Copper activation of NF-kappaB signaling in HepG2 cells.

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McElwee MK, Song MO, Freedman JH

Copper activation of NF-kappaB signaling in HepG2 cells.

J Mol Biol. 2009 Nov 13;393(5):1013-21. doi: 10.1016/j.jmb.2009.08.077. Epub 2009 Sep 8.

PubMed ID

19747488 [ View in PubMed

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Abstract

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-kappaB. Luciferase assays, quantitative reverse transcription real-time PCR, and chemical inhibition in HepG2 cells validated the microarray results and confirmed that NF-kappaB was activated by stress-inducible concentrations of copper. In addition, two novel NF-kappaB-regulated genes, SRXN1 (sulfiredoxin 1 homolog) and ZFAND2A (zinc-finger, AN1-type domain 2A), were identified. Our results indicate that the activation of NF-kappaB may be important for survival under elevated concentrations of copper.