肌原蛋白调节DUSP13以抑制由活性氧物种诱导的亡
Jing Luo1,2, Qiang Gao1,2, Hailong Qiu1,2
1Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 510080 Guangzhou, Guangdong, China.
Frontiers in bioscience (Landmark edition)
|February 29, 2024
概括
肌原蛋白通过调节DUSP13来保护心肌细胞免受氧化应激,DUSP13使p38 MAPK途径失活,并降低了细胞亡. 这揭示了一个新的心脏保护机制为肌原蛋白.
科学领域:
- 心血管生物学 心血管生物学
- 分子心脏病学分子心脏病学
- 干细胞研究 干细胞研究
背景情况:
- 肌原蛋白是一种已知的骨肌肉转录因子.
- 它在心脏保护中的作用,特别是对氧化应激的作用,尚未完全理解.
- 之前的研究表明,肌原蛋白抑制心肌细胞中的亡.
研究的目的:
- 阐明肌原蛋白保护心肌细胞免受氧化压力的机制.
- 在氧化应激下识别心肌细胞中由肌原蛋白调节的基因.
- 研究DUSP13在肌原蛋白介导心脏保护中的作用.
主要方法:
- 过度表达myogenin的心肌细胞被用过氧化 (H2O2) 治疗,以诱导氧化应激.
- 使用流细胞计量量化了亡.
- 转录组测序 (RNA-seq) 确定了肌原蛋白调节的基因.
- 西部涂抹评估了DUSP13蛋白水平和p38 MAPK酸化.
- 双化酶报告员和ChIP测定证实了肌原蛋白与DUSP13促进体的结合.
- DUSP13过度表达和敲击测试评估了它的抗亡功能.
主要成果:
- 肌原蛋白过度表达显著降低了暴露于H2O2.2.的心肌细胞中的亡.
- 通过RNA-seq检测,DUSP13被确定为一个由肌原蛋白升调的基因.
- 肌原蛋白增加了DUSP13表达,并降低了p38 MAPK酸化.
- 肌原蛋白直接与DUSP13促进体结合.
- DUSP13的过度表达减少了H2O2诱导的亡和亡.
- DUSP13的击倒加剧了H2O2诱导的亡.
结论:
- 肌原蛋白减弱了心肌细胞中氧化应激诱导的亡.
- 这种保护作用是由DUSP13.3的上调调节介导的.
- 肌原蛋白诱导的DUSP13上调抑制了p38 MAPK通路的活性.
- 在心肌细胞中,DUSP13在肌原蛋白的抗亡功能中起着至关重要的作用.
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