AD-like tau phosphorylation in human neuroblastoma cells following PKC hyperactivation is mediated by MAP kinase

Abstract

SH-SY-5Y human neuroblastoma cells were treated with the phorbol ester TPA and the MAP kinase inhibitors PD98059. Microdensitometric analyses revealed that TPA treatment induced 60% and 46% increases in immunoreactivity towards monoclonal antibodies (AT-8 and PHF-1, respectively; p=0.0005) that recognize tau epitopes common to paired helical filaments. These increases were attenuated by the simultaneous treatment with PD98059. Steady-state AT-8 and PHF-1 immunoreactivity were not inhibited by PD98059. These analyses corroborate studies from other laboratories that indicate that MAP kinase may not normally confer AD-like immunoreactivity to tau within intact cells, but demonstrate that hyperactivation of upstream kinase(s) may recruit otherwise benign kinases to hyperphosphorylate tau. These findings further implicate the potential involvement of hyperactivation of signal transduction pathways in the early events that propagate PHF formation. © 1997 John Wiley & Sons, Ltd.