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Metallomics: Integrated Biometal Science

Olivier Reelfs, Vincenzo Abbate, Agostino Cilibrizzi, Mark A Pook, Robert C Hider, Charareh Pourzand
Mitochondrial labile iron (LI) is a major contributor to the susceptibility of skin fibroblasts to ultraviolet A (UVA)-induced oxidative damage leading to necrotic cell death via ATP depletion. Mitochondria iron overload is a key feature of the neurodegenerative disease Friedreich's ataxia (FRDA). Here we show that cultured primary skin fibroblasts from FRDA patients are 4 to 10-fold more sensitive to UVA-induced death than their healthy counterparts. We demonstrate that FRDA cells display higher levels of mitochondrial LI (up to 6-fold on average compared to healthy counterparts) and show higher increase in mitochondrial reactive oxygen species (ROS) generation after UVA irradiation (up to 2-fold on average), consistent with their differential sensitivity to UVA...
February 19, 2019: Metallomics: Integrated Biometal Science
Ankur Jamwal, Yusuf Saibu, Tracy C MacDonald, Graham N George, Som Niyogi
The interactive effects of different doses of dietary selenium [as selenomethionine; 1.8 μg g-1 (control), 10 μg g-1 and 40 μg g-1 diet] on the toxicity of dietary arsenic [as arsenite (As3+); 80 μg As per g diet] were investigated in rainbow trout over an exposure period of 30 days. Fish fed with As3+ alone showed an increased hepatic lipid peroxidation (LPO) and a concomitant decline in cellular redox potential (determined as GSH:GSSG) in the liver tissue relative to the control fish. Interestingly, fish fed with low (10 μg g-1) or high (40 μg g-1) concentration of dietary selenomethionine in combination with As3+ showed an even higher degree of hepatic LPO and a further decrease in GSH : GSSG molar ratio relative to the fish treated with As3+ alone...
February 14, 2019: Metallomics: Integrated Biometal Science
Chunyan Fu, Junhong Lizhao, Zhenghui Luo, Tao Wang, Craig A Grapperhaus, Xueqin Ding, Y James Kang
Myocardial ischemia leads to copper efflux from the heart. The ischemic tissue with a low copper content fails to take up copper from the circulation even under the conditions of serum copper elevation. Cardiac copper repletion thus requires other available forms of this element than those currently known to bind to copper transport proteins. The copper complex of triethylenetetramine (TETA) is a metabolite of TETA, which has the potential to increase cardiac copper content in vivo. In the present study, we synthesized Cu(ii)-TETA, analyzed its crystal structure, and demonstrated the role of this compound in facilitating copper accumulation in primary cultures of neonatal rat cardiomyocytes...
February 14, 2019: Metallomics: Integrated Biometal Science
Michał Nowakowski, Joanna Czapla-Masztafiak, Igor Zhukov, Lilia Zhukova, Maciej Kozak, Wojciech M Kwiatek
Human prion protein is a subject of extensive study, related in particular to the molecular basis of neurodegenerative disease development and prevention. This protein has two main domains: the membrane C-terminal, structured domain as well as the unstructured N-terminal domain. While PrPC (23-231) has up to eight Cu(ii) binding sites in the N-terminal domain, it includes a characteristic, conservative octarepeat region PHGGGWGQ, which was studied by means of X-ray absorption near edge spectroscopy. The measurements were conducted at the SuperXAS beamline (SLS, PSI, Villigen)...
February 13, 2019: Metallomics: Integrated Biometal Science
Antonija Tangar, Valérie Derrien, Ruipeng Lei, Maria Jose Santiago Estevez, Pierre Sebban, Sophie Bernad, Jaroslava Miksovska
Here, we report the preparation and photo-physical characterization of hexa-coordinated vertebrate globins, human neuroglobin (hNgb) and cytoglobin (hCygb), with the native iron protoporphyrin IX (FePPIX) cofactor replaced by a fluorescent isostructural analogue, zinc protoporphyrin IX (ZnPPIX). To facilitate insertion of ZnPPIX into hexa-coordinated globins, apoproteins prepared via butanone extraction were unfolded by the addition of GuHCl and subsequently slowly refolded in the presence of ZnPPIX. The absorption/emission spectra of ZnPPIX reconstituted hCygb are similar to those observed for ZnPPIX reconstituted myoglobin whereas the absorption and emission spectra of ZnPPIX reconstituted hNgb are blue shifted by ∼2 nm...
February 8, 2019: Metallomics: Integrated Biometal Science
Isidro Abreu, Paula Mihelj, Daniel Raimunda
A group of bacteria known as rhizobia are key players in symbiotic nitrogen fixation (SNF) in partnership with legumes. After a molecular exchange, the bacteria end surrounded by a plant membrane forming symbiosomes, organelle-like structures, where they differentiate to bacteroids and fix nitrogen. This symbiotic process is highly dependent on dynamic nutrient exchanges between the partners. Among these are transition metals (TM) participating as inorganic and organic cofactors of fundamental enzymes. While the understanding of how plant transporters facilitate TMs to the very near environment of the bacteroid is expanding, our knowledge on how bacteroid transporters integrate to TM homeostasis mechanisms in the plant host is still limited...
February 8, 2019: Metallomics: Integrated Biometal Science
Giuseppe Sciortino, José-Emilio Sánchez-Aparicio, Jaime Rodríguez-Guerra Pedregal, Eugenio Garribba, Jean-Didier Maréchal
In an organism, cisplatin and its derivatives are known to interact with proteins besides their principal DNA target. These off-target interactions have major therapeutic consequences including undesired side effects, loss of bioavailability and emergence of resistance. Insulin is one of the prototypical protein targets of platinum drugs as it has been seen to be involved in bioavailability reduction and might also determine resistance in certain cancer lines. However, despite the interest in understanding the nature of the oxaliplatin-insulin adducts, no 3D models have been achieved so far...
February 6, 2019: Metallomics: Integrated Biometal Science
Daisy L Wong, Natalie C Korkola, Martin J Stillman
The 20-cysteine mammalian metallothioneins are considered to be central to the homeostatic control of the essential metals Zn(ii) and Cu(i) and, as part of their metal-loaded status, play a role in reversing oxidative stress. Native apo-MT does not adopt a well-known structural motif, being described as a random-coil or intrinsically-disordered. Conclusions reached from a combination of ESI-mass spectral charge states, As(iii) metallation of apo-MT at low pH, from molecular dynamic calculations and from metallation of the α-domain fragment, suggest that in fact the native apo-MT adopts a structure that is highly efficient towards metallation at physiological pH...
February 6, 2019: Metallomics: Integrated Biometal Science
Fadi Bou-Abdallah, Nicholas Flint, Tyler Wilkinson, Samantha Salim, Ayush Kumar Srivastava, Maura Poli, Paolo Arosio, Artem Melman
The excessively high and inconsistent literature values for Km,Fe and Km,O2 prompted us to examine the iron oxidation kinetics in ferritin, the major iron storage protein in mammals, and to determine whether a traditional Michaelis-Menten enzymatic behavior is obeyed. The kinetics of Fe(ii) oxidation and mineralization catalyzed by three different types of ferritins (recombinant human homopolymer 24H, HuHF, human heteropolymer ∼21H:3L, HL, and horse spleen heteropolymer ∼3.3H:20.7L, HosF) were therefore studied under physiologically relevant O2 concentrations, but also in the presence of excess Fe(ii) and O2 concentrations...
February 5, 2019: Metallomics: Integrated Biometal Science
Yu Lin, Jie Wang, Wei Zheng, Qun Luo, Kui Wu, Jun Du, Yao Zhao, Fuyi Wang
Peroxiredoxins (Prxs) are a family of ubiquitous antioxidant proteins and the inhibition of Prxs would elevate the reactive oxygen species level so as to induce cancer cell death. The interactions of organometallic ruthenium arene anticancer complexes with proteins play important roles in their mechanisms of action. Herein, we demonstrate that Ru complexes [(η6-arene)Ru(en)Cl]+ (en = ethylenediamine, arene = p-cymene (1), biphenyl (2) and 9,10-dihydrophenanthrene (3)) can inhibit the enzymatic activity of human peroxiredoxin I (Prx-I) in an order of 1 > 3 > 2...
January 29, 2019: Metallomics: Integrated Biometal Science
Natalia V Dolgova, Susan Nehzati, Tracy C MacDonald, Kelly L Summers, Andrew M Crawford, Patrick H Krone, Graham N George, Ingrid J Pickering
Mercury is one of the most toxic elements threatening the biosphere, with levels steadily rising due to both natural and human activities. Selenium is an essential micronutrient, required for normal development and functioning of many organisms. While selenium is known to counteract mercury's toxicity under some conditions, to date information about the mercury-selenium relationship is fragmented and often controversial. As part of a systematic study of mercury and selenium interactions, zebrafish (Danio rerio) larvae (a model verterbrate) were exposed to methylmercury chloride or mercuric chloride...
January 28, 2019: Metallomics: Integrated Biometal Science
Cornelia Große, Anja Poehlein, Kathrin Blank, Claudia Schwarzenberger, Grit Schleuder, Martin Herzberg, Dietrich H Nies
The role of extracytoplasmic function (ECF) sigma factors in multiple metal homeostasis of the metallophilic bacterium Cupriavidus metallidurans was studied. RNA sequencing was used to predict 3084 operons in the genome of this bacterium, including 11 for ECF sigma factors, and to measure transcript abundances. Mutants carrying multiple deletions in genes for ECF sigma factors were constructed and characterized. Mutants and parent were challenged with a metal mix, changes in the global gene expression profile and the overall metal content determined...
January 25, 2019: Metallomics: Integrated Biometal Science
Nieka A Wahono, Dianne Ford, Luisa A Wakeling, Ruth A Valentine
Zinc (Zn) is distributed throughout the body and within cells by saturable processes mediated by the transport proteins of the ZnT (SLC30) and ZIP (SLC39) families. The two families function in opposite directions. ZnT transporters mediate cellular zinc efflux or intracellular sequestration. Zn is found in human tooth enamel and dentine at levels that have been related to environmental exposures, such as pollution, disease, and dietary intake. The mechanism by which Zn in the odontoblast is deposited in the hard tissue of the tooth, however, is unknown but is important in determining the physical properties, and hence resilience, of enamel and in the context of the use of tooth zinc level as a biomarker of exposure...
January 24, 2019: Metallomics: Integrated Biometal Science
Manju Shri, Pradyumna Kumar Singh, Maria Kidwai, Neelam Gautam, Sonali Dubey, Giti Verma, Debasis Chakrabarty
Arsenic (As), classified as a "metalloid" element, is well known for its carcinogenicity and other toxic effects to humans. Arsenic exposure in plants results in the alteration of the physiochemical and biological properties and consequently, loss of crop yield. Being a staple food for half of the world's population, the consumption of As-contaminated rice grain by humans may pose serious health issues and risks for food security. In this study, we have described the principal understanding of the molecular basis of arsenic toxicity and accumulation in plant parts...
January 23, 2019: Metallomics: Integrated Biometal Science
Suraj Kumar Mandal, Rahi Adhikari, Anjaney Sharma, Monika Chandravanshi, Prerana Gogoi, Shankar Prasad Kanaujia
Micronutrients such as metal ions are indispensable for the growth and survival of microorganisms in assorted environmental niches. However, change in cellular concentration of metal ions is pernicious for an organism; thus metal ion homeostasis is crucial for their survival and growth. An eminent mechanism for maintaining metal ion homeostasis in microorganisms is ATP-binding cassette (ABC) transporters, which transport metal ions in their ionic/complex forms across the cell membrane. For the uptake, metals are sequestered by substrate-binding proteins (SBPs) and transferred to transmembrane domains (TMDs) for their transport...
January 23, 2019: Metallomics: Integrated Biometal Science
Lanjun Cheng, Chan Li, Zhaoyong Xi, Kaiju Wei, Siming Yuan, Fabio Arnesano, Giovanni Natile, Yangzhong Liu
Cisplatin is an anticancer drug widely used in clinics; it induces the apoptosis of cancer cells by targeting DNA. However, its interaction with proteins has been found to be crucial in modulating the pre and post-target activity. Nuclear DNA is tightly assembled with histone proteins to form nucleosomes in chromatin; this can impede the drug to access DNA. On the other hand, the linker histone H1 is considered 'the gate to nucleosomal DNA' due to its exposed location and dynamic conformation; therefore, this protein can influence the platination of DNA...
January 23, 2019: Metallomics: Integrated Biometal Science
Antony van der Ent, François Malaisse, Peter D Erskine, Jolanta Mesjasz-Przybyłowicz, Wojciech J Przybyłowicz, Alban D Barnabas, Marta Sośnicka, Hugh H Harris
The Central African Copperbelt of the DR Congo and Zambia hosts more than 30 known Cu-Co hyperaccumulator plant species. These plants can accumulate extraordinarily high concentrations of Cu and Co in their living tissues without showing any signs of toxicity. Haumaniastrum robertii is the most extreme Co hyperaccumulator (able to accumulate up to 1 wt% Co), whereas Aeolanthus biformifolius is the most extreme Cu hyperaccumulator (with up to 1 wt% Cu). The phenomenon of Cu-Co hyperaccumulator plants was studied intensively in the 1970s through to the 1990s, but doubts arose regarding earlier observations due to surficial contamination of plant material with mineral particles...
January 21, 2019: Metallomics: Integrated Biometal Science
Mercè Capdevila, Òscar Palacios
No abstract text is available yet for this article.
January 16, 2019: Metallomics: Integrated Biometal Science
Jing Zhou, Hongyue Ma, Yuanyuan Wu, Xiang Lv, Jiajia Wang, Shengjin Liu, Dandan Li, Hengbin Wang, Yanqing Yan, Niancui Luo, Quan Li, Huiqin Xu, Qichun Zhang, Li Yu, Hongbo Guo, Uros Kuzmanov, Liuqing Di, Qinan Wu, Jinao Duan
Arsenic sulfide compounds provide nearly all of the world's supply of arsenic. However, the risk of arsenic trisulfide exposure is still not fully investigated. Here, we systemically assessed the toxicology of As4S4 in rats by combining arsenic metabolite detection, routine testing and lipidomic profiling. It was revealed that the oral administration of As4S4 for two months increased the total arsenic content in the liver reaching a saturation level. Further analysis by anion exchange chromatography coupled with inductively coupled plasma mass spectrometry (ICP-MS) technology showed no trace of inorganic arsenic, but there was significant presence of dimethylarsinic acid (DMA), in the livers of rats...
January 16, 2019: Metallomics: Integrated Biometal Science
Ali Younes, Gaëlle Creff, Maria Rosa Beccia, Philippe Moisy, Jérôme Roques, Jean Aupiais, Christoph Hennig, Pier Lorenzo Solari, Christophe Den Auwer, Claude Vidaud
Uranium is widespread in the environment, resulting both from natural occurrences and anthropogenic activities. Its toxicity is mainly chemical rather than radiological. In the blood it is transported as uranyl UO22+ cation and forms complexes with small ligands like carbonates and with some proteins. From there it reaches the skeleton, its main target organ for accumulation. Fetuin is a serum protein involved in biomineralization processes, and it was demonstrated to be the main UO22+-binder in vitro. Fetuin's life cycle ends in bone...
January 15, 2019: Metallomics: Integrated Biometal Science
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