Beta-amyloid-induced calcium influx induces apoptosis in culture by oxidative stress rather than tau phosphorylation.
Beta-amyloid (betaA) 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 betaA-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 microM betaA. Under these conditions, vitamin E prevented ROS generation and apoptosis, but did not prevent intracellular calcium accumulation or tau phosphorylation. W7 prevented tau phosphorylation but did not block betaA-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 betaA-induced calcium influx into cultured cells.