FoxO3 transcription factor promotes autophagy after oxidative stress injury in HT22 cells

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide (H₂O₂) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced H₂O₂-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced H₂O₂-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3-methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation, and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on H₂O₂-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit H₂O₂-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain.