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Copper activation of NF-kappaB signaling in HepG2 cells.
- Source :
-
Journal of molecular biology [J Mol Biol] 2009 Nov 13; Vol. 393 (5), pp. 1013-21. Date of Electronic Publication: 2009 Sep 08. - Publication Year :
- 2009
-
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.
- Subjects :
- Cell Line, Tumor
Computational Biology
Gene Expression Regulation drug effects
Gene Regulatory Networks
Humans
Hydrogen Peroxide pharmacology
I-kappa B Kinase antagonists & inhibitors
Protein Kinase Inhibitors pharmacology
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Small Interfering metabolism
Transcription Factor RelA metabolism
Transcription, Genetic drug effects
Copper pharmacology
NF-kappa B metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1089-8638
- Volume :
- 393
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 19747488
- Full Text :
- https://doi.org/10.1016/j.jmb.2009.08.077