Lysosomal deposition of copper oxide nanoparticles triggers HUVEC cells death
Lysosomal deposition of copper oxide nanoparticles triggers HUVEC cells death
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氧化铜纳米粒子的溶酶体沉积触发 HUVEC 细胞死亡
DOI：
10.1016/j.biomaterials.2018.01.048
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发表时间：
2018
期刊：
影响因子：
14
通讯作者：
Yu C
中科院分区：
文献类型：
--
作者：
Zhang Jun;Zou Zhen;Wang Bin;Xu Ge;Wu Qiong;Zhang Yuchan;Yuan Zhiyi;Yang Xi;Yu Chao;Yu C
随着纳米氧化铜(CuONPs)的使用日益增多，其突出的物理化学性质及其对环境和人类健康的潜在毒性引起了人们的极大关注。本研究的目的是探讨CuONPs对血管内皮细胞毒性的可能机制。我们发现，CuONPs通过caspase非依赖性途径诱导人脐静脉内皮细胞(HUVECs)死亡。我们的结果还表明，CuONPs普遍沉积在溶酶体中。CuONPs的溶酶体沉积导致溶酶体功能障碍，导致自噬通量的降低和未降解的自噬小体的积累。然而，阻断CuONPs的溶酶体沉积可以显著减轻HUVEC细胞的死亡。有趣的是，我们发现CuONPs对溶酶体沉积的抑制减少了铜离子的释放，这被认为是CuONPs毒性的关键因素。综上所述，我们的结果表明，CuONPs的溶酶体沉积(同时促进了CuONPs中铜离子的释放)触发了CuONPs诱导的HUVEC细胞死亡。我们的发现为有毒金属氧化物纳米颗粒暴露对心血管系统的毒性机制提供了一个洞察力。
AbstractsThe increasing use of copper oxide nanoparticles (CuONPs) has led to major concerns regarding both the predominant physicochemical properties and the potential toxic effects on the environment and human health. The objective of this study is to explore the possible mechanisms underlying the toxicity of CuONPs in vascular endothelial cells. We found that CuONPs induced the cell death in human umbilical vein endothelial cells (HUVECs) through a caspase-independent pathway. Our results also demonstrated that CuONPs were prevalently deposited within lysosomes. The lysosomal deposition of CuONPs led to lysosomal dysfunction, resulting in the impairment of autophagic flux and the accumulation of undegraded autophagosomes. Nevertheless, blockage of the lysosomal deposition of CuONPs could significantly attenuate HUVEC cell death. Interestingly, we found that the inhibition of lysosomal deposition of CuONPs reduced the release of Cu ions, which has been considered as the crucial factor for the toxicity of CuONPs. In summary, our results indicate that the lysosomal deposition of CuONPs (along with the enhanced release of Cu ions form CuONPs) triggers CuONPs-induced HUVEC cell death. Our findings provide an insight into the mechanism of toxicity to the cardiovascular system induced by toxic metal oxide nanoparticles exposure.