Rice University, Department of Chemical and Biomolecular Engineering, 6100 Main St, MS-362, Houston, TX 77005, USA.
Rice University, Department of BioSciences, 6100 Main St, MS-362, Houston, TX 77005, USA.
Acta Biomater. 2018 Oct 1;79:354-363. doi: 10.1016/j.actbio.2018.08.021. Epub 2018 Aug 19.
Titanium dioxide is "generally regarded as safe" and titanium dioxide nanoparticles (TiO NPs) are used in a wide variety of consumer products. Cellular exposure to TiO NPs results in complex effects on cell physiology including induction of oxidative stress and impairment of lysosomal function, raising concerns about the impact of TiO NPs on biological systems. We investigated the effects of TiO NPs (15, 50, and 100 nm in diameter) on the lysosome-autophagy system, the main cellular catabolic pathway that mediates degradation of nanomaterials. Specifically, we monitored a comprehensive set of markers of the lysosome-autophagy system upon cell exposure to TiO NPs, ranging from transcriptional activation of genes required for the formation of autophagic vesicles to clearance of autophagic substrates. This study reveals that uptake of TiO NPs induces a response of the lysosome-autophagy system mediated by the transcription factor EB and consequent upregulation of the autophagic flux. Prolonged exposure to TiO NPs, however, was found to induce lysosomal dysfunction and membrane permeabilization, leading to a blockage in autophagic flux. Results from this study will inform the design of TiO NP based devices with specific autophagy-modulating properties.
二氧化钛被“普遍认为是安全的”，并且纳米二氧化钛（TiO NPs）被广泛应用于各种消费产品。细胞暴露于 TiO NPs 会对细胞生理学产生复杂的影响，包括诱导氧化应激和溶酶体功能障碍，这引发了人们对 TiO NPs 对生物系统影响的担忧。我们研究了 TiO NPs（直径为 15、50 和 100nm）对溶酶体-自噬系统的影响，该系统是介导纳米材料降解的主要细胞分解代谢途径。具体而言，我们在细胞暴露于 TiO NPs 时监测了溶酶体-自噬系统的一组综合标记物，范围从参与自噬小泡形成的基因的转录激活到自噬底物的清除。这项研究揭示了 TiO NPs 的摄取会诱导由转录因子 EB 介导的溶酶体-自噬系统的反应，从而导致自噬通量的上调。然而，长时间暴露于 TiO NPs 会导致溶酶体功能障碍和膜通透性增加，从而导致自噬通量受阻。这项研究的结果将为设计具有特定自噬调节特性的 TiO NP 基器件提供信息。
