalia Estrada-Ortiz, Gerian G H Prins, Margot van der Zee, Bente Gammelgaard, Stefan Stürup, Inge A M de Graaf, Geny M M Groothuis, Angela Casini
Mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. Here, we studied the toxic effects and accumulation mechanisms of cisplatin in healthy rat kidneys ex vivo, using the Precision Cut Tissue Slices (PCTS) method. In addition, for the first time, we investigated the nephrotoxic effects of an experimental anticancer cyclometallated complex [Au(py(b)-H)(PTA)Cl]PF6 (PTA = 1,3,5-triazaphosphaadamantane). The viability of the kidney slices after metallodrug treatment was evaluated by ATP content determination and histomorphology analysis...
November 6, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29094140/multi-metal-dependent-nucleic-acid-enzymes
#8
REVIEW
Wenhu Zhou, Juewen Liu
Nucleic acid enzymes (NAEs) are catalytically active RNA and DNA molecules. NAEs with RNA-cleaving activity are most extensively studied for applications in analytical chemistry, gene therapy and nanotechnology. Most NAEs require metal ions for activity. From a biochemical standpoint, these NAEs are reminiscent of metalloprotein enzymes with metal binding sites. While most NAEs require a single metal for the reaction, more and more recent examples have emerged that use two or even three metals for the reaction...
November 2, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29082389/chronic-intoxication-by-methylmercury-leads-to-oxidative-damage-and-cell-death-in-salivary-glands-of-rats
#9
Paulo Mecenas Alves Farias-Junior, Francisco Bruno Teixeira, Nathalia Carolina Fernandes Fagundes, Giza Hellen Nonato Miranda, Leonardo Oliveira Bittencourt, Ricardo Sousa de Oliveira Paraense, Márcia Cristina Freitas Silva, Fernanda do Espírito Santo Sagica, Edivaldo Herculano de Oliveira, Maria Elena Crespo-López, Rafael Rodrigues Lima
Methylmercury (MeHg) is one of the most toxic species of mercury, causing several systemic damages; however, its effect on the salivary glands has rarely been explored to date. This study was aimed at analyzing the mercury deposit, oxidative stress markers, and cell viability in parotid and submandibular rat salivary glands after chronic methylmercury intoxication. Herein, forty male Wistar rats (40 days old) were used in the experiment. The animals of the experimental group were intoxicated by intragastric gavage with MeHg at a dose of 0...
October 30, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29043347/zinc-ing-it-out-zinc-homeostasis-mechanisms-and-their-impact-on-the-pathogenesis-of-human-pathogen-group-a-streptococcus
#10
REVIEW
Nishanth Makthal, Muthiah Kumaraswami
Group A Streptococccus (GAS) is a major human pathogen that causes significant morbidity and mortality. Zinc is an essential trace element required for GAS growth, however, zinc can be toxic at excess concentrations. The bacterial strategies to maintain zinc sufficiency without incurring zinc toxicity play a crucial role in host-GAS interactions and have a significant impact on GAS pathogenesis. The host deploys nutritional immune mechanisms to retard GAS growth by causing either zinc deprivation or zinc poisoning...
October 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29022606/zinc-supplementation-mitigates-its-dyshomeostasis-in-experimental-diabetic-rats-by-regulating-the-expression-of-zinc-transporters-and-metallothionein
#11
Susmita Barman, Seetur R Pradeep, Krishnapura Srinivasan
Zinc depletion during diabetes projects a role for zinc nutrition in this condition. This study explored whether zinc supplementation annuls diabetes-induced zinc dyshomeostasis through modulation of zinc transporters and metallothionein. Groups of hyperglycemic rats were exposed for six weeks to supplemental zinc (5 or 10-times the normal level). Intracellular zinc concentration and zinc transporter and metallothionein expression levels in different tissues were analysed. Depleted zinc concentrations in different organs were restored by zinc supplementation...
October 12, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29019354/iron-sulfur-cluster-biosynthesis-and-trafficking-impact-on-human-disease-conditions
#12
C Wachnowsky, I Fidai, J A Cowan
Iron-sulfur clusters (Fe-S) are one of the most ancient, ubiquitous and versatile classes of metal cofactors found in nature. Proteins that contain Fe-S clusters constitute one of the largest families of proteins, with varied functions that include electron transport, regulation of gene expression, substrate binding and activation, radical generation, and, more recently discovered, DNA repair. Research during the past two decades has shown that mitochondria are central to the biogenesis of Fe-S clusters in eukaryotic cells via a conserved cluster assembly machinery (ISC assembly machinery) that also controls the synthesis of Fe-S clusters of cytosolic and nuclear proteins...
October 11, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28831476/phenylarsine-oxide-pao-induces-apoptosis-in-hepg2-cells-via-ros-mediated-mitochondria-and-er-stress-dependent-signaling-pathways
#13
Ping Huang, Yu Hua Zhang, Xiao Wei Zheng, Yu Jia Liu, Hong Zhang, Luo Fang, Yi Wen Zhang, Chang Yang, Khairul Islam, Chao Wang, Hua Naranmandura
Arsenic trioxide (As2O3) is an old drug that has recently been reintroduced as a therapeutic agent for acute promyelocytic leukemia (APL). Although As2O3 is also applied to treat other types of cancer in vitro and in vivo, it has been reported that single agent As2O3 has poor efficacy against non-hematologic malignant cancers in clinical trials. Recently, a few reports have indicated that organic arsenic compounds can be a possible alternative for the treatment of As2O3-resistant cancers. In this study, we aimed to investigate whether the organic arsenic compound phenylarsine oxide (PAO) has potent cytotoxic effects against human hepatocellular carcinoma (HCC) HepG2 cells...
August 23, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29086787/iron-in-biology
#14
EDITORIAL
Vincenzo Abbate, Robert Hider
No abstract text is available yet for this article.
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29072765/the-cytochrome-b5-cybe-is-regulated-by-iron-availability-and-is-crucial-for-azole-resistance-in-a-fumigatus
#15
Matthias Misslinger, Fabio Gsaller, Peter Hortschansky, Christoph Müller, Franz Bracher, Michael J Bromley, Hubertus Haas
Cytochrome P450 enzymes (P450) play essential roles in redox metabolism in all domains of life including detoxification reactions and sterol biosynthesis. The activity of P450s is fuelled by two electron-transferring mechanisms, heme-independent P450 reductase (CPR) and the heme-dependent cytochrome b5 (CYB5)/cytochrome b5 reductase (CB5R) system. In this study, we characterised the role and regulation of the cytochrome b5 CybE in the fungal pathogen Aspergillus fumigatus. Deletion of the CybE encoding gene (cybE) caused a severe growth defect in two different A...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29072738/correlations-in-the-elemental-and-metabolic-profiles-of-the-lichen-dirinaria-picta-after-road-traffic-exposure
#16
Xulei Huang, Lei Wang, Anna Karen Carrasco Laserna, Sam Fong Yau Li
Lichens can be used as cost-effective biomonitors of elements from road traffic in the urban environment. However, the nature of comprehensive interactions between hazardous heavy metals from road traffic and lichen metabolites remains unclear. In this study, elemental and metabolic profiles of the lichen Dirinaria picta after exposure to road traffic for 3 months in 9 sites of Singapore city were investigated. Concentrations of 34 elements reveal strong correlations among each other and a general increase with traffic exposure level...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29063080/studies-of-copper-trafficking-in-a-mouse-model-of-alzheimer-s-disease-by-positron-emission-tomography-comparison-of-64-cu-acetate-and-64-cugtsm
#17
Erica M Andreozzi, Julia Baguña Torres, Kavitha Sunassee, Joel Dunn, Simon Walker-Samuel, Istvan Szanda, Philip J Blower
Alzheimer's disease can involve brain copper dyshomeostasis. We aimed to determine the effect of AD-like pathology on (64)Cu trafficking in mice, using positron emission tomography (PET imaging), during 24 hours after intravenous administration of ionic (64)Cu (Cu(ii) acetate) and (64)Cu-GTSM (GTSMH2 = glyoxalbis(thiosemicarbazone)). Copper trafficking was evaluated in 6-8-month-old and 13-15 month-old TASTPM transgenic and wild-type mice, by imaging 0-30 min and 24-25 h after intravenous administration of (64)Cu tracer...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29058747/cobalt-and-nickel-impair-dna-metabolism-by-the-oxidative-stress-independent-pathway
#18
Vineet Kumar, Rajesh Kumar Mishra, Gursharan Kaur, Dipak Dutta
The oxidative stress that evolves under cobalt and nickel exposure is thought to exert toxicity, though the exact routes of such metal poisoning remain ambiguous. We revisited the metal toxicity in Escherichia coli to show that cobalt and nickel exposure at levels as low as 0.5 and 1 mM, respectively, visibly inhibits growth. We also observed that acidic conditions aggravated, while alkaline conditions alleviated the metal toxicity. Besides, 1 mM manganese, which is non-cytotoxic, as judged by the growth of E...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29058732/selenium-mediated-arsenic-excretion-in-mammals-a-synchrotron-based-study-of-whole-body-distribution-and-tissue-specific-chemistry
#19
Olena Ponomarenko, Paul F La Porte, Satya P Singh, George Langan, David E B Fleming, Julian E Spallholz, Mohammad Alauddin, Habibul Ahsan, Selim Ahmed, Jürgen Gailer, Graham N George, Ingrid J Pickering
Arsenicosis, a syndrome caused by ingestion of arsenic contaminated drinking water, currently affects millions of people in South-East Asia and elsewhere. Previous animal studies revealed that the toxicity of arsenite essentially can be abolished if selenium is co-administered as selenite. Although subsequent studies have provided some insight into the biomolecular basis of this striking antagonism, many details of the biochemical pathways that ultimately result in the detoxification and excretion of arsenic using selenium supplements have yet to be thoroughly studied...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29057997/defining-the-domains-of-cia2-required-for-its-essential-function-in-vivo-and-in-vitro
#20
Amanda T Vo, Nicholas M Fleischman, Melissa D Marquez, Eric J Camire, Stephanie U Esonwune, John D Grossman, Kelly A Gay, Jessica A Cosman, Deborah L Perlstein
The cytosolic iron-sulfur cluster assembly (CIA) system biosynthesizes iron-sulfur (FeS) cluster cofactors for cytosolic and nuclear proteins. The yeast Cia2 protein is the central component of the targeting complex which identifies apo-protein targets in the final step of the pathway. Herein, we determine that Cia2 contains five conserved motifs distributed between an intrinsically disordered N-terminal domain and a C-terminal domain of unknown function 59 (DUF59). The disordered domain is dispensible for binding the other subunits of the targeting complex, Met18 and Cia1, and the apo-target Rad3 in vitro...
November 15, 2017: Metallomics: Integrated Biometal Science
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