Abstract
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 Aβ25–35. The viability of PC12 and dPC12 cells decreased by 30–40% after a 48-hour exposure to 20 µM Aβ25–35. Microscopic examination showed that Aβ25–35 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 Aβ25–35. 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 Aβ25–35 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 Aβ25–35 toxicity. Therefore, the protective effects of antioxidants against Aβ may depend upon the redox state of the cells.
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Sung, YJ., Cheng, Cl., Chen, CS. et al. Distinct mechanisms account for β-amyloid toxicity in PC12 and differentiated PC12 neuronal cells. J Biomed Sci 10, 379–388 (2003). https://doi.org/10.1007/BF02256429
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DOI: https://doi.org/10.1007/BF02256429