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Open Access item Cell Survival from Chemotherapy Depends on NF-κB Transcriptional Up-Regulation of Coenzyme Q Biosynthesis.

Authors:Brea-Calvo, Gloria
Siendones, Emilio
Sánchez-Alcázar, José Antonio
Cabo, Rafael de
Navas, Plácido
Keywords:Coenzyme Q, CPT, COQ7, NF-κB, Mitochondrial respiratory, Chemotherapy
Issue Date:23-Apr-2009
Publisher:Public Library of Science
Citation:PLoS ONE 4(4): e5301.
Abstract:[Background] Coenzyme Q (CoQ) is a lipophilic antioxidant that is synthesized by a mitochondrial complex integrated by at least ten nuclear encoded COQ gene products. CoQ increases cell survival under different stress conditions, including mitochondrial DNA (mtDNA) depletion and treatment with cancer drugs such as camptothecin (CPT). We have previously demonstrated that CPT induces CoQ biosynthesis in mammal cells.
[Methodology/Principal Findings] CPT activates NF-κB that binds specifically to two κB binding sites present in the 5′-flanking region of the COQ7 gene. This binding is functional and induces both the COQ7 expression and CoQ biosynthesis. The inhibition of NF-κB activation increases cell death and decreases both, CoQ levels and COQ7 expression induced by CPT. In addition, using a cell line expressing very low of NF-κB, we demonstrate that CPT was incapable of enhancing enhance both CoQ biosynthesis and COQ7 expression in these cells.
[Conclusions/Significance] We demonstrate here, for the first time, that a transcriptional mechanism mediated by NF-κB regulates CoQ biosynthesis. This finding contributes new data for the understanding of the regulation of the CoQ biosynthesis pathway.
Description:9 pages and 6 figures.
Publisher version (URL):http://dx.doi.org/10.1371/journal.pone.0005301
Appears in Collections:(CABD) Artículos

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