There were accumulated evidences that agents may attenuate neurological disorders through a hormetic effect. This study was designed to investigate hormetic effect of BME on the oxygen-glucose deprivation (OGD)-induced mitochondrial apoptosis in NGF-differentiated PC12 cells. The effect of BME on the intracellular reactive oxygen species (iROS) formation and pro-survival signals mediated by ERK and Akt as well as transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathways was also determined. The present results showed that, at low concentrations, pretreatment with BME triggered stress response by causing ROS production, then, activated survival-promoting signals via ERK and Akt activated Nrf2/HO-1 signaling pathway, resulting in decrease in cytotoxicity induced by the OGD. It may be accepted that mild pretreatment with BME stimulated transient and moderate ROS production, but activated hormetic signals and induced stress responsive genes. In contrast, high concentrations of BME displayed toxic action due to massive ROS production. These results suggested that the effect of BME on the OGD-induced PC12 cells may be hormetic mechanism including induction of oxidative stress and subsequent activation of stress response gene expression.
Keywords: BME; Hormetic effect; Nrf2; Oxygen-glucose deprivation; PC12 cells.
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