心脏缺血预调促进MG53分泌通过H2O2-激活的蛋白激酶C-δ信号
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
概括
缺血预调会触发MG53蛋白质的分泌,这是保护心脏免受伤害的关键因素. 这种分泌通过特定的H2O2-蛋白激酶-C-delta通路发生,突出MG53
科学领域:
- 心血管生物学
- 细胞信号传输
- 分子医学
背景情况:
- 缺血性心脏病是全球的主要健康负担.
- 缺血预调 (IPC) 提供了对心脏缺血/再输血损伤的内在保护.
- MG53 (密苏古53) 是TRIM家族中的一种蛋白质,对于IPC介导的心脏保护和机械损伤修复至关重要.
研究的目的:
- 研究IPC介导的心脏保护与MG53分泌之间的因果关系.
- 阐明在IPC期间驱动MG53分泌的潜在分子机制.
- 探索分泌的MG53在保护心脏免受缺血/再输血损伤方面的功能作用.
主要方法:
- 在动物模型中使用蛋白质组分析,遗传和药理方法 (体内,隔离的透心脏,培养心肌细胞).
- 检查了MG53分泌物对IPC的反应,并探索了潜在的信号通路.
- 研究了复合MG53蛋白的心脏保护作用.
主要成果:
- 在不损害细胞膜完整性的情况下强烈诱导MG53分泌.
- MG53的分泌是由H2O2引起的蛋白激酶-C-delta (PKCδ) 的激活,特别是Y311的酸化.
- 在MG53缺陷的小鼠中,系统的复合MG53恢复了IPC功能,并独立于IPC保护了心脏免受缺血/再输血损伤.
结论:
- IPC和氧化应激通过H2O2-PKCδ依赖的机制触发MG53的分泌.
- 细胞外MG53在IPC介导的预防心脏缺血/再输血损伤方面发挥着重要作用.
- MG53是缓解心脏损伤的潜在治疗点.
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