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首页> 外文期刊>International Journal of Nanomedicine >Silver nanoparticles induce reactive oxygen species-mediated cell cycle delay and synergistic cytotoxicity with 3-bromopyruvate in Candida albicans , but not in Saccharomyces cerevisiae
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Silver nanoparticles induce reactive oxygen species-mediated cell cycle delay and synergistic cytotoxicity with 3-bromopyruvate in Candida albicans , but not in Saccharomyces cerevisiae

机译:银纳米颗粒在白色念珠菌中诱导活性氧介导的细胞周期延迟和与3-溴丙酮酸盐的协同细胞毒性,而在酿酒酵母中则不

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Background: Silver nanoparticles (AgNPs) inhibit the proliferation of various fungi; however, their mechanisms of action remain poorly understood. To better understand the inhibitory mechanisms, we focused on the early events elicited by 5 nm AgNPs in pathogenic Candida albicans and non-pathogenic Saccharomyces cerevisiae. Methods: The effect of 5 nm and 100 nm AgNPs on fungus cell proliferation was analyzed by growth kinetics monitoring and spot assay. We examined cell cycle progression, reactive oxygen species (ROS) production, and cell death using flow cytometry. Glucose uptake was assessed using tritium-labeled 2-deoxyglucose. Results: The growth of both C. albicans and S. cerevisiae was suppressed by treatment with 5 nm AgNPs but not with 100 nm AgNPs. In addition, 5 nm AgNPs induced cell cycle arrest and a reduction in glucose uptake in both fungi after 30 minutes of culture in a dose-dependent manner ( P 0.05). However, in C. albicans only, an increase in ROS production was detected after exposure to 5 nm AgNPs. Concordantly, an ROS scavenger blocked the effect of 5 nm AgNPs on the cell cycle and glucose uptake in C. albicans only. Furthermore, the growth-inhibition effect of 5 nm AgNPs was not greater in S. cerevisiae mutant strains deficient in oxidative stress response genes than it was in wild type. Finally, 5 nm AgNPs together with a glycolysis inhibitor, 3-bromopyruvate, synergistically enhanced cell death in C. albicans ( P 0.05) but not in S. cerevisiae . Conclusion: AgNPs exhibit antifungal activity in a manner that may or may not be ROS dependent, according to the fungal species. The combination of AgNPs with 3-bromopyruvate may be more useful against infection with C. albicans .
机译:背景:银纳米颗粒(AgNPs)抑制各种真菌的增殖。但是,它们的作用机理仍然知之甚少。为了更好地理解其抑制机制,我们集中于致病性白色念珠菌和非致病性酿酒酵母中5 nm AgNP引发的早期事件。方法:通过生长动力学监测和斑点测定分析5 nm和100 nm AgNPs对真菌细胞增殖的影响。我们使用流式细胞仪检查了细胞周期进程,活性氧(ROS)产生和细胞死亡。使用tri标记的2-脱氧葡萄糖评估葡萄糖摄取。结果:用5 nm AgNPs抑制白念珠菌和酿酒酵母的生长,但用100 nm AgNPs抑制。此外,在培养30分钟后,5 nm AgNPs诱导了两种真菌的细胞周期停滞和葡萄糖摄取的降低,呈剂量依赖性(P <0.05)。但是,仅在白色念珠菌中,暴露于5 nm AgNP后检测到ROS的增加。相应地,ROS清除剂仅阻断了白色念珠菌对5 nm AgNPs对细胞周期和葡萄糖摄取的影响。此外,在缺乏氧化应激反应基因的酿酒酵母突变株中,5 nm AgNPs的生长抑制作用并不比野生型更大。最后,5 nm AgNPs与糖酵解抑制剂3-bromopyruvate协同增加白念珠菌的细胞死亡(P <0.05),而不是酿酒酵母。结论:根据真菌种类,AgNPs可能以或不以ROS依赖性的方式表现出抗真菌活性。 AgNP与3-溴丙酮酸的组合可能更有效地抵抗白色念珠菌感染。

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