CLOCK-SIRT1によるNAD+回収経路の循環制御
Yasukazu Nakahata1, Saurabh Sahar, Giuseppe Astarita
1Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Science (New York, N.Y.)
|March 17, 2009
まとめ
昼間の時計は,NAMPT酵素発現を制御することによって,細胞内NAD+レベルを調節する. これにより,細胞代謝と昼夜リズムとの間のフィードバックループが形成されます.
科学分野:
- 分子生物学は分子生物学である.
- クロノバイオロジーはクロノバイオロジーを用います.
- バイオケミストリー バイオケミストリー
背景:
- シルカディアンリズムは,多くの生理学的プロセスを調節する.
- 昼夜調節器のコアであるCLOCKはヒストンアセチルトランスフェラーゼである.
- SIRT1はNAD+に依存するヒストン脱酸化酵素であり,CLOCKの活性に相殺する.
研究 の 目的:
- 細胞内NAD+レベルの昼夜調節を調査する.
- 昼間の遺伝子発現におけるNAMPTの役割を明らかにする.
- 細胞代謝と昼夜リズムとの相互作用を明らかにする.
主な方法:
- NAD+レベルにおける昼間振動の分析.
- NAMPT表現のCLOCK:BMAL1規制を調査する.
- NAMPT阻害剤FK866を用いて,昼間遺伝子発現への影響を評価する.
主要な成果:
- 細胞内NAD+レベルは,日中時計によって制御される24時間のリズムを示します.
- CLOCK:BMAL1は,NAMPTの昼夜表現を直接調節する.
- NAMPTは,昼間の遺伝子発現を調節するために不可欠です.
結論:
- 細胞代謝と昼夜リズムの間には,相互に繋がった転写-酵素フィードバックループが存在します.
- SIRT1は,NAD+の昼間合成に役割を果たしています.
- NAMPTの活動は,昼夜リズムを維持するために不可欠です.
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