Metallomics最新文献_第10页

Repurposing sunscreen as an antibiotic: zinc-activated avobenzone inhibits methicillin-resistant Staphylococcus aureus. 将防晒霜重新用作抗生素：锌激活的阿伏苯酮抑制耐甲氧西林金黄色葡萄球菌。

IF 2.9 3区生物学

Metallomics Pub Date : 2023-09-05 DOI: 10.1093/mtomcs/mfad049

Rachel M Andrews, Gretchen E Bollar, A Sophia Giattina, Alex G Dalecki, John R Wallace, Leah Frantz, Kayla Eschliman, Obdulia Covarrubias-Zambrano, Johnathan D Keith, Alexandra Duverger, Frederic Wagner, Frank Wolschendorf, Stefan H Bossmann, Susan E Birket, Olaf Kutsch

{"title":"Repurposing sunscreen as an antibiotic: zinc-activated avobenzone inhibits methicillin-resistant Staphylococcus aureus.","authors":"Rachel M Andrews, Gretchen E Bollar, A Sophia Giattina, Alex G Dalecki, John R Wallace, Leah Frantz, Kayla Eschliman, Obdulia Covarrubias-Zambrano, Johnathan D Keith, Alexandra Duverger, Frederic Wagner, Frank Wolschendorf, Stefan H Bossmann, Susan E Birket, Olaf Kutsch","doi":"10.1093/mtomcs/mfad049","DOIUrl":"10.1093/mtomcs/mfad049","url":null,"abstract":"Methicillin-resistant Staphylococcus aureus (MRSA) is a major healthcare concern with associated healthcare costs reaching over ${$}$1 billion in a single year in the USA. Antibiotic resistance in S. aureus is now observed against last line of defense antibiotics, such as vancomycin, linezolid, and daptomycin. Unfortunately, high throughput drug discovery approaches to identify new antibiotics effective against MRSA have not resulted in much tangible success over the last decades. Previously, we demonstrated the feasibility of an alternative drug discovery approach, the identification of metallo-antibiotics, compounds that gain antibacterial activity only after binding to a transition metal ion and as such are unlikely to be detected in standard drug screens. We now report that avobenzone, the primary active ingredient of most sunscreens, can be activated by zinc to become a potent antibacterial compound against MRSA. Zinc-activated avobenzone (AVB-Zn) potently inhibited a series of clinical MRSA isolates [minimal inhibitory concentration (MIC): 0.62-2.5 µM], without pre-existing resistance and activity without zinc (MIC: >10 µM). AVB-Zn was also active against clinical MRSA isolates that were resistant against the commonly used zinc-salt antibiotic bacitracin. We found AVB-Zn exerted no cytotoxicity on human cell lines and primary cells. Last, we demonstrate AVB-Zn can be deployed therapeutically as lotion preparations, which showed efficacy in a mouse wound model of MRSA infection. AVB-Zn thus demonstrates Zn-activated metallo-antibiotics are a promising avenue for future drug discovery.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10169112","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

High-energy interference-free K-lines synchrotron X-ray fluorescence microscopy of rare earth elements in hyperaccumulator plants. 超积累植物中稀土元素的高能无干扰K线同步辐射X射线荧光显微镜。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-09-05 DOI: 10.1093/mtomcs/mfad050

Antony van der Ent, Dennis Brueckner, Kathryn M Spiers, Ken Vidar Falch, Gerald Falkenberg, Clément Layet, Wen-Shen Liu, Hong-Xiang Zheng, Marie Le Jean, Damien Blaudez

{"title":"High-energy interference-free K-lines synchrotron X-ray fluorescence microscopy of rare earth elements in hyperaccumulator plants.","authors":"Antony van der Ent, Dennis Brueckner, Kathryn M Spiers, Ken Vidar Falch, Gerald Falkenberg, Clément Layet, Wen-Shen Liu, Hong-Xiang Zheng, Marie Le Jean, Damien Blaudez","doi":"10.1093/mtomcs/mfad050","DOIUrl":"10.1093/mtomcs/mfad050","url":null,"abstract":"Synchrotron-based micro-X-ray fluorescence analysis (µXRF) is a nondestructive and highly sensitive technique. However, element mapping of rare earth elements (REEs) under standard conditions requires care, since energy-dispersive detectors are not able to differentiate accurately between REEs L-shell X-ray emission lines overlapping with K-shell X-ray emission lines of common transition elements of high concentrations. We aim to test REE element mapping with high-energy interference-free excitation of the REE K-lines on hyperaccumulator plant tissues and compare with measurements with REE L-shell excitation at the microprobe experiment of beamline P06 (PETRA III, DESY). A combination of compound refractive lens optics (CRLs) was used to obtain a micrometer-sized focused incident beam with an energy of 44 keV and an extra-thick silicon drift detector optimized for high-energy X-ray detection to detect the K-lines of yttrium (Y), lanthanum (La), cerium (Ce), praseodymium (Pr), and neodymium (Nd) without any interferences due to line overlaps. High-energy excitation from La to Nd in the hyperaccumulator organs was successful but compared to L-line excitation less efficient and therefore slow (∼10-fold slower than similar maps at lower incident energy) due to lower flux and detection efficiency. However, REE K-lines do not suffer significantly from self-absorption, which makes XRF tomography of millimeter-sized frozen-hydrated plant samples possible. The K-line excitation of REEs at the P06 CRL setup has scope for application in samples that are particularly prone to REE interfering elements, such as soil samples with high concomitant Ti, Cr, Fe, Mn, and Ni concentrations.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229392","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

Critical evaluation of cell lysis methods for metallodrug studies in cancer cells. 癌症细胞中金属药物研究的细胞裂解方法的关键评估。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-09-05 DOI: 10.1093/mtomcs/mfad048

Mie Riisom, Stephen M F Jamieson, Christian G Hartinger

{"title":"Critical evaluation of cell lysis methods for metallodrug studies in cancer cells.","authors":"Mie Riisom, Stephen M F Jamieson, Christian G Hartinger","doi":"10.1093/mtomcs/mfad048","DOIUrl":"10.1093/mtomcs/mfad048","url":null,"abstract":"Intracellular accumulation studies are a key step in metallodrug development but often variable results are obtained. Therefore, we aimed here to investigate different protocols for efficient and reproducible lysis of cancer cells in terms of protein content in lysates and in cell uptake studies of the Ru anticancer complex [chlorido(8-oxyquinolinato)(η6-p-cymene)ruthenium(II)] ([Ru(cym)(HQ)Cl]). The physical lysis methods osmosis and sonication were chosen for comparison with chemical lysis with the radioimmunoprecipitation assay (RIPA) buffer. Based on the protein content and the total Ru accumulated in the lysates, the latter determined using inductively coupled plasma-mass spectrometry, RIPA buffer was the most efficient lysis method. Measurements of plastic adsorption blanks revealed that the higher Ru content determined in the RIPA buffer lysis samples may be due a higher amount of Ru extracted from the plastic incubation plates compared with osmosis and sonication. Overall, we found that the choice of lysis method needs to be matched to the information sought and we suggest the least disruptive osmosis method might be the best choice for labile drug-biomolecule adducts. Minimal differences were found for experiments aimed at measuring the overall cell uptake of the Ru complex.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10539203","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 transformations of arsenic in the rhizosphere-root interface of Pityrogramma calomelanos and Pteris vittata. 甘美兰和凤蝶根际界面中砷的化学转化。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-08-01 DOI: 10.1093/mtomcs/mfad047

Amelia Corzo Remigio, Hugh H Harris, David J Paterson, Mansour Edraki, Antony van der Ent

{"title":"Chemical transformations of arsenic in the rhizosphere-root interface of Pityrogramma calomelanos and Pteris vittata.","authors":"Amelia Corzo Remigio, Hugh H Harris, David J Paterson, Mansour Edraki, Antony van der Ent","doi":"10.1093/mtomcs/mfad047","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad047","url":null,"abstract":"Pityrogramma calomelanos and Pteris vittata are cosmopolitan fern species that are the strongest known arsenic (As) hyperaccumulators, with potential to be used in the remediation of arsenic-contaminated mine tailings. However, it is currently unknown what chemical processes lead to uptake of As in the roots. This information is critical to identify As-contaminated soils that can be phytoremediated, or to improve the phytoremediation process. Therefore, this study identified the in situ distribution of As in the root interface leading to uptake in P. calomelanos and P. vittata, using a combination of synchrotron micro-X-ray fluorescence spectroscopy and X-ray absorption near-edge structure imaging to reveal chemical transformations of arsenic in the rhizosphere-root interface of these ferns. The dominant form of As in soils was As(V), even in As(III)-dosed soils, and the major form in P. calomelanos roots was As(III), while it was As(V) in P. vittata roots. Arsenic was cycled from roots growing in As-rich soil to roots growing in control soil. This study combined novel analytical approaches to elucidate the As cycling in the rhizosphere and roots enabling insights for further application in phytotechnologies to remediated As-polluted soils.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10018072","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

Human serum albumin as a copper source for anticancer thiosemicarbazones. 人血清白蛋白作为抗癌硫代氨基甲酸铜的铜源。

IF 2.9 3区生物学

Metallomics Pub Date : 2023-08-01 DOI: 10.1093/mtomcs/mfad046

Martin Schaier, Enrico Falcone, Tomas Prstek, Bertrand Vileno, Sonja Hager, Bernhard K Keppler, Petra Heffeter, Gunda Koellensperger, Peter Faller, Christian R Kowol

{"title":"Human serum albumin as a copper source for anticancer thiosemicarbazones.","authors":"Martin Schaier, Enrico Falcone, Tomas Prstek, Bertrand Vileno, Sonja Hager, Bernhard K Keppler, Petra Heffeter, Gunda Koellensperger, Peter Faller, Christian R Kowol","doi":"10.1093/mtomcs/mfad046","DOIUrl":"10.1093/mtomcs/mfad046","url":null,"abstract":"Thiosemicarbazones (TSCs) are a class of biologically active compounds with promising anticancer activity. Their typical mechanism, especially of the clinically far developed representative Triapine, is chelation of iron (Fe), with the Fe-containing enzyme ribonucleotide reductase as primary intracellular target. However, for the subclass of terminally disubstituted, nanomolar-active derivatives like Dp44mT and Me2NNMe2, recent findings suggest that the chelation, stability, and reduction properties of the copper(II) (Cu) complexes are essential for their modes of action. Consequently, it is important to elucidate whether blood serum Cu(II) is a potential metal source for these TSCs. To gain more insights, the interaction of Triapine, Dp44mT or Me2NNMe2 with purified human serum albumin (HSA) as the main pool of labile Cu(II) was investigated by UV-vis and electron paramagnetic resonance measurements. Subsequently, a size-exclusion chromatography inductively coupled plasma mass spectrometry method for the differentiation of Cu species in serum was developed, especially separating the non-labile Cu enzyme ceruloplasmin from HSA. The results indicate that the TSCs specifically chelate copper from the N-terminal Cu-binding site of HSA. Furthermore, the Cu(II)-TSC complexes were shown to form ternary HSA conjugates, most likely via histidine. Noteworthy, Fe-chelation from transferrin was not overserved, even not for Triapine. In summary, the labile Cu pool of HSA is a potential source for Cu-TSC complex formation and, consequently, distinctly influences the anticancer activity and pharmacological behavior of TSCs.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10405564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318664","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

Interactions between chromium species and DNA in vitro and their potential role in the toxicity of hexavalent chromium. 铬与DNA的相互作用及其在六价铬毒性中的潜在作用。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-08-01 DOI: 10.1093/mtomcs/mfad045

R Mezencev, C Gibbons

{"title":"Interactions between chromium species and DNA in vitro and their potential role in the toxicity of hexavalent chromium.","authors":"R Mezencev, C Gibbons","doi":"10.1093/mtomcs/mfad045","DOIUrl":"https://doi.org/10.1093/mtomcs/mfad045","url":null,"abstract":"Epidemiological and animal studies have supported the carcinogenicity of hexavalent chromium [Cr(VI)]; however, molecular changes responsible for the induction of cancer by Cr(VI) are not entirely understood. Numerous mechanistic studies suggested the role of oxidative stress and genotoxicity in Cr(VI)-mediated carcinogenesis; however, specific types of DNA damage have not yet been conclusively attributed to specific chromium species or other reactive byproducts generated in biological systems exposed to Cr(VI). Due to the remarkably complex chemistry and biological effects of chromium species generated through the intracellular reduction of Cr(VI), their relevance for Cr(VI)-mediated carcinogenesis has not yet been fully elucidated and continues to be a subject of ongoing discussions in the field. In this report, we describe a complex world of chromium species and their reactivity with DNA and other biologically relevant molecules in vitro to inform a more complete understanding of Cr(VI)-mediated toxicity. In addition, we discuss previous results in the context of in vitro models and analytical methods to reconcile some conflicting findings on the biological role of chromium species.","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":"10372366","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

A bioinformatic analysis of zinc transporters in intestinal Lactobacillaceae. 肠道乳酸菌中锌转运体的生物信息学分析。

IF 2.9 3区生物学

Metallomics Pub Date : 2023-08-01 DOI: 10.1093/mtomcs/mfad044

Uyen Huynh, Hazel N Nguyen, Brittany K Trinh, Joanna Elhaj, Melissa L Zastrow

{"title":"A bioinformatic analysis of zinc transporters in intestinal Lactobacillaceae.","authors":"Uyen Huynh, Hazel N Nguyen, Brittany K Trinh, Joanna Elhaj, Melissa L Zastrow","doi":"10.1093/mtomcs/mfad044","DOIUrl":"10.1093/mtomcs/mfad044","url":null,"abstract":"As the second most abundant transition element and a crucial cofactor for many proteins, zinc is essential for the survival of all living organisms. To maintain required zinc levels and prevent toxic overload, cells and organisms have a collection of metal transport proteins for uptake and efflux of zinc. In bacteria, metal transport proteins are well defined for model organisms and many pathogens, but fewer studies have explored metal transport proteins, including those for zinc, in commensal bacteria from the gut microbiota. The healthy human gut microbiota comprises hundreds of species and among these, bacteria from the Lactobacillaceae family are well documented to have various beneficial effects on health. Furthermore, changes in dietary metal intake, such as for zinc and iron, are frequently correlated with changes in abundance of Lactobacillaceae. Few studies have explored zinc requirements and zinc homeostasis mechanisms in Lactobacillaceae, however. Here we applied a bioinformatics approach to identify and compare predicted zinc uptake and efflux proteins in several Lactobacillaceae genera of intestinal relevance. Few Lactobacillaceae had zinc transporters currently annotated in proteomes retrieved from the UniProt database, but protein sequence-based homology searches revealed that high-affinity ABC transporter genes are likely common, albeit with genus-specific domain features. P-type ATPase transporters are probably also common and some Lactobacillaceae genera code for predicted zinc efflux cation diffusion facilitators. This analysis confirms that Lactobacillaceae harbor genes for various zinc transporter homologs, and provides a foundation for systematic experimental studies to elucidate zinc homeostasis mechanisms in these bacteria.","PeriodicalId":89,"journal":{"name":"Metallomics","volume":"15 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10391621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10336015","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

Synchrotron science for sustainability: life cycle of metals in the environment. 可持续发展的同步加速器科学：环境中金属的生命周期。

IF 3.4 3区生物学

Metallomics Pub Date : 2023-08-01 DOI: 10.1093/mtomcs/mfad041

Louisa Smieska, Mary Lou Guerinot, Karin Olson Hoal, Matthew Reid, Olena Vatamaniuk

引用次数: 0

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