Autophagic response to cellular exposure to titanium dioxide nanoparticles
Autophagic response to cellular exposure to titanium dioxide nanoparticles
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DOI：
10.1016/j.actbio.2018.08.021
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发表时间：
2018-10-01
影响因子：
9.7
通讯作者：
Segatori, Laura
中科院分区：
文献类型：
--
作者：
Popp, Lauren;Vinh Tran;Segatori, Laura
二氧化钛“通常被认为是安全的”，二氧化钛纳米颗粒（TiO2 NPs）用于各种消费品。细胞暴露于TiO2 NPs导致对细胞生理学的复杂影响，包括诱导氧化应激和损害溶酶体功能，引起了对TiO2 NPs对生物系统影响的担忧。我们研究了TiO2纳米颗粒（直径为15，50和100 nm）对溶酶体自噬系统的影响，溶酶体自噬系统是介导纳米材料降解的主要细胞分解代谢途径。具体来说，我们监测了一套全面的标志物的溶酶体自噬系统后，细胞暴露于二氧化钛纳米粒子，从转录激活的基因所需的自噬囊泡的形成，清除自噬底物。这项研究表明，二氧化钛纳米颗粒的吸收诱导的溶酶体自噬系统的转录因子EB介导的响应和随之而来的自噬通量上调。然而，长时间暴露于TiO2纳米颗粒，发现诱导溶酶体功能障碍和膜透化，导致自噬通量的阻断。本研究的结果将为具有特定自噬调节特性的基于TiO2 NP的器械的设计提供信息。(C)2018 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Titanium dioxide is "generally regarded as safe" and titanium dioxide nanoparticles (TiO2 NPs) are used in a wide variety of consumer products. Cellular exposure to TiO2 NPs results in complex effects on cell physiology including induction of oxidative stress and impairment of lysosomal function, raising concerns about the impact of TiO2 NPs on biological systems. We investigated the effects of TiO2 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 TiO2 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 TiO2 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 TiO2 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 TiO2 NP based devices with specific autophagy-modulating properties. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.