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二苯二硒醚诱导活性氧的产生先于酿酒酵母细胞形态和通透性的改变。

Induction of reactive oxygen species by diphenyl diselenide is preceded by changes in cell morphology and permeability in Saccharomyces cerevisiae.

机构信息

a Laboratório de Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas , Universidade Federal de Santa , Maria , Brazil.

b Departamento Bioquímica, Centro de Ciências Biológicas , Universidade Federal de Santa Catarina , Florianópolis , Brazil.

出版信息

Free Radic Res. 2017 Jul-Aug;51(7-8):657-668. doi: 10.1080/10715762.2017.1355054. Epub 2017 Aug 25.

Abstract

Organoselenium compounds, such as diphenyl diselenide (PhSe) and phenylselenium zinc chloride (PhSeZnCl), show protective activities related to their thiol peroxidase activity. However, depending on experimental conditions, organoselenium compounds can cause toxicity by oxidising thiol groups of proteins and induce the production of reactive oxygen species (ROS). Here, we analysed the toxicity of (PhSe) and PhSeZnCl in yeast Saccharomyces cerevisiae. Cell growth of S. cerevisiae after 1, 2, 3, 4, 6, and 16 h of treatment with 2, 4, 6, and 10 μM of (PhSe) was evaluated. For comparative purpose, PhSeZnCl was analysed only at 16 h of incubation at equivalent concentrations of selenium (i.e. 4, 8, 12, and 20 μM). ROS production (DCFH-DA), size, granularity, and cell membrane permeability (propidium iodide) were determined by flow cytometry. (PhSe) inhibited cell growth at 2 h (10 μM) of incubation, followed by increase in cell size. The increase of cell membrane permeability and granularity (10 μM) was observed after 3 h of incubation, however, ROS production occurs only at 16 h of incubation (10 μM) with (PhSe), indicating that ROS overproduction is a more likely consequence of (PhSe) toxicity and not its determinant. All tested parameters showed that only concentration of 20 μM induced toxicity in samples incubated with PhSeZnCl. In summary, the results suggest that (PhSe) toxicity in S. cerevisiae is time and concentration dependent, presenting more toxicity when compared with PhSeZnCl.

摘要

有机硒化合物,如二苯基二硒(PhSe)和苯硒化锌(PhSeZnCl),具有与硫醇过氧化物酶活性相关的保护活性。然而,根据实验条件的不同,有机硒化合物可能会通过氧化蛋白质的巯基基团而引起毒性,并诱导活性氧物种(ROS)的产生。在这里,我们分析了(PhSe)和 PhSeZnCl 在酵母酿酒酵母中的毒性。用 2、4、6 和 10 μM 的(PhSe)处理酿酒酵母细胞 1、2、3、4、6 和 16 小时后,评估细胞生长情况。为了进行比较,仅在孵育 16 小时后用相当于硒的浓度(即 4、8、12 和 20 μM)分析 PhSeZnCl。通过流式细胞术测定 ROS 产生(DCFH-DA)、大小、粒度和细胞膜通透性(碘化丙啶)。(PhSe)在孵育 2 小时(10 μM)时抑制细胞生长,随后细胞体积增大。孵育 3 小时后观察到细胞膜通透性和粒度增加(10 μM),然而,仅在孵育 16 小时(10 μM)时才观察到 ROS 产生(PhSe),表明 ROS 过度产生更可能是(PhSe)毒性的结果,而不是其决定因素。所有测试参数均表明,仅在孵育含 PhSeZnCl 的样品时,浓度为 20 μM 才会引起毒性。总之,结果表明(PhSe)在酿酒酵母中的毒性与时间和浓度有关,与 PhSeZnCl 相比毒性更大。

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