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Dynamic intra-renal changes in cadmium distribution detected by LA-ICP-MS in mice administered cadmium-metallothionein. 用LA-ICP-MS检测镉金属硫蛋白给药小鼠肾内镉分布的动态变化。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-06-03 DOI: 10.1093/mtomcs/mfaf017
Hitomi Fujishiro, Kanako Matsumoto, Hitomi Umemoto, Koichi Tsuneyama, Takehisa Matsukawa, Ayano Kubota, Seiichiro Himeno, Daigo Sumi
{"title":"Dynamic intra-renal changes in cadmium distribution detected by LA-ICP-MS in mice administered cadmium-metallothionein.","authors":"Hitomi Fujishiro, Kanako Matsumoto, Hitomi Umemoto, Koichi Tsuneyama, Takehisa Matsukawa, Ayano Kubota, Seiichiro Himeno, Daigo Sumi","doi":"10.1093/mtomcs/mfaf017","DOIUrl":"10.1093/mtomcs/mfaf017","url":null,"abstract":"<p><p>Administration of the cadmium-metallothionein (Cd-MT) complex has been known to cause acute nephrotoxicity due to free Cd ions during the breakdown of the Cd-MT protein in renal cells. However, the fate of the renal Cd after Cd-MT administration remains elusive. We applied Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) to visualize Cd distribution in the kidneys of mice administered Cd-MT. In the initial several hours, Cd was detected predominantly in the renal cortex. Elevated urinary β2-microglobulin and glucose within a day and rapid induction of MT-I mRNA indicated the generation of toxic free Cd ions. Unexpectedly, however, the Cd distribution changed drastically: from the cortex to the boundary of the cortex and outer medulla until 3 days. From 3 to 18 h, renal Cd concentrations decreased rapidly, accompanied by a large amount of urinary Cd excretion. These results suggest that the injected Cd-MT was transiently distributed in the surface nephrons in the cortex, and the free Cd ions derived from the decomposed Cd-MT were released into the lumen of proximal tubules and then partly reabsorbed at the boundary of the cortex and outer medulla, where the S3-segment proximal tubules exist abundantly. Thus, the LA-ICP-MS revealed dynamic changes in Cd distribution, suggesting the intra-renal transport of the Cd-MT-derived free Cd ions in the kidneys.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223775","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}
引用次数: 0
Redox-sensitive δ65Cu isotopic fractionation in the tissue of the scleractinian coral Stylophora pistillata: a biomarker of holobiont photophysiology following volcanic ash exposure. 硬核珊瑚柱头(Stylophora pistilllata)组织中氧化还原敏感的δ65Cu同位素分馏:火山灰暴露后全生物光生理的生物标志物。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-05-05 DOI: 10.1093/mtomcs/mfaf011
Frank Förster, Lucie Sauzéat, Christine Ferrier-Pagès, Stéphanie Reynaud, Tom E Sheldrake
{"title":"Redox-sensitive δ65Cu isotopic fractionation in the tissue of the scleractinian coral Stylophora pistillata: a biomarker of holobiont photophysiology following volcanic ash exposure.","authors":"Frank Förster, Lucie Sauzéat, Christine Ferrier-Pagès, Stéphanie Reynaud, Tom E Sheldrake","doi":"10.1093/mtomcs/mfaf011","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf011","url":null,"abstract":"<p><p>Volcanic ash is a significant source of micronutrients including iron (Fe), copper (Cu), and zinc (Zn) in oligotrophic tropical waters. These bioactive metals enhance primary productivity, influencing local and global biogeochemical cycles. This study explores how volcanic ash exposure affects trace metal uptake and photophysiological response, and how redox-sensitive metal stable isotope measurements in the tissues of the scleractinian coral Stylophora pistillata can provide crucial information on coral health. Controlled coral culture experiments were conducted in which coral nubbins were exposed to varying intensity and duration of volcanic ash. Throughout the experiment, coral symbionts showed enhanced photosynthetic performance irrespective of intensity or duration of ash exposure. Stable isotopes, such as δ65Cu and δ56Fe, in the coral tissue are marked by systematic variations, not associated with intensity or duration of ash exposure. Instead, we suggest biologically modulated redox-sensitive fractionation associated with ash exposure, linked to the coral host's oxidative stress state. This is evidenced by significant correlations between δ65Cu in coral hosts and photophysiology, with lighter Cu isotope ratios associated with higher photosynthetic performances. Hence, we propose that δ65Cu, and more generally redox-sensitive isotopic ratios (i.e. δ56Fe), in coral hosts serves as an indicator of the physiological state of symbiotic corals.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"17 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958515","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}
引用次数: 0
Synthesis, characterization, DNA interaction studies, and biological evaluation of copper(II) hybrids containing azole drugs and intercalating ligands against neglected diseases. 含唑类药物和嵌入配体的铜(II)杂合体抗被忽视疾病的合成、表征、DNA相互作用研究和生物学评价。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-05-05 DOI: 10.1093/mtomcs/mfaf012
José Aleixo de Azevedo-França, Victor Feliciano Dos Santos Ramos, Patrícia Salvador Tessaro, Heveline Silva, Luigi Messori, Fabio Santanni, Lorenzo Sorace, Luana Pereira Borba-Santos, Sonia Rozental, Juliany Cola Fernandes Rodrigues, Maribel Navarro
{"title":"Synthesis, characterization, DNA interaction studies, and biological evaluation of copper(II) hybrids containing azole drugs and intercalating ligands against neglected diseases.","authors":"José Aleixo de Azevedo-França, Victor Feliciano Dos Santos Ramos, Patrícia Salvador Tessaro, Heveline Silva, Luigi Messori, Fabio Santanni, Lorenzo Sorace, Luana Pereira Borba-Santos, Sonia Rozental, Juliany Cola Fernandes Rodrigues, Maribel Navarro","doi":"10.1093/mtomcs/mfaf012","DOIUrl":"10.1093/mtomcs/mfaf012","url":null,"abstract":"<p><p>In an attempt to treat neglected diseases such as leishmaniasis and fungal infections, three novel copper(II) hybrid have been developed: [Cu(dppz)(CTZ)(NO3)](NO3) (1), [Cu(dppz)(KTZ)(H2O)(NO3)](NO3) (2), and [Cu(dppz)(FLZ)(NO3)]2(NO3)2 (3). They were synthesized by coordinating antifungal imidazole based drugs and dipyridophenazine as ligands to copper(II) under mild conditions and in good yields. These coordination compounds were characterized by various analytical and spectroscopic techniques which confirmed the coordination of both ligands to the metal, and the monodentate (1) or bidentate (2 and 3) coordination of the nitrate and as counterion. These copper hybrids were stable in solid state, in dimethyl sulfoxide (DMSO) and the DMSO-water mixture. DNA interactions were studied using absorption and fluorescence titrations, viscosity measurements, and electrophoresis assays. Complexes 1 and 2 formed strong interaction with DNA. The activity against Leishmania was the highest with complex 3, unlike against Sporothrix brasiliensis, where the free imidazole-based drugs (ITZ and KTZ) performed better.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956342","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}
引用次数: 0
The metal(loid)s' dilemma. What's the next step for a new era of inorganic molecules in medicine? 金属(金属)的困境。无机分子在医学领域的新时代的下一步是什么?
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-05-05 DOI: 10.1093/mtomcs/mfaf013
Lorenzo Chiaverini, Riccardo Di Leo, Luca Famlonga, Matteo Pacini, Emma Baglini, Elisabetta Barresi, Massimiliano F Peana, Iogann Tolbatov, Alessandro Marrone, Diego La Mendola, Jürgen Gailer, Tiziano Marzo
{"title":"The metal(loid)s' dilemma. What's the next step for a new era of inorganic molecules in medicine?","authors":"Lorenzo Chiaverini, Riccardo Di Leo, Luca Famlonga, Matteo Pacini, Emma Baglini, Elisabetta Barresi, Massimiliano F Peana, Iogann Tolbatov, Alessandro Marrone, Diego La Mendola, Jürgen Gailer, Tiziano Marzo","doi":"10.1093/mtomcs/mfaf013","DOIUrl":"10.1093/mtomcs/mfaf013","url":null,"abstract":"<p><p>In this paper, we critically examine the key challenges associated with the development of inorganic drugs, a field that remains underrepresented despite its significant therapeutic potential. Currently, most clinically approved pharmaceuticals are organic compounds, a trend driven by multiple interconnected factors that have historically limited the adoption and regulatory approval of metal(loid)-based entities. These challenges include issues related to stability, selectivity, pharmacokinetics, and potential toxicity, which require systematic investigation and innovative solutions. Nevertheless, the profound clinical impact of approved inorganic drugs-particularly transition metal(loid)-based agents for both therapeutic and diagnostic applications-is well-established. The success of these compounds underscores the need for expanded research efforts and optimized clinical protocols to fully harness the advantages of metal-based pharmaceuticals. In this context, we explore emerging strategies to overcome current limitations and accelerate the development of next-generation inorganic drugs. These include the rational design of metal-based therapeutics, the integration of advanced metallomics and metalloproteomics, and the application of AI-driven predictive modeling to improve drug selectivity, bioavailability, and safety. By overcoming these challenges through an interdisciplinary approach, metal-based medicine will advance significantly, expanding its impact across a wide range of therapeutic applications.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109171","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}
引用次数: 0
Pharmacokinetics of metal excretion following different doses of sodium EDTA infusion. 不同剂量EDTA钠输注后金属排泄的药代动力学。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-05-05 DOI: 10.1093/mtomcs/mfaf010
Kathrin Schilling, Francisco Ujueta, Siyue Gao, Will A Anderson, Esteban Escolar, Ana Mon, Ana Navas-Acien, Gervasio A Lamas
{"title":"Pharmacokinetics of metal excretion following different doses of sodium EDTA infusion.","authors":"Kathrin Schilling, Francisco Ujueta, Siyue Gao, Will A Anderson, Esteban Escolar, Ana Mon, Ana Navas-Acien, Gervasio A Lamas","doi":"10.1093/mtomcs/mfaf010","DOIUrl":"https://doi.org/10.1093/mtomcs/mfaf010","url":null,"abstract":"<p><p>Chelation therapy is a promising approach to mitigating health risks associated with toxic metal exposure, which contributes to cardiovascular disease, neurotoxicity, and other chronic conditions. disodium ethylene diamine tetraacetic acid (EDTA) is widely used, but its optimal dosing strategy remains unclear. This study evaluates the dose-dependent efficacy of EDTA in mobilizing toxic metals, including lead (Pb), cadmium (Cd), and gadolinium (Gd), while minimizing the loss of essential metals like copper (Cu) and manganese (Mn) to optimize therapeutic safety and efficacy. Ten volunteers (≥50 years) received 3 infusions at doses of 0.5, 1, and 3 g of EDTA over 30 min, 1 h, and 3 h, respectively. Urine and blood samples were analyzed pre- and post-infusion to assess pharmacokinetics of metal chelation. Urinary Pb excretion increased by 2200% at 0.5 g, with only a marginal gain at higher doses (3300%), supporting low-dose EDTA efficacy. Urinary Cd clearance required 3 g EDTA due to its strong tissue binding. Notably, Gd excretion increased by up to 78 000% even at 0.5 g EDTA, highlighting EDTA's potential to reduce long-term Gd burden post-MRI. Urinary excretion of essential metals varied, with Mn and Zn loss increasing at higher EDTA doses, underscoring the need for dose optimization while Cu and Ca only showed a clear increase urinary excretion at 3 g EDTA. Overall, a 0.5 g EDTA dose effectively mobilized Pb and Gd while minimizing essential metal depletion, reducing infusion time to 30 min, and improving patient compliance. These findings align with TACT and TACT 2 studies, reinforcing EDTA's long-term benefits in Pb reduction and supporting low-dose EDTA as a safe, efficient, and well-tolerated detoxification strategy.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"17 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951936","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}
引用次数: 0
Selective inhibition of NikA mediated Ni(II) import in E. coli by the Indium(III)-EDTA complex. 铟(III)-EDTA络合物选择性抑制NikA介导的大肠杆菌中Ni(II)的进口。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-03-28 DOI: 10.1093/mtomcs/mfaf008
Stephanie Sebastiampillai, Mark Nitz
{"title":"Selective inhibition of NikA mediated Ni(II) import in E. coli by the Indium(III)-EDTA complex.","authors":"Stephanie Sebastiampillai, Mark Nitz","doi":"10.1093/mtomcs/mfaf008","DOIUrl":"10.1093/mtomcs/mfaf008","url":null,"abstract":"<p><p>Nickel is a required nutrient for bacteria to produce [NiFe]-hydrogenase and urease enzymes. [NiFe]-hydrogenase catalyzes the reversible conversion of hydrogen into protons and electrons and urease catalyzes the hydrolysis of urea into carbon dioxide and ammonia-both key in bacterial pathogenesis. As such, nickel trafficking and homeostasis are interesting targets for potential antibacterial strategies. In E. coli, NikA binds a Ni(II)-(L-His)2 chelate in the periplasm and delivers this complex to the NikBCDE transporter. Blocking Ni(II) uptake by NikA would prevent the biosynthesis of active [NiFe]-hydrogenase. Fe(III)-EDTA is a potent ligand for NikA, however due to the potential for reduction of Fe(III) to Fe(II), it has limited utility. Using Fe(III)-EDTA as a starting point for inhibitor design, similar stable complexes of Bismuth(III), Lutetium(III) and Indium(III) were investigated. The In(III)-EDTA complex is a potent inhibitor of cellular [NiFe]-hydrogenase activity (IC50 of 600 μM ± 100 μM) while being nontoxic to bacterial growth. The mechanism of In(III)-EDTA hydrogenase inhibition was confirmed by the inhibition of Ni(II)-dependent processing of HycE (hydrogenase-3), which could be rescued with the addition of exogenous nickel. To elucidate the binding affinity of In(III)-EDTA to NikA, isothermal titration calorimetry (ITC) was carried out, revealing stoichiometric 1:1 binding with a Kd of 17.3 µM ± 3.0 µM. Indium concentrations determined by inductively coupled plasma mass spectrometry in E. coli cells in the presence or absence of NikA showed no discernable difference, further supporting the competitive inhibition of nickel uptake by blocking NikA.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555312","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}
引用次数: 0
Correlative analysis of metallomic gene expression and metal ion content within the mouse hippocampus. 小鼠海马金属组学基因表达与金属离子含量的相关性分析。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-03-28 DOI: 10.1093/mtomcs/mfaf009
Somayra S A Mamsa, Gaewyn Ellison, Julia Koehn, Keea Inder-Smith, Cameron W Evans, Ross M Graham, Daryl L Howard, Mark J Hackett
{"title":"Correlative analysis of metallomic gene expression and metal ion content within the mouse hippocampus.","authors":"Somayra S A Mamsa, Gaewyn Ellison, Julia Koehn, Keea Inder-Smith, Cameron W Evans, Ross M Graham, Daryl L Howard, Mark J Hackett","doi":"10.1093/mtomcs/mfaf009","DOIUrl":"10.1093/mtomcs/mfaf009","url":null,"abstract":"<p><p>Brain metal homeostasis is essential for healthy neurological function, and disturbed brain metal homeostasis has deleterious consequences for neurodevelopment or cognitive outcome following injury or during disease. Specific regions of the brain (e.g. the hippocampus and subregions within) are known to be enriched with transition metals (i.e. ions of iron, copper, and zinc). Neither the physiological need for localized enrichment, nor the mechanisms driving the enrichment, however, are well understood. In this study we have applied a multimodal template, incorporating elemental mapping using X-ray fluorescence microscopy with spatial transcriptomics, to help reveal a molecular basis for metallomic heterogeneity across key subregions of the hippocampus. Our results reveal that significant differences in iron, zinc, and copper enrichment are associated with regional enrichment of specific transcripts related to metal transport, metal storage, and metal regulatory proteins. In addition to providing novel biological insight into the neurometallomic profile of the hippocampus, this study also provides an important template for others to integrate transcriptomics into multimodal workflows investigating the neurometallome.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12086694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770770","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}
引用次数: 0
Perturbations in levels of essential metals less severe in Parkinson's disease without dementia than in Parkinson's disease dementia. 基本金属水平的扰动在无痴呆的帕金森病中比在帕金森病痴呆中更轻。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-03-07 DOI: 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":"10.1093/mtomcs/mfaf006","url":null,"abstract":"<p><p>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 multiregional decreases in Cu. The current work uses the same methods to ascertain whether this metallomic dysfunction is also present in the PD brain. To do this, tissue from 9 PD cases free of cognitive decline and 15 equivalent controls was obtained from 7 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. It was found that 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. 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":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895508/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
On the origin of metal species in the human brain: a perspective on key physicochemical properties. 人脑中金属种类的起源:从关键物理化学性质的角度看。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-03-07 DOI: 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":"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":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890113/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Time-resolved proteomic profiling of Cupriavidus metallidurans CH34 in the copper-induced viable-but-nonculturable state. 铜诱导的活但不可培养状态下金属铜球菌CH34的时间分辨蛋白质组学分析。
IF 2.9 3区 生物学
Metallomics Pub Date : 2025-03-07 DOI: 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-nonculturable state.","authors":"Timothej Patocka, Surya Gupta, Felice Mastroleo, Natalie Leys, Jean-Yves Matroule, Rob Van Houdt","doi":"10.1093/mtomcs/mfaf007","DOIUrl":"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-nonculturable (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 liquid chromatography tandem mass spectrometry (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":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11886801/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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