反红素D螺旋与血管GAG相互作用的生理意义
Indranil Biswas1, Sumith R Panicker1, Florea Lupu1
1Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK.
Blood advances
|December 13, 2024
概括
抗血素 (AT) 主要使用其D-螺旋来与血管糖氨基酸相互作用,以获得抗炎作用,而不仅仅是蛋白酶抑制. 这一发现澄清了AT在调节血液凝固和体内炎症方面的双重作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 反凝血素 (AT) 是一种关键的抗凝血剂,它调节凝血蛋白酶.
- 此外,AT还表现出抗炎功能,与其抗凝剂作用不同.
- 亚特的D螺旋介导与血管糖氨酸甘油 (GAG) 进行抗炎信号的相互作用.
研究的目的:
- 研究血管GAG在AT的D-螺旋依赖抗凝剂和抗炎功能的体内作用.
- 为了在体内区分AT蛋白酶抑制功能的贡献与其D螺旋介导信号的贡献.
主要方法:
- 使用了两种AT突变:AT-4Mut (没有肝素亲和力或D螺旋信号) 和AT-R425del (不活跃的信号突变).
- 在siRNA诱导的AT缺乏的小鼠模型中,与野生型AT (AT-WT) 的AT突变体的AT特征进行了体内比较.
- 评估了促凝和促炎表型的救援,包括血凝固时间,纤维素沉积,VCAM-1表达和白细胞透.
主要成果:
- AT-WT和AT-4Mut都恢复了正常的凝血时间,并抑制了AT缺乏小鼠中的纤维素沉积.
- AT-WT显著减轻了炎症,而AT-4Mut没有做到这一点.
- AT-R425del有效降低了炎症,这表明D-螺旋体-GAG相互作用的作用独立于蛋白酶抑制.
结论:
- 在体内,AT的D螺旋与血管GAG的相互作用对其抗炎信号至关重要.
- AT的抗炎功能主要由D-螺旋体-GAG相互作用介导,而不是其蛋白酶抑制活性.
- 这项研究阐明了AT抗凝和抗炎作用背后的独特机制.
相关概念视频
Glycosaminoglycans
4.7K
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
4.7K
Anticoagulant Drugs: Low-Molecular-Weight Heparins
616
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
616
Intracellular Signaling Affects Focal Adhesions
2.6K
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...
2.6K
Fibril-associated Collagen
2.5K
Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
2.5K
Proteoglycans
3.9K
Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
3.9K
Matrix Proteoglycans and Glycoproteins
3.8K
Proteoglycans are extensively glycosylated proteins, commonly found in the extracellular matrix, interwoven with collagen fibers. Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers associated with large amounts of proteoglycans. These proteoglycans have long negative charges that attract cations, which in turn attract water molecules. This influx of ions and water molecules swells up the proteoglycan like a water-soaked gel that can...
3.8K


