Figure 6.

Foxo3a inhibits necrosis through miR-874 and caspase-8. (a) Foxo3a levels are decreased in cardiomyocytes exposed to H₂O₂. Cardiomyocytes were exposed to H₂O₂. Cells were harvested at the indicated time for the analysis of Foxo3a levels by immunoblot. (b and c) Enforced expression of Foxo3a reduces miR-874 levels and necrotic cell death induced by H₂O₂. Cardiomyocytes were infected with adenoviral Foxo3a or β-gal. Twenty-four hours after infection, cells were treated with H₂O₂. miR-874 levels (b), caspase-8 levels (c, upper panel) and PI exclusion were analyzed (c, low panel), *P<0.05 versus H₂O₂ alone. (d and e) Foxo3a transgenic mice attenuates miR-874 levels and increased caspase-8 levels upon I/R. WT and Foxo3a transgenic mice were subjected to I/R as described in methods. miR-874 levels (d) and caspase-8 levels (e) were analyzed. (f and g) Foxo3a transgenic mice attenuates myocyte necrosis and MI upon I/R. WT and Foxo3a transgenic mice were subjected to I/R as described in methods. Myocyte necrosis (f) and MI (g) were analyzed, *P<0.05 versus WT+I/R