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Inhibition of excitatory neuronal cell death by cell‐permeable calcineurin autoinhibitory peptide
Author(s) -
Terada Hiroaki,
Matsushita Masayuki,
Lu YunFei,
Shirai Takeshi,
Li ShengTian,
Tomizawa Kazuhito,
Moriwaki Akiyoshi,
Nishio Shinsaku,
Date Isao,
Ohmoto Takashi,
Matsui Hideki
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02098.x
Subject(s) - calcineurin , programmed cell death , excitatory postsynaptic potential , glutamate receptor , microbiology and biotechnology , phosphatase , biology , calmodulin , fkbp , apoptosis , biochemistry , chemistry , enzyme , receptor , transplantation , phosphorylation , medicine , surgery
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.