内质网在纳米材料毒性效应形成中的作用及机制
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摘要
随着纳米材料在食品、药物、生物医学等多领域的应用,其在生产使用过程中对人类健康的影响引起了广泛关注.内质网是蛋白质折叠与加工修饰、脂质合成以及Ca~(2+)储存的主要场所,是维护细胞内稳态的重要细胞器.内质网作为纳米材料的主要靶细胞器之一,在纳米材料引起的毒性效应中起重要作用.本文结合近年来国内外相关研究进展,阐述了纳米银(Ag-NPs)、纳米金(Au-NPs)、纳米二氧化钛(TiO_2-NPs)、纳米氧化锌(ZnO-NPs)、纳米二氧化硅(SiO_2-NPs)、富勒烯(C_(60))、单壁与多壁碳纳米管(SWCNTs/MWCNTs)以及石墨烯与氧化石墨烯(GO)等典型纳米材料对内质网结构与功能的影响,并归纳总结了内质网在不同纳米材料诱导的毒性效应中的作用及其异同点.纳米材料可通过引起内质网应激诱导细胞凋亡、炎症反应以及细胞自噬,还可通过激活IP_3信号通路诱导内质网Ca~(2+)释放激活钙依赖的细胞凋亡.纳米材料可在内质网中积累造成结构损伤及功能障碍,还可诱导内质网自噬.
With the wide application of nanomaterials in many fields such as food, drug and biomedicine, their negative impacts on the health of human beings in the process of production and uses have attracted much attention. Endoplasmic reticulum(ER), an important organelle and functions in folding and assembling of cellular proteins, synthesis of lipids, and storage of free calcium, is sensitive to stress. ER as one of the most sensitive targets of nanomaterials plays important roles in the toxicity of nanomaterials. This review summarizes the recent studies on the role of ER in the nanotoxicology of several typical nanomaterials, including silver nanoparticles(Ag-NPs), titanium dioxide nanoparticles(TiO_2-NPs), zinc oxide nanoparticles(ZnO-NPs), gold nanoparticles(Au-NPs), silica nanoparticles(SiO_2-NPs), fullerene, single/multi-walled carbon nanotubes(SWCNTs/MWCNTs)and grapheme/grapheme oxide(GO), and analyzes the difference. The nanomaterials can cause ER stress, and in turn induce apoptosis, inflammation and autophagy. They can also activate the release of Ca~(2+)from the ER Ca~(2+) stores through IP_3 pathway and further trigger calcium-regulated apoptotic cell death. Nanomaterials tend to accumulate in ER causing damage of ER and inducing ER autophagy.
With the wide application of nanomaterials in many fields such as food, drug and biomedicine, their negative impacts on the health of human beings in the process of production and uses have attracted much attention. Endoplasmic reticulum(ER), an important organelle and functions in folding and assembling of cellular proteins, synthesis of lipids, and storage of free calcium, is sensitive to stress. ER as one of the most sensitive targets of nanomaterials plays important roles in the toxicity of nanomaterials. This review summarizes the recent studies on the role of ER in the nanotoxicology of several typical nanomaterials, including silver nanoparticles(Ag-NPs), titanium dioxide nanoparticles(TiO_2-NPs), zinc oxide nanoparticles(ZnO-NPs), gold nanoparticles(Au-NPs), silica nanoparticles(SiO_2-NPs), fullerene, single/multi-walled carbon nanotubes(SWCNTs/MWCNTs)and grapheme/grapheme oxide(GO), and analyzes the difference. The nanomaterials can cause ER stress, and in turn induce apoptosis, inflammation and autophagy. They can also activate the release of Ca~(2+)from the ER Ca~(2+) stores through IP_3 pathway and further trigger calcium-regulated apoptotic cell death. Nanomaterials tend to accumulate in ER causing damage of ER and inducing ER autophagy.
引文
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