Metallomics最新文献_第4页

Antisense transcription is associated with expression of metal resistance determinants in Cupriavidus metallidurans CH34. 反义转录与Cupriavidus metallidurans CH34中抗金属决定因子的表达有关。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-12-02 DOI: 10.1093/mtomcs/mfae057

Cornelia Große, Jan Grau, Martin Herzberg, Dietrich H Nies

{"title":"Antisense transcription is associated with expression of metal resistance determinants in Cupriavidus metallidurans CH34.","authors":"Cornelia Große, Jan Grau, Martin Herzberg, Dietrich H Nies","doi":"10.1093/mtomcs/mfae057","DOIUrl":"10.1093/mtomcs/mfae057","url":null,"abstract":"Cupriavidus metallidurans is able to thrive in metal-rich environments but also survives metal starvation. Expression of metal resistance determinants in C. metallidurans was investigated on a global scale. Cupriavidus metallidurans was challenged with a MultiTox metal mix specifically designed for the wildtype strain CH34 and its plasmid-free derivative AE104, including treatment with ethylenediamintetraacetate (EDTA), or without challenge. The sense and antisense transcripts were analyzed in both strains and under all three conditions by RNASeq. A total of 10 757 antisense transcripts (ASTs) were assigned to sense signals from genes and untranslated regions, and 1 319 of these ASTs were expressed and were longer than 50 bases. Most of these (82%) were dual-use transcripts that contained antisense and sense regions, but ASTs (16%) were also observed that had no sense regions. Especially in metal-treated cells of strains CH34 and AE104, up- or down-regulated sense transcripts were accompanied by antisense transcription activities that were also regulated. The presence of selected asRNAs was verified by reverse transcription polymerase chain reaction (RT-PCR). Following metal stress, expression of genes encoding components of the respiratory chain, motility, transcription, translation, and protein export were down-regulated. This should also affect the integration of the metal efflux pumps into the membrane and the supply of the energy required to operate them. To solve this dilemma, transcripts for the metal efflux pumps may be stabilized by interactions with ASTs to allow their translation and import into the membrane. Alternatively, metal stress possibly causes recruitment of RNA polymerase from housekeeping genes for preferential expression of metal resistance determinants.","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/PMC11647585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674424","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

Alterations in zinc, copper, and iron levels in the retina and brain of Alzheimer's disease patients and the APP/PS1 mouse model. 阿尔茨海默病患者视网膜和大脑以及 APP/PS1 小鼠模型中锌、铜和铁水平的变化。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-12-02 DOI: 10.1093/mtomcs/mfae053

Seyed Mostafa Hosseinpour Mashkani, David P Bishop, Mika T Westerhausen, Paul A Adlard, S Mojtaba Golzan

{"title":"Alterations in zinc, copper, and iron levels in the retina and brain of Alzheimer's disease patients and the APP/PS1 mouse model.","authors":"Seyed Mostafa Hosseinpour Mashkani, David P Bishop, Mika T Westerhausen, Paul A Adlard, S Mojtaba Golzan","doi":"10.1093/mtomcs/mfae053","DOIUrl":"10.1093/mtomcs/mfae053","url":null,"abstract":"Transition metals like copper (Cu), iron (Fe), and zinc (Zn) are vital for normal central nervous system function and are also linked to neurodegeneration, particularly in the onset and progression of Alzheimer's disease (AD). Their alterations in AD, identified prior to amyloid plaque aggregation, offer a unique target for staging pre-amyloid AD. However, analysing their levels in the brain is extremely challenging, necessitating the development of alternative approaches. Here, we utilized laser ablation-inductively coupled plasma-mass spectrometry and solution nebulization-inductively coupled plasma-mass spectrometry to quantitatively measure Cu, Fe, and Zn concentrations in the retina and hippocampus samples obtained from human donors (i.e. AD and healthy controls), and in the amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of AD and wild-type (WT) controls, aged 9 and 18 months. Our findings revealed significantly elevated Cu, Fe, and Zn levels in the retina (*P < .05, P < .01, and P < .001) and hippocampus (*P < .05, *P < .05, and *P < .05) of human AD samples compared to healthy controls. Conversely, APP/PS1 mouse models exhibited notably lower metal levels in the same regions compared to WT mice-Cu, Fe, and Zn levels in the retina (**P < .01, *P < .05, and *P < .05) and hippocampus (**P < .01, **P < .01, and *P < .05). The contrasting metal profiles in human and mouse samples, yet similar patterns within each species' retina and brain, suggest the retina mirrors cerebral metal dyshomoeostasis in AD. Our findings lay the groundwork for staging pre-AD pathophysiology through assessment of transition metal levels in the retina.","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/PMC11630249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612942","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

Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring. 人体尿液中钙同位素变化的幅度和时间尺度：对骨量平衡监测的影响。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-07 DOI: 10.1093/mtomcs/mfae050

François L H Tissot, Dylan Cleveland, Rosa Grigoryan, Michael A Kipp, Roxana T Shafiee, Emily Miaou, Rithika Chunduri, Hayward Melton, Theo Tacail, Dan Razionale

{"title":"Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring.","authors":"François L H Tissot, Dylan Cleveland, Rosa Grigoryan, Michael A Kipp, Roxana T Shafiee, Emily Miaou, Rithika Chunduri, Hayward Melton, Theo Tacail, Dan Razionale","doi":"10.1093/mtomcs/mfae050","DOIUrl":"10.1093/mtomcs/mfae050","url":null,"abstract":"Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19-60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24-h pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2‰), which is partly due to anthropometric differences, as shown by a correlation between the participants' body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼±0.2-0.3‰) over timescales >160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross-sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB are presented.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589615","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

Nitrogen fertilizers activate siderophore production by the common scab causative agent Streptomyces scabiei. 氮肥能激活常见疮痂病病原菌疮痂链霉菌（Streptomyces scabiei）产生嗜苷酸盐。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-07 DOI: 10.1093/mtomcs/mfae048

Nudzejma Stulanovic, Yasmine Kerdel, Loïc Belde, Lucas Rezende, Benoit Deflandre, Pierre Burguet, Romane Denoel, Déborah Tellatin, Augustin Rigolet, Marc Hanikenne, Loïc Quinton, Marc Ongena, Sébastien Rigali

{"title":"Nitrogen fertilizers activate siderophore production by the common scab causative agent Streptomyces scabiei.","authors":"Nudzejma Stulanovic, Yasmine Kerdel, Loïc Belde, Lucas Rezende, Benoit Deflandre, Pierre Burguet, Romane Denoel, Déborah Tellatin, Augustin Rigolet, Marc Hanikenne, Loïc Quinton, Marc Ongena, Sébastien Rigali","doi":"10.1093/mtomcs/mfae048","DOIUrl":"10.1093/mtomcs/mfae048","url":null,"abstract":"Streptomyces scabiei is the causative agent of common scab on root and tuber crops. Life in the soil imposes intense competition between soil-dwelling microorganisms, and we evaluated here the antimicrobial properties of S. scabiei. Under laboratory culture conditions, increasing peptone levels correlated with increased growth inhibitory properties of S. scabiei. Comparative metabolomics showed that production of S. scabiei siderophores (desferrioxamines, pyochelin, scabichelin, and turgichelin) increased with the quantity of peptone, thereby suggesting that they participate in growth inhibition. Mass spectrometry imaging further confirmed that the zones of secreted siderophores and growth inhibition coincided. Moreover, either the repression of siderophore production or the neutralization of their iron-chelating activity led to increased microbial growth. Replacement of peptone by natural nitrogen sources regularly used as fertilizers such as ammonium nitrate, ammonium sulfate, sodium nitrate, and urea also triggered siderophore production in S. scabiei. The observed effect is not mediated by alkalinization of the medium as increasing the pH without providing additional nitrogen sources did not induce siderophore production. The nitrogen-induced siderophore production also inhibited the growth of important plant pathogens. Overall, our work suggests that not only the iron availability but also the nitrogen fertilizer sources could significantly impact the competition for iron between crop-colonizing microorganisms.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491266","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

Iron-sulfur cluster-dependent enzymes and molybdenum-dependent reductases in the anaerobic metabolism of human gut microbes. 人类肠道微生物厌氧代谢中的铁硫簇依赖酶和钼依赖还原酶。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-07 DOI: 10.1093/mtomcs/mfae049

Leah E Zahn, Paige M Gannon, Lauren J Rajakovich

引用次数: 0

Genome-wide identification and expression analysis of the ZRT, IRT-like protein (ZIP) family in Nicotiana tabacum. 烟草中 ZRT、IRT 样蛋白（ZIP）家族的全基因组鉴定和表达分析。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-07 DOI: 10.1093/mtomcs/mfae047

Zhijie Duan, Deka Reine Judesse Soviguidi, Bangzhen Pan, Rihua Lei, Zhongbang Song, Gang Liang

{"title":"Genome-wide identification and expression analysis of the ZRT, IRT-like protein (ZIP) family in Nicotiana tabacum.","authors":"Zhijie Duan, Deka Reine Judesse Soviguidi, Bangzhen Pan, Rihua Lei, Zhongbang Song, Gang Liang","doi":"10.1093/mtomcs/mfae047","DOIUrl":"10.1093/mtomcs/mfae047","url":null,"abstract":"Iron (Fe) and Zinc (Zn) are essential micronutrients for plant growth and development. ZIP (ZRT, IRT-like protein) transporters, known for their role in the regulation of Zinc and Iron uptake, are pivotal in facilitating the absorption, transport, and maintenance of Fe/Zn homeostasis in plants. Nicotiana tabacum has been widely used as a model plant for gene function analysis; however, the tobacco ZIP genes have not been identified systematically. In this study, we have identified a comprehensive set of 32 NtZIP genes, which were phylogenetically categorized into three distinct clades. The gene structures, characterized by their exon/intron organization, and the protein motifs are relatively conserved, particularly among genes within the same clade. These NtZIP genes exhibit an uneven distribution across 12 chromosomes. The gene localization analysis revealed the presence of 11 pairs of homeologous locus genes and 7 pairs of tandem duplication genes within the genome. To further explore the functionality of these genes, real-time quantitative reverse transcription PCR was employed to assess their expression levels in roots subjected to metal deficiency. The results indicated that certain NtZIP genes are specifically upregulated in response to either Fe or Zn deficiency. Additionally, the presence of specific cis-elements within their promoter regions, such as the E-box associated with Fe deficiency response and the ZDRE box linked to Zn deficiency response, was identified. This study lays a foundational groundwork for future research into the biological functions of NtZIP genes in tobacco in micronutrient regulation and homeostasis.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398749","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

Cellular targets of cytotoxic copper phenanthroline complexes: a multimodal imaging quantitative approach in single PC3 cells. 细胞毒性菲罗啉铜复合物的细胞靶标：单个 PC3 细胞的多模态成像定量方法。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-11-07 DOI: 10.1093/mtomcs/mfae051

Teresa Pinheiro, Luís C Alves, António P Matos, Isabel Correia, João Costa Pessoa, Fernanda Marques

{"title":"Cellular targets of cytotoxic copper phenanthroline complexes: a multimodal imaging quantitative approach in single PC3 cells.","authors":"Teresa Pinheiro, Luís C Alves, António P Matos, Isabel Correia, João Costa Pessoa, Fernanda Marques","doi":"10.1093/mtomcs/mfae051","DOIUrl":"10.1093/mtomcs/mfae051","url":null,"abstract":"Metal complexes are emerging as promising alternatives to traditional platinum-based cancer treatments, offering reduced side effects. However, understanding their cellular uptake and distribution and quantifying their presence at the single cell level remains challenging. Advanced imaging techniques, including transmission electron microscopy, synchrotron radiation X-ray fluorescence, and energetic ion beam-based nuclear microscopy (scanning transmission ion microscopy, particle-induced X-ray emission, elastic backscattering spectrometry), allow detailed high-resolution visualization of structure and morphology, high sensitivity for elemental detection with quantification within single cells, and the construction of 3D models of metal distribution, positioning them as powerful tools for assessing the cellular uptake and compartmentalization of complexes. Three Cu(II) complexes [Cu(phen)2(H2O)](NO3)2 (1), [Cu(Me2phen)2(NO3)]NO3 (2) and [Cu(amphen)2(H2O)](NO3)2 (3), (phen = 1,10-phenanthroline, Me2phen = 4,7-dimethyl-1,10-phen, amphen = 5-amino-phen) were investigated for Cu uptake and distribution in PC3 prostate cancer cells. All complexes show significant Cu uptake regardless of media concentration. Cu concentrations in the cytoplasm and nucleus are similar between treatments. Complexes 1 and 3 concentrate Cu in the nuclear region and show a vesicle-like pattern around the nucleus, while 2 shows a dispersed cytoplasmic pattern with large vesicles. The 3D models confirm that Cu is not retained at the plasma membrane, with complex 1 targeting the nucleus and 2 remaining in the cytoplasm. These results highlight the importance of quantifying metal distribution and correlating it with structural changes to understand the relevance of the ligand in the mechanisms of cellular uptake and targeting, crucial for the development of effective metal-based cancer therapies.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602433","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

ATH434, a promising iron-targeting compound for treating iron regulation disorders. ATH434，一种有望治疗铁调节紊乱的铁靶向化合物。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-10-04 DOI: 10.1093/mtomcs/mfae044

Ashley E Pall, Silas Bond, Danielle K Bailey, Christopher S Stoj, Isabel Deschamps, Penny Huggins, Jack Parsons, Margaret J Bradbury, Daniel J Kosman, Timothy L Stemmler

{"title":"ATH434, a promising iron-targeting compound for treating iron regulation disorders.","authors":"Ashley E Pall, Silas Bond, Danielle K Bailey, Christopher S Stoj, Isabel Deschamps, Penny Huggins, Jack Parsons, Margaret J Bradbury, Daniel J Kosman, Timothy L Stemmler","doi":"10.1093/mtomcs/mfae044","DOIUrl":"10.1093/mtomcs/mfae044","url":null,"abstract":"Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. ≤10-31) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd's of 1-4 µM), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low/moderate affinities for Fe3+(0.46-9.59 µM) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337493","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

Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development. 哺乳动物细胞发育中铜介导转录调控的新视角

IF 2.9 3区生物学

Metallomics Pub Date : 2024-10-04 DOI: 10.1093/mtomcs/mfae046

Fa'alataitaua M Fitisemanu, Teresita Padilla-Benavides

{"title":"Emerging perspectives of copper-mediated transcriptional regulation in mammalian cell development.","authors":"Fa'alataitaua M Fitisemanu, Teresita Padilla-Benavides","doi":"10.1093/mtomcs/mfae046","DOIUrl":"10.1093/mtomcs/mfae046","url":null,"abstract":"Copper (Cu) is a vital micronutrient necessary for proper development and function of mammalian cells and tissues. Cu mediates the function of redox active enzymes that facilitate metabolic processes and signaling pathways. Cu levels are tightly regulated by a network of Cu-binding transporters, chaperones, and small molecule ligands. Extensive research has focused on the mammalian Cu homeostasis (cuprostasis) network and pathologies, which result from mutations and perturbations. There are roles for Cu-binding proteins as transcription factors (Cu-TFs) and regulators that mediate metal homeostasis through the activation or repression of genes associated with Cu handling. Emerging evidence suggests that Cu and some Cu-TFs may be involved in the regulation of targets related to development-expanding the biological roles of Cu-binding proteins. Cu and Cu-TFs are implicated in embryonic and tissue-specific development alongside the mediation of the cellular response to oxidative stress and hypoxia. Cu-TFs are also involved in the regulation of targets implicated in neurological disorders, providing new biomarkers and therapeutic targets for diseases such as Parkinson's disease, prion disease, and Friedreich's ataxia. This review provides a critical analysis of the current understanding of the role of Cu and cuproproteins in transcriptional regulation.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386461","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

Electron microscopy evidence of gadolinium toxicity being mediated through cytoplasmic membrane dysregulation. 电子显微镜证据表明，钆的毒性是通过细胞质膜失调介导的。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-10-04 DOI: 10.1093/mtomcs/mfae042

Trevor Arino, David Faulkner, Karen C Bustillo, Dahlia D An, Danielle Jorgens, Solène Hébert, Carla McKinley, Michael Proctor, Alex Loguinov, Christopher Vulpe, Rebecca J Abergel

{"title":"Electron microscopy evidence of gadolinium toxicity being mediated through cytoplasmic membrane dysregulation.","authors":"Trevor Arino, David Faulkner, Karen C Bustillo, Dahlia D An, Danielle Jorgens, Solène Hébert, Carla McKinley, Michael Proctor, Alex Loguinov, Christopher Vulpe, Rebecca J Abergel","doi":"10.1093/mtomcs/mfae042","DOIUrl":"10.1093/mtomcs/mfae042","url":null,"abstract":"Past functional toxicogenomic studies have indicated that genes relevant to membrane lipid synthesis are important for tolerance to the lanthanides. Moreover, previously reported imaging of patient's brains following administration of gadolinium-based contrast agents shows gadolinium lining the vessels of the brain. Taken together, these findings suggest the disruption of cytoplasmic membrane integrity as a mechanism by which lanthanides induce cytotoxicity. In the presented work we used scanning transmission electron microscopy and spatially resolved elemental spectroscopy to image the morphology and composition of gadolinium, europium, and samarium precipitates that formed on the outside of yeast cell membranes. In no sample did we find that the lanthanide contaminant had crossed the cell membrane, even in experiments using yeast mutants with disrupted genes for sphingolipid synthesis-the primary lipids found in yeast cytoplasmic membranes. Rather, we have evidence that lanthanides are co-located with phosphorus outside the yeast cells. These results lead us to hypothesize that the lanthanides scavenge or otherwise form complexes with phosphorus from the sphingophospholipid head groups in the cellular membrane, thereby compromising the structure or function of the membrane, and gaining the ability to disrupt membrane function without entering the cell.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306616","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