Copper activation of NF-kappaB signaling in HepG2 cells.
J Mol Biol, 2009/11/13;393(5):1013-21.
McElwee MK[1], Song MO, Freedman JH
Affiliations
PMID: 19747488DOI: 10.1016/j.jmb.2009.08.077
Impact factor: 6.151
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.
MeSH terms
Cell Line, Tumor; Computational Biology; Copper; Gene Expression Regulation; Gene Regulatory Networks; Humans; Hydrogen Peroxide; I-kappa B Kinase; NF-kappa B; Protein Kinase Inhibitors; RNA, Messenger; RNA, Small Interfering; Signal Transduction; Transcription Factor RelA; Transcription, Genetic
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download