S. Pundreddy et Tb. Shea, AD-LIKE TAU-PHOSPHORYLATION IN HUMAN NEUROBLASTOMA-CELLS FOLLOWING PKC HYPERACTIVATION IS MEDIATED BY MAP KINASE, Neuroscience research communications, 21(3), 1997, pp. 173-177
SH-SY-5Y human neuroblastoma cells were treated with the phorbol ester
TPA and the MAP kinase kinase inhibitors PD98059. Microdensitometric
analyses revealed that TPA treatment induced 60% and 46% increases in
immunoreactivity towards monoclonal antibodies (AT8 and PHF-1, respect
ively; p=0.0005) that recognize tau epitopes common to paired helical
filaments. These increases were attenuated by the simultaneous treatme
nt with PD98059. Steady-state AT-8 and PHF-1 immunoreactivity were not
inhibited by PD98059. These analyses corroborate studies from other l
aboratories that indicate that MAP kinase may not normally confer AD-l
ike immunoreactivity to tau within intact cells, but demonstrate that
hyperactivation of upstream kinase(s) may recruit otherwise benign kin
ases to hyperphosphorylate tau. These findings further implicate the p
otential involvement of hyperactivation of signal transduction pathway
s in the early events that propagate PHF formation.