Metallomics最新文献

{"title":"Bile from the hemojuvelin-deficient mouse model of iron excess is enriched in iron and ferritin.","authors":"Milankumar Prajapati, Lauren Chiu, Jared Z Zhang, Grace S Chong, Nicholas A DaSilva, Thomas B Bartnikas","doi":"10.1093/mtomcs/mfae043","DOIUrl":"10.1093/mtomcs/mfae043","url":null,"abstract":"<p><p>Iron is an essential nutrient but is toxic in excess. Iron deficiency is the most prevalent nutritional deficiency and typically linked to inadequate intake. Iron excess is also common and usually due to genetic defects that perturb expression of hepcidin, a hormone that inhibits dietary iron absorption. Our understanding of iron absorption far exceeds that of iron excretion, which is believed to contribute minimally to iron homeostasis. Prior to the discovery of hepcidin, multiple studies showed that excess iron undergoes biliary excretion. We recently reported that wild-type mice raised on an iron-rich diet have increased bile levels of iron and ferritin, a multi-subunit iron storage protein. Given that genetic defects leading to excessive iron absorption are much more common causes of iron excess than dietary loading, we set out to determine if an inherited form of iron excess known as hereditary hemochromatosis also results in bile iron loading. We employed mice deficient in hemojuvelin, a protein essential for hepcidin expression. Mutant mice developed bile iron and ferritin excess. While lysosomal exocytosis has been implicated in ferritin export into bile, knockdown of Tfeb, a regulator of lysosomal biogenesis and function, did not impact bile iron or ferritin levels. Bile proteomes differed between female and male mice for wild-type and hemojuvelin-deficient mice, suggesting sex and iron excess impact bile protein content. Overall, our findings support the notion that excess iron undergoes biliary excretion in genetically determined iron excess.</p>","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/PMC11459263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306615","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":"Putative retina metal/metalloid-binding proteins: molecular functions, biological processes and retina disease associations.","authors":"Marta Ugarte, Craig Lawless","doi":"10.1093/mtomcs/mfae045","DOIUrl":"10.1093/mtomcs/mfae045","url":null,"abstract":"<p><p>The mammalian retina contains high amounts of metals/metalloid-selenium. Their dyshomeostases are associated with certain retinal diseases. We carried out this bioinformatics study to identify the relationships between putative retinal metal/selenium binding proteins, their molecular functions, and biological processes. Identification of putative mouse metal/selenium binding proteins was based on known binding motifs, domains, patterns, and profiles. Annotations were obtained from Uniprot keywords 'metal binding', 'metal ion co-factors', 'selenium proteins'. Protein functions were estimated by associative frequency with key words in UniProt annotations. The raw data of five mouse proteomics PRIDE datasets (available to date) were downloaded and processed with Mascot against the mouse taxa of Uniprot (SwissProt/Trembl) and MaxQuant (version 1.6.10.43) for qualitative and quantitative datasets, respectively. Clinically relevant variants were evaluated using archives and aggregated information in ClinVar. The 438 proteins common to all the retina proteomics datasets were used to identify over-represented Gene Ontology categories. The putative mouse retinal metal/metalloid binding proteins identified are mainly involved in: (1) metabolic processes (enzymes), (2) homeostasis, (3) transport (vesicle mediated, transmembrane, along microtubules), (4) cellular localization, (5) regulation of signalling and exocytosis, (6) organelle organization, (7) (de)phosphorylation, and (8) complex assembly. Twenty-one proteins were identified as involved in response to light stimulus and/or visual system development. An association of metal ion binding proteins rhodopsin, photoreceptor specific nuclear receptor, calcium binding protein 4 with disease-related mutations in inherited retinal conditions was identified, where the mutations affected an area within or in close proximity to the metal binding site or domain. These findings suggest a functional role for the putative metal/metalloid binding site in retinal proteins in certain retinal disorders.</p>","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/PMC11523097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337494","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":"Thermodynamic origin of the affinity, selectivity and domain specificity of metallothionein for essential and toxic metal ions.","authors":"Colette F Quinn,Dean E Wilcox","doi":"10.1093/mtomcs/mfae041","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae041","url":null,"abstract":"The small Cys-rich protein metallothionein (MT) binds several metal ions in clusters within its two domains. While the affinity of MT for both toxic and essential metals has been well studied, the thermodynamics of this binding has not. We have used isothermal titration calorimetry measurements to quantify the change in enthalpy (ΔH) and change in entropy (ΔS) when metal ions bind to the two ubiquitous isoforms of MT. The seven Zn2+ that bind sequentially at pH 7.4 do so in two populations with different coordination thermodynamics, an initial four that bind randomly with individual tetra-thiolate coordination and a subsequent three that bind with bridging thiolate coordination to assemble the metal clusters. The high affinity of MT for both populations is due to a very favourable binding entropy that far outweighs an unfavourable binding enthalpy. This originates from a net enthalpic penalty for Zn2+ displacement of protons from the Cys thiols and a favourable entropic contribution from the displaced protons. The thermodynamics of other metal ions binding to MT were determined by their displacement of Zn2+ from Zn7MT and subtraction of the Zn2+-binding thermodynamics. Toxic Cd2+, Pb2+ and Ag+, and essential Cu+, also bind to MT with a very favourable binding entropy but a net binding enthalpy that becomes increasingly favourable as the metal ion becomes a softer Lewis acid. These thermodynamics are the origin of the high affinity, selectivity and domain specificity of MT for these metal ions and the molecular basis for their in vivo binding competition.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"41 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261234","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":"Nanoscale elemental and morphological imaging of nitrogen-fixing cyanobacteria.","authors":"Bobby G Duersch,Steven A Soini,Yanqi Luo,Xiaoyang Liu,Si Chen,Vivian M Merk","doi":"10.1093/mtomcs/mfae040","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae040","url":null,"abstract":"Nitrogen-fixing cyanobacteria bind atmospheric nitrogen and carbon dioxide using sunlight. This experimental study focused on a laboratory-based model system, Anabaena sp., in nitrogen-depleted culture. When combined nitrogen is scarce, the filamentous procaryotes reconcile photosynthesis and nitrogen fixation by cellular differentiation into heterocysts. To better understand the influence of micronutrients on cellular function, 2D and 3D synchrotron X-ray fluorescence mappings were acquired from whole biological cells in their frozen-hydrated state at the Bionanoprobe, Advanced Photon Source. To study elemental homeostasis within these chain-like organisms, biologically relevant elements were mapped using X-ray fluorescence spectroscopy and energy-dispersive X-ray microanalysis. Higher levels of cytosolic K+, Ca2+, and Fe2+ were measured in the heterocyst than in adjacent vegetative cells, supporting the notion of elevated micronutrient demand. P-rich clusters, identified as polyphosphate bodies involved in nutrient storage, metal detoxification and osmotic regulation, were consistently co-localized with K+ and occasionally sequestered Mg2+, Ca2+, Fe2+, and Mn2+ ions. Machine-learning based k-mean clustering revealed that P/K clusters were associated with either Fe or Ca, with Fe and Ca clusters also occurring individually. In accordance with XRF nanotomography, distinct P/K-containing clusters close to the cellular envelope were surrounded by larger Ca-rich clusters. The transition metal Fe, which is part of nitrogenase enzyme, was detected as irregular shaped clusters. The elemental composition and cellular morphology of diazotrophic Anabaena sp. was visualized by multimodal imaging using AFM, SEM, and fluorescence microscopy. This paper discusses the first experimental results obtained with a combined in-line optical and X-ray fluorescence microscope at the Bionanoprobe.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"40 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261235","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":"Decreased spinal cord motor neuron numbers in mice depleted of central nervous system copper.","authors":"J R Liddell,J B W Hilton,Y J Wang,J L Billings,S Nikseresht,K Kysenius,J P Fuller-Jackson,D J Hare,P J Crouch","doi":"10.1093/mtomcs/mfae036","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae036","url":null,"abstract":"Disrupted copper availability in the central nervous system (CNS) is implicated as a significant feature of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). Solute carrier family 31 member 1 (Slc31a1; Ctr1) governs copper uptake in mammalian cells and mutations affecting Slc31a1 are associated with severe neurological abnormalities. Here, we examined the impact of decreased CNS copper caused by ubiquitous heterozygosity for functional Slc31a1 on spinal cord motor neurons in Slc31a1+/- mice. Congruent with the CNS being relatively susceptible to disrupted copper availability, brain and spinal cord tissue from Slc31a1+/- mice contained significantly less copper than wild-type littermates, even though copper levels in other tissues were unaffected. Slc31a1+/- mice had less spinal cord α-motor neurons compared to wild-type littermates but they did not develop any overt physical signs of motor impairment. By contrast, ALS model SOD1G37R mice had fewer α-motor neurons than control mice and exhibited clear signs of motor function impairment. With the expression of Slc31a1 notwithstanding, spinal cord expression of genes related to copper handling revealed only minor differences between Slc31a1+/- and wild-type mice. This contrasted with SOD1G37R mice where changes in the expression of copper handling genes were pronounced. Similarly, the expression of genes related to toxic glial activation were unchanged in spinal cords from Slc31a1+/- mice but highly up-regulated in SOD1G37R mice. Together, results from the Slc31a1+/- mice and SOD1G37R mice indicate that although depleted CNS copper has a significant impact on spinal cord motor neuron numbers, the manifestation of overt ALS-like motor impairment requires additional factors.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"7 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142204052","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":"Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer's disease.","authors":"Brandon Mahan, Yan Hu, Esther Lahoud, Mark Nestmeyer, Alex McCoy-West, Grace Manestar, Christopher Fowler, Ashley I Bush, Frédéric Moynier","doi":"10.1093/mtomcs/mfae038","DOIUrl":"10.1093/mtomcs/mfae038","url":null,"abstract":"<p><p>The Alzheimer's disease (AD)-affected brain purges K with concurrently increasing serum K, suggesting brain-blood K transferal. Here, natural stable K isotope ratios-δ41K-of human serum samples were characterized in an AD biomarker pilot study (plus two paired Li-heparin and potassium ethylenediaminetetraacetic acid [K-EDTA] plasma samples). AD serum was found to have a significantly lower mean δ41K relative to controls. To mechanistically explore this change, novel ab initio calculations (density functional theory) of relative K isotope compositions between hydrated K+ and organically bound K were performed, identifying hydrated K+ as isotopically light (lower δ41K) compared to organically bound K. Taken together with literature, serum δ41K and density functional theory results are consistent with efflux of hydrated K+ from the brain to the bloodstream, manifesting a measurable decrease in serum δ41K. These data introduce serum δ41K for further investigation as a minimally invasive AD biomarker, with cost, scalability, and stability advantages over current techniques.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102323","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":"NtZIP5A/B is involved in the regulation of Zn/Cu/Fe/Mn/Cd homeostasis in tobacco.","authors":"Małgorzata Palusińska, Anna Barabasz, Danuta Maria Antosiewicz","doi":"10.1093/mtomcs/mfae035","DOIUrl":"10.1093/mtomcs/mfae035","url":null,"abstract":"<p><p>Plants grow in soils with varying concentrations of microelements, often in the presence of toxic metals e.g. Cd. To cope, they developed molecular mechanisms to regulate metal cross-homeostasis. Understanding underlying complex relationships is key to improving crop productivity. Recent research suggests that the Zn and Cd uptake protein NtZIP5A/B [Zinc-regulated, Iron-regulated transporter-like Proteins (ZIPs)] from tobacco (Nicotiana tabacum L. v. Xanthi) is involved in the regulation of a cross-talk between the two metals. Here, we support this conclusion by showing that RNAi-mediated silencing of NtZIP5A/B resulted in a reduction of Zn accumulation and that this effect was significantly enhanced by the presence of Cd. Our data also point to involvement of NtZIP5B in regulating a cross-talk between Cu, Fe, and Mn. Using yeast growth assays, Cu (but not Fe or Mn) was identified as a substrate for NtZIP5B. Furthermore, GUS-based analysis showed that the tissue-specific activity of the NtZIP5B promoter was different in each of the Zn-/Cu-/Fe-/Mn deficiencies applied with/without Cd. The results indicate that NtZIP5B is involved in maintaining multi-metal homeostasis under conditions of Zn, Cu, Fe, and Mn deficiency, and also in the presence of Cd. It was concluded that the protein regulates the delivery of Zn and Cu specifically to targeted different root cells depending on the Zn/Cu/Fe/Mn status. Importantly, in the presence of Cd, the activity of the NtZIP5B promoter is lost in meristematic cells and increased in mature root cortex cells, which can be considered a manifestation of a defense mechanism against its toxic effects.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858251","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":"Insight into brain metallothioneins from bidirectional Zn2+ signaling in synaptic dynamics.","authors":"Atsushi Takeda, Haruna Tamano","doi":"10.1093/mtomcs/mfae039","DOIUrl":"10.1093/mtomcs/mfae039","url":null,"abstract":"<p><p>The basal levels as the labile Zn2+ pools in the extracellular and intracellular compartments are in the range of ∼10 nM and ∼100 pM, respectively. The influx of extracellular Zn2+ is used for memory via cognitive activity and is regulated for synaptic plasticity, a cellular mechanism of memory. When Zn2+ influx into neurons excessively occurs, however, it becomes a critical trigger for cognitive decline and neurodegeneration, resulting in acute and chronic pathogenesis. Aging, a biological process, generally accelerates vulnerability to neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). The basal level of extracellular Zn2+ is age relatedly increased in the rat hippocampus, and the influx of extracellular Zn2+ contributes to accelerating vulnerability to the AD and PD pathogenesis in experimental animals with aging. Metallothioneins (MTs) are Zn2+-binding proteins for cellular Zn2+ homeostasis and involved in not only supplying functional Zn2+ required for cognitive activity, but also capturing excess (toxic) Zn2+ involved in cognitive decline and neurodegeneration. Therefore, it is estimated that regulation of MT synthesis is involved in both neuronal activity and neuroprotection. The present report provides recent knowledge regarding the protective/preventive potential of MT synthesis against not only normal aging but also the AD and PD pathogenesis in experimental animals, focused on MT function in bidirectional Zn2+ signaling in synaptic dynamics.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118406","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":"Retraction of: Characterising the spatial and temporal brain metal profile in a mouse model of tauopathy.","authors":"","doi":"10.1093/mtomcs/mfae037","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae037","url":null,"abstract":"","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"29 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261236","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":"P-based referencing for correcting tissue artifacts in laser ablation-inductively coupled plasma-mass spectrometry imaging of cancer samples.","authors":"Katharina Kronenberg, Emily Hoffmann, Lena Hiddeßen, Bastian Maus, Mirjam Gerwing, Cornelius Faber, Michael Sperling, Moritz Wildgruber, Uwe Karst","doi":"10.1093/mtomcs/mfae034","DOIUrl":"10.1093/mtomcs/mfae034","url":null,"abstract":"<p><p>A referencing strategy based on the element P is presented to compensate for cryosectioning tissue artifacts in laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) data. The study examines how the gadolinium-based contrast agent Gadofosveset is distributed in murine cancer tissue, and illustrates how referenced images can compensate for tissue artifacts like folds, overlaps, and density variations. Compared to non-referenced images that provide information on the absolute distribution of the analyte, referenced images allow for the representation of the analyte distribution relative to the amount of material introduced into the instrument, which in this case is correlated to the P signal. Tissue artifacts were corrected in referenced images for both Gadofosveset and endogenous elements, such as Fe and Zn. Additionally, the referencing approach provides valuable information on the Gd uptake relative to the tissue density in necrotic compared to vital tumor areas, which is not obtained from in vivo magnetic resonance imaging (MRI) data. However, validation of in vivo MRI and ex vivo LA-ICP-MS methods was possible by establishing a mean ratio of necrotic to vital tumor areas in the T1-weighted image post Gadofosveset injection and the non-referenced LA-ICP-MS image of Gd. In summary, P-based correction of LA-ICP-MS imaging data allows for a more accurate spatial representation of certain elements, including endogenous and exogenous elements such as injected contrast agents.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858252","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}