Distinct mechanisms account for β-amyloid toxicity in PC12 and differentiated PC12 neuronal cells

Whether reactive oxygen species (ROS) mediate β-amyloid (Aβ) neurotoxicity remains controversial. Naive PC12 cells (PC12) and nerve growth factor-differentiated PC12 cells (dPC12) were used to study the role of ROS in cell death induced by Aβ_25-35. The viability of PC12 and) dPC12 cells decreased by 30-40% after a 48-hour exposure to 20 μM Aβ_25-35. Microscopic examination showed that Aβ_25-35 induced necrosis in PC12 cells and apoptosis in dPC12 cells. Vitamin E (100 μM) and other antioxidants protected PC12 cells, but not dPC12 cells, against the cytotoxic effect of Aβ_25-35. Since H₂O₂ has been proposed to be involved in Aβ toxicity, the effects of H₂O₂ on PC12 and dPC12 cells were studied. Differentiated PC12 cells appeared to be sgnificantly more resistant to H₂O₂ than naive PC12 cells. These data suggest that ROS may mediate Aβ_25-35 toxicity in PC12 cells but not in dPC12 cells. Because the intracellular levels of ROS were elevated during the differentiation of PC12 cells, the baseline levels of ROS in these two model cell types may determine the intracellular mediators for Aβ_25-35 toxicity. Therefore, the protective effects of antioxidants against Aβ may depend upon the redox state of the cells.