Metallomics最新文献_第8页

ESI-MS analysis of Cu(I) binding to apo and Zn7 human metallothionein 1A, 2, and 3 identifies the formation of a similar series of metallated species with no individual isoform optimization for Cu(I). 对 Cu（I）与 apo 和 Zn7 人金属硫蛋白 1A、2 和 3 的结合进行的 ESI-MS 分析表明，形成了一系列类似的金属化物种，但没有对 Cu（I）进行单独的同工酶优化。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-04-05 DOI: 10.1093/mtomcs/mfae015

Adyn Melenbacher, Martin J Stillman

{"title":"ESI-MS analysis of Cu(I) binding to apo and Zn7 human metallothionein 1A, 2, and 3 identifies the formation of a similar series of metallated species with no individual isoform optimization for Cu(I).","authors":"Adyn Melenbacher, Martin J Stillman","doi":"10.1093/mtomcs/mfae015","DOIUrl":"10.1093/mtomcs/mfae015","url":null,"abstract":"Metallothioneins (MTs) are cysteine-rich proteins involved in metal homeostasis, heavy metal detoxification, and protection against oxidative stress. Whether the four mammalian MT isoforms exhibit different metal binding properties is not clear. In this paper, the Cu(I) binding properties of the apo MT1A, apo MT2, and apo MT3 are compared and the relative Cu(I) binding affinities are reported. In all three isoforms, Cu4, Cu6, and Cu10 species form cooperatively, and MT1A and MT2 also form a Cu13 species. The Cu(I) binding properties of Zn7-MT1A, Zn7-MT2, and Zn7-MT3 are compared systematically using isotopically pure 63Cu(I) and 68Zn(II). The species formed in each MT isoform were detected through electrospray ionization-mass spectrometry and further characterized using room temperature phosphorescence spectroscopy. The mixed metal Cu, Zn species forming in MT1A, MT2, and MT3 have similar stoichiometries and their emission spectral properties indicate that analogous clusters form in the three isoforms. Three parallel metallation pathways have been proposed through analysis of the detailed Cu, Zn speciation in MT1A, MT2, and MT3. Pathway ① results in Cu5Zn5-MT and Cu9Zn3-MT. Pathway ② involves Cu6Zn4-MT and Cu10Zn2-MT. Pathway ③ includes Cu8Zn4-MT. Speciation analysis indicates that Pathway ② is the preferred pathway for MT2. This is also evident in the phosphorescence spectra with the 750 nm emission from Cu6Zn4-MT being most prominent in MT2. We see no evidence for different MT isoforms being optimized or exhibiting preferences for certain metals. We discuss the probable stoichiometry for MTs in vivo based on the in vitro determined binding constants.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11004924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173638","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

The structure of Mycobacterium thermoresistibile MmpS5 reveals a conserved disulfide bond across mycobacteria. 分枝杆菌热稳定性 MmpS5 的结构揭示了分枝杆菌中保守的二硫键。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-03-12 DOI: 10.1093/mtomcs/mfae011

Bonnie J Cuthbert, Jessica Mendoza, Rodger de Miranda, Kadamba Papavinasasundaram, Christopher M Sassetti, Celia W Goulding

{"title":"The structure of Mycobacterium thermoresistibile MmpS5 reveals a conserved disulfide bond across mycobacteria.","authors":"Bonnie J Cuthbert, Jessica Mendoza, Rodger de Miranda, Kadamba Papavinasasundaram, Christopher M Sassetti, Celia W Goulding","doi":"10.1093/mtomcs/mfae011","DOIUrl":"10.1093/mtomcs/mfae011","url":null,"abstract":"The tuberculosis (TB) emergency has been a pressing health threat for decades. With the emergence of drug-resistant TB and complications from the COVID-19 pandemic, the TB health crisis is more serious than ever. Mycobacterium tuberculosis (Mtb), the causative agent of TB, requires iron for its survival. Thus, Mtb has evolved several mechanisms to acquire iron from the host. Mtb produces two siderophores, mycobactin and carboxymycobactin, which scavenge for host iron. Mtb siderophore-dependent iron acquisition requires the export of apo-siderophores from the cytosol to the host environment and import of iron-bound siderophores. The export of Mtb apo-siderophores across the inner membrane is facilitated by two mycobacterial inner membrane proteins with their cognate periplasmic accessory proteins, designated MmpL4/MmpS4 and MmpL5/MmpS5. Notably, the Mtb MmpL4/MmpS4 and MmpL5/MmpS5 complexes have also been implicated in the efflux of anti-TB drugs. Herein, we solved the crystal structure of M. thermoresistibile MmpS5. The MmpS5 structure reveals a previously uncharacterized, biologically relevant disulfide bond that appears to be conserved across the Mycobacterium MmpS4/S5 homologs, and comparison with structural homologs suggests that MmpS5 may be dimeric.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10929441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995019","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

Contribution of zinc accumulation to ischemic brain injury and its mechanisms about oxidative stress, inflammation, and autophagy: an update. 锌积累对缺血性脑损伤的贡献及其与氧化应激、炎症和自噬有关的机制：最新进展。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-03-12 DOI: 10.1093/mtomcs/mfae012

Xueqi Yang, Wei Li, Mao Ding, Ke Jian Liu, Zhifeng Qi, Yongmei Zhao

{"title":"Contribution of zinc accumulation to ischemic brain injury and its mechanisms about oxidative stress, inflammation, and autophagy: an update.","authors":"Xueqi Yang, Wei Li, Mao Ding, Ke Jian Liu, Zhifeng Qi, Yongmei Zhao","doi":"10.1093/mtomcs/mfae012","DOIUrl":"10.1093/mtomcs/mfae012","url":null,"abstract":"Ischemic stroke is a leading cause of death and disability worldwide, and presently, there is no effective neuroprotective therapy. Zinc is an essential trace element that plays important physiological roles in the central nervous system. Free zinc concentration is tightly regulated by zinc-related proteins in the brain under normal conditions. Disruption of zinc homeostasis, however, has been found to play an important role in the mechanism of brain injury following ischemic stroke. A large of free zinc releases from storage sites after cerebral ischemia, which affects the functions and survival of nerve cells, including neurons, astrocytes, and microglia, resulting in cell death. Ischemia-triggered intracellular zinc accumulation also disrupts the function of blood-brain barrier via increasing its permeability, impairing endothelial cell function, and altering tight junction levels. Oxidative stress and neuroinflammation have been reported to be as major pathological mechanisms in cerebral ischemia/reperfusion injury. Studies have showed that the accumulation of intracellular free zinc could impair mitochondrial function to result in oxidative stress, and form a positive feedback loop between zinc accumulation and reactive oxygen species production, which leads to a series of harmful reactions. Meanwhile, elevated intracellular zinc leads to neuroinflammation. Recent studies also showed that autophagy is one of the important mechanisms of zinc toxicity after ischemic injury. Interrupting the accumulation of zinc will reduce cerebral ischemia injury and improve neurological outcomes. This review summarizes the role of zinc toxicity in cellular and tissue damage following cerebral ischemia, focusing on the mechanisms about oxidative stress, inflammation, and autophagy.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139988703","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

Distinct function of Chlamydomonas CTRA-CTR transporters in Cu assimilation and intracellular mobilization. 衣藻 CTRA-CTR 转运体在铜同化和细胞内动员中的不同功能

IF 2.9 3区生物学

Metallomics Pub Date : 2024-03-12 DOI: 10.1093/mtomcs/mfae013

Daniela Strenkert, Stefan Schmollinger, Srinand Paruthiyil, Bonnie C Brown, Sydnee Green, Catherine M Shafer, Patrice Salomé, Hosea Nelson, Crysten E Blaby-Haas, Jeffrey L Moseley, Sabeeha S Merchant

{"title":"Distinct function of Chlamydomonas CTRA-CTR transporters in Cu assimilation and intracellular mobilization.","authors":"Daniela Strenkert, Stefan Schmollinger, Srinand Paruthiyil, Bonnie C Brown, Sydnee Green, Catherine M Shafer, Patrice Salomé, Hosea Nelson, Crysten E Blaby-Haas, Jeffrey L Moseley, Sabeeha S Merchant","doi":"10.1093/mtomcs/mfae013","DOIUrl":"10.1093/mtomcs/mfae013","url":null,"abstract":"Successful acclimation to copper (Cu) deficiency involves a fine balance between Cu import and export. In the green alga Chlamydomonas reinhardtii, Cu import is dependent on a transcription factor, Copper Response Regulator 1 (CRR1), responsible for activating genes in Cu-deficient cells. Among CRR1 target genes are two Cu transporters belonging to the CTR/COPT gene family (CTR1 and CTR2) and a related soluble protein (CTR3). The ancestor of these green algal proteins was likely acquired from an ancient chytrid and contained conserved cysteine-rich domains (named the CTR-associated domains, CTRA) that are predicted to be involved in Cu acquisition. We show by reverse genetics that Chlamydomonas CTR1 and CTR2 are canonical Cu importers albeit with distinct affinities, while loss of CTR3 did not result in an observable phenotype under the conditions tested. Mutation of CTR1, but not CTR2, recapitulates the poor growth of crr1 in Cu-deficient medium, consistent with a dominant role for CTR1 in high-affinity Cu(I) uptake. On the other hand, the overaccumulation of Cu(I) (20 times the quota) in zinc (Zn) deficiency depends on CRR1 and both CTR1 and CTR2. CRR1-dependent activation of CTR gene expression needed for Cu over-accumulation can be bypassed by the provision of excess Cu in the growth medium. Over-accumulated Cu is sequestered into the acidocalcisome but can become remobilized by restoring Zn nutrition. This mobilization is also CRR1-dependent, and requires activation of CTR2 expression, again distinguishing CTR2 from CTR1 and consistent with the lower substrate affinity of CTR2.One sentence summary: Regulation of Cu uptake and sequestration by members of the CTR family of proteins in Chlamydomonas.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140026873","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

Insight into the anti-proliferation activity and photoinduced NO release of four nitrosylruthenium isomeric complexes and their HSA complex adducts. 深入了解四种亚硝基钌异构体复合物及其 HSA 复合物加合物的抗增殖活性和光诱导 NO 释放。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae005

Jia Shi, Leilei Xie, Wenjun Gong, Hehe Bai, Wenming Wang, Ai Wang, Wei Cao, Hongbo Tong, Hongfei Wang

{"title":"Insight into the anti-proliferation activity and photoinduced NO release of four nitrosylruthenium isomeric complexes and their HSA complex adducts.","authors":"Jia Shi, Leilei Xie, Wenjun Gong, Hehe Bai, Wenming Wang, Ai Wang, Wei Cao, Hongbo Tong, Hongfei Wang","doi":"10.1093/mtomcs/mfae005","DOIUrl":"10.1093/mtomcs/mfae005","url":null,"abstract":"Four Ru(II)-centered isomeric complexes [RuCl(5cqn)(Val)(NO)] (1-4) were synthesized with 5cqn (5-chloro-8-hydroxyquinoline) and chiral Val (Val = L- or D-valine) as co-ligand, and their structures were confirmed using the X-ray diffraction method. The cytotoxicity and photodynamic activity of the isomeric complexes and their human serum albumin (HSA) complex adducts were evaluated. Both the isomeric complexes and their HSA complex adducts significantly affected HeLa cell proliferation, with an IC50 value in the range of 0.3-0.5 μM. The photo-controlled release of nitric oxide (NO) in solution was confirmed using time-resolved Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques. Furthermore, photoinduced NO release in living cells was observed using a selective fluorescent probe for NO. Moreover, the binding constants (Kb) of the complexes with HSA were calculated to be 0.17-1.98 × 104 M-1 and the average number of binding sites (n) was found to be close to 1, it can serve as a crucial carrier for delivering metal complexes. The crystal structure of the HSA complex adduct revealed that one [RuCl(H2O)(NO)(Val)]+ molecule binds to a pocket in domain I. This study provides insight into possible mechanism of metabolism and potential applications for nitrosylruthenium complexes.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139543996","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

Uptake and accumulation mechanisms of hexachloroplatinate(IV) ions in the unicellular alga, Pseudococcomyxa simplex. 单细胞藻类假栉水母对六氯铂(IV)离子的吸收和积累机制。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae009

Masato Tokoro, Yu Imamura, Kazuhiro Kumagai, Akiko Hokura

引用次数: 0

Calcium complexation by steroids involved in the steroidogenesis. 参与类固醇生成的类固醇的钙复合物。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae010

Gastón E Siless, Gabriela M Cabrera

{"title":"Calcium complexation by steroids involved in the steroidogenesis.","authors":"Gastón E Siless, Gabriela M Cabrera","doi":"10.1093/mtomcs/mfae010","DOIUrl":"10.1093/mtomcs/mfae010","url":null,"abstract":"Steroids that take part in the pathways of human steroidogenesis are involved in many biological mechanisms where they interact with calcium. In the present work, the binding selectivities and affinities for calcium of progestagens, mineralocorticoids, androstagens, and estrogens were studied by Electrospray Ionization-Mass Spectrometry (ESI-MS). The adduct profile of each steroid was characterized by high resolution and tandem mass spectrometry. The relative stability of the most important adducts was studied by threshold collision induced dissociation, E1/2. Doubly-charged steroid-calcium complexes [nM + Ca]2+ with n = 1-6 were predominant in the mass spectra. The adduct [5M + Ca]2+ was the base peak for most 3-keto-steroids, while ligands bearing hindered ketones or α-hydroxy-ketones also yielded [nM + Ca + mH2O]2+ with n = 3-4 and m = 0-1. Principal component analysis allowed us to spot the main differences and similarities in the binding behavior of these steroids. The isomers testosterone and dehydroepiandrosterone, androstanolone and epiandrosterone, and 17-α-hydroxyprogesterone and 11-deoxycorticosterone showed remarkable differences in their adduct profiles. Computational modeling of representative adducts was performed by density functional theory methods. The possible binding modes at low and high numbers of steroid ligands were determined by calcium Gas Phase Affinity, and through modeling of the complexes and comparison of their relative stabilities, in agreement with the experimental results.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139710922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nitrogen sources enhance siderophore-mediated competition for iron between potato common scab and late blight causative agents. 氮源增强了嗜苷酸介导的马铃薯普通疮痂病和晚疫病病原菌之间对铁的竞争。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae004

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

{"title":"Nitrogen sources enhance siderophore-mediated competition for iron between potato common scab and late blight causative agents.","authors":"Nudzejma Stulanovic, Yasmine Kerdel, Lucas Rezende, Benoit Deflandre, Pierre Burguet, Loïc Belde, Romane Denoel, Déborah Tellatin, Augustin Rigolet, Marc Hanikenne, Loïc Quinton, Marc Ongena, Sébastien Rigali","doi":"10.1093/mtomcs/mfae004","DOIUrl":"10.1093/mtomcs/mfae004","url":null,"abstract":"How do pathogens affecting the same host interact with each other? We evaluated here the types of microbe-microbe interactions taking place between Streptomyces scabiei and Phytophthora infestans, the causative agents of common scab and late blight diseases in potato crops, respectively. Under most laboratory culture conditions tested, S. scabiei impaired or completely inhibited the growth of P. infestans by producing either soluble and/or volatile compounds. Increasing peptone levels correlated with increased inhibition of P. infestans. Comparative metabolomics showed that production of S. scabiei siderophores (desferrioxamines, pyochelin, scabichelin, and turgichelin) increased with the quantity of peptone, thereby suggesting that they participate in the inhibition of the oomycete growth. Mass spectrometry imaging further uncovered that the zones of secreted siderophores and of P. infestans growth inhibition coincided. Moreover, either the repression of siderophore production or the neutralization of their iron-chelating activity led to a resumption of P. infestans growth. Replacement of peptone by natural nitrogen sources such as ammonium nitrate, sodium nitrate, ammonium sulfate, and urea also triggered siderophore production in S. scabiei. Interestingly, nitrogen source-induced siderophore production also inhibited the growth of Alternaria solani, the causative agent of the potato early blight. Overall, our work further emphasizes the importance of competition for iron between microorganisms that colonize the same niche. As common scab never alters the vegetative propagation of tubers, we propose that S. scabiei, under certain conditions, could play a protective role for its hosts against much more destructive pathogens through exploitative iron competition and volatile compound production.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511087","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

Loss of SLC30A10 manganese transporter alters expression of neurotransmission genes and activates hypoxia-inducible factor signaling in mice. SLC30A10 锰转运体的缺失会改变小鼠神经传递基因的表达，并激活缺氧诱导因子信号转导。

IF 2.9 3区生物学

Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae007

Anna Warden, R Dayne Mayfield, Kerem C Gurol, Steven Hutchens, Chunyi Liu, Somshuvra Mukhopadhyay

{"title":"Loss of SLC30A10 manganese transporter alters expression of neurotransmission genes and activates hypoxia-inducible factor signaling in mice.","authors":"Anna Warden, R Dayne Mayfield, Kerem C Gurol, Steven Hutchens, Chunyi Liu, Somshuvra Mukhopadhyay","doi":"10.1093/mtomcs/mfae007","DOIUrl":"10.1093/mtomcs/mfae007","url":null,"abstract":"The essential metal manganese (Mn) induces neuromotor disease at elevated levels. The manganese efflux transporter SLC30A10 regulates brain Mn levels. Homozygous loss-of-function mutations in SLC30A10 induce hereditary Mn neurotoxicity in humans. Our prior characterization of Slc30a10 knockout mice recapitulated the high brain Mn levels and neuromotor deficits reported in humans. But, mechanisms of Mn-induced motor deficits due to SLC30A10 mutations or elevated Mn exposure are unclear. To gain insights into this issue, we characterized changes in gene expression in the basal ganglia, the main brain region targeted by Mn, of Slc30a10 knockout mice using unbiased transcriptomics. Compared with littermates, >1000 genes were upregulated or downregulated in the basal ganglia sub-regions (i.e. caudate putamen, globus pallidus, and substantia nigra) of the knockouts. Pathway analyses revealed notable changes in genes regulating synaptic transmission and neurotransmitter function in the knockouts that may contribute to the motor phenotype. Expression changes in the knockouts were essentially normalized by a reduced Mn chow, establishing that changes were Mn dependent. Upstream regulator analyses identified hypoxia-inducible factor (HIF) signaling, which we recently characterized to be a primary cellular response to elevated Mn, as a critical mediator of the transcriptomic changes in the basal ganglia of the knockout mice. HIF activation was also evident in the liver of the knockout mice. These results: (i) enhance understanding of the pathobiology of Mn-induced motor disease; (ii) identify specific target genes/pathways for future mechanistic analyses; and (iii) independently corroborate the importance of the HIF pathway in Mn homeostasis and toxicity.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10883138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574736","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

Single nucleotide polymorphisms and Zn transport by ZIP11 shape functional phenotypes of HeLa cells. 单核苷酸多态性和 ZIP11 的锌转运塑造了 HeLa 细胞的功能表型。

IF 3.4 3区生物学

Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae006

Elizabeth Y Kim, Odette Verdejo-Torres, Karla Diaz-Rodriguez, Farah Hasanain, Leslie Caromile, Teresita Padilla-Benavides

{"title":"Single nucleotide polymorphisms and Zn transport by ZIP11 shape functional phenotypes of HeLa cells.","authors":"Elizabeth Y Kim, Odette Verdejo-Torres, Karla Diaz-Rodriguez, Farah Hasanain, Leslie Caromile, Teresita Padilla-Benavides","doi":"10.1093/mtomcs/mfae006","DOIUrl":"10.1093/mtomcs/mfae006","url":null,"abstract":"Zinc (Zn) is a vital micronutrient with essential roles in biological processes like enzyme function, gene expression, and cell signaling. Disruptions in the cellular regulation of Zn2+ ions often lead to pathological states. Mammalian Zn transporters, such as ZIP11, play a key role in homeostasis of this ion. ZIP11 resides predominately in the nucleus and Golgi apparatus. Our laboratory reported a function of ZIP11 in maintaining nuclear Zn levels in HeLa cervical cancer cells. Analyses of cervical and ovarian cancer patients' datasets identified four coding, single nucleotide polymorphisms (SNPs) in SLC39A11, the gene that encodes ZIP11, correlating with disease severity. We hypothesized that these SNPs might translate to functional changes in the ZIP11 protein by modifying access to substrate availability. We also proposed that a metal-binding site (MBS) in ZIP11 is crucial for transmembrane Zn2+ transport and required for maintenance of various pathogenic phenotypes observed in HeLa cells. Here, we investigated these claims by re-introducing single the SLC39A11 gene encoding for mutant residues associated with the SNPs, as well as MBS mutations into HeLa cells knocked down for the transporter. Some SNPs-encoding ZIP11 variants rescued Zn levels, proliferation, migration, and invasiveness of knockdown (KD) cells. Conversely, single MBS mutations mimicked the traits of KD cells, confirming the transporter's role in establishing and maintaining proliferative, migratory, and invasive traits. Overall, the intricate role of Zn in cellular dynamics and cancer progression underscores the significance of Zn transporters like ZIP11 in potential therapeutic interventions.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139574737","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