Copper is a potent inhibitor of both the canonical and non-canonical NFκB pathways
Autor: | Colin S. Duckett, George E Hucks, Andrew J. Kocab, Annie L McCollom, Niall S. Kenneth |
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Rok vydání: | 2014 |
Předmět: |
chemistry.chemical_element
X-Linked Inhibitor of Apoptosis Protein Biology Cell Line Mice Downregulation and upregulation NF-KappaB Inhibitor alpha Cell Line Tumor Report medicine Animals Humans Phosphorylation Molecular Biology Ionophores Clioquinol NF-kappa B Cell Biology Free Radical Scavengers NFKB1 Copper Cell biology Acetylcysteine IκBα Oxidative Stress chemistry Biochemistry I-kappa B Proteins Signal transduction Intracellular Developmental Biology medicine.drug Signal Transduction |
Zdroj: | Cell cycle (Georgetown, Tex.). 13(6) |
ISSN: | 1551-4005 |
Popis: | Copper is an essential trace element that plays key roles in many metabolic processes. Homeostatic regulation of intracellular copper is normally tightly controlled, but deregulated copper levels are found in numerous metabolic and neurodegenerative diseases, as well as in a range of neoplasms. There are conflicting reports regarding the exact role of copper in the regulation of NFκB-responsive genes, specifically whether copper leads to increased activation of the NFκB pathways, or downregulation. Here we show that increased intracellular levels of copper, using the ionophore clioquinol, leads to a potent inhibition of NFκB pathways, induced by multiple distinct stimuli. Addition of copper to cells inhibits ubiquitin-mediated degradation of IκBα by preventing its phoshorylation by the upstream IKK complex. Intriguingly, copper-dependent inhibition of NFκB can be reversed by the addition of the reducing agent, N-acetylcysteine (NAC). These results suggest that the oxidative properties of excess copper prevent NFκB activation by blocking IκBα destruction, and that NFκB activity should be assessed in diseases associated with copper excess. |
Databáze: | OpenAIRE |
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