Metallomics最新文献_第10页

Screening the complex biological behavior of late lanthanides through genome-wide interactions. 通过全基因组相互作用筛选晚期镧系元素的复杂生物学行为。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-08-01 DOI: 10.1093/mtomcs/mfad039

Roger M Pallares, Dahlia D An, Solene Hebert, Alex Loguinov, Michael Proctor, Jonathan A Villalobos, Kathleen A Bjornstad, Chris J Rosen, Christopher Vulpe, Rebecca J Abergel

{"title":"Screening the complex biological behavior of late lanthanides through genome-wide interactions.","authors":"Roger M Pallares, Dahlia D An, Solene Hebert, Alex Loguinov, Michael Proctor, Jonathan A Villalobos, Kathleen A Bjornstad, Chris J Rosen, Christopher Vulpe, Rebecca J Abergel","doi":"10.1093/mtomcs/mfad039","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad039","url":null,"abstract":"Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanthanides, based on their interactions with biological systems. In particular, the late lanthanides demonstrate distinct, but poorly understood biological activity. In the current study, we employed genome-wide functional screening to help understand biological effects of exposure to Yb(III) and Lu(III), which were selected as representatives of the late lanthanides. As a model organism, we used Saccharomyces cerevisiae, since it shares many biological functions with humans. Analysis of the functional screening results indicated toxicity of late lanthanides is consistent with disruption of vesicle-mediated transport, and further supported a role for calcium transport processes and mitophagy in mitigating toxicity. Unexpectedly, our analysis suggested that late lanthanides target proteins with SH3 domains, which may underlie the observed toxicity. This study provides fundamental insights into the unique biological chemistry of late lanthanides, which may help devise new avenues toward the development of decorporation strategies and bio-inspired separation processes.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10017343","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

Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine, and glutathione. 重新审视铜的促氧化活性:抗坏血酸、半胱氨酸和谷胱甘肽的相互作用。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-07-10 DOI: 10.1093/mtomcs/mfad040

Enrico Falcone, Francesco Stellato, Bertrand Vileno, Merwan Bouraguba, Vincent Lebrun, Marianne Ilbert, Silvia Morante, Peter Faller

{"title":"Revisiting the pro-oxidant activity of copper: interplay of ascorbate, cysteine, and glutathione.","authors":"Enrico Falcone, Francesco Stellato, Bertrand Vileno, Merwan Bouraguba, Vincent Lebrun, Marianne Ilbert, Silvia Morante, Peter Faller","doi":"10.1093/mtomcs/mfad040","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad040","url":null,"abstract":"Copper (Cu) is essential for most organisms, but it can be poisonous in excess, through mechanisms such as protein aggregation, trans-metallation, and oxidative stress. The latter could implicate the formation of potentially harmful reactive oxygen species (O2•-, H2O2, and HO•) via the redox cycling between Cu(II)/Cu(I) states in the presence of dioxygen and physiological reducing agents such as ascorbate (AscH), cysteine (Cys), and the tripeptide glutathione (GSH). Although the reactivity of Cu with these reductants has been previously investigated, the reactions taking place in a more physiologically relevant mixture of these biomolecules are not known. Hence, we report here on the reactivity of Cu with binary and ternary mixtures of AscH, Cys, and GSH. By measuring AscH and thiol oxidation, as well as HO• formation, we show that Cu reacts preferentially with GSH and Cys, halting AscH oxidation and also HO• release. This could be explained by the formation of Cu-thiolate clusters with both GSH and, as we first demonstrate here, Cys. Moreover, we observed a remarkable acceleration of Cu-catalyzed GSH oxidation in the presence of Cys. We provide evidence that both thiol-disulfide exchange and the generated H2O2 contribute to this effect. Based on these findings, we speculate that Cu-induced oxidative stress may be mainly driven by GSH depletion and/or protein disulfide formation rather than by HO• and envision a synergistic effect of Cys on Cu toxicity.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9799033","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: 1

Stable potassium isotope distribution in mouse organs and red blood cells: implication for biomarker development. 稳定钾同位素在小鼠器官和红细胞中的分布:对生物标志物发育的影响。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-07-10 DOI: 10.1093/mtomcs/mfad033

Meng-Meng Cui, Frédéric Moynier, Ben-Xun Su, Wei Dai, Yan Hu, Dimitri Rigoussen, Brandon Mahan, Marie Le Borgne

{"title":"Stable potassium isotope distribution in mouse organs and red blood cells: implication for biomarker development.","authors":"Meng-Meng Cui, Frédéric Moynier, Ben-Xun Su, Wei Dai, Yan Hu, Dimitri Rigoussen, Brandon Mahan, Marie Le Borgne","doi":"10.1093/mtomcs/mfad033","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad033","url":null,"abstract":"Potassium (K) is an essential electrolyte for cellular functions in living organisms, and disturbances in K+ homeostasis could lead to various chronic diseases (e.g. hypertension, cardiac disease, diabetes, and bone health). However, little is known about the natural distribution of stable K isotopes in mammals and its application to investigate the bodily homeostasis and/or as a biomarker for diseases. Here, we measured K isotopic compositions (δ41K, per mil deviation of 41K/39K from the NIST SRM 3141a standard) of brain, liver, kidney, and red blood cells (RBCs) from 10 mice (five females and five males) with three different genetic backgrounds. Our results reveal that different organs and RBCs have distinct K isotopic signatures. Specifically, the RBCs have heavy K isotopes enrichment with δ41K ranging from 0.67 to 0.08 ‰, while the brains show lighter K isotopic compositions with δ41K ranging from -1.13 to -0.09 ‰ compared to the livers (δ41K = -0.12 ± 0.58 ‰) and kidneys (δ41K = -0.24 ± 0.57 ‰). We found that the K isotopic and concentration variability is mostly controlled by the organs, with a minor effect of the genetic background and sex. Our study suggest that the K isotopic composition could be used as a biomarker for changes in K+ homeostasis and related diseases such as hypertension, cardiovascular, and neurodegenerative diseases.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9796763","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: 1

Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells. Atp7a RNA的调控有助于骨骼肌细胞中分化依赖性铜的再分配。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-07-10 DOI: 10.1093/mtomcs/mfad042

Thomas J Whitlow, Yu Zhang, Nathan Ferguson, Alexandra M Perez, Hemchandra Patel, Josephine A Link-Kemp, Ethan M Larson, Allison T Mezzell, Vinit C Shanbhag, Michael J Petris, Katherine E Vest

{"title":"Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells.","authors":"Thomas J Whitlow, Yu Zhang, Nathan Ferguson, Alexandra M Perez, Hemchandra Patel, Josephine A Link-Kemp, Ethan M Larson, Allison T Mezzell, Vinit C Shanbhag, Michael J Petris, Katherine E Vest","doi":"10.1093/mtomcs/mfad042","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad042","url":null,"abstract":"Cu (Cu) is essential for several biochemical pathways due to its role as a catalytic cofactor or allosteric regulator of enzymes. Its import and distribution are tightly controlled by transporters and metallochaperones and Cu homeostasis is maintained by balancing Cu uptake and export. Genetic diseases are caused by impaired Cu transporters CTR1, ATP7A, or ATP7B but little is known about the regulatory mechanisms by which these proteins meet the fluctuating demands of Cu in specific tissues. Cu is required for differentiation of skeletal myoblasts to myotubes. Here, we demonstrate that ATP7A is needed for myotube formation and that its increased abundance during differentiation is mediated by stabilization of Atp7a mRNA via the 3' untranslated region. Increased ATP7A levels during differentiation resulted in increased Cu delivery to lysyl oxidase, a secreted cuproenzyme that needed for myotube formation. These studies identify a previously unknown role for Cu in regulating muscle differentiation and have broad implications for understanding Cu-dependent differentiation in other tissues.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10339032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9798203","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

Zn deficiency disrupts Cu and S homeostasis in Chlamydomonas resulting in over accumulation of Cu and Cysteine. Zn 缺乏会破坏衣藻中 Cu 和 S 的平衡，导致 Cu 和半胱氨酸过度积累。

IF 2.9 3区生物学

Metallomics Pub Date : 2023-07-10 DOI: 10.1093/mtomcs/mfad043

Daniela Strenkert, Stefan Schmollinger, Yuntao Hu, Christian Hofmann, Kristen Holbrook, Helen W Liu, Samuel O Purvine, Carrie D Nicora, Si Chen, Mary S Lipton, Trent R Northen, Stephan Clemens, Sabeeha S Merchant

{"title":"Zn deficiency disrupts Cu and S homeostasis in Chlamydomonas resulting in over accumulation of Cu and Cysteine.","authors":"Daniela Strenkert, Stefan Schmollinger, Yuntao Hu, Christian Hofmann, Kristen Holbrook, Helen W Liu, Samuel O Purvine, Carrie D Nicora, Si Chen, Mary S Lipton, Trent R Northen, Stephan Clemens, Sabeeha S Merchant","doi":"10.1093/mtomcs/mfad043","DOIUrl":"10.1093/mtomcs/mfad043","url":null,"abstract":"Growth of Chlamydomonas reinhardtii in zinc (Zn) limited medium leads to disruption of copper (Cu) homeostasis, resulting in up to 40-fold Cu over-accumulation relative to its typical Cu quota. We show that Chlamydomonas controls its Cu quota by balancing Cu import and export, which is disrupted in a Zn deficient cell, thus establishing a mechanistic connection between Cu and Zn homeostasis. Transcriptomics, proteomics and elemental profiling revealed that Zn-limited Chlamydomonas cells up-regulate a subset of genes encoding \"first responder\" proteins involved in sulfur (S) assimilation and consequently accumulate more intracellular S, which is incorporated into L-cysteine, γ-glutamylcysteine, and homocysteine. Most prominently, in the absence of Zn, free L-cysteine is increased ∼80-fold, corresponding to ∼2.8 × 109 molecules/cell. Interestingly, classic S-containing metal binding ligands like glutathione and phytochelatins do not increase. X-ray fluorescence microscopy showed foci of S accumulation in Zn-limited cells that co-localize with Cu, phosphorus and calcium, consistent with Cu-thiol complexes in the acidocalcisome, the site of Cu(I) accumulation. Notably, cells that have been previously starved for Cu do not accumulate S or Cys, causally connecting cysteine synthesis with Cu accumulation. We suggest that cysteine is an in vivo Cu(I) ligand, perhaps ancestral, that buffers cytosolic Cu.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10275577","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

Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties. 铜(II)与2-萘酚和6-喹啉二甲基衍生物的单核和双核配合物:合成及体外抗肿瘤特性研究。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-06-01 DOI: 10.1093/mtomcs/mfad037

Vnira R Akhmetova, El'mira M Galimova, Ekaterina S Mescheryakova, Lilya U Dzhemileva, Usein M Dzhemilev, Vladimir A D'yakonov

{"title":"Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties.","authors":"Vnira R Akhmetova, El'mira M Galimova, Ekaterina S Mescheryakova, Lilya U Dzhemileva, Usein M Dzhemilev, Vladimir A D'yakonov","doi":"10.1093/mtomcs/mfad037","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad037","url":null,"abstract":"1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-containing products to study cytotoxic properties. New mononuclear and binuclear Cu(II) complexes with 1-(N,N-dimethylamino)methyl-6-quinolinol were synthesized for the first time. The same way Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized. The structures of mono- and binuclear Cu(II) complexes with 1-aminomethyl-2-naphtol were confirmed by X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat, K562, U937, MDA-MB-231, MCF7, T47D, and HEK293 cells. The induction of apoptosis and the effect of novel Cu complexes on the cell cycle were investigated. The cells showed a higher sensitivity to mononuclear Cu(II) complex with 1-(N,N-dimethylamino)methyl-6-quinolinolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9728744","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: 1

Examining the inorganic elemental composition of lobster phyllosoma (Panulirus ornatus) with X-ray fluorescence microscopy. 用 X 射线荧光显微镜观察龙虾鳃瘤（Panulirus ornatus）的无机元素组成。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-06-01 DOI: 10.1093/mtomcs/mfad038

Daniel R McDougall, Robert Deas, Daryl L Howard, Quinn P Fitzgibbon, Gregory G Smith, Andrew G Jeffs, Duncan J McGillivray

{"title":"Examining the inorganic elemental composition of lobster phyllosoma (Panulirus ornatus) with X-ray fluorescence microscopy.","authors":"Daniel R McDougall, Robert Deas, Daryl L Howard, Quinn P Fitzgibbon, Gregory G Smith, Andrew G Jeffs, Duncan J McGillivray","doi":"10.1093/mtomcs/mfad038","DOIUrl":"10.1093/mtomcs/mfad038","url":null,"abstract":"The ornate spiny rock lobster, Panulirus ornatus, is an attractive candidate for aquaculture. The larval stages of spiny lobsters, known as phyllosoma, are complex with many developmental stages. Very little is known about the inorganic element composition of phyllosoma. In this study, a novel method using synchrotron X-ray fluorescence microscopy (XFM) was applied to investigate the distributions of metals potassium (K), calcium (Ca), copper (Cu), zinc (Zn), the metalloid arsenic (As), and nonmetal bromine (Br) within individual phyllosoma at stages 3, 4, and 8 of their development. For the first time, 1 µm resolution synchrotron XFM images of whole phyllosoma as well as closer examinations of their eyes, mouths, setae, and tails were obtained. Elements accumulated in certain locations within phyllosoma, providing insight into their likely biological role for these organisms. This information may be useful for the application of dietary supplementation in the future to closed larval cycle lobster aquaculture operations.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10311473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9734333","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

Physiological responses of plants to in vivo X-ray damage from X-ray fluorescence measurements: insights from anatomical, elemental, histochemical, and ultrastructural analyses. 植物对x射线荧光测量的体内x射线损伤的生理反应:从解剖、元素、组织化学和超微结构分析的见解。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-06-01 DOI: 10.1093/mtomcs/mfad034

Gabriel Sgarbiero Montanha, João Paulo Rodrigues Marques, Eduardo Santos, Michael W M Jones, Hudson Wallace Pereira de Carvalho

{"title":"Physiological responses of plants to in vivo X-ray damage from X-ray fluorescence measurements: insights from anatomical, elemental, histochemical, and ultrastructural analyses.","authors":"Gabriel Sgarbiero Montanha, João Paulo Rodrigues Marques, Eduardo Santos, Michael W M Jones, Hudson Wallace Pereira de Carvalho","doi":"10.1093/mtomcs/mfad034","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad034","url":null,"abstract":"X-ray fluorescence spectroscopy (XRF) is a powerful technique for the in vivo assessment of plant tissues. However, the potential X-ray exposure damages might affect the structure and elemental composition of living plant tissues, leading to artefacts in the recorded data. Herein, we exposed in vivo soybean (Glycine max (L.) Merrill) leaves to several X-ray doses through a polychromatic benchtop microprobe X-ray fluorescence spectrometer, modulating the photon flux density by adjusting either the beam size, current, or exposure time. Changes in the irradiated plant tissues' structure, ultrastructure, and physiology were investigated through light and transmission electron microscopy (TEM). Depending on X-ray exposure dose, decreased K and X-ray scattering intensities and increased Ca, P, and Mn signals on soybean leaves were recorded. Anatomical analysis indicated the necrosis of epidermal and mesophyll cells on the irradiated spots, where TEM images revealed the collapse of cytoplasm and cell wall breaking. Furthermore, the histochemical analysis detected the production of reactive oxygen species and the inhibition of chlorophyll autofluorescence in these areas. Under certain X-ray exposure conditions, e.g. high photon flux density and long exposure time, XRF measurements may affect the soybean leaves structures, elemental composition, and cellular ultrastructure, inducing programmed cell death. Our characterization shed light on the plant's responses to the X-ray-induced radiation damage and might help to establish proper X-ray radiation limits and novel strategies for in vivo benchtop-XRF analysis of vegetal materials.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727440","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: 2

ZnT1 induces a crosstalk between T-type and L-type calcium channels through interactions with Raf-1 kinase and the calcium channel β2 subunit. ZnT1通过与Raf-1激酶和钙通道β2亚基的相互作用诱导t型和l型钙通道之间的串扰。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-06-01 DOI: 10.1093/mtomcs/mfad031

Merav Mor, Ofer Beharier, David I Cook, Craig R Campbell, Levi A Gheber, Amos Katz, Arie Moran, Yoram Etzion

{"title":"ZnT1 induces a crosstalk between T-type and L-type calcium channels through interactions with Raf-1 kinase and the calcium channel β2 subunit.","authors":"Merav Mor, Ofer Beharier, David I Cook, Craig R Campbell, Levi A Gheber, Amos Katz, Arie Moran, Yoram Etzion","doi":"10.1093/mtomcs/mfad031","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad031","url":null,"abstract":"ZnT1 is a major zinc transporter that regulates cellular zinc homeostasis. We have previously shown that ZnT1 has additional functions that are independent of its activity as a Zn2+ extruder. These include inhibition of the L-type calcium channel (LTCC) through interaction with the auxiliary β-subunit of the LTCC and activation of the Raf-ERK signaling leading to augmented activity of the T-type calcium channel (TTCC). Our findings indicate that ZnT1 increases TTCC activity by enhancing the trafficking of the channel to the plasma membrane. LTCC and TTCC are co-expressed in many tissues and have different functions in a variety of tissues. In the current work, we investigated the effect of the voltage-gated calcium channel (VGCC) β-subunit and ZnT1 on the crosstalk between LTCC and TTCC and their functions. Our results indicate that the β-subunit inhibits the ZnT1-induced augmentation of TTCC function. This inhibition correlates with the VGCC β-subunit-dependent reduction in ZnT1-induced activation of Ras-ERK signaling. The effect of ZnT1 is specific, as the presence of the β-subunit did not change the effect of endothelin-1 (ET-1) on TTCC surface expression. These findings document a novel regulatory function of ZnT1 serving as a mediator in the crosstalk between TTCC and LTCC. Overall, we demonstrate that ZnT1 binds and regulates the activity of the β-subunit of VGCC and Raf-1 kinase and modulates surface expression of the LTCC and TTCC catalytic subunits, consequently modulating the activity of these channels.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731350","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

Chemical-genomic profiling identifies genes that protect yeast from aluminium, gallium, and indium toxicity. 化学基因组分析鉴定保护酵母免受铝，镓和铟毒性的基因。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-06-01 DOI: 10.1093/mtomcs/mfad032

Yves Schulze, Payam Ghiaci, Liqian Zhao, Marc Biver, Jonas Warringer, Montserrat Filella, Markus J Tamás

{"title":"Chemical-genomic profiling identifies genes that protect yeast from aluminium, gallium, and indium toxicity.","authors":"Yves Schulze, Payam Ghiaci, Liqian Zhao, Marc Biver, Jonas Warringer, Montserrat Filella, Markus J Tamás","doi":"10.1093/mtomcs/mfad032","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad032","url":null,"abstract":"Aluminium, gallium, and indium are group 13 metals with similar chemical and physical properties. While aluminium is one of the most abundant elements in the Earth's crust, gallium and indium are present only in trace amounts. However, the increased use of the latter metals in novel technologies may result in increased human and environmental exposure. There is mounting evidence that these metals are toxic, but the underlying mechanisms remain poorly understood. Likewise, little is known about how cells protect themselves from these metals. Aluminium, gallium, and indium are relatively insoluble at neutral pH, and here we show that they precipitate in yeast culture medium at acidic pH as metal-phosphate species. Despite this, the dissolved metal concentrations are sufficient to induce toxicity in the yeast Saccharomyces cerevisiae. By chemical-genomic profiling of the S. cerevisiae gene deletion collection, we identified genes that maintain growth in the presence of the three metals. We found both shared and metal-specific genes that confer resistance. The shared gene products included functions related to calcium metabolism and Ire1/Hac1-mediated protection. Metal-specific gene products included functions in vesicle-mediated transport and autophagy for aluminium, protein folding and phospholipid metabolism for gallium, and chorismate metabolic processes for indium. Many of the identified yeast genes have human orthologues involved in disease processes. Thus, similar protective mechanisms may act in yeast and humans. The protective functions identified in this study provide a basis for further investigations into toxicity and resistance mechanisms in yeast, plants, and humans.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731351","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