Abstract
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 γ-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.
| Original language | English |
|---|---|
| Pages (from-to) | 334-341 |
| Number of pages | 8 |
| Journal | Toxicology Letters |
| Volume | 211 |
| Issue number | 3 |
| DOIs | |
| State | Published - 20 Jun 2012 |
Bibliographical note
Funding Information:This work was supported by the National Research Foundation of Korea Grant ( 2011-0017977 , 2011-0003619 ) funded by the Korean government and the Research Fund, 2011 of The Catholic University of Korea.
Keywords
- G2/M arrest
- GSH
- NRF2
- Renal epithelial cells
- Silver nanoparticles