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- Yamada Mariko
- Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan
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- Hayashi Hideki
- Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan
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- Iwatani Yui
- Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan
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- Suzuki Kaori
- Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan
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- Yuan Bo
- Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan
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- Takagi Norio
- Applied Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan
抄録
<p>Ischemic stroke induces neuronal damage by various causes such as glutamate excitotoxicity, oxidative stress and trophic factor deficiency. A large amount of glutamate accumulated in an extracellular space is a major factor to lead intracellular Ca2+ elevation through the N-methyl-D-aspartate (NMDA) receptor after ischemia and then causes neuronal death. Although it has been identified that several proteolytic enzymes are activated by elevated intracellular Ca2+, roles of proteolytic enzymes associated with NMDA-induced neuronal death are not fully understood. Here, we determined whether inhibitions of proteolytic enzymes affected on NMDA-induced damage in rat cortical neurons. Primary cultures of rat cortical neurons were prepared from embryonic day 16 in this study. For cell viability assay, mitochondrial activity was measured by a XTT assay 24 hours after NMDA treatment with or without inhibitors of proteolytic enzymes. Inhibitions of matrix metalloproteinase, gamma-secretase, protein convertase subtilisin / kexin type 9 and furin were examined whether these proteases were associated with neuronal damage. Importantly, the furin inhibitor significantly protected cortical neurons from NMDA-induced neuronal death in a dose-dependent manner. Moreover, calpain activation induced by NMDA treatment was markedly blocked by the furin inhibitor without affecting intracellular Ca2+ concentration. Thus, the calpain activation would be involved in downstream of furin under NMDA-induced toxicity in rat cortical neurons. These results demonstrate that the furin inhibition may provide a therapeutic approach against ischemic neuronal damage.</p>
収録刊行物
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- 日本薬理学会年会要旨集
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日本薬理学会年会要旨集 WCP2018 (0), PO2-1-8-, 2018
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390848647546674688
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- NII論文ID
- 130007900803
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- ISSN
- 24354953
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可