Copper is a persistent environmental contaminant, and exposure to elevated levels of this transition metal can result in a variety of pathologies. Copper affects the transcription of multiple defense and repair genes to protect against metal-induced pathologies. HepG2 cells were treated with copper under multiple conditions and microarray analyses were previously performed to better understand the mechanisms by which copper affects the transcription of stress-responsive genes. Analysis of the microarray data indicated that copper modulates multiple signal transduction pathways, including those mediated by NF-κB. Luciferase assays, quantitative reverse transcription real-time PCR, and chemical inhibition in HepG2 cells validated the microarray results and confirmed that NF-κB was activated by stress-inducible concentrations of copper. In addition, two novel NF-κB-regulated genes, SRXN1 (sulfiredoxin 1 homolog) and ZFAND2A (zinc-finger, AN1-type domain 2A), were identified. Our results indicate that the activation of NF-κB may be important for survival under elevated concentrations of copper.
Bibliographical noteFunding Information:
This work was supported (in part) by National Institutes of Health Grants U19ES011375 and P42 ES10356 and by the Intramural Research Program of the National Institutes of Health and National Institute of Environmental Health Sciences ( Z01ES102045 ).
- HepG2 cells
- gene expression