Attenuation of LPS-induced apoptosis in NGF-differentiated PC12 cells via NF-κB pathway and regulation of cellular redox status by an oxazine derivative

Abstract

Neuronal cell death due to apoptosis is a common characteristic of neurodegenerative diseases. In this study, we report protective effect of 2-ethoxy-4,5-diphenyl-1,3-oxazine-6-one (EDPOO) against lipopolysaccharide (LPS)-induced cell death in rat pheochromocytoma (PC12) cells, as assessed by MTT test, acridine orange/ethidium bromide staining, determination of Bax, Bcl-2 and caspase-3 levels. We further show that this compound could increase heat shock proteins Hsp-70 and Hsp-32 levels. EDPOO also modulates nuclear levels of Nrf2 and NF-κB, transcription factors that are activated by intracellular reactive oxygen species and/or mediators generated due to chemical exposure of cells. Pretreatment of the cells with this oxazine derivative also increases γ-GCS level, as well as antioxidant enzyme activities, in a dose-dependent manner. Protective effect of this compound could represent a promising approach for treatment of neurodegenerative diseases.