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H2O活性化タンパク質キナーゼC-δシグナル伝達によるMG53分泌を促進する
Dan Shan1, Sile Guo1, Hong-Kun Wu1
1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine (D.S., S.G., H.-K.W., F. Lv, L.J., M.Z., P.X., Y.W., Y.S., X.H., C.-M.C., Y.Z., R.-P.X.), Peking University, China.
Circulation
|July 18, 2020
まとめ
心臓の損傷から守る重要な要因であるMG53タンパク質の分泌を誘発します この分泌は,特定のH2O2-タンパク質キナーゼ-C-デルタ経路を通じて発生し,MG53を強調する.
科学分野:
- 心血管生物学
- セルラー・シグナル
- 分子医学
背景:
- 心臓発作は 世界的に大きな健康問題です
- 発血前準備 (IPC) は,心不全/再輸血による損傷に対する本質的な保護を提供します.
- TRIMファミリーのタンパク質であるMG53 (ミツグミン53) は,IPC媒介による心臓保護と機械的損傷修復に不可欠です.
研究 の 目的:
- IPC媒介の心臓保護とMG53分泌の因果関係を調査する.
- IPC中にMG53の分泌を誘導する基本的な分子機構を明らかにする.
- 心臓のイシュケミア/再注射損傷に対するMG53の機能的役割を調査する.
主な方法:
- タンパク質解析,遺伝,および薬理学的アプローチをネズミのモデル (in vivo,分離された浸透した心臓,培養された心筋細胞) で利用した.
- IPCに対するMG53の分泌を検査し,信号伝達経路を調査した.
- 再結合MG53タンパク質の心臓保護効果を研究した.
主要な成果:
- 細胞膜の整合性を損なわずにMG53の分泌を強烈に誘導した.
- MG53の分泌は,タンパク質キナーゼ-C-デルタ (PKCδ) のH2O2誘発活性化,特にY311でのリン酸化によって媒介された.
- 再結合MG53の全身投与により,MG53欠乏したマウスのIPC機能が回復し,IPCとは無関係に心臓が ischemia/ reperfusion 損傷から保護された.
結論:
- IPCと酸化ストレスは,H2O2-PKCδ依存メカニズムを通じてMG53の分泌を誘発する.
- 細胞外MG53は,心不全/再輸血損傷に対するIPC媒介による保護において重要な役割を果たします.
- MG53は心臓の損傷を緩和する潜在的な治療目標です.
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