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哈达的乳化促进了败血症诱导的心肌衰竭

Tie-Ning Zhang¹, Xin-Mei Huang², Linus Li³

¹Department of Pediatrics, PICU (T.-N.Z., Y.-P.L., R.W., Y.-H.Y., T.Z., C.-F.L., N.Y.), Shengjing Hospital of China Medical University, Shenyang.

Circulation research

|June 27, 2025

概括

对HADHA蛋白的乳酸修饰会损害心脏细胞的能量产生,导致败血症引起的心脏功能障碍. 这一发现为治疗败血症期间的心肌抑郁症提供了新的治疗点.

科学领域:

生物化学生物化学
心脏病学心脏病学
分子生物学分子生物学

背景情况:

血清乳酸水平评估组织缺氧和败血症和败血性休克的结果.
乳酸盐可以经历乳化,这是一个翻译后的修改.
败血症经常导致心肌抑郁,需要对乳酸的作用进行调查.

研究的目的:

为了研究乳酸在败血症引起的心肌抑郁症中的作用.
为了确定受乳化影响的特定蛋白质和机制,在败血性心脏中.

主要方法:

在老鼠的败血症模型 (LPS 管理,CLP) 和H9c2细胞.
蛋白质组分析以确定乳酸化部位.
在K166和K728.8的HADHA (三功能酶亚单元α) 的位点定向突变发生.
转录组和代谢组分析.
评估线粒体功能,ATP生产和心肌细胞收缩性.

主要成果:

确定了1127个氨酸乳酸化位点,其中83个被差异修饰.
在HADHA K166和K728中确认了乳化,受乳酸水平的影响.
乳化抑制了HADHA活性,破坏了线粒体功能,ATP生产和能量代谢.
在体外和体内观察到心肌细胞收缩力的减少.
鉴定出 Sirtuin 1 和 Sirtuin 3 是 HADHA 乳酸化调节剂.

结论:

乳显著影响心肌细胞的新陈代谢.
乳酸诱导的HADHA乳酸化破坏了线粒体功能,并促进了败血症诱导的心脏功能障碍.
这些发现表明,对于败血症引起的心肌抑郁症,有新的治疗点.

关键词:

能量代谢能量代谢脂多糖类糖类 (lipopolysaccharides) 是一种多糖类的化合物.lysine lysine lysine lysine 是一种类型的氨酸.肌细胞,心脏细胞.冲击,败血症的冲击,败血症的感染

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