通过自流调节NAD+恒温的控制调节线粒体和心脏功能
Quanjiang Zhang1,2, Zhonggang Li2,3, Qiuxia Li1,2
1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, David Geffen School of Medicine and UCLA Health, University of California-Los Angeles, Los Angeles, CA, 90095, USA.
The EMBO journal
|January 11, 2024
概括
损坏的自会通过增加NNMT来降低心脏尼古丁胺胺氨基二核酸 (NAD+). 通过NMN或NNMT抑制恢复NAD+水平,可以改善自性缺陷模型中的心脏功能.
科学领域:
- 心脏病学 心脏病学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 损伤的自会导致线粒体功能障碍和心力衰竭.
- 连接自流缺陷与心脏功能障碍的精确机制尚未完全理解.
研究的目的:
- 为了研究自流在维持心肌细胞中尼古丁胺氨酸二核酸 (NAD+) 水平中的自流的作用.
- 阐明受损自会影响心脏功能的分子机制.
主要方法:
- 使用自性缺陷的心脏和心肌细胞模型.
- 评估了尼古丁胺胺氨基二核酸 (NAD+) 水平,线粒体功能和心脏性能.
- 研究了尼古丁胺N-甲基转移酶 (NNMT) 和SQSTM1-NF-κB信号传递的作用.
主要成果:
- 受损的自流导致心肌细胞中细胞NAD+可用性降低.
- 这种NAD+缺乏症是由增加的NNMT活性介导的,NNMT活性甲基化尼古丁胺 (NAM).
- 尼古丁胺胺单核酸 (NMN) 或NNMT抑制的使用恢复了NAD+水平,改善了心脏和线粒体功能障碍.
- 自抑制导致SQSTM1积累,激活NF-κB信号,促进NNMT转录.
结论:
- 自流对于通过调节细胞NAD+水平来维持心脏线粒体功能至关重要.
- 一个涉及SQSTM1-NF-κB-NNMT信号传输的新途径将受损的自与NAD+枯竭和心脏功能障碍联系在一起.
- 用NMN或NNMT抑制剂向这种途径为与自性损害相关的心力衰竭提供了潜在的治疗策略.
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