I. Vincent et al., INCREASED PRODUCTION OF PAIRED HELICAL FILAMENT EPITOPES IN A CELL-CULTURE SYSTEM REDUCES THE TURNOVER OF TAU, Journal of neurochemistry, 62(2), 1994, pp. 715-723
To investigate the regulation of posttranslational modifications of ta
u that might be pertinent to the production of the paired helical fila
ment (PHF) of Alzheimer's disease, we incubated human neuroblastoma ce
lls with the protein phosphatase inhibitor okadaic acid. This treatmen
t results in increased immunoreactivity of tau With the monoclonal ant
ibodies Alz-50, PHF-1, T3P, and NP8, a reduction in Tau-1 immunoreacti
vity, and an elevation in apparent molecular weight of tau. Moreover,
our data demonstrate that accumulation of phosphates in tau leads to a
decrease in the turnover rate of tau in the neuroblastoma cells. It i
s suggested that similar build-up of hyperphosphorylated tau in the ne
uronal perikarya may represent an early event in PHF formation. The pr
esent system facilitates the investigation of regulatory mechanisms go
verning the occurrence of PHF epitopes, their effects on neuronal cell
metabolism, and possible pharmacological intervention.