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上皮细胞向间充质细胞转化、eIF2α 磷酸化和 Hsp70 表达使 A549 细胞对 TiO2 纳米颗粒比对 ZnO 纳米颗粒有更高的耐受性。

Epithelial to Mesenchymal transition, eIF2α phosphorylation and Hsp70 expression enable greater tolerance in A549 cells to TiO over ZnO nanoparticles.

机构信息

CMBL, Department of Biological Sciences, Birla Institute of Technology and Sciences, K K Birla Goa Campus, Sancoale, South Goa, 403726, India.

出版信息

Sci Rep. 2019 Jan 24;9(1):436. doi: 10.1038/s41598-018-36716-2.

Abstract

Type II alveolar cells are highly robust in nature, yet susceptible to aerosolized nanoparticles (NPs). Dysfunction in these specialized cells, can often lead to emphysema, edema, and pulmonary inflammation. Long-time exposure can also lead to dangerous epigenetic modifications and cancer. Among the manufactured nanomaterials, metal oxide nanoparticles are widely encountered owing to their wide range of applications. Scores of published literatures affirm ZnO NPs are more toxic to human alveolar cells than TiO. However, signalling cascades deducing differences in human alveolar responses to their exposure is not well documented. With A549 cells, we have demonstrated that epithelial to mesenchymal transition and an increased duration of phosphorylation of eIF2α are crucial mechanisms routing better tolerance to TiO NP treatment over exposure to ZnO. The increased migratory capacity may help cells escape away from the zone of stress. Further, expression of chaperone such as Hsp70 is also enhanced during the same dose-time investigations. This is the first report of its kind. These novel findings could be successfully developed in the future to design relief strategies to alleviate metal oxide nanoparticle mediated stress.

摘要

II 型肺泡细胞具有很强的稳定性,但容易受到气溶胶纳米颗粒(NPs)的影响。这些特化细胞功能失调,通常会导致肺气肿、水肿和肺部炎症。长期暴露也可能导致危险的表观遗传修饰和癌症。在制造的纳米材料中,由于其广泛的应用,金属氧化物纳米颗粒被广泛遇到。大量已发表的文献证实,与 TiO 相比,ZnO NPs 对人肺泡细胞的毒性更大。然而,关于人类肺泡对其暴露的反应差异的信号级联尚未有详细记录。我们已经用 A549 细胞证明,上皮到间充质转化和 eIF2α 磷酸化持续时间的延长是使细胞对 TiO NP 处理比 ZnO 暴露具有更好耐受性的关键机制。迁移能力的增加可能有助于细胞从应激区逃逸。此外,在相同的剂量-时间研究中,伴侣蛋白如 Hsp70 的表达也增强。这是此类研究的首次报道。这些新发现将来可以成功开发,以设计缓解策略来减轻金属氧化物纳米颗粒介导的应激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d22/6346025/062374f2baaf/41598_2018_36716_Fig1_HTML.jpg

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