Inhibition of excitatory neuronal cell death by cell-permeable calcineurin autoinhibitory peptide |
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Authors: | Terada Hiroaki Matsushita Masayuki Lu Yun-Fei Shirai Takeshi Li Sheng-Tian Tomizawa Kazuhito Moriwaki Akiyoshi Nishio Shinsaku Date Isao Ohmoto Takashi Matsui Hideki |
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Affiliation: | Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. |
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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. |
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Keywords: | autoinhibitory domain calcineurin neuronal cell death protein transduction domain 11 arginine |
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