Mutual dependence of Foxo3a and PGC-1alpha in the induction of oxidative stress genes.

ABSTRACT: 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.

SUBMITTER: Olmos Y 

PROVIDER: S-EPMC2682896 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature