Abstract
We have established a stably transformed human neuroblastoma cell line (MC65) that conditionally expresses a C-terminal derivative of the amyloid β protein precursor (βPP) termed SβC (a fusion protein composed of the amino-17 and carboxyl-99 residues of βPP). Conditional expression of SggbC (mediated by the withdrawal of tetracycline from the culture medium) induces pronounced nuclear DNA fragmentation and cytotoxicity in this cell line. These effects are enhanced by hyperoxygen and suppressed by hypooxygen and antioxidants. This cell line is relatively insensitive to the extracellular application of amyloid β25-35, and coculture experiments suggest that this cytotoxicity 0 is mediated by an intracellular process. These findings suggest that the overexpression of the C-terminal domain of βPP can disrupt normal cellular processes in these cells in such a way as to induce a directed (deoxyribonuclease-mediated) mechanism of cell death. This process appears to be modulated and/or mediated by a reactive oxygen specie(s) (ROS). Consistent with a role for ROS in the process of SβC-mediated toxicity, we have found that the MC65 cell line is hypersensitive to oxidative stress and that it is this sensitivity that appears (at least in part) to underlie its susceptibility to SβC.
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Sopher, B.L., Fukuchi, KI., Kavanagh, T.J. et al. Neurodegenerative mechanisms in alzheimer disease. Molecular and Chemical Neuropathology 29, 153–168 (1996). https://doi.org/10.1007/BF02814999
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DOI: https://doi.org/10.1007/BF02814999