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Title

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

AuthorsBrea-Calvo, Gloria ; Siendones, Emilio ; Sánchez-Alcázar, José Antonio ; Cabo, Rafael de; Navas, Plácido
KeywordsCoenzyme Q
CPT
COQ7
NF-κB
Mitochondrial respiratory
Chemotherapy
Issue Date23-Apr-2009
PublisherPublic Library of Science
CitationPLoS 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.
Description9 pages and 6 figures.
Publisher version (URL)http://dx.doi.org/10.1371/journal.pone.0005301
URIhttp://hdl.handle.net/10261/14129
DOI10.1371/journal.pone.0005301
ISSN1932-6203
Appears in Collections:(CABD) Artículos
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