减少与氧化NAD+前体驱动肝细胞中独特的转录基因,蛋白质基因和代谢特征
Kasper T Vinten1,2, Bauke V Schomakers1,3, Simone Denis1
1Laboratory Genetic Metabolic Diseases, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
概括
减少的尼古丁胺胺二核酸 (NAD+) 前体,NMNH和NRH,显示出比NMN和NR更大的潜力来提高NAD+水平和影响细胞过程,为衰老研究提供了新的途径.
科学领域:
- 生物化学 生物化学
- 细胞的新陈代谢
- 衰老研究研究 衰老研究
背景情况:
- 尼古丁胺胺二核酸 (NAD+) 对于细胞功能至关重要,并且随着年龄的增长而下降.
- 目前的NAD+前体如NMN和NR具有有限的增强能力.
- 减少的NAD+前体 (NMNH,NRH) 是强大的增强剂,但人们对其了解甚少.
研究的目的:
- 综合比较减少的NAD+前体 (NMNH,NRH) 与它们的氧化形式 (NMN,NR) 的作用.
- 研究这些NAD+前体在小鼠肝细胞中的代谢和转录影响.
- 描述NMNH和NRH作为NAD+增强剂的独特特性.
主要方法:
- 使用RNA测序,蛋白质组学和代谢学进行比较分析.
- 用NMN,NMNH,NR和NRH治疗培养的小鼠肝细胞.
- 全球代谢分析和基因表达分析.
主要成果:
- 与NR和NMN相比,NRH和NMNH诱导了更广泛的代谢变化.
- NRH 独特地抑制了与能量代谢相关的代谢物.
- 减少的前体触发了更差异地表达的基因,包括与压力相关的GST,而不会引起氧化应激.
结论:
- 减少的NAD+前体 (NMNH,NRH) 是不同的,比NMN和NR更强大的NAD+增强剂.
- NMNH和NRH影响着更广泛的细胞过程,超出了NAD+的提升.
- 这些发现突显了降低NAD+前体在衰老和代谢研究中的独特治疗潜力.
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