Lysosomal impairment-mediated autophagy dysfunction responsible for the vascular endothelial apoptosis caused by silica nanoparticle via ROS/PARP1/AIF signaling pathway
Lysosomal impairment-mediated autophagy dysfunction responsible for the vascular endothelial apoptosis caused by silica nanoparticle via ROS/PARP1/AIF signaling pathway
复制标题
溶酶体损伤介导的自噬功能障碍通过ROS/PARP1/AIF信号通路导致二氧化硅纳米颗粒引起的血管内皮细胞凋亡
DOI：
10.1016/j.envpol.2022.119202
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发表时间：
2022-03-31
影响因子：
8.9
通讯作者：
Guo, Caixia
中科院分区：
文献类型：
--
作者：
Abulikemu, Alimire;Zhao, Xinying;Guo, Caixia
理解纳米粒子（NPs）与细胞的潜在相互作用对纳米毒理学研究至关重要。有证据表明，溶酶体是内化纳米粒子积累后的一个重要靶点，溶酶体损伤和自噬功能障碍是纳米粒子引发毒性的新兴分子机制。然而，与溶酶体的相互作用、随之产生的不良影响及其潜在机制在很大程度上仍然不清楚，尤其是在纳米粒子诱导的血管毒性方面。在本研究中，利用二氧化硅纳米粒子（SiNPs），通过体外培养人内皮细胞（HUVECs）来探究其对血管内皮细胞溶酶体的不良影响，并深入研究了相关机制。结果表明，内化的SiNPs明显在溶酶体中积累，并导致溶酶体功能障碍，这主要表现为溶酶体膜通透性增加、溶酶体数量减少、溶酶体酸性环境破坏以及溶酶体酶活性紊乱，从而导致自噬通量阻断和自噬功能障碍。更重要的是，机制研究结果显示，SiNPs导致的溶酶体损伤以及由此产生的自噬功能障碍可促进氧化应激、DNA损伤，并通过ROS/PARP1/AIF信号通路激活最终的细胞凋亡。这些发现增进了对SiNPs诱导的血管损伤的理解，并可能为SiNPs在纳米医学领域的应用提供新的信息和警示。
Understanding the underlying interactions of nanoparticles (NPs) with cells is crucial to the nanotoxicological research. Evidences suggested lysosomes as a vital target upon the accumulation of internalized NPs, and lysosomal damage and autophagy dysfunction are emerging molecular mechanisms for NPs-elicited toxicity. Nevertheless, the interaction with lysosomes, ensuing adverse effects and the underlying mechanisms are still largely obscure, especially in NPs-induced vascular toxicity. In this study, silica nanoparticles (SiNPs) were utilized to explore the adverse effects on lysosome in vascular endothelial cells by using in vitro cultured human endothelial cells (HUVECs), and in-depth investigated the mechanisms involved. Consequently, the internalized SiNPs accumulated explicitly in the lysosomes, and caused lysosomal dysfunction, which were prominent on the increased lysosomal membrane permeability, decline in lysosomal quantity, destruction of acidic environment of lysosome, and also disruption of lysosomal enzymes activities, resulting in autophagy flux blockage and autophagy dysfunction. More importantly, mechanistic results revealed the SiNPs-caused lysosomal impairments and resultant autophagy dysfunction could promote oxidative stress, DNA damage and the eventual cell apoptosis activated by ROS/PARP1/AIF signaling pathway. These findings improved the understanding of SiNPs-induced vascular injury, and may provide novel information and warnings for SiNPs applications in the fields of nanomedicine.