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Metallomics: Integrated Biometal Science

Agnieszka Belczyk-Ciesielska, Brigitta Csipak, Bálint Hajdu, Aleksandra Sparavier, Masamitsu N Asaka, Kyosuke Nagata, Béla Gyurcsik, Wojciech Bal
In this work we demonstrate that the previously described reaction of sequence specific Ni(ii)-dependent hydrolytic peptide bond cleavage can be performed in complex metalloprotein molecules, such as the Cys2His2 zinc finger proteins. The cleavage within a zinc finger unit possessing a (Ser/Thr)-X-His sequence is not hindered by the presence of the Zn(ii) ions. It results in loss of the Zn(ii) ion, oxidation of the SH groups and thus, in a collapse of the functional structure. We show that such natural Ni(ii)-cleavage sites in zinc finger domains can be edited out without compromising the DNA binding specificity...
July 16, 2018: Metallomics: Integrated Biometal Science
Pallavi Chandwadkar, Hari Sharan Misra, Celin Acharya
It has become increasingly apparent that the environmental microorganisms residing in uranium (U) enriched sites offer the possibility of understanding the biological mechanisms catalyzing the processes important for uranium bioremediation. Here, we present the results of uranium biomineralization over a wide pH range by a metal tolerant Serratia sp. strain OT II 7 isolated from the subsurface soil of a U ore deposit at Domiasiat in India. The Serratia cells actively expressed acid and alkaline phosphatase enzymes which hydrolyzed differential amounts of phosphate from an organophosphate substrate in the presence of uranium between pH 5 to 9...
July 12, 2018: Metallomics: Integrated Biometal Science
Qixiao Zhai, Yue Xiao, Arjan Narbad, Wei Chen
Our previous work demonstrated the protective effects of Lactobacillus plantarum (L. plantarum) strains against cadmium (Cd) toxicity in vivo, and also indicated that the Cd tolerance of the strains played an important role in this protection. The goal of this study was to investigate the Cd resistance mechanism of L. plantarum by liquid chromatography-mass spectrometry (LC-MS) based metabolomic analysis, with a focus on the global Cd stress response. L. plantarum CCFM8610 (strongly resistant to Cd) and L. plantarum CCFM191 (sensitive to Cd) were selected as target strains, and their metabolomic profiles with and without Cd exposure were compared...
July 12, 2018: Metallomics: Integrated Biometal Science
Charles E Zogzas, Somshuvra Mukhopadhyay
SLC30 proteins belong to the cation diffusion facilitator (CDF) superfamily of metal transporters. SLC30A10 mediates manganese efflux, while other SLC30 members transport zinc. Metal specificity of CDFs may be conferred by amino acids that form a transmembrane metal binding site (Site A). Site A of zinc-transporting CDFs, such as SLC30A1/ZnT1, have a HXXXD motif, but manganese transporters, such as SLC30A10, harbor a NXXXD motif. This critical histidine-to-asparagine substitution, at residue 43, was proposed to underlie manganese transport specificity of SLC30A10...
July 10, 2018: Metallomics: Integrated Biometal Science
Yaling Sun, Jinghua Yang, Xiaoyu Hu, Xiang Gao, Yingqi Li, Miao Yu, Shiyu Liu, Yanxin Lu, Jing Wang, Liling Huang, Xiaobo Lu, Cuihong Jin, Shengwen Wu, Yuan Cai
Lanthanum (La) can accumulate in the brain and impair learning and memory. However, the underlying mechanism of La-induced neurotoxicity has remained elusive. Under physiological conditions, it has been reported that moderately excitatory astrocytes play an important role in the regulation of neuronal signals and synaptic plasticity. However, under pathological conditions, overly excitatory astrocytes can release excess excitatory transmitters, such as glutamate (Glu) and d-serine, and induce the over-activation of NMDA receptors (NMDAR) in neurons, ultimately leading to neuronal excitotoxicity...
July 10, 2018: Metallomics: Integrated Biometal Science
Ana V Vujačić Nikezić, Goran V Janjić, Aleksandra M BondŽić, BoŽidarka L Zarić, Dragana D Vasić-Anićijević, Tatjana G Momić, Vesna M Vasić
The present paper deals with investigation of the interaction between selected simple structure Au(iii) ([AuCl4]-, [AuCl2(dmso)2]+, [AuCl2(bipy)]+) and Pt(ii) ([PtCl2(dmso)2]) complexes with Na/K-ATPase as the target enzyme, using an experimental and theoretical approach. Reaction stoichiometries and binding constants for these enzyme/complex systems were determined, while kinetic measurements were used in order to reveal the type of inhibition. Based on the results obtained by quantum mechanical calculations (electrostatic surface potential (ESP), volume and surface of the complexes) the nature of the investigated complexes was characterized...
July 6, 2018: Metallomics: Integrated Biometal Science
Hamid Sattar, Jie Yang, Xia Zhao, Jingzeng Cai, Qi Liu, Muhammad Ishfaq, Zijiang Yang, Menghao Chen, Ziwei Zhang, Shiwen Xu
Selenium (Se) is a major component of male reproduction which exerts its effects via selenoproteins. Selenoprotein U (SelU), a newly identified protein, is expressed highly in eukaryotes and possesses a conserved motif similar to that existing in other thiol-dependent redox regulating selenoproteins; however its function is unknown. To investigate the role of SelU in testis autophagic and/or apoptosis cell death mechanisms, we established a Sertoli cell (SC) model isolated from 45 day old layer roosters. Small interfering RNA (siRNA) technology was used to develop SelU-knockdown (SelU-KD) and normal (N) SC models...
July 2, 2018: Metallomics: Integrated Biometal Science
Juana Pérez, José Muñoz-Dorado, Aurelio Moraleda-Muñoz
The complex copper response of the multicellular proteobacterium M. xanthus includes structural genes similar to those described in other bacteria, such as P1B-type ATPases, multicopper oxidases, and heavy metal efflux systems. However, the two time-dependent expression profiles of the different copper systems are unique. There are a number of genes responsible for an immediate response, whose expression increases after the addition of copper, but rapidly decreases thereafter to basal levels. The regulatory element that controls this early response is CorE, a novel extracytoplasmic function σ factor that is activated by Cu2+ and inactivated by Cu+...
July 2, 2018: Metallomics: Integrated Biometal Science
Alexandrea E Sestok, Richard O Linkous, Aaron T Smith
Virtually all organisms require iron and have evolved to obtain this element in free or chelated forms. Under anaerobic or low pH conditions commonly encountered by numerous pathogens, iron predominantly exists in the ferrous (Fe2+) form. The ferrous iron transport (Feo) system is the only widespread mechanism dedicated solely to bacterial ferrous iron import, and this system has been linked to pathogenic virulence, bacterial colonization, and microbial survival. The canonical feo operon encodes for three proteins that comprise the Feo system: FeoA, a small cytoplasmic β-barrel protein; FeoB, a large, polytopic membrane protein with a soluble G-protein domain capable of hydrolyzing GTP; and FeoC, a small, cytoplasmic protein containing a winged-helix motif...
June 28, 2018: Metallomics: Integrated Biometal Science
Lucia Merolle, Gerhard Sponder, Azzurra Sargenti, Lucia Mastrototaro, Concettina Cappadone, Giovanna Farruggia, Alessandra Procopio, Emil Malucelli, Pietro Parisse, Alessandra Gianoncelli, Jörg R Aschenbach, Martin Kolisek, Stefano Iotti
The mechanism of action of the mitochondrial Mg channel MRS2 and its involvement in cell viability remain unclear. Deletion of MRS2 has been reported to abolish Mg influx into mitochondria, to induce functional defects in mitochondrial organelles, and to result in cell death. We evaluated whether MRS2 expression had an impact on total Mg cellular content by inducing the overexpression of MRS2 in HEK-293 cells. We observed a remarkable increase of total intracellular Mg concentration in cells overexpressing MRS2 compared with control cells...
June 28, 2018: Metallomics: Integrated Biometal Science
Elena G Salina, Stanislav Huszár, Júlia Zemanová, Jan Keruchenko, Olga Riabova, Elena Kazakova, Artyom Grigorov, Tatyana Azhikina, Arseny Kaprelyants, Katarína Mikušová, Vadim Makarov
With the emerging primary resistance of Mycobacterium tuberculosis to current drugs and wide distribution of latent tuberculosis infection, the need for new compounds with a novel mode of action is growing. Copper-mediated innate immunity and its antibacterial toxicity pose novel strategies for tuberculosis drug discovery and development. Transcriptome response to 1-hydroxy-5-R-pyridine-2(1H)-thiones, which were found to be highly active in vitro against actively growing and dormant nonculturable M. tuberculosis, revealed signs of copper toxicity...
June 27, 2018: Metallomics: Integrated Biometal Science
Thao V Nguyen, Andrea C Alfaro, Fabrice Merien, Ronald Lulijwa, Tim Young
Copper is a common contaminant in aquatic environments, which may cause physiological dysfunction in marine organisms. However, the toxicity mechanisms of copper in marine bivalves is not fully understood. In this study, we applied an integrated approach that combines flow cytometry and Gas Chromatography-Mass Spectrometry (GC-MS)-based metabolomics to characterize cellular and molecular mechanisms of copper immunotoxicity in New Zealand Greenshell™ mussel (Perna canaliculus) haemolymph. Flow cytometric results showed significant increases in haemocyte mortality, production of reactive oxygen species and apoptosis (via alteration of caspase 3/7 and mitochondrial membrane potential) of haemocytes exposed to increasing total concentrations of Cu2+ (62...
June 22, 2018: Metallomics: Integrated Biometal Science
Maria Maares, Ayşe Duman, Claudia Keil, Tanja Schwerdtle, Hajo Haase
The molecular mechanisms of intestinal zinc resorption and its regulation are still topics of ongoing research. To this end, the application of suitable in vitro intestinal models, optimized with regard to their cellular composition and medium constituents, is of crucial importance. As one vital aspect, the impact of cell culture media or buffer compounds, respectively, on the speciation and cellular availability of zinc has to be considered when investigating zinc resorption. Thus, the present study aims to investigate the impact of serum, and in particular its main constituent serum albumin, on zinc uptake and toxicity in the intestinal cell line Caco-2...
June 22, 2018: Metallomics: Integrated Biometal Science
Xiangrong Geng, Liu Liu, Amy Banes-Berceli, Zhouyuan Yang, Pengde Kang, Jian Shen, Kan-Jen Tsai, Zijuan Liu
ZIP8 is a recently identified membrane transporter which facilitates uptake of many substrates including both essential and toxic divalent metals (e.g. zinc, manganese, iron, cadmium) and inorganic selenium. Many ZIP8 regulated downstream signals and pathways remain to be elucidated. In this study, we investigated ZIP8 regulatory roles in downstream targets in ZIP8-gain and loss cells and in ZIP8 overexpressed lungs. Our results show that the overexpression of ZIP8 in mouse fibroblast cells (MEF) induces significant morphological change and re-organization of filament actin (F-actin), along with increased cell proliferation and migration rate...
June 21, 2018: Metallomics: Integrated Biometal Science
Huanhuan Lv, Peng Shang
The labile iron pool (LIP) is a pool of chelatable and redox-active iron, not only essential for a wide variety of metabolic process, but also as a catalyst in the Fenton reaction, causing the release of hazardous reactive oxygen species (ROS) with potential for inducing oxidative stress and cell damage. The cellular LIP represents the entirety of every heterogenous sub-pool of iron, not only present in the cytosol, but also in mitochondria, lysosomes and the nucleus, which have all been detected and characterized by various fluorescent methods...
June 20, 2018: Metallomics: Integrated Biometal Science
Rui-Feng Fan, Chang-Yu Cao, Meng-Hao Chen, Qun-Xiang Shi, Shi-Wen Xu
Selenoprotein K (SELENOK) is primarily observed in the endoplasmic reticulum, and serves to maintain the normal physiological functions of skeletal muscle. Skeletal muscle development and regeneration are associated with significant changes in the expression of specific microRNAs (miRNAs). Downregulated SELENOK expression is observed in chicken muscles deficient of Se. However, the mechanisms of miRNA regulation of SELENOK expression remain elusive. Here, deep sequencing was used to detect the miRNA profiles of muscle in Se deficient (-Se group) and normal (C group) chickens...
June 15, 2018: Metallomics: Integrated Biometal Science
Aliabbas A Saleh, Gary W Jones, Frances C Tinley, Stephen F Delaney, Sahar H Alabbadi, Keith Fenlon, Sean Doyle, Rebecca A Owens
The non-ribosomal peptide gliotoxin, which autoinduces its own biosynthesis, has potent anti-fungal activity, especially in the combined absence of the gliotoxin oxidoreductase GliT and bis-thiomethyltransferase GtmA. Dithiol gliotoxin (DTG) is a substrate for both of these enzymes. Herein we demonstrate that DTG chelates Zn2+ (m/z 424.94), rapidly chelates Zn2+ from Zn(4-(2-pyridylazo)-resorcinol) (Zn(PAR)2) and also inhibits a Zn2+-dependent alkaline phosphatase (AP). Zn2+ addition rescues AP function following DTG-associated inhibition, and pre-incubation of DTG with Zn2+ completely protects AP activity...
June 13, 2018: Metallomics: Integrated Biometal Science
Pengcheng Sun, Song Wang, Jian Wang, Jing Sun, Min Peng, Ping Shi
Chemerin exhibits a tumor-inhibitory role in hepatocellular carcinoma. However, the effect of chemerin on essential metal elements in hepatic cells remains unclear. In our study, the contents of six important metal ions, including potassium, calcium, sodium, magnesium, iron and zinc, were detected in human hepatoma SMMC7721 and immortal hepatic QSG7701 cells by ICP-AES. The data showed that chemerin only decreases the content of intracellular iron in SMMC7721 cells. The reduction was due to the blockage of iron entry through the decrease in the mRNA levels of divalent metal transporter 1, iron regulatory proteins and transferrin receptors...
June 20, 2018: Metallomics: Integrated Biometal Science
Stuart D Portbury, Dominic J Hare, David P Bishop, David I Finkelstein, Philip A Doble, Paul A Adlard
Zinc (Zn) deficiency is a clinical consequence of brain injury that can result in neuropathological outcomes that are exacerbated with age. Here, we present laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging data showing modulation of brain Zn levels by the disaccharide trehalose in aged mice following a controlled cortical impact model of traumatic brain injury. In this proof-of-concept study, trehalose induced an increase in brain zinc levels, providing important preliminary data for larger studies using this simple carbohydrate as a modulator of this essential micronutrient in traumatic brain injury...
June 20, 2018: Metallomics: Integrated Biometal Science
Tasuku Hirayama, Satoki Kadota, Masato Niwa, Hideko Nagasawa
Mitochondria are iron-rich organelles that are involved in the process of energy production through the electron-transporting system and heme synthesis. We developed a new mitochondria-targeted fluorescent probe, MtFluNox/Ac-MtFluNox, for Fe(ii) based on N-oxide chemistry, which we recently established as a Fe(ii)-selective fluorogenic switch. The deacetylated form MtFluNox showed a turn-on response towards Fe(ii) with high metal selectivity in cuvette experiments, and an imaging study using its cell-compatible analogue Ac-MtFluNox demonstrated mitochondria-specific fluorescence enhancement in response to Fe(ii) in living cells...
June 20, 2018: Metallomics: Integrated Biometal Science
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