RT Journal Article
T1 SirT1 regulation of antioxidant genes is dependent on the formation of a FoxO3a/PGC-1α complex
A1 Olmos Buchelt, Yolanda
A1 Sánchez Gómez, Francisco J.
A1 Wild, Brigitte
A1 García Quintans, Nieves
A1 Cabezudo, Sofía
A1 Lamas, Santiago
A1 Monsalve, María
AB SirT1 is a class III histone deacetylase that has been implicated in metabolic and reactive oxygen species control. In the vasculature it has been shown to decrease endothelial superoxide production, prevent endothelial dysfunction and atherosclerosis. However, the mechanisms that mediate SirT1 antioxidant functions remain to be characterized. The transcription factor FoxO3a and the transcriptional coactivator peroxisome proliferator activated receptor γ-coactivator 1α (PGC-1α) have been shown to induce the expression of antioxidant genes and to be deacetylated by SirT1. Aims: Here we investigated SirT1 regulation of antioxidant genes and the roles played by FoxO3a and PGC-1α in this regulation. Results: We found that SirT1 regulates the expression of several antioxidant genes in bovine aortic endothelial cells, including Mn superoxide dismutase (MnSOD), catalase, peroxiredoxins 3 and 5 (Prx3, Prx5), thioredoxin 2 (Trx2), thioredoxin reductase 2 (TR2), and uncoupling protein 2 (UCP-2) and can be localized in the regulatory regions of these genes. We also found that knockdown of either FoxO3a or PGC-1α prevented the induction of antioxidant genes by SirT1 over-expression. Furthermore, SirT1 increased the formation of a FoxO3a/PGC-1α complex as determined by co-immunoprecipitation (IP) assays, concomitantly reducing H2O2-dependent FoxO3a and PGC-1α acetylation. Data showing that FoxO3a knockdown increases PGC-1α acetylation levels and vice versa, suggest that SirT1 activity on FoxO3a and PGC-1α may be dependent of the formation of a FoxO3a/PGC-1α complex. Innovation: A unifying mechanism for SirT1 activities is suggested. Conclusion: We show that SirT1 regulation of antioxidant genes in vascular endothelial cells depends on the formation of a FoxO3a/PGC-1α complex.
PB Mary Ann Liebert
SN 1523-0864
YR 2013
FD 2013-11-01
LK https://hdl.handle.net/20.500.14352/105016
UL https://hdl.handle.net/20.500.14352/105016
LA eng
NO Olmos Y, Sánchez-Gómez FJ, Wild B, García-Quintans N, Cabezudo S, Lamas S, et al. SirT1 Regulation of Antioxidant Genes Is Dependent on the Formation of a FoxO3a/PGC-1α Complex. Antioxidants & Redox Signaling. 2013;19(13):1507-21.
NO Ministerio de Economía y Competitividad (España)
NO Comunidad de Madrid
DS Docta Complutense
RD 22 ene 2026