Rabbit Anti-FOXO3A monoclonal antibody, clone TU50-12

Cardiomyocyte death is an important pathogenic feature of ischemia and heart failure. Through this study, we showed the synergistic role of HIF-1 and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF-1 and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death. Our results highlighted the importance of the synergistic role of HIF-1 and FoxO3a in cardiomyocyte death which may add insight into therapeutic approaches to pathophysiology associated with ischemic diabetic cardiomyopathies.

The aim of the present study was to elucidate the expression and role of the phosphatidylinositol 3-kinase (PI3K)/Akt/forkhead box O3 (FOXO3a) pathway in the regeneration of the spinal cord following spinal cord injury (SCI), and its regulatory effect on tumor necrosis factor (TNF)- and cyclin-dependent kinase inhibitor 1B (p27(kip1)) expression. Firstly, in a Sprague-Dawley rat model of SCI, western blot analysis revealed that the protein levels of PI3K, phosphorylated Akt and FOXO3a were markedly inhibited compared with those in the sham control group. In vitro experiments were also conducted, in which primary dissociated cultures of rat dorsal spinal cord cells were induced with lipopolysaccharide (LPS; 4 g/ml). The downregulation of PI3K using LY294002 markedly suppressed cell viability, reduced the protein levels of FOXO3a and p27(kip1), and increased TNF- protein production in the LPS-induced spinal cord cells. In addition, when the LPS-induced spinal cord cells were infected with FOXO3a adenoviral vectors, the overexpression of FOXO3 markedly promoted cell proliferation, activated p27(kip1) protein levels and inhibited TNF- protein production in the spinal cord cells. These results suggest that the PI3K/Akt/FOXO3a pathway regulates regeneration following SCI in adult rats via its modulatory effects on TNF- and p27(kip1) expression.