拉斯GRP2减弱TAGE修饰血管内皮细胞中eNOS的修饰
Shouhei Miyazaki1, Jun-Ichi Takino1, Kentaro Nagamine2
1Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
Biological & pharmaceutical bulletin
|March 18, 2025
概括
来自糖 (GA) 的有毒高级糖化最终产品 (TAGEs) 导致细胞死亡和蛋白质损伤. 拉斯瓜尼尔核酸释放蛋白2 (RasGRP2) 保护血管细胞免受GA诱导的TAGE形成和eNOS修饰.
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:
- 来自甘 (GA) 的有毒高级糖化最终产品 (TAGEs),表现出细胞毒性,并导致与生活方式相关的疾病.
- 对TAGE的GA修饰导致蛋白质功能障碍,影响细胞过程.
- 内皮氧化合成酶 (eNOS) 对于血管内皮细胞中氧化的产生至关重要,是TAGE修饰的潜在目标.
研究的目的:
- 调查Ras guanyl核酸释放蛋白2 (RasGRP2) 在缓解TAGE形成和GA诱导的eNOS修饰中的作用.
- 确定RasGRP2在血管内皮细胞中对GA诱导的细胞死亡的保护作用.
主要方法:
- 利用RasGRP2-过度表达 (R) 和模拟 (M) 永久化人类静脉内皮细胞.
- 施用不同度的GA来诱导TAGE形成并评估细胞活力.
- 通过生物化学试验评估TAGE形成和eNOS修饰.
- 研究了aminoguanidine,一个AGE形成抑制剂,对GA诱导的细胞损伤的影响.
主要成果:
- 治疗GA以度依赖的方式降低了内皮细胞活力.
- 在M细胞中,GA显著增加了TAGE形成和eNOS修饰,而在R细胞中这种效应被抑制.
- 氨基瓜尼丁减轻了GA诱导的细胞死亡和eNOS修饰,证实了AGE形成的作用.
结论:
- 在血管内皮细胞中,GA诱导细胞死亡,TAGE形成和eNOS修饰.
- RasGRP2作为一种保护因子,抑制TAGE的形成和随后的细胞损伤.
- 这些发现突出了RasGRP2作为缓解TAGE相关血管功能障碍的潜在治疗点.
相关概念视频
01:22Activation and Inactivation of G Proteins
6.5K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.5K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
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...
2.5K
01:28Nitric Oxide Signaling Pathway
4.9K
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...
4.9K
01:12GPCR Desensitization
5.7K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
5.7K
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K