IF 3.4 3区生物学

Metallomics Pub Date : 2024-06-12 DOI: 10.1093/mtomcs/mfae029

Steven Hutchens, Ashvini Melkote, Thomas Jursa, William Shawlot, Leonardo Trasande, Donald R Smith, Somshuvra Mukhopadhyay

{"title":"Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter.","authors":"Steven Hutchens, Ashvini Melkote, Thomas Jursa, William Shawlot, Leonardo Trasande, Donald R Smith, Somshuvra Mukhopadhyay","doi":"10.1093/mtomcs/mfae029","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae029","url":null,"abstract":"Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is a Mn efflux transporter that controls body Mn levels. We previously reported that full-body Slc30a10 knockout mice: (1) recapitulate the body Mn retention phenotype of humans with loss-of-function SLC30A10 mutations; and (2) unexpectedly, develop hypothyroidism induced by Mn accumulation in the thyroid, which reduces intra-thyroid thyroxine. Subsequent analyses of National Health and Nutrition Examination Survey data identified an association between serum Mn and subclinical thyroid changes. The emergence of thyroid deficits as a feature of Mn toxicity suggests that changes in thyroid function may be an underappreciated, but critical, modulator of Mn-induced disease. To better understand the relationship between thyroid function and Mn toxicity, here we further defined the mechanism of Mn-induced hypothyroidism using mouse and rat models. Slc30a10 knockout mice exhibited a profound deficit in thyroid iodine levels that occurred contemporaneously with increases in thyroid Mn and preceded the onset of overt hypothyroidism. Wild-type Mn-exposed mice also exhibited increased thyroid Mn levels, an inverse correlation between thyroid Mn and iodine levels, and subclinical hypothyroidism. In contrast, thyroid iodine levels were unaltered in newly-generated Slc30a10 knockout rats despite an increase in thyroid Mn, and the knockout rats were euthyroid. Thus, Mn-induced thyroid dysfunction in genetic or Mn exposure-induced mouse models occurs due to a reduction in thyroid iodine subsequent to an increase in thyroid Mn. Moreover, rat and mouse thyroids have differential sensitivities to Mn, which may impact the manifestations of Mn-induced disease in these routinely-used animal models.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309686","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

Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro. 红细胞释放的碳酸酐酶 I 与人体血浆在体外的相互作用。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-06-04 DOI: 10.1093/mtomcs/mfae028

Maryam Doroudian, Jürgen Gailer

{"title":"Interaction of carbonic anhydrase I released from red blood cells with human plasma in vitro.","authors":"Maryam Doroudian, Jürgen Gailer","doi":"10.1093/mtomcs/mfae028","DOIUrl":"10.1093/mtomcs/mfae028","url":null,"abstract":"Red blood cells (RBCs) constitute ∼50% of the bloodstream and represent an important target for environmental pollutants and bacterial/viral infections, which can result in their rupture. In addition, diseases such as sickle cell anaemia and paroxysmal nocturnal haemoglobinuria can also result in the rupture of RBCs, which can be potentially life-threatening. With regard to the release of cytosolic metalloproteins from RBCs into the blood-organ system, the biochemical fate of haemoglobin is rather well understood, while comparatively little is known about another highly abundant Zn-metalloprotein, carbonic anhydrase (CA I). To gain insight into the interaction of CA I with human blood plasma constituents, we have employed a metallomics tool comprised of size-exclusion chromatography (SEC) coupled online with an inductively coupled plasma atomic emission spectrometer (ICP-AES), which allows to simultaneously observe all Cu, Fe, and Zn-metalloproteins. After the addition of CA I to human blood plasma incubated at 37°C, the SEC-ICP-AES analysis using phosphate buffered saline (pH 7.4) after 5 min, 1 h, and 2 h revealed that CA I eluted after all endogenous Zn-metalloproteins in the 30 kDa range. Matrix-assisted laser desorption-time of flight mass spectrometry analysis of the collected Zn-peak confirmed that CA I eluted from the column intact. Our in vitro results suggest that CA I released from RBCs to plasma remains free and may be actively involved in health-relevant adverse processes that unfold at the bloodstream-endothelial interface, including atherosclerosis and vision loss.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173751","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

Novel binuclear copper(II) complexes with sulfanylpyrazole ligands: synthesis, crystal structure, fungicidal, cytostatic, and cytotoxic activity. 具有硫酰吡唑配体的新型双核铜（II）配合物：合成、晶体结构、杀菌、细胞抑制和细胞毒性活性。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-06-04 DOI: 10.1093/mtomcs/mfae024

Vnira R Akhmetova, Nail S Akhmadiev, Aidar T Gubaidullin, Aida I Samigullina, Andrey B Glazyrin, Rais A Sadykov, Diana V Ishmetova, Yulia V Vakhitova

引用次数: 0

Dietary and homeostatic controls of Zn isotopes in rats: a controlled feeding experiment and modeling approach. 大鼠体内锌同位素的膳食和体内平衡控制：控制进食实验和建模方法。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-06-04 DOI: 10.1093/mtomcs/mfae026

Nicolas Bourgon, Théo Tacail, Klervia Jaouen, Jennifer N Leichliter, Jeremy McCormack, Daniela E Winkler, Marcus Clauss, Thomas Tütken

{"title":"Dietary and homeostatic controls of Zn isotopes in rats: a controlled feeding experiment and modeling approach.","authors":"Nicolas Bourgon, Théo Tacail, Klervia Jaouen, Jennifer N Leichliter, Jeremy McCormack, Daniela E Winkler, Marcus Clauss, Thomas Tütken","doi":"10.1093/mtomcs/mfae026","DOIUrl":"10.1093/mtomcs/mfae026","url":null,"abstract":"The stable isotope composition of zinc (δ66Zn), which is an essential trace metal for many biological processes in vertebrates, is increasingly used in ecological, archeological, and paleontological studies to assess diet and trophic level discrimination among vertebrates. However, the limited understanding of dietary controls and isotopic fractionation processes on Zn isotope variability in animal tissues and biofluids limits precise dietary reconstructions. The current study systematically investigates the dietary effects on Zn isotope composition in consumers using a combined controlled feeding experiment and box-modeling approach. For this purpose, 21 rats were fed one of seven distinct animal- and plant-based diets and a total of 148 samples including soft and hard tissue, biofluid, and excreta samples of these individuals were measured for δ66Zn. Relatively constant Zn isotope fractionation is observed across the different dietary groups for each tissue type, implying that diet is the main factor controlling consumer tissue δ66Zn values, independent of diet composition. Furthermore, a systematic δ66Zn diet-enamel fractionation is reported for the first time, enabling diet reconstruction based on δ66Zn values from tooth enamel. In addition, we investigated the dynamics of Zn isotope variability in the body using a box-modeling approach, providing a model of Zn isotope homeostasis and inferring residence times, while also further supporting the hypothesis that δ66Zn values of vertebrate tissues are primarily determined by that of the diet. Altogether this provides a solid foundation for refined (paleo)dietary reconstruction using Zn isotopes of vertebrate tissues.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955253","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

Association of barium deficiency with Type 2 diabetes mellitus incident risk was mediated by mitochondrial DNA copy number (mtDNA-CN): A follow-up study. 线粒体DNA拷贝数（mtDNA-CN）介导钡缺乏症与2型糖尿病发病风险的关系：随访研究。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-21 DOI: 10.1093/mtomcs/mfae027

Yiqin Zhang, Jing Ye, Lina Zhou, Xianfa Xuan, Liping Xu, Xia Cao, Tianyu Lv, Jianhua Yan, Siyu Zhang, Yuxin Wang, Qingyu Huang, Meiping Tian

{"title":"Association of barium deficiency with Type 2 diabetes mellitus incident risk was mediated by mitochondrial DNA copy number (mtDNA-CN): A follow-up study.","authors":"Yiqin Zhang, Jing Ye, Lina Zhou, Xianfa Xuan, Liping Xu, Xia Cao, Tianyu Lv, Jianhua Yan, Siyu Zhang, Yuxin Wang, Qingyu Huang, Meiping Tian","doi":"10.1093/mtomcs/mfae027","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae027","url":null,"abstract":"Accumulating evidence indicates that plasma metals levels may associate with Type 2 diabetes mellitus (T2DM) incident risk. Mitochondrial function such as mitochondrial DNA copy number (mtDNA-CN) might be linked metal exposure and physiological metabolism. Mediation analysis was conducted to determine the mediating roles of mtDNA-CN in the associations of plasma metals with diabetes risk. In the present study, we investigated associations between plasma metals levels, mtDNA-CN and T2DM incident in elderly population with 6-year follow-up (2 times) study. Ten plasma metals (i.e. manganese (Mg), aluminium (Al), calcium (Ca), ferrum (Fe), barium (Ba), arsenic (As), copper (Cu), selenium (Se), titanium (Ti) and cesium (Sr) were measured by using inductively coupled plasma mass spectrometry (ICP-MS). Mitochondrial DNA copy number was measured by real-time PCR. Multivariable linear regression and logistic regression models were carried out to estimate the relationship between plasma metal concentrations, mtDNA-CN and T2DM incident risk in the current work. Plasma Ba deficiency and mtDNA-CN decline associated with T2DM incident risk during aging process. Meanwhile plasma Ba found to be positively associated with mtDNA-CN. Mitochondrial function mtDNA-CN demonstrated mediating effects in association between plasma Ba deficiency and T2DM incident risk, and 49.8% of the association was mediated by mtDNA-CN. These findings extend the knowledge of T2DM incident risk factors and highlight the point that mtDNA-CN may be linked metals element and T2DM incident risk.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074383","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

Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript. 草履虫暴露于镉的特异性阶段确定了独特的转录组反应级联和一种未表征的镉反应转录本。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae016

Norah Almutairi, Naema Khan, Alexandra Harrison-Smith, Volker M Arlt, Stephen R Stürzenbaum

{"title":"Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript.","authors":"Norah Almutairi, Naema Khan, Alexandra Harrison-Smith, Volker M Arlt, Stephen R Stürzenbaum","doi":"10.1093/mtomcs/mfae016","DOIUrl":"10.1093/mtomcs/mfae016","url":null,"abstract":"Age/stage sensitivity is considered a significant factor in toxicity assessments. Previous studies investigated cadmium (Cd) toxicosis in Caenorhabditis elegans, and a plethora of metal-responsive genes/proteins have been identified and characterized in fine detail; however, most of these studies neglected age sensitivity and stage-specific response to toxicants at the molecular level. This present study compared the transcriptome response between C. elegans L3 vs L4 larvae exposed to 20 µM Cd to explore the transcriptional hallmarks of stage sensitivity. The results showed that the transcriptome of the L3 stage, despite being exposed to Cd for a shorter period, was more affected than the L4 stage, as demonstrated by differences in transcriptional changes and magnitude of induction. Additionally, T08G5.1, a hitherto uncharacterized gene located upstream of metallothionein (mtl-2), was transcriptionally hyperresponsive to Cd exposure. Deletion of one or both metallothioneins (mtl-1 and/or mtl-2) increased T08G5.1 expression, suggesting that its expression is linked to the loss of metallothionein. The generation of an extrachromosomal transgene (PT08G5.1:: GFP) revealed that T08G5.1 is constitutively expressed in the head neurons and induced in gut cells upon Cd exposure, not unlike mtl-1 and mtl-2. The low abundance of cysteine residues in T08G5.1 suggests, however, that it may not be involved directly in Cd sequestration to limit its toxicity like metallothionein, but might be associated with a parallel pathway, possibly an oxidative stress response.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11066929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140317392","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

Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence. 利用同步加速器显微 X 射线荧光分析人脑组织中汞和硒的分布。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae018

Alexis N Webb, Olga Antipova, Serena Shughoury, Jose M Farfel, David A Bennett, Yansheng Du, Wei Zheng, Linda H Nie

{"title":"Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence.","authors":"Alexis N Webb, Olga Antipova, Serena Shughoury, Jose M Farfel, David A Bennett, Yansheng Du, Wei Zheng, Linda H Nie","doi":"10.1093/mtomcs/mfae018","DOIUrl":"10.1093/mtomcs/mfae018","url":null,"abstract":"Mercury is a well-recognized environmental contaminant and neurotoxin, having been associated with a number of deleterious neurological conditions including neurodegenerative diseases, such as Alzheimer's disease. To investigate how mercury and other metals behave in the brain, we used synchrotron micro-X-ray fluorescence to map the distribution pattern and quantify concentrations of metals in human brain. Brain tissue was provided by the Rush Alzheimer's Disease Center and samples originated from individuals diagnosed with Alzheimer's disease and without cognitive impairment. Data were collected at the 2-ID-E beamline at the Advanced Photon Source at Argonne National Laboratory with an incident beam energy of 13 keV. Course scans were performed at low resolution to determine gross tissue features, after which smaller regions were selected to image at higher resolution. The findings revealed (1) the existence of mercury particles in the brain samples of two subjects; (2) co-localization and linear correlation of mercury and selenium in all particles; (3) co-localization of these particles with zinc structures; and (4) association with sulfur in some of these particles. These results suggest that selenium and sulfur may play protective roles against mercury in the brain, potentially binding with the metal to reduce the induced toxicity, although at different affinities. Our findings call for further studies to investigate the relationship between mercury, selenium, and sulfur, as well as the potential implications in Alzheimer's disease and related dementias.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11064728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874430","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

Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro. 甘氨酰-L-组氨酰-L-赖氨酸（GHK）可在体外防止铜和锌诱导的蛋白质聚集和中枢神经系统细胞死亡。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae019

Jin-Hong Min, Heela Sarlus, Robert A Harris

{"title":"Glycyl-l-histidyl-l-lysine prevents copper- and zinc-induced protein aggregation and central nervous system cell death in vitro.","authors":"Jin-Hong Min, Heela Sarlus, Robert A Harris","doi":"10.1093/mtomcs/mfae019","DOIUrl":"10.1093/mtomcs/mfae019","url":null,"abstract":"Common features of neurodegenerative diseases are oxidative and inflammatory imbalances as well as the misfolding of proteins. An excess of free metal ions can be pathological and contribute to cell death, but only copper and zinc strongly promote protein aggregation. Herein we demonstrate that the endogenous copper-binding tripeptide glycyl-l-histidyl-l-lysine (GHK) has the ability to bind to and reduce copper redox activity and to prevent copper- and zinc-induced cell death in vitro. In addition, GHK prevents copper- and zinc-induced bovine serum albumin aggregation and reverses aggregation through resolubilizing the protein. We further demonstrate the enhanced toxicity of copper during inflammation and the ability of GHK to attenuate this toxicity. Finally, we investigated the effects of copper on enhancing paraquat toxicity and report a protective effect of GHK. We therefore conclude that GHK has potential as a cytoprotective compound with regard to copper and zinc toxicity, with positive effects on protein solubility and aggregation that warrant further investigation in the treatment of neurodegenerative diseases.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140846367","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

Quest for a stable Cu-ligand complex with a high catalytic activity to produce reactive oxygen species. 探索具有高催化活性的稳定铜配体复合物，以产生 ROS。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae020

Merwan Bouraguba, Adeline M Schmitt, Venkata Suseela Yelisetty, Bertrand Vileno, Frédéric Melin, Elise Glattard, Christophe Orvain, Vincent Lebrun, Laurent Raibaut, Marianne Ilbert, Burkhard Bechinger, Petra Hellwig, Christian Gaiddon, Angélique Sour, Peter Faller

{"title":"Quest for a stable Cu-ligand complex with a high catalytic activity to produce reactive oxygen species.","authors":"Merwan Bouraguba, Adeline M Schmitt, Venkata Suseela Yelisetty, Bertrand Vileno, Frédéric Melin, Elise Glattard, Christophe Orvain, Vincent Lebrun, Laurent Raibaut, Marianne Ilbert, Burkhard Bechinger, Petra Hellwig, Christian Gaiddon, Angélique Sour, Peter Faller","doi":"10.1093/mtomcs/mfae020","DOIUrl":"10.1093/mtomcs/mfae020","url":null,"abstract":"Metal ion-catalyzed overproduction of reactive oxygen species (ROS) is believed to contribute significantly to oxidative stress and be involved in several biological processes, from immune defense to development of diseases. Among the essential metal ions, copper is one of the most efficient catalysts in ROS production in the presence of O2 and a physiological reducing agent such as ascorbate. To control this chemistry, Cu ions are tightly coordinated to biomolecules. Free or loosely bound Cu ions are generally avoided to prevent their toxicity. In the present report, we aim to find stable Cu-ligand complexes (Cu-L) that can efficiently catalyze the production of ROS in the presence of ascorbate under aerobic conditions. Thermodynamic stability would be needed to avoid dissociation in the biological environment, and high ROS catalysis is of interest for applications as antimicrobial or anticancer agents. A series of Cu complexes with the well-known tripodal and tetradentate ligands containing a central amine linked to three pyridyl-alkyl arms of different lengths were investigated. Two of them with mixed arm length showed a higher catalytic activity in the oxidation of ascorbate and subsequent ROS production than Cu salts in buffer, which is an unprecedented result. Despite these high catalytic activities, no increased antimicrobial activity toward Escherichia coli or cytotoxicity against eukaryotic AGS cells in culture related to Cu-L-based ROS production could be observed. The potential reasons for discrepancy between in vitro and in cell data are discussed.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848346","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

Impact of aging on copper isotopic composition in the murine brain. 衰老对鼠脑中铜同位素组成的影响

IF 3.4 3区生物学

Metallomics Pub Date : 2024-05-02 DOI: 10.1093/mtomcs/mfae008

Esther Lahoud, Frédéric Moynier, Tu-Han Luu, Brandon Mahan, Marie Le Borgne

{"title":"Impact of aging on copper isotopic composition in the murine brain.","authors":"Esther Lahoud, Frédéric Moynier, Tu-Han Luu, Brandon Mahan, Marie Le Borgne","doi":"10.1093/mtomcs/mfae008","DOIUrl":"10.1093/mtomcs/mfae008","url":null,"abstract":"Aging is the main risk factor for Alzheimer's disease (AD). AD is linked to alterations in metal homeostasis and changes in stable metal isotopic composition can occur, possibly allowing the latter to serve as relevant biomarkers for potential AD diagnosis. Copper stable isotopes are used to investigate changes in Cu homeostasis associated with various diseases. Prior work has shown that in AD mouse models, the accumulation of 63Cu in the brain is associated with the disease's progression. However, our understanding of how the normal aging process influences the brain's isotopic composition of copper remains limited. In order to determine the utility and predictive power of Cu isotopes in AD diagnostics, we aim-in this study-to develop a baseline trajectory of Cu isotopic composition in the normally aging mouse brain. We determined the copper concentration and isotopic composition in brains of 30 healthy mice (WT) ranging in age from 6 to 12 mo, and further incorporate prior data obtained for 3-mo-old healthy mice; this range approximately equates to 20-50 yr in human equivalency. A significant 65Cu enrichment has been observed in the 12-mo-old mice compared to the youngest group, concomitant with an increase in Cu concentration with age. Meanwhile, literature data for brains of AD mice display an enrichment in 63Cu isotope compared to WT. It is acutely important that this baseline enrichment in 65Cu is fully constrained and normalized against if any coherent diagnostic observations regarding 63Cu enrichment as a biomarker for AD are to be developed.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641217","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

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