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Liquid chromatography (LC)-Inductively coupled plasma mass spectrometry (ICPMS) for metal distribution

Spectroscopic methods can be used to evaluate distribution of metals in the mitochondria of yeast cells.

Paul Lindahl and colleagues at the Texas A&M University, USA, investigated the function of the Mtm1p, a carrier protein found in the yeast Saccharomyces cervisiae. Deleting the Mtm1p gene, they evaluated the iron and manganese presence in the cells and discovered that iron and manganese accumulate in mitochondria and inactivate the enzyme Mn-superoxide dismutase. Metal concentrations in cells and mitochondria were efficiently measured using inductively coupled plasma mass spectrometry.

To know more about this research, please access the full article below. This paper will be free to read until May 24^th.

Insights into the iron-ome and manganese-ome of Δmtm1 Saccharomyces cerevisiae mitochondria Jinkyu
Park, Sean P. McCormick, Mrinmoy Chakrabarti and   Paul A. Lindahl 
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT00041A

Investigating anti-cancer metal compounds in vivo and in vitro with XAS and micro-SXRF

X-ray absorption spectroscopy (XAS) and micro-synchrotron based X-ray fluorescence (micro-SXRF) are valuable tools for the investigation of changes in the chemical environment of metal centres.

This tutorial review, written by Alfred Hummer and Annette Rompel from the University of Vienna, Austria, introduces the use of XAS and micro-SXRF techniques into the field of inorganic medicinal chemistry.

Currently, several review articles are available on the anti-tumoural activity of metal complexes as well as the application of XAS and micro-SXRF in biological systems. This new review provides a glimpse into the possibilities, applications and outcomes of these spectroscopic techniques in metal based cancer research. In particular, the authors describe the latest results of XAS and micro- SXRF in vitro and in vivo investigations and discuss the proposed modes of action of compounds based on platinum, ruthenium, gallium, gold and cobalt.

To read the full article, please access the link below. This paper will be free to read until May 14^th.

The use of X-ray absorption and synchrotron based micro-X-ray fluorescence spectroscopy to investigate anti-cancer metal compounds in vivo and in vitro
Alfred A. Hummer and   Annette Rompel
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT20261E

 Researchers at the Peking University in China explain how vanadium compounds can be used to prevent type II diabetes.

Vanadium compounds inhibit breakdown of lipids into free fatty acids

Lipolysis is an important cellular process which leads to breakdown of lipids via lysis of triglycerides into free fatty acids. Accumulation of free fatty acids in plasma caused by excessive lipolysis is considered one of the major risk factors to develop type II diabetes.

Vanadium-based compounds are known anti-diabetic drugs showing effects similar to insulin. However, their mechanism of action has not yet been explained and we do not know how they reduce the levels of fatty acids in blood.

In their study, Xiao-Gai Yang and colleagues used an adipocyte cell line and analysed the signalling pathways which lead to degradation of lipids. They found that vanadium compounds inhibit lipolysis by regulating the signalling pathway involved in the lipolytic process in adipocytes via the activation of specific protein kinases.

This work underlines the relevance to study the mechanisms of action of these new compounds before they can be used safely and efficiently. ‘Only with answers to such mechanistic questions we can optimise the therapeutic potential and minimise the adverse effects of vanadium compounds’, write the authors.

To know more about this research, please access the link below. This paper will be free to read until May 13^th.

Bis(acetylacetonato)-oxovanadium(IV), bis(maltolato)-oxovanadium(IV) and sodium metavanadate induce antilipolytic effects by regulating hormone-sensitive lipase and perilipin via activation of Akt
Jing-Cheng Liu,ab   You Yu,b   Gang Wang,b   Kui Wangab and   Xiao-Gai Yang*b  
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT00001J

X-ray fluorescence microscopy can be used to analyse elemental distribution in nematodes.

X-ray fluorescence microscopy showing distribution of Ca and Zn in C. elegans

Gawain McColl and colleagues at the University of Melbourne, Australia, studied Caenorhabditis elegans, a transparent multicellular organism ideally suited for transgenic expression of fluorescent proteins and already used to study eukaryotic metalloproteins. In their work, they successfully used X-ray fluorescence microscopy with minimal experimental interference and directly visualised elemental co-localisation with anatomical structures. They conclude that C. elegans is a good tool for imaging of biologically important elements.

To know all about this work, please access the link below. This paper will be free to read until April 19^th.

Direct in vivo imaging of essential bioinorganics in Caenorhabditis elegans
Simon A. James ,  Martin D. de Jonge ,  Daryl L. Howard ,  Ashley I. Bush ,  David Paterson and Gawain McColl
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT00010A

This article reports the use of liquid chromatography in combination with inductively coupled plasma mass spectrometry (LC-ICP-MS) to enable accurate intact cisplatin quantification in cell model experiments.

The research was perfomed by Gunda Koellensperger’s group at the University of Natural Resources and Life Sciences, Austria, in collaboration with Walter Berger at the Medical University Vienna.

LC-ICP-MS for cisplatin quantification

For the first time, intracellular drug degradation, drug accumulation and drug efflux were studied by actually quantifying the intact drug, along with the total Pt content of the cell nucleus, the cytosol and the low molecular weight fraction of the cytosol. The drug accumulation experiments revealed rapid uptake of the drug into the cytosol and the nucleus. Moreover, a significant fraction of Pt was bound to intracellular high molecular weight biomolecules after one hour of exposure. With ongoing time, the intracellular Pt concentration increased but, the cisplatin concentration remained constant during 5 hours of continuous exposure. These findings support the hypothesis of passive diffusion as an uptake mechanism. Finally, a model experiment was designed resembling the situation of limited drug exposure time.

To know more about this research, please access the full paper by clicking the link below. This article will be free to read until April 19^th.

In vitro studies on cisplatin focusing on kinetic aspects of intracellular chemistry by LC-ICP-MS
Gerrit Hermann ,  Petra Heffeter ,  Thomas Falta ,  Walter Berger ,  Stephan Hann and Gunda Koellensperger
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT20251H

Stereochemistry of αKG-oxygenase active sites

In this critical review just published in Metallomics, Michael Knapp and colleagues from the University of Massachusetts, USA, explain how iron stereochemistry relates to enzyme function.

The researchers highlight the functions of a group of enzymes, called Fe(II)αketoglutarate (αKG) oxygenases, which catalise a variety of reactions such as protein modification, DNA repair and lipid metabolism. According to the authors, understanding the functions of enzymes by studying the primary protein structure can help in designing inhibitors or activators for therapeutic use.

To read the full review, please access the link below. This article will be free to read until April 4^th.

Imposing function down a (cupin)-barrel: secondary structure and metal stereochemistry in the αKG-dependent oxygenases
John A. Hangasky ,  Cornelius Y. Taabazuing ,  Meaghan A. Valliere and Michael J. Knapp
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT20153H

Size exclusion HPLC to measure protein-receptor binding

Lanthanide (Ln) and actinide (An) fission products are contaminants generated by both the industry and defence sectors. They can bind to the human iron transporter transferrin and enter the cells increasing toxicity.

Rebecca Abergel and researchers at the Lawrence Berkeley National Laboratory, USA, report a novel method to recognise binding of the human transferrin receptor (Tfr) to free transferrin or metal-bound transferrin, using size exclusion high performance liquid chromatography (HPLC). The study suggests a  new molecular process involved in contamination of Ln and An,  and proposes a role for Tfr in translocation of exogenous metals by acting as a selective barrier for cellular entry.

To know more about this research, please access the link below. This paper will be free to read until April 2^nd .

Receptor recognition of transferrin bound to lanthanides and actinides: a discriminating step in cellular acquisition of f-block metals
Gauthier J.-P. Deblonde ,  Manuel Sturzbecher-Hoehne ,  Anne B. Mason and Rebecca J. Abergel
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT20237B

Identification of biomarkers for copper deficiency (CAS) and excess (SDH1-2)

Copper-based pesticides are still in use today in organic farming. However, given the phyto-toxicity of copper and its ability to persist in the environment, the use of copper pesticides raises some concerns.

Lola Peñarrubia and colleagues from the University of Valencia addressed the issue proposing new molecular markers for mild copper deficiency and excess. In fact, whereas copper abuse is toxic, low availability in soils can affect plant productivity and reduce the nutritional value of food. The researchers exposed Arabidopsis thaliana plants to different conditions and performed microarray analysis in plants affected by copper deficiency or exposed to excessive copper. They finally identified the chloroplast Ca²⁺ transducer CAS gene as a marker for copper deficiency, and the flavoprotein subunit of succinate dehydrogenase in mithocondria SDH1-2 as a marker for copper excess.

To access the full article, please click on the link below. This paper will be free to read until April 2^nd.

Comparison of global responses to mild deficiency and excess copper levels in Arabidopsis seedlings
Nuria Andrés-Colás ,  Ana Perea-García ,  Sonia Mayo de Andrés ,  Antoni Garcia-Molina ,  Eavan Dorcey ,  Susana Rodríguez-Navarro ,  Miguel A. Pérez-Amador ,  Sergi Puig and Lola Peñarrubia
Metallomics, 2013, Advance Article
DOI: 10.1039/C3MT00025G