Increased Production of Paired Helical Filament Epitopes in a Cell Culture System Reduces the Turnover of τ
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 62, Issue 2, pages 715–723, February 1994
How to Cite
Vincent, I., Rosado, M., Kim, E. and Davies, P. (1994), Increased Production of Paired Helical Filament Epitopes in a Cell Culture System Reduces the Turnover of τ. Journal of Neurochemistry, 62: 715–723. doi: 10.1046/j.1471-4159.1994.62020715.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received March 17, 1993; revised manuscript received May 27, 1993; accepted July 9, 1993.
- Alzheimer's disease;
- Okadaic acid;
- Protein phosphorylation;
- Protein phosphatase 2A
Abstract: To investigate the regulation of posttranslational modifications of τ that might be pertinent to the production of the paired helical filament (PHF) of Alzheimer's disease, we incubated human neuroblastoma cells with the protein phosphatase inhibitor okadaic acid. This treatment results in increased immunoreactivity of τ with the monoclonal antibodies Alz-50, PHF-1, T3P, and NP8, a reduction in Tau-1 immunoreactivity, and an elevation in apparent molecular weight of τ. Moreover, our data demonstrate that accumulation of phosphates in τ leads to a decrease in the turnover rate of τ in the neuroblastoma cells. It is suggested that similar build-up of hyperphosphorylated τ in the neuronal perikarya may represent an early event in PHF formation. The present system facilitates the investigation of regulatory mechanisms governing the occurrence of PHF epitopes, their effects on neuronal cell metabolism, and possible pharmacological intervention.