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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
{"title":"Uptake and accumulation mechanisms of hexachloroplatinate(IV) ions in the unicellular alga, Pseudococcomyxa simplex.","authors":"Masato Tokoro, Yu Imamura, Kazuhiro Kumagai, Akiko Hokura","doi":"10.1093/mtomcs/mfae009","DOIUrl":"10.1093/mtomcs/mfae009","url":null,"abstract":"<p><p>Platinum uptake was examined by adding hexachloroplatinate(IV) solution to the unicellular alga Pseudococcomyxa simplex. After the addition of platinum solution ([Pt] = 100 mg/kg, pH 3.2-3.2) for a certain time, the cells were quickly frozen and subjected to μ-XRF (X-ray fluorescence) analysis using synchrotron X-rays. The beam size of approximately 1 micrometer allowed visualization of the platinum distribution within a single cell. On the other hand, we examined platinum uptake in enzyme-treated protoplasts and lyophilized cells and found that the platinum uptake concentrations in these samples were higher than in living in-vivo cells. Cell wall and cell metabolism were presumed to interfere with the uptake of hexachloroplatinate(IV) ions. All platinum ions taken up by the cells were reduced to divalent form. The effect of light on platinum addition was also investigated. When platinum was added under light conditions, some samples showed higher platinum accumulation than under shade conditions.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139649838","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
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":"<p><p>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.</p>","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":"<p><p>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.</p>","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 4.6 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":"<p><p>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.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":4.6,"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":"<p><p>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.</p>","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
Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum. 长期膳食微量元素供应不足不会影响小鼠小脑的微量元素稳态。
IF 3.4 3区 生物学
Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae003
Sharleen Friese, Giovanna Ranzini, Max Tuchtenhagen, Kristina Lossow, Barbara Hertel, Gabriele Pohl, Franziska Ebert, Julia Bornhorst, Anna Patricia Kipp, Tanja Schwerdtle
{"title":"Long-term suboptimal dietary trace element supply does not affect trace element homeostasis in murine cerebellum.","authors":"Sharleen Friese, Giovanna Ranzini, Max Tuchtenhagen, Kristina Lossow, Barbara Hertel, Gabriele Pohl, Franziska Ebert, Julia Bornhorst, Anna Patricia Kipp, Tanja Schwerdtle","doi":"10.1093/mtomcs/mfae003","DOIUrl":"10.1093/mtomcs/mfae003","url":null,"abstract":"<p><p>The ageing process is associated with alterations of systemic trace element (TE) homeostasis increasing the risk, e.g. neurodegenerative diseases. Here, the impact of long-term modulation of dietary intake of copper, iron, selenium, and zinc was investigated in murine cerebellum. Four- and 40-wk-old mice of both sexes were supplied with different amounts of those TEs for 26 wk. In an adequate supply group, TE concentrations were in accordance with recommendations for laboratory mice while suboptimally supplied animals received only limited amounts of copper, iron, selenium, and zinc. An additional age-adjusted group was fed selenium and zinc in amounts exceeding recommendations. Cerebellar TE concentrations were measured by inductively coupled plasma-tandem mass spectrometry. Furthermore, the expression of genes involved in TE transport, DNA damage response, and DNA repair as well as selected markers of genomic stability [8-oxoguanine, incision efficiency toward 8-oxoguanine, 5-hydroxyuracil, and apurinic/apyrimidinic sites and global DNA (hydroxy)methylation] were analysed. Ageing resulted in a mild increase of iron and copper concentrations in the cerebellum, which was most pronounced in the suboptimally supplied groups. Thus, TE changes in the cerebellum were predominantly driven by age and less by nutritional intervention. Interestingly, deviation from adequate TE supply resulted in higher manganese concentrations of female mice even though the manganese supply itself was not modulated. Parameters of genomic stability were neither affected by age, sex, nor diet. Overall, this study revealed that suboptimal dietary TE supply does not substantially affect TE homeostasis in the murine cerebellum.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10873500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139649837","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
Antiproliferative activity of platinum(II) and copper(II) complexes containing novel biquinoxaline ligands. 含有新型双喹喔啉配体的铂(II)和铜(II)配合物的抗增殖活性。
IF 3.4 3区 生物学
Metallomics Pub Date : 2024-02-07 DOI: 10.1093/mtomcs/mfae001
Hager Sadek El-Beshti, Zuhal Gercek, Hakan Kayi, Yasemin Yildizhan, Yuksel Cetin, Zelal Adigüzel, Gamze Güngör, Şeniz Özalp-Yaman
{"title":"Antiproliferative activity of platinum(II) and copper(II) complexes containing novel biquinoxaline ligands.","authors":"Hager Sadek El-Beshti, Zuhal Gercek, Hakan Kayi, Yasemin Yildizhan, Yuksel Cetin, Zelal Adigüzel, Gamze Güngör, Şeniz Özalp-Yaman","doi":"10.1093/mtomcs/mfae001","DOIUrl":"10.1093/mtomcs/mfae001","url":null,"abstract":"<p><p>Nowadays, cancer represents one of the major causes of death in humans worldwide, which renders the quest for new and improved antineoplastic agents to become an urgent issue in the field of biomedicine and human health. The present research focuses on the synthesis of 2,3,2',3'-tetra(pyridin-2-yl)-6,6'-biquinoxaline) and (2,3,2',3'-tetra(thiophen-2-yl)-6,6'-biquinoxaline) containing copper(II) and platinum(II) compounds as prodrug candidates. The binding interaction of these compounds with calf thymus DNA (CT-DNA) and human serum albumin were assessed with UV titration, thermal decomposition, viscometric, and fluorometric methods. The thermodynamical parameters and the temperature-dependent binding constant (K'b) values point out to spontaneous interactions between the complexes and CT-DNA via the van der Waals interactions and/or hydrogen bonding, except Cu(ttbq)Cl2 for which electrostatic interaction was proposed. The antitumor activity of the complexes against several human glioblastomata, lung, breast, cervix, and prostate cell lines were investigated by examining cell viability, oxidative stress, apoptosis-terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, in vitro migration and invasion, in vitro-comet DNA damage, and plasmid DNA interaction assays. The U87 and HeLa cells were investigated as the cancer cells most sensitive to our complexes. The exerted cytotoxic effect of complexes was attributed to the formation of the reactive oxygen species in vitro. It is clearly demonstrated that Cu(ttbq)Cl2, Pt(ttbq)Cl2, and Pt(tpbq)Cl2 have the highest DNA degradation potential and anticancer effect among the tested complexes by leading apoptosis. The wound healing and invasion analysis results also supported the higher anticancer activity of these two compounds.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10849753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110555","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
Evidence for decreased copper associated with demyelination in the corpus callosum of cuprizone-treated mice. 铜绿素处理过的小鼠胼胝体中与脱髓鞘有关的铜减少的证据。
IF 3.4 3区 生物学
Metallomics Pub Date : 2024-01-05 DOI: 10.1093/mtomcs/mfad072
James B W Hilton, Kai Kysenius, Jeffrey R Liddell, Stephen W Mercer, Dominic J Hare, Gojko Buncic, Bence Paul, YouJia Wang, Simon S Murray, Trevor J Kilpatrick, Anthony R White, Paul S Donnelly, Peter J Crouch
{"title":"Evidence for decreased copper associated with demyelination in the corpus callosum of cuprizone-treated mice.","authors":"James B W Hilton, Kai Kysenius, Jeffrey R Liddell, Stephen W Mercer, Dominic J Hare, Gojko Buncic, Bence Paul, YouJia Wang, Simon S Murray, Trevor J Kilpatrick, Anthony R White, Paul S Donnelly, Peter J Crouch","doi":"10.1093/mtomcs/mfad072","DOIUrl":"10.1093/mtomcs/mfad072","url":null,"abstract":"<p><p>Demyelination within the central nervous system (CNS) is a significant feature of debilitating neurological diseases such as multiple sclerosis and administering the copper-selective chelatorcuprizone to mice is widely used to model demyelination in vivo. Conspicuous demyelination within the corpus callosum is generally attributed to cuprizone's ability to restrict copper availability in this vulnerable brain region. However, the small number of studies that have assessed copper in brain tissue from cuprizone-treated mice have produced seemingly conflicting outcomes, leaving the role of CNS copper availability in demyelination unresolved. Herein we describe our assessment of copper concentrations in brain samples from mice treated with cuprizone for 40 d. Importantly, we applied an inductively coupled plasma mass spectrometry methodology that enabled assessment of copper partitioned into soluble and insoluble fractions within distinct brain regions, including the corpus callosum. Our results show that cuprizone-induced demyelination in the corpus callosum was associated with decreased soluble copper in this brain region. Insoluble copper in the corpus callosum was unaffected, as were pools of soluble and insoluble copper in other brain regions. Treatment with the blood-brain barrier permeant copper compound CuII(atsm) increased brain copper levels and this was most pronounced in the soluble fraction of the corpus callosum. This effect was associated with significant mitigation of cuprizone-induced demyelination. These results provide support for the involvement of decreased CNS copper availability in demyelination in the cuprizone model. Relevance to human demyelinating disease is discussed.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10797489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139096747","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
Cyclometalated ruthenium complexes overcome cisplatin resistance through PI3K/mTOR/Nrf2 signaling pathway. 环金属化钌复合物通过 PI3K/mTOR/Nrf2 信号通路克服顺铂耐药性
IF 3.4 3区 生物学
Metallomics Pub Date : 2024-01-05 DOI: 10.1093/mtomcs/mfae002
Lanmei Chen, Wenzhu Yu, Hong Tang, Shenting Zhang, Jie Wang, Qianqian Ouyang, Miao Guo, Xufeng Zhu, Zunnan Huang, Jincan Chen
{"title":"Cyclometalated ruthenium complexes overcome cisplatin resistance through PI3K/mTOR/Nrf2 signaling pathway.","authors":"Lanmei Chen, Wenzhu Yu, Hong Tang, Shenting Zhang, Jie Wang, Qianqian Ouyang, Miao Guo, Xufeng Zhu, Zunnan Huang, Jincan Chen","doi":"10.1093/mtomcs/mfae002","DOIUrl":"10.1093/mtomcs/mfae002","url":null,"abstract":"<p><p>Currently, cisplatin resistance remains a primary clinical obstacle in the successful treatment of non-small cell lung cancer. Here, we designed, synthesized, and characterized two novel cyclometalated Ru(II) complexes, [Ru(bpy)2(1-Ph-7-OCH3-IQ)] (PF6) (bpy = 2,2'-bipyridine, IQ = isoquinoline, RuIQ7)and [Ru(bpy)2(1-Ph-6,7-(OCH3)2-IQ)] (PF6) (RuIQ8). As experimental controls, we prepared complex [Ru(bpy)2(1-Ph-IQ)](PF6) (RuIQ6) lacking a methoxy group in the main ligand. Significantly, complexes RuIQ6-8 displayed higher in vitro cytotoxicity when compared to ligands, precursor cis-[Ru(bpy)2Cl2], and clinical cisplatin. Mechanistic investigations revealed that RuIQ6-8 could inhibit cell proliferation by downregulating the phosphorylation levels of Akt and mTOR proteins, consequently affecting the rapid growth of human lung adenocarcinoma cisplatin-resistant cells A549/DDP. Moreover, the results from qRT-PCR demonstrated that these complexes could directly suppress the transcription of the NF-E2-related factor 2 gene, leading to the inhibition of downstream multidrug resistance-associated protein 1 expression and effectively overcoming cisplatin resistance. Furthermore, the relationship between the chemical structures of these three complexes and their anticancer activity, ability to induce cell apoptosis, and their efficacy in overcoming cisplatin resistance has been thoroughly examined and discussed. Notably, the toxicity test conducted on zebrafish embryos indicated that the three Ru-IQ complexes displayed favorable safety profiles. Consequently, the potential of these developed compounds as innovative therapeutic agents for the efficient and low-toxic treatment of NSCLC appears highly promising.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110556","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
TauSTED super-resolution imaging of labile iron in primary hippocampal neurons. 原发性海马神经元中易变铁的 TauSTED 超分辨率成像。
IF 3.4 3区 生物学
Metallomics Pub Date : 2024-01-05 DOI: 10.1093/mtomcs/mfad074
Aiyarin Kittilukkana, Asuncion Carmona, Chalermchai Pilapong, Richard Ortega
{"title":"TauSTED super-resolution imaging of labile iron in primary hippocampal neurons.","authors":"Aiyarin Kittilukkana, Asuncion Carmona, Chalermchai Pilapong, Richard Ortega","doi":"10.1093/mtomcs/mfad074","DOIUrl":"10.1093/mtomcs/mfad074","url":null,"abstract":"<p><p>Iron dyshomeostasis is involved in many neurological disorders, particularly neurodegenerative diseases where iron accumulates in various brain regions. Identifying mechanisms of iron transport in the brain is crucial for understanding the role of iron in healthy and pathological states. In neurons, it has been suggested that iron can be transported by the axon to different brain regions in the form of labile iron; a pool of reactive and exchangeable intracellular iron. Here we report a novel approach to imaging labile ferrous iron, Fe(II), in live primary hippocampal neurons using confocal and TauSTED (stimulated emission depletion) microscopy. TauSTED is based on super-resolution STED nanoscopy, which combines high spatial resolution imaging (<40 nm) with fluorescence lifetime information, thus reducing background noise and improving image quality. We applied TauSTED imaging utilizing biotracker FerroFarRed Fe(II) and found that labile iron was present as submicrometric puncta in dendrites and axons. Some of these iron-rich structures are mobile and move along neuritic pathways, arguing for a labile iron transport mechanism in neurons. This super-resolution imaging approach offers a new perspective for studying the dynamic mechanisms of axonal and dendritic transport of iron at high spatial resolution in living neurons. In addition, this methodology could be transposed to the imaging of other fluorescent metal sensors.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039202","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}
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