Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD+ Biosynthesis

被引：873

作者：

Ramsey, Kathryn Moynihan ^{[2
,3
,4
,5
]}

Yoshino, Jun ^{[1
]}

Brace, Cynthia S. ^{[1
]}

Abrassart, Dana ^{[2
,3
]}

Kobayashi, Yumiko ^{[2
,3
,4
,5
]}

Marcheva, Biliana ^{[2
,3
]}

Hong, Hee-Kyung ^{[3
]}

Chong, Jason L. ^{[3
]}

Buhr, Ethan D. ^{[3
]}

Lee, Choogon ^{[6
]}

Takahashi, Joseph S. ^{[3
,7
]}

Imai, Shin-ichiro ^{[1
]}

Bass, Joseph ^{[2
,3
,4
,5
]}

机构：

[1] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63110 USA

[2] Northwestern Univ, Feinberg Sch Med, Dept Med, Evanston, IL 60208 USA

[3] Northwestern Univ, Feinberg Sch Med, Dept Neurobiol & Physiol, Evanston, IL 60208 USA

[4] NorthShore Univ Hlth Syst Res Inst, Evanston, IL 60201 USA

[5] Evanston Hosp Corp, Dept Med, Evanston, IL 60201 USA

[6] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA

[7] Northwestern Univ, Howard Hughes Med Inst, Evanston, IL 60208 USA

来源：

SCIENCE | 2009年 / 324卷 / 5927期

关键词：

NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; GLUCOSE-HOMEOSTASIS; CALORIE RESTRICTION; LIFE-SPAN; SIRT1; TRANSCRIPTION; EXTENSION; COMPONENT; BINDING; CELLS;

D O I：

10.1126/science.1171641

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：651 / 654

页数：4

共 25 条

[1] Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae [J].