Reversible heat stress-related loss of phosphorylated Alzheimer-type epitopes in tau proteins of human neuroblastoma cells

M. F. Chiang, W. K. Liu, S. H. Yen

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Human neuroblastoma cells, LAN, were used to study the phosphorylation and dephosphorylation of tau proteins. These cells contained mainly a form of tau comparable to fetal brain tau in molecular weight (55 kDa). Neuroblastoma tau reacted with antibodies that recognize epitopes spanning the whole tau molecule (E-1, Alz50, Tau-1, and Tau46), and antibodies (PHF-1, NP8, and T3P) that recognize hyperphosphorylated tau (PHF-tau) in Alzheimer's disease (AD) brains. Exposure of the cells to 45°C heat stress resulted in dephosphorylation of the epitopes recognized by PHF-1, NP8, and T3P. Transfer of the heat-stressed cells to 37°C led to rephosphorylation of the dephosphorylated epitopes. Cells that had been treated with okadaic acid (OA), regardless of whether they were subsequently subjected to heat stress or heat stress and recovery, all contained tau with a molecular weight similar to that of control cells. These tau proteins, similar to tau in control cells, also reacted with antibodies to phosphorylated epitopes. However, unlike the tau from control or heat-stressed cells, the OA-treated and heat-stressed tau had decreased reactivity with Tau-1. Alteration of Tau- 1 immunoreactivity has been reported to be an early event in AD neurodegeneration. The reduction of Tau-1 immunoreactivity observed in OA- treated samples could be restored by incubation of electroblots of isolated tau with alkaline phosphatase, indicating an induction of the Tau-1 epitope phosphorylation by OA. The results of our studies suggest that neuroblastoma cells may contain phosphatases/kinases that are comparable to that in AD, and that culture cells may be used for studying the mechanisms involved in AD neurofibrillary formation.

Original languageEnglish (US)
Pages (from-to)4854-4860
Number of pages7
JournalJournal of Neuroscience
Volume13
Issue number11
DOIs
StatePublished - Jan 1 1993

Keywords

  • dephosphorylation
  • heat stress
  • human neuroblastoma cells
  • okadaic acid
  • phosphorylation

ASJC Scopus subject areas

  • Neuroscience(all)

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