在勃起功能障碍中,HMGB1/2的N-homocysteinylation促进体洞内皮老化
Peng Hu1,2, Sen Fu1,2, Beining Li1,2
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
International journal of biological sciences
|November 24, 2025
概括
高水平的homocysteine (Hcy) 导致老年人的勃起功能障碍 (ED). 用N-乙赛氨酸 (NAC) 向甲基-tRNA合成酶1 (MARS1) -同型氨酸硫黄素 (HTL) 途径显示出对治疗Hcy诱导的ED有希望.
科学领域:
- 生物医学科学 生物医学科学
- 血管生物学 血管生物学
- 衰老研究研究 衰老研究
背景情况:
- 同型氨酸 (Hcy) 是勃起功能障碍 (ED) 的确立危险因素,特别是在老年人群中.
- 目前以叶酸为基础的降低Hcy的疗法已显示出有限的疗效,这表明需要探索替代性致病机制.
- 内皮功能障碍是ED的关键因素,其与衰老中的Hcy的联系需要进一步阐明.
研究的目的:
- 调查同类氨酸对勃起功能障碍有所贡献的年龄相关机制.
- 在中老年和老年人中确定同类氨酸诱导的ED的新疗法标.
- 评估N-乙半氨酸 (NAC) 在缓解内皮衰老和改善勃起功能方面的疗效.
主要方法:
- 在衰老的内皮细胞中分析 metionyl-tRNA合成酶1 (MARS1) 活性.
- 测量同型氨酸硫黄素 (HTL) 和蛋白质N-同型氨酸化 (K-Hcy) 的水平.
- 评估高流动性组盒子蛋白1和2 (HMGB1/2) 的转位和细胞外释放.
- 在临床前模型中评估N-乙半氨酸 (NAC) 治疗对内皮衰老和勃起功能的影响,单独和与tadalafil.
主要成果:
- 衰老的内皮细胞显示MARS1对Hcy的反应增加,导致HTL产量增加和广泛的蛋白K-Hcy.
- K-Hcy促进细胞质转移和HMGB1/2的细胞外释放,加剧了与衰老相关的分泌表型 (SASP).
- NAC可以竞争性地抑制MARS1,降低HTL水平并减轻内皮老化.
- NAC治疗改善了中年高血糖血症患者的勃起功能,并与tadalafil协同作用.
结论:
- 年龄依赖的MARS1-HTL轴是同类氨酸诱导ED的发病的一个关键因素.
- 用NAC针对MARS1提供了一种潜在的治疗策略,通过减少HTL,在老年人群中治疗ED.
- 这种方法为老年人管理ED相关的高homocysteinemia提供了一种新的治疗途径.
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
01:17Male Sexual Response: Erection & Ejaculation
18.1K
Sexual stimulation can take various forms, such as physical touch and visual or auditory cues. When this happens, the parasympathetic reflex in the sacral portion of the spinal cord is activated. This reflex stimulates the release of nitric oxide (NO), which then dilates the arterioles in the penis, increasing blood flow to the erectile tissues - the corpora cavernosa and corpus spongiosum.
The blood filling the erectile tissues compresses the veins, which helps to prevent blood from leaving...
The blood filling the erectile tissues compresses the veins, which helps to prevent blood from leaving...
18.1K
01:26Coronary Artery Disease II: Pathophysiology
348
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
348
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
538
Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
538