Ekinci Fatma J. Linsley Maria-Dawn. Shea Thomas B [a].
beta-Amyloid-induced calcium influx induces apoptosis in
culture by oxidative stress rather than tau phosphorylation, Molecular Brain Research 76(2) :389-395, 2000.
Abstract
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 muM 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.
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