营养传感器CRTC和Sarcalumenin / Thinman代表了心脏缩的新途径
bioRxiv : the preprint server for biology
|October 24, 2023
概括
调节转录协活性剂 (CRTC) 在心脏健康方面发挥着新的作用,调节新陈代谢并预防心脏缩. 这一途径在各个物种中得到保护,为心脏病提供了新的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 代谢调节 代谢调节 代谢调节
- 分子心脏病学分子心脏病学
背景情况:
- 肥胖和2型糖尿病与左心室缩有关.
- 氨酸 (CaN) 在肝脏中激活调节转录辅激剂 (CRTC) 进行葡萄糖生成.
- CRTC在心脏中的作用以前未被确定,尽管已知CaN的心脏功能.
研究的目的:
- 研究CRTC在心脏功能和新陈代谢中的作用.
- 为了确定心脏中CRTC的下游影响者.
- 为了探索心脏缩中的CaN-CRTC信号通路.
主要方法:
- 使用了具有CRTC零突变和心脏特异性淘汰的Drosophila模型.
- 在心中进行了对比基因表达分析.
- 在斑马鱼模型中研究了CRTC功能.
主要成果:
- 在Drosophila中CRTC功能丧失导致心脏缺陷和代谢失调.
- CRTC 作为心脏中的代谢开关,调节葡萄糖,脂肪酸和氨基酸代谢.
- 确定了sarcalumenin (thinman) 作为CRTC的下游效应体,介导心脏表型.
结论:
- 氨酸-CRTC信号传递调解心脏缩,可能作为NFAT的替代品.
- CRTC对于心肌细胞的维护至关重要,其心脏作用在脊椎动物中得到保护.
- 该CaN-CRTC-sarcalumenin/tmn通路代表了一种新的,保守的机制,是心脏缩的基础.
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