β-Amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation

beta-Amyloid (beta A) toxicity in culture is accompanied by multiple events culminating in apoptosis. Calcium influx may represent the initial event, since calcium chelation prevents all subsequent events, while subsequent events include increased generation of reactive oxygen species (ROS) and hyperphosphorylation of tau. In the present study, we undertook to determine whether ROS generation or tau hyperphosphorylation mediate beta A-induced apoptosis. The anti-oxidant vitamin E or the kinase inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenslfonamide (W7) was added following brief treatment of differentiated SH-SY-5Y human neuroblastoma cells with 22 mu M beta A. Under these conditions, vitamin E prevented ROS generation and apoptosis, but did not prevent intracellular calcium accumulation or tan phosphorylation. W7 prevented tau phosphorylation but did not block beta A-induced calcium influx, ROS generation or apoptosis. While these studies do not address the long-term consequences of PHF formation, they indicate that ROS generation, rather than tau hyperphosphorylation, leads to apoptosis following beta A-induced calcium influx into cultured cells. (C) 2000 Published by Elsevier Science B.V. All rights reserved.