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SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1a complex in vascular endothelial cells 

AuthorsWild, Brigitte; Olmos, Yolanda; García-Quintans, Nieves CSIC; Cabezudo, Sofía CSIC ORCID; Monsalve, María CSIC ORCID
Issue Date2012
CitationInternational Symposium on Redox Signaling and Oxidative Stress in Health and Disease (2012)
AbstractExcessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. SirT1 is a class III histone deacetylase that has been implicated in metabolic and ROS control. In the vasculature, decreased endothelial SirT1 expression increases endothelial superoxide production, NF-κB signaling, and expression of adhesion molecules. However, the mechanisms that mediate SirT1 function on the endothelium remain to be characterized. FoxO3a and PGC-1a have been shown to be molecular targets of SirT1 and to control endothelial ROS production. Here we investigated SirT1 regulation of antioxidant genes in vascular endothelial cells and the role played by FoxO3a and PGC-1a in this regulation. We found that SirT1 regulates the expression of several antioxidant genes in BAEC, including MnSOD, catalase, Prx3, Prx5, UCP-2, Trx2 and TR, and can be localized in the regulatory regions of these genes. We also found that knockdown of either FoxO3a or PGC-1a prevented SirT1 antioxidant gene induction. Furthermore, SirT1 increased the formation of a FoxO3a PGC-1a complex as determined by co-IP assays, concomitantly reducing H2O2 dependent FoxO3a and PGC-1a acetylation. Data showing that FoxO3a knockdown increases PGC-1a acetylation levels and vice versa, suggests that SirT1 activity on FoxO3a and PGC-1a may be dependent of the formation of a FoxO3a/PGC-1a complex. In conclusion, we show that SirT1 regulation of antioxidant genes in vascular endothelial cells depends of the formation of a FoxO3a/PGC-1a complex.
DescriptionResumen del trabajo presentado al International Symposium on Redox Signaling and Oxidative Stress in Health and Disease, IV Spanish and Portuguese Meeting on Free Radicals; celebrado en Valencia (España) del 5 al 7 de junio de 2012.
Appears in Collections:(IIBM) Comunicaciones congresos
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