Bioengineering Laboratory-CIETI, Chemical Engineering Department , ISEP-School of Engineering of Polytechnic Institute of Porto , Rua Dr António Bernardino de Almeida, 431 , 4249-015 Porto , Portugal.
CEB-Centre of Biological Engineering , University of Minho, Campus de Gualtar , 4710-057 Braga , Portugal.
Chem Res Toxicol. 2019 Feb 18;32(2):245-254. doi: 10.1021/acs.chemrestox.8b00265. Epub 2019 Feb 4.
The expansion of the industrial use of nickel oxide (NiO) nanoparticles (NPs) raises concerns about their potential adverse effects. Our work aimed to investigate the mechanisms of toxicity induced by NiO NPs, using the yeast Saccharomyces cerevisiae as a cell model. Yeast cells exposed to NiO NPs exhibited typical hallmarks of regulated cell death (RCD) by apoptosis [loss of cell proliferation capacity (cell viability), exposure of phosphatidylserine at the outer cytoplasmic membrane leaflet, nuclear chromatin condensation, and DNA damage] in a process that required de novo protein synthesis. The execution of yeast cell death induced by NiO NPs is Yca1p metacaspase-dependent. NiO NPs also induced a decrease in the mitochondrial membrane potential and an increase in the frequency of respiratory-deficient mutants, which supports the involvement of mitochondria in the cell death process. Cells deficient in the apoptosis-inducing factor ( aif1Δ) displayed higher tolerance to NiO NPs, which reinforces the involvement of mitochondria in RCD by apoptosis. In summary, this study shows that NiO NPs induce caspase- and mitochondria-dependent apoptosis in yeast. Our results warn about the possible harmful effects associated with the use of NiO NPs.
氧化镍 (NiO) 纳米颗粒 (NPs) 的工业用途不断扩大，引起了人们对其潜在不良影响的关注。我们的工作旨在使用酵母酿酒酵母作为细胞模型，研究 NiO NPs 诱导毒性的机制。暴露于 NiO NPs 的酵母细胞表现出典型的细胞凋亡的调控细胞死亡 (RCD) 特征[细胞增殖能力丧失 (细胞活力)、质膜外叶磷脂酰丝氨酸暴露、核染色质浓缩和 DNA 损伤]，这一过程需要新的蛋白质合成。NiO NPs 诱导的酵母细胞死亡的执行依赖于 Yca1p 效应子半胱氨酸蛋白酶。NiO NPs 还导致线粒体膜电位降低和呼吸缺陷突变体频率增加，这支持了线粒体在细胞死亡过程中的参与。缺乏凋亡诱导因子 (aif1Δ) 的细胞对 NiO NPs 的耐受性更高，这进一步证实了线粒体在细胞凋亡的 RCD 中的作用。总之，本研究表明 NiO NPs 诱导酵母中的 caspase 和线粒体依赖性细胞凋亡。我们的研究结果警告了与使用 NiO NPs 相关的可能有害影响。
