Silver nanoparticles-mediated G2/M cycle arrest of renal epithelial cells is associated with NRF2-GSH signaling

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• 作者：Su Jin Kang^a ; Young Joon Lee^a ; Eun-Kyung Lee^b ; Mi-Kyoung Kwak^c ; ^{mkwak@catholic.ac.kr}
• 关键词：nAg ; silver nanoparticle ; NRF2i ; NRF2 knockdown HK-2 ; SCi ; nonspecific control HK-2 ; scRNA ; scrambled RNA ; ARE ; antioxidant-response element ; ROS ; reactive oxygen species ; GSH ; glutathione ; NQO1 ; NAP(D)H ; quinone oxidoreductase-1 ; GCLC ; catalytic subunit o
• 刊名：Toxicology Letters
• 出版年：2012
• 期刊代码：49_03784274
• 类别：pha
• 出版时间：20 June, 2012
• 卷：211
• 期：3
• 页码：334-341
• 文件大小：776 K

摘要

Silver nanoparticles (nAg) are known to evoke reactive oxygen species (ROS) generation and consequent cell damage. The transcription factor NF-E2-related factor 2 (NRF2) controls both the basal and inducible expression of multiple antioxidant genes. This study was aimed to investigate the role of NRF2 in nAg-induced renal epithelial cell damage. nAg treatment intensified DNA damage and G2/M cell cycle arrest by nAg in NRF2 knockdown HK-2 (NRF2i) compared with the control cells. As a signaling mechanism associated with nAg-mediated growth arrest, the levels of phospho-CDC25C and phospho-CDC2 were significantly increased in NRF2i. Target gene analysis revealed that nAg-mediated increase in 纬-glutamate cysteine ligase expression is NRF2-dependent: nAg-treated NRF2i showed a reduction in glutathione (GSH) content and elevation in ROS level in comparison with the control cells. Additionally, pretreatment of N-acetylcystein in nAg-treated NRF2i alleviated ROS-mediated DNA damage and G2/M cell cycle arrest, while GSH depletion exacerbated DNA damage and cell cycle arrest in the control cells. Taken together, these results suggest that NRF2-mediated GSH increase plays a protective role in nAg-induced DNA damage and subsequent G2/M cell cycle arrest in human renal epithelial cells.