Journal
TOXICOLOGY LETTERS
Volume 211, Issue 3, Pages 334-341Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2012.04.016
Keywords
Silver nanoparticles; NRF2; Renal epithelial cells; GSH; G2/M arrest
Categories
Funding
- National Research Foundation of Korea [2011-0017977, 2011-0003619]
- Korean government
- Research Fund, of The Catholic University of Korea
- National Research Foundation of Korea [2010-0013857, 2009-0066689] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
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 gamma-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. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available