Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide

Hiroaki Terada, Masayuki Matsushita, Yun Fei Lu, Takeshi Shirai, Sheng Tian Li, Kazuhito Tomizawa, Akiyoshi Moriwaki, Shinsaku Nishio, Isao Date, Takashi Ohmoto, Hideki Matsui

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35 Citations (Scopus)

Abstract

In glutamate-mediated excitatory neuronal cell death, immunosuppressants (FK506, Cys-A) are powerful agents that protect neurons from apoptosis. Immunosuppressants inhibit two types of enzyme, calcium/calmodulin-dependent protein phosphatase (calcineurin: CaN), and peptidyl-prolyl cis-trans-isomerase (PPlase) activity such as the FKBP family. In this study, we used a protein transduction approach to determine the functional role of CaN and to produce a potential therapeutic agent for glutamate-mediated neuronal cell death. We created a novel cell-permeable CaN autoinhibitory peptide using the 11 arginine protein transduction domain. This peptide was highly efficient at transducing into primary culture neurons, potently inhibited CaN phosphatase activities, and inhibited glutamate-mediated neuronal cell death. These results showed that CaN plays an important role in excitatory neuronal cell death and cell-permeable CaN autoinhibitory peptide could be a new drug to protect neurons from excitatory neuronal death.

Original languageEnglish
Pages (from-to)1145-1151
Number of pages7
JournalJournal of Neurochemistry
Volume87
Issue number5
DOIs
Publication statusPublished - Dec 2003

Keywords

  • 11 arginine
  • Autoinhibitory domain
  • Calcineurin
  • Neuronal cell death
  • Protein transduction domain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Terada, H., Matsushita, M., Lu, Y. F., Shirai, T., Li, S. T., Tomizawa, K., Moriwaki, A., Nishio, S., Date, I., Ohmoto, T., & Matsui, H. (2003). Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide. Journal of Neurochemistry, 87(5), 1145-1151. https://doi.org/10.1046/j.1471-4159.2003.02098.x