Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 393, Issue 5, Pages 1013-1021Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2009.08.077
Keywords
copper; NF-kappa B; HepG2 cells; gene expression; microarray
Categories
Funding
- National Institutes of Health [U19ES011375, P42 ES10356]
- National Institutes of Health
- National Institute of Environmental Health Sciences [Z01ES102045]
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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-kappa B. Luciferase assays, quantitative reverse transcription real-time PCR, and chemical inhibition in HepG2 cells validated the microarray results and confirmed that NF-kappa B was activated by stress-inducible concentrations of copper. In addition, two novel NF-kappa B-regulated genes, SRXN1 (sulfiredoxin 1 homolog) and ZFAND2A (zinc-finger, AN1-type domain 2A), were identified. Our results indicate that the activation of NF-kappa B may be important for survival under elevated concentrations of copper. Published by Elsevier Ltd.
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