Mn3O4 nanoparticles cause endoplasmic reticulum stress-dependent toxicity to Saccharomyces cerevisiae
Mn3O4 nanoparticles cause endoplasmic reticulum stress-dependent toxicity to Saccharomyces cerevisiae
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DOI：
10.1039/c7ra07458a
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发表时间：
2017-09
期刊：
影响因子：
3.9
通讯作者：
Xiao Yi;Weili Zhao;Jianrong Li;Bing Zhang;Qilin Yu;Mingchun Li
中科院分区：
文献类型：
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作者：
Xiao Yi;Weili Zhao;Jianrong Li;Bing Zhang;Qilin Yu;Mingchun Li
Mn_3O_4纳米粒子具有优异的物理化学性质，是一种重要的纳米材料。然而，人们对其生物学效应知之甚少。在这项研究中，我们研究了合成的Mn 3 O 4纳米粒子（NPs）（与尺寸为10-25 nm）的重要真菌模型，酿酒酵母的影响。生长抑制试验表明，Mn 3 O 4纳米颗粒对酿酒酵母具有剂量依赖性毒性（IC 50 = 340 ppm）。质膜（PM）没有被NPs破坏，并且添加ROS清除剂不能减弱NPs对酵母细胞的生长抑制，排除了PM损伤和氧化应激对这种毒性的贡献。有趣的是，Mn 3 O 4纳米颗粒引起的HAC 1 mRNA剪接和显着上调的未折叠蛋白反应（UPR）基因，表明纳米颗粒诱导严重的内质网（ER）应激。此外，治疗的NP严重降低了细胞外转化酶和表面铁还原酶的活性，这可能是由于ER应激相关的分泌途径中断。本研究揭示了Mn 3 O 4纳米颗粒对真核细胞的一种新的毒性机制，为评估纳米颗粒的环境影响提供了有用的信息。
Mn3O4 nanoparticles (NPs) are a significant nanomaterial (NM) due to their excellent physiochemical properties. However, little is known about their biological effects. In this study, we investigated the effect of the synthesized Mn3O4 nanoparticles (NPs) (with the size of 10–25 nm) on the important fungus model, Saccharomyces cerevisiae. Growth inhibition assays showed that Mn3O4 NPs had dose-dependent toxicity to Saccharomyces cerevisiae (IC50 = 340 ppm). The plasma membrane (PM) was not damaged by the NPs, and the addition of ROS scavengers could not attenuate growth inhibition of the NPs to yeast cells, ruling out the contribution of PM damage and oxidative stress to this toxicity. Interestingly, Mn3O4 NPs caused HAC1 mRNA splicing and remarkable up-regulation of the unfolded protein response (UPR) genes, indicating that the NPs induce severe endoplasmic reticulum (ER) stress. Moreover, treatment of the NPs severely reduced the activity of both extracellular invertase and surface ferric reductase, which might be attributable to ER stress-related disruption of the secretion pathway. This study uncovers a novel toxicity mechanism of Mn3O4 NPs against eukaryotic cells, and provides useful information for assessing the environmental impact of NMs.