Nrf-2-driven long noncoding RNA ODRUL contributes to modulating silver nanoparticle-induced effects on erythroid cells
Nrf-2-driven long noncoding RNA ODRUL contributes to modulating silver nanoparticle-induced effects on erythroid cells
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Nrf-2驱动的长非编码RNA ODRUL有助于调节银纳米粒子诱导的对红细胞的影响
DOI：
10.1016/j.biomaterials.2017.03.027
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发表时间：
2017-06-01
期刊：
影响因子：
14
通讯作者：
Zhang, Chengdong
中科院分区：
文献类型：
--
作者：
Gao, Ming;Zhao, Beibei;Zhang, Chengdong
纳米银对人体健康的生物安全性和生物学效应日益受到关注。尽管已经进行了大量的研究来揭示agnp诱导效应的分子机制，但目前的理解主要集中在由Ag颗粒和/或Ag离子激活的氧化应激相关信号通路上。然而，这些应激信号通路激活的分子基础尚未完全阐明。在本研究中，我们旨在从长链非编码rna的角度揭示agnp诱导红系细胞作用的分子基础。我们发现了一种长链非编码RNA分子ODRUL，它在K562红系细胞对AgNPs的反应中显著增强，并伴随着细胞死亡的加速。此外，我们发现氧化应激驱动的Nrf2转录促进了K562细胞中ODRUL的表达。在Nrf2-ODRUL被AgNPs激活的下游，ODRUL被认为与PI4Ka蛋白相互作用，调节其靶点AKT和JNK的活性。因此，在agnp诱导的应激下，PI4K-AKT/JNK信号通路负调控Bcl-2水平，导致细胞死亡加剧。总之，我们的研究发现nrf2介导的lncRNA ODRUL是agnp诱导红系细胞毒性不可缺少的，它通过与PI4Ka的物理相互作用调控AKT/JNK-Bcl-2信号传导。因此，本研究将为揭示agnp对红细胞影响的分子基础开辟一条新的途径。(C) 2017 Elsevier Ltd.版权所有。
The biosafety and biological effects of silver nanoparticles (AgNPs) on human health attract increasing concern. Although considerable studies have been performed to reveal the molecular mechanisms responsible for AgNP-induced effects, the current understanding mainly focuses on oxidative stress-associated signaling pathways activated by Ag particles and/or Ag ions. However, the molecular bases underlying the activation of these stress signaling pathways have not been thoroughly elucidated yet. In the current study, we aimed to shed light on the molecular bases of AgNP-induced effects on erythroid cells from the perspective of long noncoding RNAs. We identified a long-noncoding RNA molecule, ODRUL, which was substantially enhanced in K562 erythroid cells responding to AgNPs, coupled to accelerated cell death. Further, we uncovered oxidative stress-driven Nrf2 transcriptionally promoted ODRUL expression in K562 cells. Downstream of Nrf2-ODRUL activation by AgNPs, ODRUL was recognized to interact with PI4Ka protein to modulate the activities of its targets AKT and JNK. As a result, the Bcl-2 level was negatively regulated by PI4K-AKT/JNK signaling under AgNP-induced stress, leading to enhanced cell death. Together, our findings unearthed that Nrf2-mediated lncRNA ODRUL was indispensable for AgNP-induced toxicity in erythroid cells through regulation of AKT/JNK-Bcl-2 signaling dependent on a physical interaction with PI4Ka. Thus, this study would open a new path to depict the molecular bases of AgNP-induced effects on erythroid cells. (C) 2017 Elsevier Ltd. All rights reserved.