显示样式:     当前分类: 生命    当前期刊: Metallomics    加入关注    导出
我的关注
我的收藏
您暂时未登录!
登录
  • Platinum(II)-chloroquine complexes are antimalarial agents against blood and liver stages by impairing mitochondrial function
    Metallomics (IF 3.975) Pub Date : 2017-09-19
    Tais Soares Macedo, Wilmer Jose Villarreal Pena, Camila C Couto, Diogo R Moreira, Maribel Navaro, Marta Machado, Miguel Prudêncio, Alzir A Batista, Milena Botelho Soares

    Chloroquine is an antimalarial agent with strong activity against the blood stage of Plasmodium infection, but with low activity against the parasite’s liver stage. In addition, the resistance to chloroquine is limiting its clinical use. Finding new molecules possessing a multistage activity and overcoming drug resistance is needed. One possible strategy to achieve this lies in combining antimalarial quinolones with the pharmacological effects of transition metals. We investigated the antimalarial activity of four platinum(II) complexes composed of chloroquine and phosphine ligands, denoted WV-90, WV-92, WV-93 and WV-94. In comparison to Chloroquine, complexes were less potent against the chloroquine-sensitive 3D7 strain but they were as active as in inhibiting the chloroquine-resistant W2 strain of P. falciparum. Regarding selectivity, the complexes WV-90 and WV-93 displayed the higher indexes. Unlike chloroquine, complexes act as irreversible parasiticidal agents against trophozoites and WV-93 complex displayed activity against the hepatic stage of P. berghei. The in vivo suppression activity against P. berghei in the Peters 4-day test displayed by the complexes was similar to that of chloroquine. However, efficacy in an established P. berghei infection in the Thompson test was superior for WV-93 complex than chloroquine. The complexes’ antimalarial mechanism of action is initiated by inhibiting the hemozoin formation. While chloroquine efficiently inhibits hemozoin, parasites treated with platinum complexes displayed residual hemozoin crystals. This is explained since platinum complexes interaction with ferriprotoporphyrin is weaker than chloroquine. However, complexes caused a loss of mitochondrial integrity and subsequent reduction of its activity, and their effects on mitochondria were more pronounced than chloroquine-treated parasites. The dual effect of platinum complexes may explain their activity against the hemozoin-lacking parasites (hepatic stage), where chloroquine has no activity. Our findings support that platinum(II)-chloroquine complexes are multifunctional antimalarial compounds and reinforce the importance of metal complexes in antimalarial drug discovery.

    更新日期:2017-09-20
  • Computational approaches for deciphering equilibrium and kinetic properties of iron transport proteins
    Metallomics (IF 3.975) Pub Date : 2017-09-19
    Haleh Abdizadeh, Ali Rana Atilgan, Canan Atilgan, Burcu Dedeoglu

    With the advances in three-dimensional structure determination techniques, high quality structures of iron transport proteins transferrin and the bacterial ferric binding protein (FbpA) have been deposited in the past decade. These are proteins of relatively large size, and developments in hardware and software have only recently made it possible to study their dynamics on standard computational resources. We review computational techniques towards understanding the equilibrium and kinetic properties of iron transport proteins under different environmental conditions. At the detail that requires quantum chemical treatments, the octahedral geometry around iron has been scrutinized and that the iron coordinating tyrosines are in an unusual deprotonated state has been established. At the atomistic detail, both the N-lobe and the full bilobal structure of transferrin have been studied under varying conditions of pH, ionic strength and binding of other metal ions by molecular dynamics (MD) simulations. These studies have allowed answering questions, among others, on the function of second shell residues in iron release, the role of synergistic anions on preparing the active site for iron binding, and the differences between the kinetics of the N- and the C-lobe. MD simulations on FbpA have led to the detailed observation of the binding kinetics of phosphate to the apo form, and to the conformational preferences of the holo form in conditions mimicking the environmental niches provided by the periplasmic space. To study the dynamics of these proteins with their receptors, one must resort to coarse-grained methodologies, since these systems are prohibitively large for atomistic simulations. Study of the complex of human transferrin (hTf) with its pathogenic receptor by such methods has revealed a potential mechanistic explanation for the defense mechanism that arises in the evolutionary warfare. Meanwhile, the motions in the transferrin receptor bound hTf have been shown to disfavor apo hTf dissociation, explaining why the two proteins remain in complex during the recycling process from the endosome to the cell surface. Open problems and possible technological applications related to metal ion binding-release in iron transport proteins that may be handled by hybrid use of quantum mechanical, MD and coarse-grained approaches are discussed.

    更新日期:2017-09-20
  • Vanadate oxidative and apoptotic effect are mediated by MAPK-Nrf2 Pathway in Layer Oviduct Magnum Epithelial Cells
    Metallomics (IF 3.975) Pub Date : 2017-09-18
    Jianping Wang, Xuanyang Huang, Keying Zhang, Xiangbing Mao, Xuemei Ding, Qiufeng Zeng, Shiping Bai, Yue Xuan, Huanwei Peng

    Vanadium is a metal of high physiological, environmental and industrial importantce. However, vanadium-induced oxidative stress can reduce egg quality of poultry, be potentially harmful to humans, and the underlying mechanism is not clear. In this study, we investigated the underlying relationship between the oxidant-sensitive mitogen-activated protein kinase (MAPK) signaling pathway and vanadium-induced oxidative stress in oviduct magnum epithelial (OME) cells. Cultured OME cells were treated by 100 μmol/L vanadium and/or MAPK inhibitors [P38 MAPK inhibitor, SB203580; extracellular regulated protein kinase 1 and 2 (ERK1/2) inhibitor, U0126; c-JUN N-terminal kinases (JNK) inhibitor, SP600125]. Cell viability, apoptosis, along with generation of reactive oxygen species (ROS) were assessed using flow cytometry. The expression of oxidative stress related genes and their proteins were measured by reverse transcription-polymerase chain reaction and Western blotting. Vanadium treatment reduced cell viability, whereas pretreated OME cells with SB203580 and U0126 prevented the reducing effect of vanadium on cell viability (P < 0.05). Likewise, MAPK inhibitors effectively suppressed vanadium-induced apoptosis and ROS generation (P < 0.05). In the OME cells treated by vanadium, SB203580 (P < 0.05) and SP600125 (P = 0.08) increased catalase activity by 89.3% and 55.3%; SB203580 and U0126 increased (P < 0.05) glutathione peroxidase activity by 44.9% and 51.1%, respectively. Incubation OME cells with MAPK inhibitors also prevent the malondialdehyde concentration increase and lactose dehydrogenase activity decrease in response to vanadium (P < 0.05). Vanadium downregulated P38, ERK1/2, JNK, Nrf2, sMaf, GCLC, NQO1 and HO-1 mRNA expression (P < 0.05). By contrast, inhibition JNK with SP600125 upregulated P38, ERK1/2, JNK, Nrf2, GCLC and HO-1 mRNA expression (P < 0.05); inhibition P38 with SB203580 upregulated JNK, NQO1 and HO-1 mRNA expression (P < 0.05); inhibition ERK1/2 with U0126 upregulated ERK1/2, GCLC and HO-1 mRNA expression (P < 0.05). Moreover, phosphorylation of P38, ERK1/2, JNK, and Nrf2 proteins were enhanced by V incubation; however, SP600125 blocked the phosphorylation of these proteins, whereas SB203580 blocked the phosphorylation of P38 and Nrf2. These results indicate that vanadium inducing oxidative stress in OME cells might be, at least, associated with the phosphorylation of P38MAPK/JNK-Nrf2 pathway, which reduce the expression of phrase II detoxifying enzymes.

    更新日期:2017-09-18
  • DUODENAL CYTOCHROME B (CYBRD1) FERRIC REDUCTASE FUNCTIONAL STUDIES IN CELLS
    Metallomics (IF 3.975) Pub Date : 2017-09-15
    Fabian Schlottmann, Mayra Vera-Aviles, Yemisi Latunde-Dada

    Dietary non-heme ferric iron is reduced by the ferric reductase enzyme, duodenal cytochrome b (Dcytb), before absorption by the divalent metal transporter 1 (DMT1). A single nucleotide polymorphism (SNP rs10455 mutant) that is located in the last exon of Dcytb gene was reported in C282Y haemochrotomatosis HFE subjects. The present work therefore investigated the phenotype of this mutant Dcytb in Chinese hamster ovary (CHO) cells. These cultured cells were transfected with either wild type (WT) or the SNP vector plasmids of Dcytb. Ferric reductase assays were performed in Dcytb transgenic CHO cells using the ferrozine spectrophometric assay protocol. The Dcytb SNP rs10455 showed a gain of function capability since ferric reductase activity increased significantly (P<0.01) in the transgenic cells. Increased ferric reductase activity was found when CHO cells were pretreated with modulators of Dcytb protein expression. Although ferric reductase in endogenous CHO cells increased with deferoxamine or CoCl2, iron loading with ferric ammonium citrate (FAC) had the opposite effect. Taken together, the study reveals a gain-of-function phenotype for Dcytb rs10455 mutation that could be a putative modifier of colorectal cancer risk, with attendant variability in penetrance among human HFE C282Y homozygotes.

    更新日期:2017-09-15
  • Differences in cisplatin distribution in sensitive and resistant ovarian cancer cells: a TEM/NanoSIMS study
    Metallomics (IF 3.975) Pub Date : 2017-09-07
    Ronald F. S. Lee, Tina Riedel, Stéphane Escrig, Catherine Maclachlan, Graham W. Knott, Curt A. Davey, Kai Johnsson, Anders Meibom, Paul J. Dyson
    更新日期:2017-09-15
  • Tyr25, Tyr58 and Trp133 of Escherichia coli bacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre
    Metallomics (IF 3.975) Pub Date : 2017-09-06
    Justin M. Bradley, Dimitri A. Svistunenko, Geoffrey R. Moore, Nick E. Le Brun
    更新日期:2017-09-15
  • Subcellular compartmentalisation of copper, iron, manganese, and zinc in the Parkinson's disease brain
    Metallomics (IF 3.975) Pub Date : 2017-09-13
    Sian Genoud, Blaine R Roberts, Adam P. Gunn, Glenda M. Halliday, Simon J. G. Lewis, Helen J Ball, Dominic J. Hare, Kay L Double

    Elevated iron and decreased copper levels are cardinal features of the degenerating substantia nigra pars compacta in the Parkinson’s disease brain. Both of these redox-active metals, and fellow transition metals manganese and zinc, are found at high concentrations within the midbrain and participate in a range of unique biological reactions. We examined the total metal content and cellular compartmentalisation of manganese, iron, copper and zinc in the degenerating substantia nigra, disease-affected but non-degenerating fusiform gyrus, and unaffected occipital cortex in the post mortem Parkinson’s disease brain compared with age-matched controls. An expected increase in iron and a decrease in copper concentration was isolated to the soluble cellular fraction, encompassing both interstitial and cytosolic metals and metal-binding proteins, rather than the membrane-associated or insoluble fractions. Manganese and zinc levels did not differ between experimental groups. Altered Fe and Cu levels were unrelated to Braak pathological staging in our cases of late-stage (Braak stage V and VI) disease. The data supports our hypothesis that regional alterations in Fe and Cu, and in proteins that utilise these metals, contribute to the regional selectively of neuronal vulnerability in this disorder.

    更新日期:2017-09-13
  • Effects of developmental arsenite exposure on hippocampal synapses in mouse offspring
    Metallomics (IF 3.975) Pub Date : 2017-08-21
    Fenghong Zhao, Yingjun Liao, Hongge Tang, Jie Piao, Gaoyang Wang, Yaping Jin
    更新日期:2017-09-13
  • Amino- and chloro-8-hydroxyquinolines and their copper complexes as proteasome inhibitors and antiproliferative agents
    Metallomics (IF 3.975) Pub Date : 2017-09-11
    Valentina Oliveri, Valeria Lanza, Danilo Milardi, maurizio Viale, Carmelo Sgarlata, Irena Maric, Graziella Vecchio

    Proliferation and programmed cell death are tightly correlated with the ubiquitin-proteasome system (UPS). Alterations in the UPS may be implicated in pathological conditions such as the proteasome over-activity in cancer cells. Mounting evidence indicates that many types of actively proliferating malignant cells are more sensitive to proteasome inhibition than normal cells, and therefore UPS inhibitors are actively pursued as anticancer agents. The approval of the proteasome inhibitor drug bortezomib for the treatment of myeloma and lymphoma further highlights the need for UPS inhibitors. Recent studies have suggested that clioquinol and 5-amino-8-hydroxyquinoline can inhibit proteasome activity and induce apoptosis in human cancer cells. As for clioquinol, a copper-dependent and -independent mechanism has been proposed to explain the inhibition of proteasome whereas the activity of 5-amino-8-hydroxyquinoline has been not explored in the presence of copper(II) ions. Herein, we investigated the biological activity of some 8-hydroxyquinolines by using human ovarian (A2780) and lung (A549) cancer cells. The effect of copper(II) on the activity of these compounds was also evaluated. The investigated systems inhibit the chymotrypsin-like activity of the proteasome and induce growth inhibition and apoptosis in a concentration-dependent manner. Copper(II) ions increase the activity of 8-hydroxyquinoline derivatives except in the case of 5-amino-8-hydroxyquinoline. This study suggests the great potential of amino- and chloro-8-hydroxyquinolines as anticancer agents. Furthermore, it clarifies some aspects concerning the activity of 5-amino-8-hydroxyquinoline that has previously been proposed as a proteasome inhibitor capable of overcoming the resistance to bortezomib.

    更新日期:2017-09-11
  • From direct to indirect lithium targets: a comprehensive review of omics data
    Metallomics (IF 3.975) Pub Date : 2017-08-30
    Magali Roux, Anthony Dosseto
    更新日期:2017-09-08
  • Sulphur fertilization influences the sulphur species composition in Allium sativum: sulphomics using HPLC-ICPMS/MS-ESI-MS/MS
    Metallomics (IF 3.975) Pub Date : 2017-09-07
    A Raab, Marilena RONZAN, Jorg Feldmann

    Garlic (A. sativum) contains a large number of small sulphur (S)-containing metabolites, which are important for its taste and smell and vary with A. sativum variety and growth conditions. This study was designed to investigate the influence of different sulphur-fertilization regimes on the low molecular weight S-species by attempting the first sulphur mass balance in A. sativum roots and bulbs using HPLC-ICPMS/MS-ESI-MS/MS. Species unspecific quantification of acid soluble S-containing metabolites was achieved using HPLC-ICP-MS/MS. For identification of the compounds high resolution ESI-MS (Orbitrap LTQ and q-TOF) was used. The plants contained up to 54 separated sulphur-containing compounds, which constitute about 80 % of the total sulphur present in A. sativum. Roots and bulbs of A.sativum contained the same compounds, but not necessarily the same amounts and proportions. The S-containing metabolites in the roots reacted more sensitive to manipulations of sulphur fertilization than those compounds in the bulbs. In addition to known compounds (eg. γ-glutamyl-S-1-propenylcysteine) we were able to identify and partially quantify 31 compounds. Three as yet undescribed S-containing compounds were also identified and quantified for the first time. Putative structures were assigned to the oxidised forms of S-1-propenylmercaptoglutathione, S-2-propenylmercaptoglutathione, S-allyl/propenyl-containing PC-2 and 2-amino-3-[(2-carboxypropyl)sulfanyl]propanoic acid. The parallel use of ICP-MS/MS as sulphur-specific detector and ESI-MS as molecular detector simplifies the identification and quantification of sulphur containing metabolites without species specific standards. This non-target analysis approach enables a mass balance approach and identifies the occurrence of so far unidentified organosulphur compounds. The experiments showed that the sulphur-fertilization regime does not influence sulphur-speciation, but the concentration of some S-containing compounds in roots is depending on the sulphur fertilization.

    更新日期:2017-09-07
  • Differences in cisplatin distribution in sensitive and resistant ovarian cancer cells: a TEM/NanoSIMS study
    Metallomics (IF 3.975) Pub Date : 2017-09-07
    Ronald F.S. Lee, Tina Riedel, Stéphane Escrig, Catherine Maclachlan, Graham Knott, Curt A Davey, Kai Johnsson, Anders Meibom, Paul Dyson

    Cisplatin is a widely used anti-cancer drug, but its effect is often limited by acquired resistance to the compound during treatment. Here, we use a combination of transmission electron microscopy (TEM) and nanoscale-secondary ion mass spectrometry (NanoSIMS) to reveal differences between cisplatin uptake in human ovarian cancers cells, which are known to be susceptible to acquired resistance to cisplatin. Both cisplatin sensitive and resistant cell lines were studied, revealing markedly less cisplatin in the resistant cell line. In cisplatin sensitive cells, Pt was seen to distribute diffusely in the cells with hotspots in the nucleolus, mitochondria, and autophagosomes. Inductively coupled plasma mass spectrometry (ICP-MS) was used to validate the NanoSIMS results

    更新日期:2017-09-07
  • The elemental role of iron in DNA synthesis and repair
    Metallomics (IF 3.975) Pub Date : 2017-08-31
    Sergi Puig, Lucía Ramos-Alonso, Antonia María Romero, María Teresa Martínez-Pastor
    更新日期:2017-09-07
  • Tyr25, Tyr58 and Trp133 of Escherichia coli bacterioferritin transfer electrons between iron in the central cavity and the ferroxidase centre
    Metallomics (IF 3.975) Pub Date : 2017-09-06
    Justin Michael Bradley, Dimitri Svistunenko, G R Moore, Nick Le Brun

    Ferritins are 24meric proteins that overcome problems of toxicity, insolubility and poor bioavailability of iron in all types of cells by storing it in the form of a ferric mineral within their central cavities. In the bacterioferritin (BFR) from Escherichia coli iron mineralization kinetics have been shown to be dependent on an intra-subunit catalytic diiron cofactor site (the ferroxidase centre), three closely located aromatic residues and an inner surface iron site. One of the aromatic residues, Tyr25, is the site of formation of a transient radical, but the roles of the other two residues, Tyr58 and Trp133, are unknown. Here we show that these residues are important for the rates of formation and decay of the Tyr25 radical and decay of a secondary radical observed during Tyr25 radical decay. The data support a mechanism in which these aromatic residues function in electron transfer from the inner surface site to the ferroxidase centre.

    更新日期:2017-09-06
  • Proteomic and genetic analysis of the response of S. cerevisiae to soluble copper leads to improvement of the antimicrobial function of cellulosic copper nanoparticles
    Metallomics (IF 3.975) Pub Date : 2017-08-18
    Xiaoqing Rong-Mullins, Matthew J. Winans, Justin B. Lee, Zachery R. Lonergan, Vincent A. Pilolli, Lyndsey M. Weatherly, Thomas W. Carmenzind, Lihua Jiang, Jonathan R. Cumming, Gloria S. Oporto, Jennifer E. G. Gallagher
    更新日期:2017-09-04
  • The elemental role of iron in DNA synthesis and repair
    Metallomics (IF 3.975) Pub Date : 2017-08-31
    Sergi Puig, Lucía Ramos-Alonso, Antonia María Romero, María Teresa Martínez-Pastor

    Iron is an essential redox element that functions as a cofactor in many metabolic pathways. Critical enzymes in DNA metabolism, including multiple DNA repair enzymes (helicases, nucleases, glycosylases, demethylases) and ribonucleotide reductase, use iron as an indispensable cofactor to function. Recent striking results have revealed that the catalytic subunit of DNA polymerases also contains conserved cysteine-rich motifs that bind iron-sulfur (Fe/S) clusters that are essential for the formation of stable and active complexes. In line with this, mitochondrial and cytoplasmic defects in Fe/S cluster biogenesis and insertion into the nuclear iron-requiring enzymes involved in DNA synthesis and repair lead to DNA damage and genome instability. Recent studies have shown that yeast cells possess multi-layered mechanisms that regulate the ribonucleotide reductase function in response to fluctuations in iron bioavailability to maintain optimal deoxyribonucleotide concentrations. Finally, a fascinating DNA charge transport model indicates how the redox active Fe/S centers present in DNA repair machinery components are critical for detecting and repairing DNA mismatches along the genome by long-range charge transfers through double-stranded DNA. These unexpected connections between iron and DNA replication and repair have to be considered to properly understand cancer, aging and other DNA-related diseases.

    更新日期:2017-08-31
  • Defining the domains of Cia2 required for its essential function in vivo and in vitro
    Metallomics (IF 3.975) Pub Date : 2017-08-23
    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 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 identifes 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. While in vivo assays reveal that the C-terminal domain is sufficient to support viability, several phenotypic assays indicate that deletion of the N-terminal domain negatively impacts CIA function. We additionally establish that Glu208, located within a conserved motif found only in eukaryotic DUF59 proteins, is important for the Cia1-Cia2 interaction in vitro. In vivo, E208A-Cia2 results in a diminished activity of the cytosolic iron sulfur cluster protein, Leu1 but only modest effects on hydroxyurea or methylmethane sulfonate sensitivity. Finally, we demonstrate that neither of the two highly conserved motifs of the DUF59 domain are vital for any of Cia2’s interactions in vitro yet mutation of the DPE motif in the DUF59 domain results in a nonfunctional allele in vivo. Our observation that four of the five highly conserved motifs of Cia2 are dispensable for targeting complex formation and apo-target binding suggests that Cia2 is not simply a protein-protein interaction mediator but it likely possesses an additional, currently cryptic, function during the final cluster insertion step of CIA.

    更新日期:2017-08-23
  • Phenylarsine oxide (PAO) induces apoptosis in HepG2 cells via ROS-mediated mitochondria and ER-stress dependent signaling pathways
    Metallomics (IF 3.975) Pub Date : 2017-08-03
    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
    更新日期:2017-08-23
  • From direct to indirect lithium targets: a comprehensive review of omic data
    Metallomics (IF 3.975) Pub Date : 2017-08-22
    Anthony Dosseto, Magali Roux

    Metal ions are critical to a wide range of biological processes. Among them, lithium (Li) has been recognised for its benefit as treatment for bipolar disorder (BD). However, we are yet to grasp the extent of its role on biological processes, despite its molecular targets having been extensively studied. Here we review a wide range of transcriptomic, proteomic and metabolomic studies in order to obtain a full picture of Li effects at various levels. Multifarious patterns of Li-regulated genes, proteins and metabolites are identified. Some of these patterns are explained as the outcomes of Li individual targets. For instance, Li inhibition of GSK-3 has a wide range of effects: axis development in embryos; cell and tissue differentiation, in particular neurogenesis and osteogenesis; or control on apoptosis. This results in neuroprotection and an attenuation of cognitive deficits. Lithium has an important role on mitochondrial function, which it improves via its role on phospholipid metabolism and inositol depletion. This is also seen in metabolomics, where its role on the mitochondrial respiratory chain influences energy production and oxidative stress. Lithium also affects the proteins involved in the processing of APP, thus highlighting a possible involvement in Alzheimer’s disease. Finally, Li also impacts lipid homeostasis, with studies showing that environmental exposure can impact lipid transport and prostaglandin synthesis. It is seldom possible to establish a causal relationship between Li targets at molecular level and effects resulting at system level. For example, Li effects on adenylate cyclase regulation are not easily linked to any omic pattern despite the importance of adenylate pathway. Nevertheless, refining our knowledge on cellular functions of individual Li targets would allow improving our understanding and interpretation of omic data. This review demonstrates that Li is key to a wide range of processes at all levels, from neuroprotection to oxidative stress and energy production. A corollary of this work is the need for an increased awareness of environmental issues related to Li industrial wastes, in particular considering the widespread use of this metal in our modern society.

    更新日期:2017-08-22
  • Effects of developmental arsenite exposure on hippocampal synapse in mouse offspring
    Metallomics (IF 3.975) Pub Date : 2017-08-21
    Fenghong Zhao, Yingjun Liao, Hongge Tang, Jie Piao, Gaoyang Wang, Yaping Jin

    Arsenic exposure through drinking water can impair learning and memory ability of children in China and other countries. Synaptic plasticity plays a key role in process of learning and memory. Alterations in expressions of presynaptic and postsynaptic proteins can be used to evaluate synaptic plasticity, and further to evaluate impairment in learning and memory ability. Thereby, the aim of this study was to explore the mechanisms underlying arsenic neurotoxicity by focusing on alterations in hippocampal synapse of mouse offspring induced by developmental arsenite exposure. Mother mice and their offspring were exposed to 0, 25, 50 or 100 mg/L arsenite via drinking water from the first day of gestation until the postnatal day (PND) 35. Spatial learning and memory ability of PND 35 mice was evaluated by Morris water maze. Levels of speciated arsenicals in the brain of PND 7, 14, 21 and 35 mice were analyzed by hydride generation coupled with atomic absorption spectrophotometry. Synaptic structure and protein expression of postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the hippocampus of PND 7, 14, 21 and 35 mice were examined. Findings from this study disclosed that spatial learning ability of mice could be impaired by exposure to 25 mg/L arsenite; however spatial memory ability could not be impaired until exposure to 100 mg/L arsenite. Thickness of postsynaptic density (PSD) decreased, whereas width of synaptic cleft widened significantly in arsenite exposure groups. Moreover, protein expression of both PSD-95 and SYP decreased significantly in arsenite exposure groups. In conclusion, results of this study demonstrated that developmental arsenite exposure could depress expression of synaptic proteins, subsequently cause alteration in synaptic structures, and finally contribute to arsenite-induced deficits in spatial learning and memory ability in mouse offspring.

    更新日期:2017-08-21
  • Proteomic and genetic analysis of S. cerevisiae response to soluble copper leads to improvement of antimicrobial function of cellulosic copper nanoparticles
    Metallomics (IF 3.975) Pub Date : 2017-08-18
    Xiaoqing Claire Rong-Mullins, Matthew J Winans, Justin B. Lee, Zachery R. Lonergan, Vincent A. Pilolli, Lyndsey M. Weatherly, Thomas W. Carmenzind, Lihua Jiang, Jonathan R. Cumming, Gloria Oporto, Jennifer Gallagher

    Copper (Cu) was used in antiquity to prevent waterborne and food diseases because, as a broad-spectrum antimicrobial agent, it generates reactive oxygen species, ROS. New technologies incorporating Cu into low-cost biodegradable nanomaterials built on cellulose, known as cellulosic cupric nanoparticles or c-CuNPs, present novel approaches to deliver Cu in a controlled manner to control microbial growth. We challenged strains of Saccharomyces cerevisiae to soluble Cu and c-CuNPs to evaluate the potential of c-CuNPs as antifungal agents. Cells exposed to c-CuNPs demonstrated greater sensitivity to Cu than cells exposed to soluble Cu, although Cu-resistant strains were more tolerant than Cu-sensitive strains of c-CuNP exposure. At the same level of growth inhibition, 157 µM c-CuNP led to the same internal Cu levels as did 400 CuSO4, offering evidence for alternative mechanisms of toxicity, perhaps through -arrestin dependent endocytosis, which was supported by flow cytometry and fluorescence microscopy of c-CuNPs distributed both on the cell surface and within the cytoplasm. Genes responsible for genetic variation to copper were mapped to the ZRT2 and the CUP1 loci. Through proteomic analyses, we found that the expression of other zinc (Zn) transporters increased in Cu-tolerant yeast compared to Cu-sensitive strains. Further, the addition of Zn at low levels increased the potency of c-CuNP to inhibit even the most Cu-tolerant yeast. Through unbiased systems biological approaches, we identified Zn as a critical component of yeast response to Cu and the addition of Zn increased potency of the c-CuNPs.

    更新日期:2017-08-18
  • Atp7a and Atp7b regulate copper homeostasis in developing male germ cells in mice
    Metallomics (IF 3.975) Pub Date : 2017-08-18
    Mateusz Ogórek, Małgorzata Lenartowicz, Rafał Starzyński, Aneta Jończy, Robert Staroń, Andrzej Doniec, Wojciech Krzeptowski, Aleksandra Bednarz, Olga Pierzchała, Paweł Lipiński, Zenon Rajfur, Zbigniew Baster, Patrycja Gibas-Tybur, Paweł Grzmil
    更新日期:2017-08-18
  • Characterization of a highly efficient antibiotic-degrading metallo-β-lactamase obtained from an uncultured member of a permafrost community
    Metallomics (IF 3.975) Pub Date : 2017-07-18
    Marcelo Monteiro Pedroso, Christopher Selleck, Charmaine Enculescu, Jeffrey R. Harmer, Nataša Mitić, Whitney R. Craig, Waleed Helweh, Philip Hugenholtz, Gene W. Tyson, David L. Tierney, James A. Larrabee, Gerhard Schenk
    更新日期:2017-08-16
  • A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity
    Metallomics (IF 3.975) Pub Date : 2017-07-18
    Ahmed Mohsen, Philippe Collery, Roselyne Garnotel, Bertrand Brassart, Nicolas Etique, Gilane Mohamed Sabry, Rasha Elsherif Hassan, Pierre Jeannesson, Didier Desmaële, Hamid Morjani
    更新日期:2017-08-16
  • Copper-finger protein of Sp1: the molecular basis of copper sensing
    Metallomics (IF 3.975) Pub Date : 2017-07-18
    Siming Yuan, Siming Chen, Zhaoyong Xi, Yangzhong Liu
    更新日期:2017-08-16
  • Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel
    Metallomics (IF 3.975) Pub Date : 2017-07-13
    Ana Podolski-Renić, Szilvia Bősze, Jelena Dinić, László Kocsis, Ferenc Hudecz, Antal Csámpai, Milica Pešić
    更新日期:2017-08-16
  • Whole blood Fe isotopic signature in a sub-Saharan African population
    Metallomics (IF 3.975) Pub Date : 2017-07-13
    Justin C. Cikomola, María R. Flórez, Marta Costas-Rodríguez, Yulia Anoshkina, Karl Vandepoele, Philippe B. Katchunga, Antoine S. Kishabongo, Marijn M. Speeckaert, Frank Vanhaecke, Joris R. Delanghe
    更新日期:2017-08-16
  • Schizosaccharomyces pombe Grx4 regulates the transcriptional repressor Php4 via [2Fe–2S] cluster binding
    Metallomics (IF 3.975) Pub Date : 2017-07-12
    Adrienne C. Dlouhy, Jude Beaudoin, Simon Labbé, Caryn E. Outten
    更新日期:2017-08-16
  • 更新日期:2017-08-16
  • Analytical approaches for the characterization of nickel proteome
    Metallomics (IF 3.975) Pub Date : 2017-07-06
    Javier Jiménez-Lamana, Joanna Szpunar
    更新日期:2017-08-16
  • Remarkable differences in the biochemical fate of Cd2+, Hg2+, CH3Hg+ and thimerosal in red blood cell lysate
    Metallomics (IF 3.975) Pub Date : 2017-07-05
    Matthew A. Gibson, Sophia Sarpong-Kumankomah, Susan Nehzati, Graham N. George, Jürgen Gailer
    更新日期:2017-08-16
  • Activation of Nrf2/ARE signaling pathway attenuates lanthanum chloride induced injuries in primary rat astrocytes
    Metallomics (IF 3.975) Pub Date : 2017-07-04
    Lijin Zhang, Jinghua Yang, Shengwen Wu, Cuihong Jin, Xiaobo Lu, Xiaoyu Hu, Yaling Sun, Xiang Gao, Yuan Cai
    更新日期:2017-08-16
  • Oxygen-dependent activation of Cu,Zn-superoxide dismutase-1
    Metallomics (IF 3.975) Pub Date : 2017-06-27
    Morgan M. Fetherolf, Stefanie D. Boyd, Duane D. Winkler, Dennis R. Winge
    更新日期:2017-08-16
  • Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia
    Metallomics (IF 3.975) Pub Date : 2017-06-16
    Jingshu Xu, Stephanie J. Church, Stefano Patassini, Paul Begley, Henry J. Waldvogel, Maurice A. Curtis, Richard L. M. Faull, Richard D. Unwin, Garth J. S. Cooper
    更新日期:2017-08-16
  • Influence of iron metabolism on manganese transport and toxicity
    Metallomics (IF 3.975) Pub Date : 2017-05-31
    Qi Ye, Jo Eun Park, Kuljeet Gugnani, Swati Betharia, Alejandro Pino-Figueroa, Jonghan Kim
    更新日期:2017-08-16
  • Human calprotectin affects the redox speciation of iron
    Metallomics (IF 3.975) Pub Date : 2017-05-15
    Toshiki G. Nakashige, Elizabeth M. Nolan
    更新日期:2017-08-16
  • Mechanisms of iron and copper–frataxin interactions
    Metallomics (IF 3.975) Pub Date : 2017-05-09
    T. H. L. Han, J. M. Camadro, R. Santos, E. Lesuisse, J. M. El Hage Chahine, N. T. Ha-Duong
    更新日期:2017-08-16
  • Metallomics: the history over the last decade and a future outlook
    Metallomics (IF 3.975) Pub Date : 2017-04-21
    Hiroki Haraguchi
    更新日期:2017-08-16
  • Downregulation of hepatic multi-drug resistance protein 1 (MDR1) after copper exposure
    Metallomics (IF 3.975) Pub Date : 2017-07-31
    Sara Reinartz Groba, Sarah Guttmann, Christoph Niemietz, Friedrich Bernick, Vanessa Sauer, Oliver Hachmöller, Uwe Karst, Hans Zischka, Andree Zibert, Hartmut H. Schmidt
    更新日期:2017-08-15
  • Intracellular iron and heme trafficking and metabolism in developing erythroblasts
    Metallomics (IF 3.975) Pub Date : 2017-08-01
    Martin D. Kafina, Barry H. Paw
    更新日期:2017-08-10
  • Chronic exposure to inorganic mercury induces biochemical and morphological changes in the salivary glands of rats
    Metallomics (IF 3.975) Pub Date : 2017-07-28
    W. A. B. Aragão, N. M. M. da Costa, N. C. F. Fagundes, M. C. F. Silva, S. M. Alves-Junior, J. J. V. Pinheiro, L. L. Amado, M. E. Crespo-López, C. S. F. Maia, R. R. Lima
    更新日期:2017-08-10
  • Phenylarsine oxide (PAO) induces apoptosis in HepG2 cells via ROS-mediated mitochondria and ER-stress dependent signaling pathways.
    Metallomics (IF 3.975) Pub Date : 2017-08-03
    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 re-introduced as a therapeutic agent for acute promyelocytic leukemia (APL). Although As2O3 is also applied to treat other types of cancers 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 indicate that organic arsenic compounds can be a possible alternative for the treatment of As2O3-resistance cancers. In this study, we aimed to investigate whether the organic arsenic compound phenylarsine oxide (PAO) has potent cytotoxic effect againsthuman hepatocellular carcinoma (HCC) HepG2 cells. Our results showed that PAO not only had potent inhibitory effect on the proliferation of HepG2 cells, but also activated apoptosis-related proteins (e.g., caspase-3 and -9 and poly-ADP ribose polymerase) in a dose- and time-dependent manner. Furthermore, intracellular ROS was specifically accumulated in mitochondria and endoplasmic reticulum (ER) after exposure to PAO, implying that they are the target organelles for PAO-induced cytotoxicity. Additionally, when cells were pretreated with antioxidant N-acetylcysteine (NAC), apoptosis and ER-stress were attenuated significantly, suggesting that induction of apoptosis and cell death probably occurs through the ROS-mediated mitochondria and ER-stress dependent signaling pathways.

    更新日期:2017-08-03
  • Targeting βCys93 in hemoglobin S with an antisickling agent possessing dual allosteric and antioxidant effects
    Metallomics (IF 3.975) Pub Date : 2017-07-25
    Tigist Kassa, Michael Brad Strader, Akito Nakagawa, Warren M. Zapol, Abdu I. Alayash
    更新日期:2017-08-03
  • A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity
    Metallomics (IF 3.975) Pub Date : 2017-07-18
    Ahmed Mohsen, Philippe Collery, Roselyne Garnotel, Bertrand Brassart, Nicolas Etique, Gilane Mohamed Sabry, Rasha Elsherif Hassan, Pierre Jeannesson, Didier Desmaële, Hamid Morjani
    更新日期:2017-08-03
  • Intracellular iron and heme trafficking and metabolism in developing erythroblasts.
    Metallomics (IF 3.975) Pub Date : 2017-08-01
    Martin D. Kafina, Barry H. Paw

    Vertebrate red blood cells (RBCs) arise from erythroblasts in the human bone marrow through a process known as erythropoiesis. Iron uptake is a crucial hallmark, essential for heme biosynthesis in the differentiating erythroblasts, which are dedicated to producing hemoglobin. Erythropoiesis is facilitated by a network of intracellular transport proteins, chaperones, and circulating hormones. Intracellular iron is targeted to the mitochondria for incorporation into a porphyrin ring to form heme and cytosolic iron-sulfur proteins, including Iron Regulatory Protein 1 (IRP1). These processes are tightly regulated to prevent both excess and insufficient levels of iron and heme precursors. Crosstalk between the heme and iron-sulfur synthesizing pathways has been demonstrated to serve as a regulatory feedback mechanism. The activity of δ-aminolevulinic acid synthase (ALAS), the first and rate-limiting enzyme of heme biosynthesis, is a fundamental node of this regulation. Recently, the mitochondrial unfoldase, ClpX, has received attention as a novel key player that modulates this step in heme biogenesis, implicating a role in the pathophysiology of anemic diseases. This chapter will review the canonical pathways in intracellular iron and heme trafficking and recent findings of iron and heme metabolism in vertebrate red cells. A discussion of the molecular approaches to studying iron and heme transport will be provided to highlight opportunities for revealing therapeutic targets.

    更新日期:2017-08-03
  • Downregulation of Hepatic Multi Drug Resistance Protein 1 (MDR1) after Copper Exposure
    Metallomics (IF 3.975) Pub Date : 2017-07-31
    Sara Reinartz Groba, Sarah Guttmann, Christoph Niemietz, Friedrich Bernick, Vanessa Sauer, Oliver Hachmöller, Uwe Karst, Hans Zischka, Andree Zibert, Hartmut H.-J. Schmidt

    Copper homeostasis is strictly regulated in mammalian cells. We investigated the adaptation of hepatocytes after long-term copper exposure. Copper resistant hepatoma HepG2 cell lines lacking ATP7B were generated. Growth, copper accumulation, gene expression, and transport were determined. Hepatocyte-like cells derived from a Wilson disease (WD) patient and liver of a WD animal model were also studied. The rapidly gained copper resistance was found to be stable, as subculturing of cells in the absence of added copper (weaning) did not restore copper sensitivity. Intracellular copper levels, expression of MT1 and HSP70 were increased, whereas expression of CTR1 was reduced. However, values normalized after weaning. In contrast, downregulation of multi drug resistance protein 1 (MDR1), encoding P-glycoprotein (P-gp), was shown to be permanent. Calcein assays confirmed downregulation of MDR1 in the resistant cell lines. MDR1 knockdown by siRNA resulted in increased copper resistance and decreased intracellular copper. Treatment of the resistant cells with verapamil, known inducer of MDR1, was followed by increased copper-induced toxicity. Downregulation of MDR1 was also observed in hepatocyte-like cells derived from a WD patient after copper exposure. In addition, MDR1 was downregulated in Long-Evans Cinnamon rats when liver copper was elevated. Results indicate that downregulation of MDR1 is an adaptation of hepatic cells after sustained copper exposure when ATP7B is non-functional. Our data add to the versatile functions of MDR1 in the hepatocyte and may have an impact on the treatment of copper related disease, prominently WD.

    更新日期:2017-08-03
  • Copper-finger protein of Sp1: the molecular basis of copper sensing
    Metallomics (IF 3.975) Pub Date : 2017-07-18
    Siming Yuan, Siming Chen, Zhaoyong Xi, Yangzhong Liu
    更新日期:2017-08-03
  • Metallomics: the history over the last decade and a future outlook
    Metallomics (IF 3.975) Pub Date : 2017-04-21
    Hiroki Haraguchi
    更新日期:2017-08-03
  • CHRONIC EXPOSURE TO INORGANIC MERCURY INDUCES BIOCHEMICAL AND MORPHOLOGICAL CHANGES IN SALIVARY GLANDS OF RATS
    Metallomics (IF 3.975) Pub Date : 2017-07-28
    Walessa Alana Bragança Aragão, Natacha Malu Miranda Costa, Nathalia Carolina Fernandes Fagundes, Marcia Cristina Freitas Silva, Sergio Melo Alves-Júnior, João Jesus Viana Pinheiro, Lilian Amado, Maria Elena Crespo-López, Cristiane Socorro Ferraz Maia, Rafael Rodrigues Lima

    Mercury exposure is considered a public health problem due to the generation of toxic effects on human health as a result from environmental and occupational conditions. The inorganic form of mercury (HgCl2) can cause several biological changes in cells and tissues through its cumulative toxic potential, but little has been experimentally proven about the effects of inorganic mercury on salivary glands, an important modulator organ of oral health. This study analyzes the effects of prolonged low dose exposure to HgCl2 on the salivary glands of rats. Adult animals received a dose of 0.375mg/kg/day over a period of 45 days. The parotid and submandibular glands were collected for analysis of mercury levels and evaluation of oxidative stress, histological parameters and immunomodulation for Metallothionein I and II (MT- I/II). In this investigation, biochemical and tissue changes in salivary glands were verified due to mercury levels, causing reduction in antioxidant capacity against peroxyl radicals , with consequent cellular lipid peroxidation and an increase in nitrite levels, volumetric changes and cytoskeletal damage in submandibular glands, with less severe damage to parotid glands. The results also have shown the occurrence of a cytoprotection mechanism due to increased MT-I/II expression, but not enough to avoid the morphology and oxidative damage. This evidence highlights, for the first time, that inorganic mercury is able to alter morphology and oxidative biochemistry in salivary glands when exposed for a long time in low doses.

    更新日期:2017-08-03
  • Characterization of a highly efficient antibiotic-degrading metallo-β-lactamase obtained from an uncultured member of a permafrost community
    Metallomics (IF 3.975) Pub Date : 2017-07-18
    Marcelo Monteiro Pedroso, Christopher Selleck, Charmaine Enculescu, Jeffrey R. Harmer, Nataša Mitić, Whitney R. Craig, Waleed Helweh, Philip Hugenholtz, Gene W. Tyson, David L. Tierney, James A. Larrabee, Gerhard Schenk
    更新日期:2017-08-03
  • 更新日期:2017-08-03
  • Targeting βCys93 in hemoglobin S with an antisickling agent possessing dual allosteric and antioxidant effects
    Metallomics (IF 3.975) Pub Date : 2017-07-25
    TIGIST KASSA, MICHAEL BRAD STRADER, AKITO NAKAGAWA, A. Alayash, WARREN M. ZAPOL

    Sickle cell disease (SCD) is an inherited blood disorder caused by a β globin gene mutation of hemoglobin (HbS). Polymerization of deoxyHbS and subsequent aggregation (into long fibers) is the primary molecular event which leads to red blood cell (RBC) sickling and ultimately hemolytic anemia. We have recently suggested that HbS oxidative toxicity may also contribute to SCD pathophysiology due to its defective pseudoperoxidase activity. As a consequence, a persistent higher oxidization ferryl heme is formed which irreversibly oxidizes “hotspot” residues (particularly βCys93) causing protein unfolding and subsequent heme loss. In this report we confirmed first, the allosteric effect of a newly developed reagent (Di(5-(2,3-dihydro-1,4-benzodioxin-2-yl)- 4H-1,2,4-triazol- 3-yl)disulfide (TD-1) on oxygen affinity within SS RBCs. There was a considerable left shift in oxygen equilibrium curves (OECs) representing treated SS cells. Under hypoxic conditions, TD-1 treatment of HbS resulted in approximately 200 sec increase in the delay time of HbS polymerization over the untreated HbS control. The effect of TD-1 binding to HbS was tested next on oxidative reactions by incrementally treating HbS with increasing hydrogen peroxide (H2O2) concentrations. Under these experimental conditions, ferryl levels were consistently reduced by approximately 35% in the presence of TD-1. Mass spectrometric analysis confirmed that upon binding to Cys93, TD-1 effectively blocked irreversible oxidation of this residue. In conclusion, TD-1 appears to shield βCys93, the end point of radical formation in HbS, and when coupled with its modification of oxygen affinity it may provide new therapeutic modalities for the treatment of SCD.

    更新日期:2017-08-03
  • Ferrocene–cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel
    Metallomics (IF 3.975) Pub Date : 2017-07-13
    Ana Podolski-Renić, Szilvia Bősze, Jelena Dinić, László Kocsis, Ferenc Hudecz, Antal Csámpai, Milica Pešić
    更新日期:2017-08-03
  • Whole blood Fe isotopic signature in a sub-Saharan African population
    Metallomics (IF 3.975) Pub Date : 2017-07-13
    Justin C. Cikomola, María R. Flórez, Marta Costas-Rodríguez, Yulia Anoshkina, Karl Vandepoele, Philippe B. Katchunga, Antoine S. Kishabongo, Marijn M. Speeckaert, Frank Vanhaecke, Joris R. Delanghe
    更新日期:2017-08-03
  • Schizosaccharomyces pombe Grx4 regulates the transcriptional repressor Php4 via [2Fe–2S] cluster binding
    Metallomics (IF 3.975) Pub Date : 2017-07-12
    Adrienne C. Dlouhy, Jude Beaudoin, Simon Labbé, Caryn E. Outten
    更新日期:2017-08-03
  • Activation of Nrf2/ARE signaling pathway attenuates lanthanum chloride induced injuries in primary rat astrocytes
    Metallomics (IF 3.975) Pub Date : 2017-07-04
    Lijin Zhang, Jinghua Yang, Shengwen Wu, Cuihong Jin, Xiaobo Lu, Xiaoyu Hu, Yaling Sun, Xiang Gao, Yuan Cai
    更新日期:2017-08-03
  • Correction: Arbuscular mycorrhizal fungi enhance the copper tolerance of Tagetes patula through the sorption and barrier mechanisms of intraradical hyphae
    Metallomics (IF 3.975) Pub Date : 2017-06-29
    Xishi Zhou, Lei Fu, Yan Xia, Luqing Zheng, Chen Chen, Zhenguo Shen, Yahua Chen

    Correction for ‘Arbuscular mycorrhizal fungi enhance the copper tolerance of Tagetes patula through the sorption and barrier mechanisms of intraradical hyphae’ by Xishi Zhou et al., Metallomics, 2017, DOI: 10.1039/c7mt00072c.

    更新日期:2017-08-03
  • Iron homeostasis in plants – a brief overview
    Metallomics (IF 3.975) Pub Date : 2017-06-28
    James M. Connorton, Janneke Balk, Jorge Rodríguez-Celma
    更新日期:2017-08-03
  • Probing functional roles of Wilson disease protein (ATP7B) copper-binding domains in yeast
    Metallomics (IF 3.975) Pub Date : 2017-06-21
    Kumaravel Ponnandai Shanmugavel, Dina Petranovic, Pernilla Wittung-Stafshede
    更新日期:2017-08-03
  • BRUTUS and its paralogs, BTS LIKE1 and BTS LIKE2, encode important negative regulators of the iron deficiency response in Arabidopsis thaliana
    Metallomics (IF 3.975) Pub Date : 2017-06-16
    Maria N. Hindt, Garo Z. Akmakjian, Kara L. Pivarski, Tracy Punshon, Ivan Baxter, David E. Salt, Mary Lou Guerinot
    更新日期:2017-08-03
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
所有期刊列表A-Z