通过CLOCK-SIRT1对NAD+救援途径的循环控制
Yasukazu Nakahata1, Saurabh Sahar, Giuseppe Astarita
1Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
概括
昼夜时钟通过控制NAMPT酶表达来调节细胞内NAD+水平. 这会在细胞代谢和昼夜节律之间产生反循环.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 生物化学 生物化学
背景情况:
- 循环节律调节了许多生理过程.
- 核心的昼夜调节器 CLOCK 是一个基酸转移酶.
- SIRT1,一个依赖NAD+的基因素脱乙酶,平衡了CLOCK活动.
研究的目的:
- 为了研究细胞内NAD+水平的昼夜调节.
- 阐明NAMPT在昼夜基因表达中的作用.
- 揭示细胞代谢和昼夜节律之间的相互作用.
主要方法:
- 对NAD+水平中昼夜振荡的分析.
- 研究CLOCK:BMAL1对NAMPT表达的调控.
- 使用NAMPT抑制剂FK866来评估其对昼夜基因表达的影响.
主要成果:
- 细胞内NAD+水平表现出由昼夜时钟驱动的24小时节律.
- CLOCK:BMAL1直接调节NAMPT的昼夜表达.
- 对于调节昼夜基因表达,NAMPT是必不可少的.
结论:
- 在细胞代谢和昼夜节律之间存在一个相互锁定的转录-酶反循环.
- SIRT1在NAD+的昼夜合成中发挥作用.
- 对于维持昼夜节律来说,NAMPT活动至关重要.
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