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Metallomics: Integrated Biometal Science

Youxian Li, Man He, Beibei Chen, Bin Hu
As is well-known, arsenite (As(iii)) is a human carcinogen associated with many human cancers. As(iii) can act as a co-carcinogen to induce DNA damage with other carcinogens. Benzo(a)pyrene diol epoxide (BPDE) is one of the most-studied environmental carcinogens, which exists ubiquitously in our daily life. The elucidation of the mechanism of As(iii) as a co-carcinogen with BDPE in cells causing genotoxicity is beneficial for the evaluation of its bioeffect. In this study, a comprehensive analytical system is used for DNA damage evaluation, BPDE-DNA adduct detection, arsenic speciation and gene expression analysis...
November 15, 2018: Metallomics: Integrated Biometal Science
Rene M Boiteau, Sarah J Fansler, Yuliya Farris, Jared B Shaw, David W Koppenaal, Ljiljana Pasa-Tolic, Janet K Jansson
The chemical structure of organic molecules profoundly impacts their interactions with metal ions and mineral phases in soils. Understanding the sources and cycling of metal-chelating compounds is therefore essential for predicting the bioavailability and transport of metals throughout terrestrial environments. Here we investigate the molecular speciation of organic molecules that solubilize trace metals in calcareous soils from Eastern Washington. Ultra-high performance Fourier transform ion cyclotron resonance mass spectrometry at 21 Tesla enabled fast and confident detection and identification of metal chelators that are produced by microbes that inhabit these soils based on screening for features that match diagnostic metal isotope patterns...
November 14, 2018: Metallomics: Integrated Biometal Science
Jenifer S Calvo, Victor M Lopez, Gabriele Meloni
Mammalian metallothioneins (MT-1 through MT-4) are a class of metal binding proteins containing two metal-thiolate clusters formed through the preferential coordination of d10 metals, Cu(i) and Zn(ii), by 20 conserved cysteine residues located in two protein domains. MT metalation (homometallic or heterometallic Zn(ii)/Cu(i) species) appears to be isoform specific and controlling zinc and copper concentrations to perform specific and distinct biological functions. Structural and functional relationships, and in vivo metalation studies, identified evolutionary features defining the metal-selectivity nature for MTs...
November 13, 2018: Metallomics: Integrated Biometal Science
M J Hackett, A Hollings, S Caine, B E Bewer, M Alaverdashvili, R Takechi, J C L Mamo, M W M Jones, M D de Jonge, P G Paterson, I J Pickering, G N George
A unique combination of sensitivity, resolution, and penetration make X-ray fluorescence imaging (XFI) ideally suited to investigate trace elemental distributions in the biological context. XFI has gained widespread use as an analytical technique in the biological sciences, and in particular enables exciting new avenues of research in the field of neuroscience. In this study, elemental mapping by XFI was applied to characterise the elemental content within neuronal cell layers of hippocampal sub-regions of mice and rats...
November 6, 2018: Metallomics: Integrated Biometal Science
Mireia Tomàs Giner, Elena Jiménez-Martí, Roger Bofill Arasa, Anna Tinti, Michele Di Foggia, Chryssostomos Chatgilialoglu, Armida Torreggiani
Metallothioneins are small Cys-rich peptides capable of coordinating metal ions, and proposed to be involved in radical stress. The four Zn(ii)-GmMT complexes of soybean (Glycine max) were recombinantly synthesised and exposed to oxidative (HO˙) and reductive (H˙ atoms and eaq-) stress conditions. Gamma-irradiation was used to simulate the endogenous formation of the reactive species in both aqueous solutions and unsaturated lipid vesicle suspensions, a biomimetic model that showed that tandem protein/lipid damage occurs, in particular under reductive radical stress...
November 6, 2018: Metallomics: Integrated Biometal Science
Yirong Wang, Erin Weisenhorn, Colin W MacDiarmid, Claudia Andreini, Michael Bucci, Janet Taggart, Lucia Banci, Jason Russell, Joshua J Coon, David J Eide
Zinc is an essential cofactor for many proteins. A key mechanism of zinc homeostasis during deficiency is "zinc sparing" in which specific zinc-binding proteins are repressed to reduce the cellular requirement. In this report, we evaluated zinc sparing across the zinc proteome of Saccharomyces cerevisiae. The yeast zinc proteome of 582 known or potential zinc-binding proteins was identified using a bioinformatics analysis that combined global domain searches with local motif searches. Protein abundance was determined by mass spectrometry...
October 25, 2018: Metallomics: Integrated Biometal Science
Erik L Jensen, Alvaro M Gonzalez-Ibanez, Pierina Mendoza, Lina M Ruiz, Claudia A Riedel, Felipe Simon, Jan J Schuringa, Alvaro A Elorza
The lack of copper has been associated with anemia, myelodysplastic syndromes and leukemia as well as with a loss in complex IV activity and an enlarged mitochondrial morphology. Mitochondria play a key role during the differentiation of hematopoietic stem cells by regulating the passage from a glycolytic to oxidative metabolism. The former is associated with cell proliferation and the latter with cell differentiation. Oxidative metabolism, which occurs inside mitochondria, is sustained by the respiratory chain, where complex IV is copper-dependent...
October 25, 2018: Metallomics: Integrated Biometal Science
Clara Balsano, Cristiana Porcu, Silvia Sideri
Altered regulation of copper (Cu) homeostasis may contribute to the development of many pathologies, such as metabolic, cardiovascular, neurodegenerative and cancerous diseases. Cu serum concentrations are strictly related to oxidative stress. During the past decade, it has been well demonstrated that even marginal deficits of this element contribute to development and progression of a number of chronic diseases. On the other hand, an excess of Cu may become a potent oxidant causing the generation of reactive oxygen species (ROS) and leading to the formation of macromolecules dangerous to health...
October 19, 2018: Metallomics: Integrated Biometal Science
Louisa J Stewart, Denis Thaqi, Bostjan Kobe, Alastair G McEwan, Kevin J Waldron, Karrera Y Djoko
In bacteria, copper (Cu) is often recognised for its potential toxicity and its antibacterial activity is now considered a key component of the mammalian innate immune system. Cu ions bound in weak sites can catalyse harmful redox reactions while Cu ions in strong but adventitious sites can disrupt protein or enzyme function. For these reasons, the outward transport of Cu from bacteria has received significant attention. Yet, Cu is also a bacterial nutrient, required as a cofactor by enzymes that catalyse electron transfer processes, for instance in aerobic and anaerobic respiration...
October 18, 2018: Metallomics: Integrated Biometal Science
Christian Martín Saporito-Magriñá, Rosario Natalia Musacco-Sebio, Geoffroy Andrieux, Lucas Kook, Manuel Tomás Orrego, María Victoria Tuttolomondo, Martín Federico Desimone, Melanie Boerries, Christoph Borner, Marisa Gabriela Repetto
Copper (Cu) is a bioelement essential for a myriad of enzymatic reactions, which when present in high concentration leads to cytotoxicity. Whereas Cu toxicity is usually assumed to originate from the metal's ability to enhance lipid peroxidation, the role of oxidative stress has remained uncertain since no antioxidant therapy has ever been effective. Here we show that Cu overload induces cell death independently of the metal's ability to oxidize the intracellular milieu. In fact, cells neither lose control of their thiol homeostasis until briefly before the onset of cell death, nor trigger a consistent antioxidant response...
October 12, 2018: Metallomics: Integrated Biometal Science
C Abbehausen
Zinc finger proteins are one of the most abundant families of proteins and present a wide range of structures and functions. The structural zinc ion provides the correct conformation to specifically recognize DNA, RNA and protein sequences. Zinc fingers have essential functions in transcription, protein degradation, DNA repair, cell migration, and others. Recently, reports on the extensive participation of zinc fingers in disease have been published. On the other hand, much information remains to be unravelled as many genomes and proteomes are being reported...
October 10, 2018: Metallomics: Integrated Biometal Science
Michael J Stevenson, Kylie S Uyeda, Nathaniel H O Harder, Marie C Heffern
For over 100 years, there has been an incredible amount of knowledge amassed concerning hormones in the endocrine system and their central role in human health. Hormones represent a diverse group of biomolecules that are released by glands, communicate signals to their target tissue, and are regulated by feedback loops to maintain organism health. Many disease states, such as diabetes and reproductive disorders, stem from misregulation or dysfunction of hormones. Increasing research is illuminating the intricate roles of metal ions in the endocrine system where they may act advantageously in concert with hormones or deleteriously catalyze hormone-associated disease states...
October 1, 2018: Metallomics: Integrated Biometal Science
K Kysenius, J B Hilton, B Paul, D J Hare, P J Crouch
Mutations in the copper (Cu)- and zinc (Zn)-binding metalloenzyme Cu/Zn-superoxide dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS), a fatal adult-onset neurodegenerative disorder of the central nervous system (CNS). Transgenic over-expression of mutant SOD1 produces a robust ALS-like phenotype in mice. Despite being ubiquitously expressed from the moment of conception, the mechanisms underlying the CNS-selective phenotype of mutant SOD1 expression remain poorly understood. We have previously shown that the physiological requirement for copper in SOD1 is unsatiated in the CNS of adult mice overexpressing mutant SOD1 and that suboptimal delivery of Cu to SOD1 in these mice progressively worsens with age...
September 26, 2018: Metallomics: Integrated Biometal Science
Iñaki Gentile, Hugo A Garro, Susana Delgado Ocaña, Nazareno Gonzalez, Timo Strohäker, Daniela Schibich, Liliana Quintanar, Luis Sambrotta, Markus Zweckstetter, Christian Griesinger, Mauricio Menacho Márquez, Claudio O Fernández
The identity of the Cu(i) binding ligands at Met-X3-Met site of AcαS and its role into the affinity and structural properties of the interaction were elucidated by NMR spectroscopy. We provide evidence that the source of ligands for Cu(i) binding to the Met-X3-Met site comes from the N-terminal acetyl group and the Met-1, Asp-2 and Met-5 residues. From the study of site-directed mutants and synthetic peptide models of αS we demonstrated the critical role played by Met-1 and Met-5 residues on the binding affinity of the Cu(i) complex, acting as the main metal anchoring residues...
September 24, 2018: Metallomics: Integrated Biometal Science
Monika Rana, Anuj Kumar Sharma
The coordination chemistry of transition metal ions (Fe, Cu, Zn) with the amyloid-β (Aβ) peptides has attracted a lot of attention in recent years due to its repercussions in Alzheimer's disease (AD). Aβ peptide undergoes self-aggregation to form amyloid plaques and soluble oligomers, which are believed to play a central role in AD pathology. Metal ions and Aβ-metal adducts can generate toxic radical species capable of modifying biomolecules, ultimately causing death of the neuronal cells. The impact of these metal ions on Aβ aggregation and neurotoxic species formation is still not well understood...
September 20, 2018: Metallomics: Integrated Biometal Science
Anna Espart, Sebastián Artime, Glòria Tort-Nasarre, Edinson Yara-Varón
Cadmium (Cd) is a non-physiological heavy metal that can be harmful at low concentrations. Increasing anthropogenic activities are incrementing the risk of accumulation of this heavy metal in different organs and tissues of the body. In the case of pregnant women, the threat is more serious due to the implications affecting not only their own health but also fetal development as well. Metallothioneins (MTs), small cysteine-rich proteins, are involved in zinc (Zn) and copper homeostasis in mammals but can, however, also bind with Cd if present...
September 17, 2018: Metallomics: Integrated Biometal Science
Tasuku Hirayama, Ayaji Miki, Hideko Nagasawa
Ferroptosis is an emerging type of cell death mode that is dependent on iron. Unfortunately, the detailed analysis of the function of organelle labile Fe(ii) in oxidative damage and lethality of the cells has not been demonstrated so far, mainly due to the lack of efficient methods to visualize labile Fe(ii) at the targeted organelles. We have recently reported a series of Fe(ii)-selective fluorescent probes, i.e., Ac-MtFluNox, Lyso-RhoNox, and ER-SiRhoNox, which can detect Fe(ii) specifically in the mitochondria, lysosomes, and endoplasmic reticulum (ER), respectively...
September 14, 2018: Metallomics: Integrated Biometal Science
Changjun Fan, Guangliang Liu, Yanmin Long, Barry Rosen, Yong Cai
In recent years, methylated thioarsenicals have been widely detected in various biological and environmental matrices, suggesting their broad involvement and biological importance in arsenic metabolism. However, very little is known about the formation mechanism of methylated thioarsenicals and the relation between arsenic methylation and thiolation processes. It is timely and necessary to summarize and synthesize the reported information on thiolated arsenicals for an improved understanding of arsenic thiolation...
September 12, 2018: Metallomics: Integrated Biometal Science
Takaaki Aratake, Youichirou Higashi, Yusuke Ueba, Tomoya Hamada, Takahiro Shimizu, Shogo Shimizu, Toshio Yawata, Tetsuya Ueba, Motoaki Saito
Microglia, the resident immune cells of the central nervous system, can display a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype. Arginase (Arg)-1 expressed in interleukin-4 (IL-4)-induced M2 microglia reduces nitric oxide (NO) production by competing with inducible NO synthase for l-arginine, which contributes to the attenuation of brain inflammation. Although previous studies have indicated that brain zinc promotes M1 activation, the effect of zinc on M2 microglial activation remains to be determined...
September 12, 2018: Metallomics: Integrated Biometal Science
Jianfa Wang, Zhe Liu, Xianjing He, Shuai Lian, Jianbin Liang, Debin Yu, Dongbo Sun, Rui Wu
Selenium (Se) is an important nutritional trace element possessing antioxidant properties. Our goal was to elucidate the effect and mechanism of Se deficiency on the intestinal cell fate. One-day-old three-yellow chickens were fed a low Se diet for 1, 3, and 5 weeks. Histologic characteristics, protein expression profiles, antioxidant activities, inflammatory signaling, and the apoptosis status in duodenum mucosa were investigated. Histological results showed that Se deficiency could increase inflammatory cell infiltration, karyopyknosis of the epithelial cells, cytoplasm vacuolization and dissolution of goblet cells...
September 12, 2018: Metallomics: Integrated Biometal Science
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