Protective effect of the imidazoline I2 receptor agonist 2-BFI on oxidative cytotoxicity in astrocytes

Astrocytes perform a variety of functions that are important for normal neuronal activity and recovery after brain injury. Because astrocytes are very vulnerable to H₂O₂, protection of astrocytes from oxidative damage in various neurological diseases is important in maintaining brain function and preventing brain damage. In this study, we investigated the characteristics and mechanisms of a specific imidazoline I2 receptor agonist 2-BFI-mediated cytoprotection using a rat astrocyte cultures of H₂O₂-exposed oxidative stress. Here we show that 2-BFI in H₂O₂-exposed astrocytes protects cell death through increased lysosomal membrane stability, LC3-II conversion, and subsequently suppresses accumulation of p62. These effects of 2-BFI were significantly reversed after treatment with the lysozyme activity inhibitor Bafilomycin A1. These results suggest that the cytoprotective effects of 2-BFI, which increases lysosomal stability in oxidative stress, may involve regulation of lysosomal-associated membrane protein-dependent autophagy and autolysosome degradation in astrocytes.