在内皮细胞中提高细胞质NADPH新陈代谢可以改善血管衰老
Dan Wu1,2, Bo Tan3, Zijie Cheng1
1Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
Nature communications
|November 3, 2025
概括
在细胞内皮细胞衰老过程中,细胞酸尼古丁胺胺氨酸二核酸盐 (NADPH) 增加,由葡萄糖-6-酸盐脱酶 (G6PD) 驱动. 这一发现为血管衰老提供了新的治疗点.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 血管生物学 血管生物学
背景情况:
- 尼古丁胺胺二核酸 (NADPH) 的新陈代谢在内皮细胞 (EC) 中进行细分.
- NADPH在EC衰老和血管衰老中的作用尚不清楚.
- NADPH对于细胞的氧化还原稳定和生物合成过程至关重要.
研究的目的:
- 在EC衰老过程中研究NADPH的代谢特征和功能意义.
- 在衰老的EC中识别NADPH代谢的关键调节者.
- 探索针对血管衰老的NADPH代谢的治疗策略.
主要方法:
- 利用一种基因编码的光指示器来测量细胞内NADPH水平.
- 研究了葡萄糖-6-酸脱酶 (G6PD) 在衰老期间调节NADPH中的作用.
- 研究了G6PD操纵对体外和体内血管衰老的影响.
- 选FDA批准的药物以调节NADPH代谢和减轻血管衰老的能力.
主要成果:
- 细胞质,但不是线粒体,NADPH水平在EC衰老期间增加.
- G6PD的升级加剧了老化EC中细胞质NADPH的增加.
- 过度表达G6PD有助于缓解血管衰老,而过度表达会使血管衰老恶化.
- 通过G6PD,NADPH通过增加减少的谷氨和抑制HDAC3.3来保护血管衰老.
- 叶酸在小鼠模型中显示出缓解血管衰老的有效性.
结论:
- 在EC衰老过程中,NADPH代谢,特别是细胞质中,受到失调.
- G6PD是NADPH水平的关键调节者,在血管衰老中起着至关重要的作用.
- 针对NADPH代谢,例如用叶酸,为血管衰老提供了一个有希望的治疗途径.
相关概念视频
01:28Nitric Oxide Signaling Pathway
6.1K
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...
6.1K
01:24Regulation of Angiogenesis and Blood Supply
3.3K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.3K
01:37Mitochondria
19.5K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
19.5K