Abstract

Background Reactive oxygen species (ROS) regulate diverse cellular signaling and metabolic processes, whereas dysregulated ROS accumulation induces oxidative stress (OS) that contributes to the pathogenesis of numerous neurological disorders. However, the molecular mechanisms underlying OS-induced neuronal cell injury remain incompletely understood. Methods Here, a hydrogen peroxide (H 2 O 2 )-exposed HT22 mouse hippocampal neuronal cell model and an H 2 O 2 -exposed mouse astrocyte C8-D1A cell model were used to mimic in vitro OS. Methods, including transfection, RNA extraction, qRT-PCR, luciferase reporter assay, western blotting, cell counting kit-8, immunofluorescence staining, ROS measurement, and apoptosis assay, were used to investigate the role of Lcn2 in OS. Results We found that, Lipocalin 2 (Lcn 2), an adipokine family protein, was significantly down-regulated upon H 2 O 2 treatment. Lcn2 overexpression enhanced HT22 cell viability and effectively attenuated H 2 O 2 -induced ROS production, whereas Lcn2 silencing reduced viability and potentiated ROS accumulation. Mechanistically‌, Lcn2 protects neuronal cells by inactivating the Hippo signaling. Consistent results were obtained in mouse astrocyte C8-D1A cells. Conclusions Collectively, our findings indicate that dysregulated Lcn2 expression contributes to H 2 O 2 -induced neuronal OS, and suggest that Lcn2 may serve as a potential biomarker for predicting OS-related neurodegenerative disorders.