通过烟酰胺磷酸核糖转移酶（NAMPT）介导的烟酰胺腺嘌呤二核苷酸（NAD+）生物合成的昼夜节律时钟反馈循环。
Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.
作者信息
Ramsey Kathryn Moynihan, Yoshino Jun, Brace Cynthia S, Abrassart Dana, Kobayashi Yumiko, Marcheva Biliana, Hong Hee-Kyung, Chong Jason L, Buhr Ethan D, Lee Choogon, Takahashi Joseph S, Imai Shin-Ichiro, Bass Joseph
机构信息
Department of Medicine, Northwestern University Feinberg School of Medicine, 2200 Campus Drive, Evanston, IL 60208-3500, USA.
出版信息
Science. 2009 May 1;324(5927):651-4. doi: 10.1126/science.1171641. Epub 2009 Mar 19.
Abstract
The circadian clock is encoded by a transcription-translation feedback loop that synchronizes behavior and metabolism with the light-dark cycle. Here we report that both the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD+) biosynthesis, nicotinamide phosphoribosyltransferase (NAMPT), and levels of NAD+ display circadian oscillations that are regulated by the core clock machinery in mice. Inhibition of NAMPT promotes oscillation of the clock gene Per2 by releasing CLOCK:BMAL1 from suppression by SIRT1. In turn, the circadian transcription factor CLOCK binds to and up-regulates Nampt, thus completing a feedback loop involving NAMPT/NAD+ and SIRT1/CLOCK:BMAL1.
摘要
昼夜节律钟由一个转录-翻译反馈环编码，该反馈环使行为和代谢与明暗周期同步。我们在此报告，哺乳动物烟酰胺腺嘌呤二核苷酸（NAD+）生物合成中的限速酶烟酰胺磷酸核糖基转移酶（NAMPT）以及NAD+水平均呈现昼夜振荡，且受小鼠核心生物钟机制调控。抑制NAMPT可通过解除SIRT1对CLOCK:BMAL1的抑制来促进生物钟基因Per2的振荡。反过来，昼夜节律转录因子CLOCK结合并上调Nampt，从而完成一个涉及NAMPT/NAD+和SIRT1/CLOCK:BMAL1的反馈环。
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