2. Academic Validation
  3. 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

  • Biomaterials. 2017 Jun;130:14-27. doi: 10.1016/j.biomaterials.2017.03.027.
Ming Gao 1,  Beibei Zhao 2,  Minjun Chen 3,  Yun Liu 4,  Ming Xu 1,  Zhe Wang 5,  Sijin Liu 6,  Chengdong Zhang 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
  • 2 College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin, China.
  • 3 College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi 030006, China.
  • 4 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences and Anhui Province, Hefei, Anhui 230031, China.
  • 5 School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.
  • 6 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: sjliu@rcees.ac.cn.
  • 7 College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin, China. Electronic address: zhangchengdong@nankai.edu.cn.
PMID: 28351005 DOI: 10.1016/j.biomaterials.2017.03.027
Abstract

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 PI4Kα 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 PI4Kα. Thus, this study would open a new path to depict the molecular Bases of AgNP-induced effects on erythroid cells.

Keywords

Cell death; Erythroid cells; ODRUL; Silver nanoparticles; lncRNA.

Figures
Products