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- Title
Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide.
- Authors
Terada, Hiroaki; Matsushita, Masayuki; Yun-Fei Lu, Masayuki; Shira, Takeshi; Sheng-Tian Li, Takeshi; Tomizawa, Kazuhito; Moriwaki, Akiyoshi; Nishio, Shinsaku; Data, Isao; Ohmoto, Takashi; Matsui, Hideki
- 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 (PPIase) 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.
- Subjects
ENZYMES; AMINO acids; APOPTOSIS; BACTERIOPHAGES; CALMODULIN; IMMUNOSUPPRESSIVE agents; GENETIC transduction; PERMEABILITY; NEURONS; ARGININE
- Publication
Journal of Neurochemistry, 2003, Vol 87, Issue 5, p1145
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.02098.x