AKT的激活触发了人类大动脉内皮细胞中Rab14介导的ADAM10转移到细胞表面的过程
Chung Hee Baek1, Hyosang Kim1, Soo Young Moon2
1Division of Nephrology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Scientific reports
|March 3, 2025
概括
蛋白激酶B (AKT) 激活通过减少细胞间粘附分子-1 (ICAM-1) 表达来保护先进的糖化终产物 (AGEs). 这涉及AKT介导的ADAM10转位和RAGE脱落.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 先进的糖化终产物 (AGEs) 导致内皮功能障碍.
- 众所周知,蛋白激酶B (AKT) 激活可以减轻AGE的有害影响,但潜在的机制尚不清楚.
- 细胞间粘附分子-1 (ICAM-1) 的表达由内皮细胞中的AGEs上调,促进炎症.
研究的目的:
- 阐明AKT信号抑制人类大动脉内皮细胞 (HAEC) 中AGE诱导的ICAM-1表达的分子机制.
- 调查ADAM10,RAGE和Rab14在AKT介导的抗AGE保护中的作用.
主要方法:
- 用AGE-牛血清白蛋白 (AGE-BSA) 和AKT激活剂SC79.9治疗的HAEC细胞培养物.
- 药物抑制和siRNA介导的AKT异型,ADAM10和Rab14的药物抑制和中断.
- 对ICAM-1表达的分析,ADAM10细胞表面转位,以及RAGE外主体脱落的分析.
- 同免疫沉试验用于评估蛋白质相互作用.
主要成果:
- SC79治疗激活了AKT1,AKT2和AKT3,导致ADAM10转移到细胞表面,并导致RAGE细胞外域脱落.
- 抑制ADAM10或AKT可以防止SC79诱导的RAGE分泌和ICAM-1抑制.
- 发现Rab14与ADAM10共同免疫,并且对于SC79诱导的ADAM10细胞表面转位和RAGE脱落至关重要.
- 拉布14敲击取消了SC79对AGE-BSA诱导的ICAM-1表达的保护作用.
结论:
- 在HAEC中,AKT激活抑制了AGE-BSA诱导的ICAM-1表达.
- 这种保护作用是由ADAM10在细胞表面的Rab14依赖转位介导的,这诱导了RAGE外主体脱落.
- 这些发现揭示了一种涉及AKT,Rab14,ADAM10和RAGE的新信号通路,用于对AGE的内皮细胞保护.
相关概念视频
Intracellular Signaling Affects Focal Adhesions
2.5K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.5K
Activation of Integrins
3.2K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.2K
MAPK Signaling Cascades
5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K
Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
Rab Proteins
3.8K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.8K
Adherens Junctions
4.7K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
4.7K


