PC12 and neuro 2a cells have different susceptibilities to acetylcholinesterase–amyloid complexes, amyloid2535 fragment, glutamate, and hydrogen peroxide

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This work addresses the differential effects of several oxidative insults on two neuronal cell lines, PC12 and Neuro 2a cells, extensively used as neuronal models in vitro. We measured cellular damage using the cytotoxic assays for MTT reduction and LDH release and found that acetylcholinesterase (AChE)–amyloid–β-peptide (Aβ) complexes, Aβ25–35 fragment, glutamate and H2O2 were over 200-fold more toxic to PC12 than to Neuro 2a cells. 17α and 17β estradiol were able to protect both cell types from damage caused by H2O2 or glutamate. By contrast, other insults not related to oxidative stress, such as those caused by the nonionic detergent Triton X-100 and serum deprivation, induced a similar level of damage in both PC12 and Neuro 2a cells. Considering that the Aβ peptide, H2O2 and glutamate are cellular insults that cause an increase in reactive oxygen species (ROS), the intracellular levels of the antioxidant compound, glutathione were verified. Neuro 2a cells were found to have 4- to 5-fold more glutathione than PC12 cells. Our results suggest that Neuro 2a cells are less susceptible to exposure to AChE–Aβ complexes, Aβ25–35 fragment, glutamate and H2O2 than PC12 cells, due to higher intracellular levels of antioxidant defense factors. J. Neurosci. Res. 56:620–631, 1999. © 1999 Wiley-Liss, Inc.