RT Journal Article
T1 Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes
A1 Olmos Buchelt, Yolanda
A1 Valle, Inmaculada
A1 Borniquel, Sara
A1 Tierrez, Alberto
A1 Soria, Estrella
A1 Lamas, Santiago
A1 Monsalve, María
AB Oxidative stress is a hallmark of metabolism-related diseases and a risk factor for atherosclerosis. FoxO factors have been shown to play a key role in vascular endothelial development and homeostasis. Foxo3a can protect quiescent cells from oxidative stress through the regulation of detoxification genes such as sod2 and catalase. Here we show that Foxo3a is a direct transcriptional regulator of a group of oxidative stress protection genes in vascular endothelial cells. Importantly, Foxo3a activity requires the transcriptional co-activator PGC-1alpha, because it is severely curtailed in PGC-1alpha-deficient endothelial cells. Foxo3a and PGC-1alpha appear to interact directly, as shown by co-immunoprecipitation and in vitro interaction assays, and are recruited to the same promoter regions. The notion that Foxo3a and PGC-1alpha interact directly to regulate oxidative stress protection genes in the vascular endothelium is supported by the observation that PGC-1alpha transcriptional activity at the sod2 (manganese superoxide dismutase) promoter requires a functional FoxO site. We also demonstrate that Foxo3a is a direct transcriptional regulator of PGC-1alpha, suggesting that an auto-regulatory cycle regulates Foxo3a/PGC-1alpha control of the oxidative stress response.
PB American Society for Biochemistry and Molecular Biology
SN 0021-9258
YR 2009
FD 2009-05-22
LK https://hdl.handle.net/20.500.14352/105020
UL https://hdl.handle.net/20.500.14352/105020
LA eng
NO Olmos Y, Valle I, Borniquel S, Tierrez A, Soria E, Lamas S, et al. Mutual Dependence of Foxo3a and PGC-1α in the Induction of Oxidative Stress Genes. Journal of Biological Chemistry. 2009;284(21):14476-84.
NO Ministerio de Educación y Ciencia (España)
NO Sociedad Española de Nefrología
DS Docta Complutense
RD 11 abr 2025