Overexpression Bax interacting factor-1 protects cortical neurons against cerebral ischemia-reperfusion injury through regulation of ERK1/2 pathway.

Bax interacting factor-1 (Bif-1), a multifunctional protein, can regulate cell apoptosis and autophagy. Up-regulation of Bif-1 expression has been associated with neuronal survival. Moreover, several studies have reported that Bif-1 is involved in ischemic stroke. However, the specific function of Bif-1 in cerebral ischemia-reperfusion (I/R) injury is not well understood. The aim of this study is to expose the potential protective effect of Bif-1 against cerebral I/R injury and its related mechanism. In the current study, we showed that adenovirus-mediated Bif-1-overexpression promoted oxygen and glucose deprivation followed by reperfusion (OGD/R)-treated cortical neurons' survival and reduced the cell apoptotic rate. We found that caspase-3 activity was inhibited by Bif-1 overexpression. In addition, we observed that Bif-1 overexpression induces cell autophagy, and the autophagy-specific inhibitor 3-Methyladenine (3-MA) attenuates cell survival. Interestingly, knockdown of Bif-1 resulted in attenuation of neuron survival, promotion of cell apoptosis and suppression of cell autophagy in neurons. In addition, knockdown of Bif-1 inhibited ERK1/2 activation. Our observations implicated Bif-1 as a novel target of cerebral I/R injury and played a neuroprotective effect via promoting cell survival and reducing apoptosis.