MetallomicsPub Date : 2025-02-06DOI: 10.1093/mtomcs/mfaf003
Ines Kelkoul, Virginia Puente Muñoz, Richard Ortega, Asuncion Carmona
{"title":"Synchrotron-based correlative imaging of metals and proteins in neuronal cells: state of the art and future challenges in neurometallomics.","authors":"Ines Kelkoul, Virginia Puente Muñoz, Richard Ortega, Asuncion Carmona","doi":"10.1093/mtomcs/mfaf003","DOIUrl":"10.1093/mtomcs/mfaf003","url":null,"abstract":"<p><p>Metal homeostasis in the nervous system is subtly regulated and changes in metal distribution or content, either increases or decreases, are associated with neurodegeneration or cognitive impairment. Determining the localization and quantification of metals in different types of neurons is important information for understanding their role in neurobiology. Synchrotron X-ray fluorescence imaging is a powerful technique that provides very high sensitivity and high spatial resolution for imaging metals in cells. However, additional biological information is often required to correlate the subcellular localization of metals with specific proteins or organelles. The purpose of this article is to review the studies in neuroscience that correlate metal imaging by synchrotron X-ray fluorescence with protein localization by other techniques. This article highlights the diversity of correlative modalities that have been used, from fluorescence to super-resolution and infrared microscopy, and the wealth of information that has been extracted, but also discusses some current limitations. Future developments are needed, particularly for direct imaging of metals and proteins with a single instrument.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetallomicsPub Date : 2025-02-06DOI: 10.1093/mtomcs/mfaf002
Katarzyna Bierla, Joanna Szpunar, Ryszard Lobinski, Roger A Sunde
{"title":"Use of laser-ablation inductively-coupled plasma mass spectrometry for analysis of selenosugars bound to proteins.","authors":"Katarzyna Bierla, Joanna Szpunar, Ryszard Lobinski, Roger A Sunde","doi":"10.1093/mtomcs/mfaf002","DOIUrl":"10.1093/mtomcs/mfaf002","url":null,"abstract":"<p><p>We previously used high pressure liquid chromatography coupled with Se-specific inductively coupled plasma mass spectrometry and molecule specific (ESI Orbitrap MS/MS) detection to study the increase in liver Se in turkeys and rats supplemented as selenite in high-Se (5 µg Se/g diet) and adequate-Se diets. We found that far more Se is present as selenosugar (seleno-N-acetyl galactosamine) than is present as selenocysteine (Sec) in true selenoproteins. In high-Se liver, the increase in liver Se was due to low molecular weight selenometabolites such as glutathione-, cysteine-, and methyl-conjugates of the selenosugar, but also as high molecular weight species as selenosugars decorating general proteins via mixed Se-S bonds. To demonstrate selenosugar binding to proteins, aqueous liver extracts from animals fed Se-adequate and high-Se were subjected to sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Native-PAGE with and without pretreatment with β-mercaptoethanol (βME). The separated proteins were then electrophoretically transferred to membranes, and the membranes subsequently were subjected to laser-ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS) analysis of 78Se profiles. Without βME treatment, Se was widely distributed across the molecular weight profile for both SDS-PAGE and Native-PAGE, whereas βME pretreatment dramatically reduced Se binding, reducing the profile to true Sec-selenoproteins. This reduction was ∼50% for both high-Se rat and turkey extracts. The increased Se in non-βME treated samples was distributed across the full profile. The use of LA-ICP-MS indicates that selenosugar residues are bound to protein subunits of multiple sizes, and that targeted attachment of selenosugars to a single or limited number of protein subunits does not occur.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetallomicsPub Date : 2025-02-06DOI: 10.1093/mtomcs/mfaf005
Rui Liu, Qian Zhang, Xueting Yan, Yi Lv
{"title":"A critical review on the relevance, essentiality, and analytical techniques of trace elements in human cancer.","authors":"Rui Liu, Qian Zhang, Xueting Yan, Yi Lv","doi":"10.1093/mtomcs/mfaf005","DOIUrl":"10.1093/mtomcs/mfaf005","url":null,"abstract":"<p><p>Trace elements (TEs) are indispensable nutritional elements, playing a pivotal role in maintaining human health and serving as essential cofactors for numerous enzymes that facilitate crucial biological processes. The dysregulation (excess or deficiency) of TEs can affect the proper functioning of various organs and lead to diseases like cancer. However, the current research findings remain contentious, and the association between TE variations and cancer remains elusive. This article reviews the recent advances in the quantitative detection of TEs in tumor research to fully understand the important role of TEs in disease diagnosis and prognosis. The changes in the levels of various elements (such as Cu, Zn, Fe, Se, Ca, etc.) are analyzed and summarized from five systems of the human body, including the digestive system, urinary system, reproductive system, endocrine system, and respiratory system. By analyzing the relevant findings in diverse biological samples, we systematically investigate the disruption of TEs homeostasis in cancer patients, thereby underscoring the potential of TEs as cancer biomarkers. We also present novel analytical techniques such as isotope ratio determination and bioimaging, along with advanced auxiliary tools like machine learning, for the detection of TEs in disease research. This review aims to provide a comprehensive overview of TEs variations in the main cancer types of different systems, which addresses the knowledge gap in TEs on human health, and provides proposals for future research.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetallomicsPub Date : 2025-02-06DOI: 10.1093/mtomcs/mfaf001
Patrick Day
{"title":"Heavy medicine: the need for ethical stewardship of metal and metalloid-based medicines and technologies.","authors":"Patrick Day","doi":"10.1093/mtomcs/mfaf001","DOIUrl":"10.1093/mtomcs/mfaf001","url":null,"abstract":"<p><p>Metals and metalloids including cobalt, gadolinium, lutetium, and germanium are used in numerous medical applications spanning diverse specialities including orthopedics, radiology, oncology, and healthcare artificial intelligence. These medical advances include cobalt containing orthopedic implants, gadolinium-based contrast agents, lutetium-containing cancer drugs, and germanium-based semiconductors. While these metal and metalloid-based solutions do improve patient care, there is a heavy side to how the elements needed for these solutions are mined, extracted, and discarded. These practices often exploit and harm vulnerable populations and environments. As healthcare professionals, we should be aware of the entire mineral to medicine lifecycle. As providers and consumers of these metal and metalloid-based solutions, we must advocate for more responsible and ethical extraction and recycling practices. As researchers and educators, we must promote and support continued research and development into less resource-intense medical solutions that can both improve patient care and sustainability.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing metal-induced glycation in French fries.","authors":"Seth Nobert, Haley Wolgien-Lowe, Tamara Davis, Emma Paterson, Thérèse Wilson-Rawlins, Makan Golizeh","doi":"10.1093/mtomcs/mfae059","DOIUrl":"10.1093/mtomcs/mfae059","url":null,"abstract":"<p><p>Non-enzymatic glycation is the chemical reaction between the amine group of an amino acid and the carbonyl group of a reducing sugar. The final products of this reaction, advanced glycation end-products (AGEs), are known to play a key role in aging and many chronic diseases. The kinetics of the AGE formation reaction depends on several factors, including pH, temperature, and the presence of prooxidant metals, such as iron and copper. In this study, the effect of iron and copper on the rate and outcome of non-enzymatic glycation was examined in the test tube and a food model, using chromatography and spectrometry methods. Binding efficiencies of several chelating agents to selected metals were also assessed. Phytic acid was the most efficient of the tested chelating agents. The effect of phytic acid on AGE formation in French fries was evaluated. While phytic acid treatment increased the amounts of UV-absorbing compounds in fries, a food ingredient rich in phytic acid showed the opposite effect. This study suggests that prooxidant metals can affect the rate, outcome, and yield of the non-enzymatic glycation reaction and that they do so differently when free or chelated. Moreover, despite being an excellent iron chelator, phytic acid can promote AGE formation in fried food potentially via mechanisms other than metal-induced glycation.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetallomicsPub Date : 2024-12-02DOI: 10.1093/mtomcs/mfae054
M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly
{"title":"X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.","authors":"M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly","doi":"10.1093/mtomcs/mfae054","DOIUrl":"10.1093/mtomcs/mfae054","url":null,"abstract":"<p><p>The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Formation mechanism of iron-catechol complexes in the colored periostracum of Corbicula spp.","authors":"Kuniko Takemoto, Masataka Murakami, Yoshihiro Ueno, Daiya Bamba, Hirona Yamagishi","doi":"10.1093/mtomcs/mfae055","DOIUrl":"10.1093/mtomcs/mfae055","url":null,"abstract":"<p><p>The shell color of Corbicula clams, which are globally distributed, is roughly divided into yellowish and blackish depending on the environmental conditions of the sediment. The formation of an iron-L-3,4-dihydroxyphenylalanine (DOPA) complex in a thin organic layer, called the periostracum, on a calcareous layer causes the blackening of the clamshell. However, the iron-DOPA complex formation mechanism is unclear. To reveal how the iron is transported from the aquatic environment to the periostracum, cross-sectional analyses of the shell were conducted using an electron probe microanalyzer and Raman spectroscopy to investigate the distribution and structure of iron in the shell. Iron was only present in the periostracum, excluding deposition, and all iron was in the form of an iron-DOPA complex. Attenuated total reflection infrared spectroscopy and oxygen K-edge X-ray absorption fine structure spectroscopy revealed that the molecular structure of the native periostracum is independent of shell color. These results indicate that dissolved iron-organic complexes diffuse from the aqueous environment to the periostracum, forming iron-DOPA complex through ligand exchange. Because the iron-DOPA complex color depends on the pH, the shell color can serve as a historical indicator of the shell's growth environment.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetallomicsPub Date : 2024-12-02DOI: 10.1093/mtomcs/mfae058
Diana Galea, Martin Herzberg, Dirk Dobritzsch, Matt Fuszard, Dietrich H Nies
{"title":"Linking the transcriptome to physiology: response of the proteome of Cupriavidus metallidurans to changing metal availability.","authors":"Diana Galea, Martin Herzberg, Dirk Dobritzsch, Matt Fuszard, Dietrich H Nies","doi":"10.1093/mtomcs/mfae058","DOIUrl":"10.1093/mtomcs/mfae058","url":null,"abstract":"<p><p>Cupriavidus metallidurans CH34 is a metal-resistant bacterium. Its metal homeostasis is based on a flow equilibrium of metal ion uptake and efflux reactions, which adapts to changing metal concentrations within an hour. At high metal concentrations, upregulation of the genes for metal efflux systems occurs within minutes. Here, we investigate the changes in the bacterial proteome accompanying these genetic and physiological events after 1.5 cell duplications, which took 3 h. To that end, C. metallidurans CH34 and its plasmid-free derivative, AE104, either were challenged with a toxic metal mix or were cultivated under metal-starvation conditions, followed by bottom-up proteomics. When metal-shocked or -starved cells were compared with their respective controls, 3540 proteins changed in abundance, with 76% appearing in one, but not the other, condition; the remaining 24% were up- or downregulated. Metal-shocked C. metallidurans strains had adjusted their proteomes to combat metal stress. The most prominent polypeptides were the products of the plasmid-encoded metal-resistance determinants in strain CH34, particularly the CzcCBA transenvelope efflux system. Moreover, the influence of antisense transcripts on the proteome was also revealed. In one specific example, the impact of an asRNA on the abundance of gene products could be demonstrated and this yielded new insights into the function of the transmembrane efflux complex ZniCBA under conditions of metal starvation.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MetallomicsPub Date : 2024-12-02DOI: 10.1093/mtomcs/mfae052
Marisa S Egan, Raquel de Macedo, Joseph P Zackular
{"title":"Metals in the gut: microbial strategies to overcome nutritional immunity in the intestinal tract.","authors":"Marisa S Egan, Raquel de Macedo, Joseph P Zackular","doi":"10.1093/mtomcs/mfae052","DOIUrl":"10.1093/mtomcs/mfae052","url":null,"abstract":"<p><p>Trace metals are indispensable nutritional factors for all living organisms. During host-pathogen interactions, they serve as crucial resources that dictate infection outcomes. Accordingly, the host uses a defense strategy known as nutritional immunity, which relies on coordinated metal chelation to mitigate bacterial advances. In response, pathogens employ complex strategies to secure these resources at sites of infection. In the gastrointestinal (GI) tract, the microbiota must also acquire metals for survival, making metals a central line of competition in this complex ecosystem. In this minireview, we outline how bacteria secure iron, zinc, and manganese from the host with a focus on the GI tract. We also reflect on how host dietary changes impact disease outcomes and discuss therapeutic opportunities to target bacterial metal uptake systems. Ultimately, we find that recent discoveries on the dynamics of transition metals at the host-pathogen-microbiota interface have reshaped our understanding of enteric infections and provided insights into virulence strategies, microbial cooperation, and antibacterial strategies.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural variation of magnesium stable isotopes in human kidney stones.","authors":"Jinke Liu, Guilin Han, Yu Tian, Rui Qu, Di Wang, Yanan Shen","doi":"10.1093/mtomcs/mfae056","DOIUrl":"10.1093/mtomcs/mfae056","url":null,"abstract":"<p><p>Kidney stones, as typical biominerals produced within the human body, pose a significant threat to human health, affecting over 12% of the global population. However, the exact mechanisms underlying their formation are not fully understood. Recent metal isotopic analysis provides a new way to study the roles of metal cations in biological processes within organisms. Here, we report the Mg isotope ratios of human kidney stones for the first time. The total range of measured values for δ26Mg in kidney stones is 1.05‰, from -1.12‰ to -0.07‰. Our data exhibit a significant 24Mg enrichment compared with the values calculated from density functional theory. We suggest that the Mg-isotopic fractionations in vivo are linked to active Mg transport mediated by proteins during intestinal absorption and preferential renal reabsorption of ionized Mg2+ via tight junctional proteins. Our results indicate that the inhibitory effect of Mg on kidney stones is related to the kink-blocking mechanism, and the incorporation of hydrated Mg lessens the extent of inhibition and the magnitude of isotope discrimination. We show that metal isotopes provide new insights into the underlying biological processes and human health.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}