Role of Cell Surface Lipids and Thiol-Disulphide Exchange Pathways in Regulating the Encryption and Decryption of Tissue Factor.
Role of Cell Surface Lipids and Thiol-Disulphide Exchange Pathways in Regulating the Encryption and Decryption of Tissue Factor.
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DOI：
10.1055/s-0039-1681102
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发表时间：
2019-06
影响因子：
6.7
通讯作者：
Rao LVM
中科院分区：
文献类型：
--
作者：
Ansari SA;Pendurthi UR;Rao LVM
组织因子 (TF) 是一种跨膜糖蛋白，是凝血因子 VII (FVII) 和 VIIa (FVIIa) 的细胞受体。 TF-FVIIa 复合物的形成触发凝血途径的启动。 TF 在止血中发挥重要作用，但 TF 活性的异常表达会导致血栓性疾病。在健康状态下，TF对细胞的促凝血活性受到严格控制，以允许足够的凝血活性来实现止血，但不会引起血栓形成。这主要是通过TF在体内的选择性定位和细胞表面的TF加密来实现的。静息细胞上的绝大多数 TF 以加密状态存在，具有最小的促凝血活性，但在细胞损伤或激活后变得促血栓形成。目前，负责 TF 加密和激活（解密）的机制尚不完全清楚，但最近的研究为这些过程提供了重要的机制见解。迄今为止，磷脂酰丝氨酸外化到外叶和打开或关闭 TF 中变构二硫键的硫醇二硫化物交换途径在调节细胞表面的 TF 促凝血活性中发挥着重要作用。最近的研究表明，鞘磷脂是质膜外叶中的一种主要磷脂，在静息细胞中 TF 的加密中发挥着关键作用。本综述概述了有关上述 TF 加密和解密机制的最新文献，特别强调了我们最近的发现。
Tissue factor (TF), a transmembrane glycoprotein, is the cellular receptor of the coagulation factors VII (FVII) and VIIa (FVIIa). The formation of TF–FVIIa complex triggers the initiation of the blood coagulation pathway. TF plays an essential role in haemostasis, but an aberrant expression of TF activity contributes to thrombotic disorders. In health, TF pro-coagulant activity on cells is controlled tightly to allow sufficient coagulant activity to achieve haemostasis but not to cause thrombosis. It is achieved largely by selective localization of TF in the body and encryption of TF at the cell surface. A vast majority of TF on resting cells exists in an encrypted state with minimal pro-coagulant activity but becomes pro-thrombotic following cell injury or activation. At present, the mechanisms that are responsible for TF encryption and activation (decryption) are not entirely clear, but recent studies provide important mechanistic insights into these processes. To date, externalization of phosphatidylserine to the outer leaflet and thiol-disulphide exchange pathways that either turn on and off the allosteric disulphide bond in TF are shown to play a major role in regulating TF pro-coagulant activity on cell surfaces. Recent studies showed that sphingomyelin, a major phospholipid in the outer leaflet of plasma membrane, plays a critical role in the encryption of TF in resting cells. The present review provides an overview of recent literature on the above-described mechanisms of TF encryption and decryption with a particular emphasis on our recent findings.
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影响因子：
7.5
作者：
Ansari, Shabbir A.;Pendurthi, Usha R.;Rao, L. Vijaya Mohan
通讯作者：
Rao, L. Vijaya Mohan
影响因子：
3.7
作者：
Ansari, Shabbir A.;Pendurthi, Usha R.;Rao, L. Vijaya Mohan
通讯作者：
Rao, L. Vijaya Mohan
影响因子：
20.3
作者：
Dietzen, DJ;Page, KL;Tetzloff, TA
通讯作者：
Tetzloff, TA
影响因子：
20.3
作者：
Ebert, Julia;Wilgenbus, Petra;Horke, Sven
通讯作者：
Horke, Sven
影响因子：
20.3
作者：
Butenas, S;Bouchard, BA;Mann, KG
通讯作者：
Mann, KG