Title: Copper activation of NF-kappaB signaling in HepG2 cells.

Authors: McElwee, Matthew K; Song, Min Ok; Freedman, Jonathan H

Published In J Mol Biol, (2009 Nov 13)

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.

PubMed ID: 19747488

MeSH Terms: Cell Line, Tumor; Computational Biology; Copper/pharmacology*; Gene Expression Regulation/drug effects; Gene Regulatory Networks; Humans; Hydrogen Peroxide/pharmacology; I-kappa B Kinase/antagonists & inhibitors; NF-kappa B/metabolism*; Protein Kinase Inhibitors/pharmacology; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA, Small Interfering/metabolism; Signal Transduction/drug effects*; Transcription Factor RelA/metabolism; Transcription, Genetic/drug effects