MetallomicsPub Date : 2025-02-17DOI: 10.1093/mtomcs/mfaf007
Timothej Patocka, Surya Gupta, Felice Mastroleo, Natalie Leys, Jean-Yves Matroule, Rob Van Houdt
{"title":"Time-resolved proteomic profiling of Cupriavidus metallidurans CH34 in the copper-induced viable-but-non-culturable state.","authors":"Timothej Patocka, Surya Gupta, Felice Mastroleo, Natalie Leys, Jean-Yves Matroule, Rob Van Houdt","doi":"10.1093/mtomcs/mfaf007","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf007","url":null,"abstract":"<p><p>Copper-based materials are actively explored for their potential as antimicrobial agents. However, recent studies show that sublethal concentrations of Cu ions can induce the viable-but-non-culturable (VBNC) cell state in certain bacteria, hampering contamination control and monitoring. In this study we contribute to the unravelling of this largely enigmatic phenomenon by determining the time-resolved proteome of Cu-treated Cupriavidus metallidurans CH34 during VBNC induction and resuscitation. High-throughput quantitative LC-MS/MS analysis was performed at multiple sample time points, revealing the cellular adaptations that trigger VBNC formation and the characteristic spontaneous recovery of culturability. Entry into the VBNC state correlated with a widespread response to oxidative stress as well as downregulated pyruvate metabolism. The expression of specific metal resistance determinants changed with Cu exposure time and culminated in the strong upregulation of proteins linked to periplasmic Cu ion detoxification during the resuscitation phase. We suggest that this delayed induction of Cu resistance proteins is paralleled by the gradual reconstitution of energy reserves through metabolization of intracellular polyhydroxybutyrate, as supported by flow cytometric fluorescence measurements. Furthermore, Cu-treated cells showed upregulation of several motility and chemotaxis proteins, and increased cell motility was observed phenotypically. Our results reveal a highly dynamic proteomic response, provide fundamental insights into the VBNC state and emphasize the advantages of time-resolved proteomic analysis.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439430","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 : 2025-02-11DOI: 10.1093/mtomcs/mfaf006
Melissa Scholefield, Stephanie J Church, Garth J S Cooper
{"title":"Perturbations in levels of essential metals less severe in Parkinson's disease without dementia than in Parkinson's disease dementia.","authors":"Melissa Scholefield, Stephanie J Church, Garth J S Cooper","doi":"10.1093/mtomcs/mfaf006","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf006","url":null,"abstract":"<p><strong>Background: </strong>It is currently unknown why some individuals with Parkinson's disease (PD) go on to develop dementia (Parkinson's disease dementia; PDD), whereas others do not. One possibility is differences in susceptibility to metallomic dysregulation. A previous study of the PDD brain identified substantive perturbations in metal levels, including severe multi-regional decreases in Cu. The current work uses the same methods to ascertain whether this metallomic dysfunction is also present in the PD brain.</p><p><strong>Methods: </strong>Tissue from nine PD cases free of cognitive decline and 15 equivalent controls was obtained from seven brain regions. Levels of Na, Mg, K, Ca, Mn, Fe, Cu, Zn, and Se were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Multiple linear regression analysis was used to determine any potential confounder effects. Results were compared with those previously obtained for PDD.</p><p><strong>Results: </strong>Decreased Cu in the medulla was the only statistically significant case-control difference observed in the PD brain; this contrasts markedly with the widespread metallic dysfunction observed in PDD. PD and PDD cases were well-separated by PCA analysis. In the PD cohort, tau Braak stage correlated with Cu concentrations in several regions, but these correlations were not retained when including PDD cases.</p><p><strong>Conclusions: </strong>There is a marked difference in the metallomic profiles of PD and PDD, with an almost complete lack of metallic involvement observed in the former. This resistance to metallomic dysfunction may contribute to resilience against cognitive impairment in individuals with PD who do not develop dementia.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397625","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 : 2025-02-08DOI: 10.1093/mtomcs/mfaf004
Jake Brooks, James Everett, Peter J Sadler, Neil Telling, Joanna F Collingwood
{"title":"On the origin of metal species in the human brain: a perspective on key physicochemical properties.","authors":"Jake Brooks, James Everett, Peter J Sadler, Neil Telling, Joanna F Collingwood","doi":"10.1093/mtomcs/mfaf004","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf004","url":null,"abstract":"<p><p>Normal functioning of the human brain is dependent on adequate regulation of essential metal nutrients. However, it is also highly sensitive to metal-mediated toxicity, linked to various neurodegenerative disorders. Exposure to environmental metal sources (especially to particulate air pollution) can stimulate toxicity and neuropathologic effects, which is particularly evident in populations chronically exposed to high levels of air pollution. Identifying the sources of metal-rich deposits in the human brain is important in not only distinguishing the effects of environmentally-acquired metals from endogenous metal dysregulation, but also for tracing pollutant sources which may be subject to exposure control. This perspective reviews evidence for key physicochemical properties (size/morphology, chemical composition, oxidation state, magnetic properties and isotopic composition) concerning their capacity to distinguish sources of metals in the brain. The scope for combining analytical techniques to study properties in tandem is also discussed.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381273","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/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/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}