通过NAD辅因子的氧化还原状态来调节时钟和NPAS2的DNA结合
1Department of Biochemistry, University of Texas-Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9152, USA.
概括
昼夜时钟是指昼夜的时间表.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 时间生物学 时间生物学
背景情况:
- 生物钟在24小时周期中调节基因表达,受光线,活动和食物的影响.
- 时钟:BMAL1和NPAS2:BMAL1是控制昼夜节律的关键转录因子.
- 连接外部线索与时钟引进的精确分子机制尚未完全理解.
研究的目的:
- 调查尼古丁胺胺二核酸 (NAD) 辅因子在调节钟:BMAL1和NPAS2:BMAL1异构体的DNA结合活性中的作用.
- 探索细胞氧化还原状态的潜力,作为昼夜时钟的调节媒介.
主要方法:
- 使用纯化的系统研究了Clock:BMAL1和NPAS2:BMAL1异构体的DNA结合活性.
- 评估了NAD辅因子的不同氧化还原状态对这些转录因子的DNA结合能力的影响.
主要成果:
- 钟:BMAL1和NPAS2:BMAL1的DNA结合活性是由NAD辅因子的氧化还原状态直接调节的.
- 减少形式的NAD (NAD(H) 和NADP(H)) 显著增强DNA结合.
- 氧化形式的NAD抑制这些异构体的DNA结合活性.
结论:
- 由NAD辅因子调节的细胞氧化还原状态,直接影响核心昼夜时钟组件的DNA结合功能.
- 这一发现表明一种新的机制,即食物摄入或神经元活动可能通过直接的氧化还原调节进入昼夜时钟.
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