Metallomics最新文献_第3页

Thermodynamic origin of the affinity, selectivity and domain specificity of metallothionein for essential and toxic metal ions. 金属硫蛋白对必需金属离子和有毒金属离子的亲和力、选择性和结构域特异性的热力学起源。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-09-17 DOI: 10.1093/mtomcs/mfae041

Colette F Quinn,Dean E Wilcox

{"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}

引用次数: 0

Nanoscale elemental and morphological imaging of nitrogen-fixing cyanobacteria. 固氮蓝藻的纳米级元素和形态成像。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-09-13 DOI: 10.1093/mtomcs/mfae040

Bobby G Duersch,Steven A Soini,Yanqi Luo,Xiaoyang Liu,Si Chen,Vivian M Merk

{"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}

引用次数: 0

Decreased spinal cord motor neuron numbers in mice depleted of central nervous system copper. 缺失中枢神经系统铜的小鼠脊髓运动神经元数量减少。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-09-09 DOI: 10.1093/mtomcs/mfae036

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

{"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}

引用次数: 0

Stable potassium isotope ratios in human blood serum towards biomarker development in Alzheimer's disease. 人血清中的稳定钾同位素比值，用于开发阿尔茨海默病的生物标记物。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-09-05 DOI: 10.1093/mtomcs/mfae038

Brandon Mahan, Yan Hu, Esther Lahoud, Mark Nestmeyer, Alex McCoy-West, Grace Manestar, Christopher Fowler, Ashley I Bush, Frédéric Moynier

{"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":"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.","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}

引用次数: 0

NtZIP5A/B is involved in the regulation of Zn/Cu/Fe/Mn/Cd homeostasis in tobacco. NtZIP5A/B 参与调节烟草中锌/铜/铁/锰/镉的平衡。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-09-05 DOI: 10.1093/mtomcs/mfae035

Małgorzata Palusińska, Anna Barabasz, Danuta Maria Antosiewicz

{"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":"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.","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}

引用次数: 0

Insight into brain metallothioneins from bidirectional Zn2+ signaling in synaptic dynamics. 从突触动力学中的双向 Zn2+ 信号透视脑金属硫蛋白

IF 2.9 3区生物学

Metallomics Pub Date : 2024-09-05 DOI: 10.1093/mtomcs/mfae039

Atsushi Takeda, Haruna Tamano

{"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":"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.","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}

引用次数: 0

Retraction of: Characterising the spatial and temporal brain metal profile in a mouse model of tauopathy. 撤回：牛磺酸病小鼠模型的脑金属空间和时间分布特征。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-09-05 DOI: 10.1093/mtomcs/mfae037

引用次数: 0

P-based referencing for correcting tissue artifacts in laser ablation-inductively coupled plasma-mass spectrometry imaging of cancer samples. 在对癌症样本进行激光烧蚀-电感耦合等离子体-质谱成像时校正组织伪影的基于 P 的参照。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-08-20 DOI: 10.1093/mtomcs/mfae034

Katharina Kronenberg, Emily Hoffmann, Lena Hiddeßen, Bastian Maus, Mirjam Gerwing, Cornelius Faber, Michael Sperling, Moritz Wildgruber, Uwe Karst

{"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":"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.","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}

引用次数: 0

Disruption of bacterial biofilms by a green synthesized artemisinin nano-copper nanomaterial. 一种绿色合成青蒿素纳米铜材料对细菌生物膜的破坏作用

IF 2.9 3区生物学

Metallomics Pub Date : 2024-07-01 DOI: 10.1093/mtomcs/mfae030

Yan Zhang, Xia Hua, Xiaohu Han, Xue Fang, Peng Li, Jingbo Zhai, Lin Xie, Yanming Lv, Yonghao Lai, Chengcheng Meng, Yi Zhang, Shiwei Liu, Zeliang Chen

{"title":"Disruption of bacterial biofilms by a green synthesized artemisinin nano-copper nanomaterial.","authors":"Yan Zhang, Xia Hua, Xiaohu Han, Xue Fang, Peng Li, Jingbo Zhai, Lin Xie, Yanming Lv, Yonghao Lai, Chengcheng Meng, Yi Zhang, Shiwei Liu, Zeliang Chen","doi":"10.1093/mtomcs/mfae030","DOIUrl":"10.1093/mtomcs/mfae030","url":null,"abstract":"Bacterial biofilms are associated with antibiotic resistance and account for ∼80% of all bacterial infections. In this study, we explored novel nanomaterials for combating bacteria and their biofilms. Artemisinin nano-copper (ANC) was synthesized using a green synthesis strategy, and its shape, size, structure, elemental composition, chemical valence, zeta potential, and conductivity were characterized using transmission electron microscopy, X-ray diffractometer, X-ray photoelectron spectroscopy, zeta potential, and dynamic light scattering. The results showed that ANC was successfully synthesized utilizing a liquid phase chemical reduction method using chitosan as a modified protectant and l-ascorbic acid as a green reducing agent. The stability of ANC was evaluated using dynamic light scattering. The results showed that the particle size of ANC at different concentrations was comparable to that of the original solution after 7 days of storage, and there was no significant change in the polydispersity index (P > 0.05). The antibacterial effects of ANC on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were determined by disc diffusion and broth dilution methods. The results demonstrated that ANC inhibited and killed E. coli and S. aureus. The effect of ANC on bacterial biofilms was investigated using crystal violet staining, scanning electron microscopy, laser confocal microscopy, and quantitative polymerase chain reaction. The results showed that ANC treatment was able to destroy bacterial biofilms and downregulate biofilm- and virulence-related genes in E. coli (HlyA, gyrA, and F17) and S. aureus (cna, PVL, ClfA, and femB). Green-synthesized ANC possesses excellent antibiofilm properties and is expected to exhibit antibacterial and antibiofilm properties.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464456","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

Elevated thyroid manganese reduces thyroid iodine to induce hypothyroidism in mice, but not rats, lacking SLC30A10 transporter. 在缺乏 SLC30A10 转运体的小鼠（而非大鼠）体内，甲状腺锰升高会减少甲状腺碘，从而诱发甲状腺功能减退症。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-07-01 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":"10.1093/mtomcs/mfae029","url":null,"abstract":"Elevated manganese (Mn) accumulates in the brain and induces neurotoxicity. SLC30A10 is an 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 levels 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 levels, 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 levels. 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":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216084/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0