禁食心脏的表皮转录学调节:对心脏健康的影响
Daniel Benak1,2, Kristyna Holzerova1, Jaroslav Hrdlicka1
1Laboratory of Developmental Cardiology, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
RNA biology
|February 7, 2024
概括
禁食通过改变RNA修饰 (m6A和m6Am) 和它们在心脏中的调节器来提高心脏耐受性. 抑制关键的脱甲基酶降低了缺氧耐受性,这表明表皮转录组学对禁食诱导的心脏保护至关重要.
科学领域:
- 心血管生物学 心血管生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子心脏病学分子心脏病学
背景情况:
- 像禁食这样的饮食干预措施可以提高心脏对缺血的耐受性.
- 对RNA的表观遗传修饰,或表观转录学,是基因表达的关键调节者.
- N6-甲基氨酸 (m6A) 和N6,2'-O-二甲基氨酸 (m6Am) 是影响细胞功能的流行mRNA修饰.
研究的目的:
- 研究表皮转录体调节剂在心脏适应禁食时的作用.
- 分析老鼠心脏中禁食后m6A和m6Am甲基化水平及其相关蛋白质的变化.
- 确定抑制特定RNA脱甲基酶对心肌细胞低毒性耐受性的影响.
主要方法:
- 在老鼠心中对33个表表转录学调节者的RT-qPCR和西部斑分析.
- 针对性蛋白质组分析以量化甲基化调节剂.
- 在成年大鼠初级心肌细胞 (AVCMs) 中抑制FTO和ALKBH5脱甲基酶的体外实验.
主要成果:
- 禁食显著改变了mRNA和蛋白质水平上大多数分析的表皮转录学调节者的表达.
- 甲基酶FTO和ALKBH5的上调,与心脏RNA中的全球m6A和m6Am水平降低相关.
- 抑制FTO和ALKBH5降低了空腹大鼠AVCM的低毒性耐受性,并且观察到*Nox4*和*Hdac1*转录的甲基化发生变化.
结论:
- 调节m6A和m6Am修饰的表皮转录机械在禁食的心脏中被动态控制.
- 这些表皮转录学变化是禁食期间心脏适应的组成部分,有助于其心脏保护作用.
- 准表体转录体调节器可能为增强心脏弹性提供新的治疗策略.
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