Inhibition of Tissue Factor-Factor VIIa-catalyzed Factor X Activation by Factor Xa-Tissue Factor Pathway Inhibitor

Inhibition of Tissue Factor-Factor VIIa-catalyzed Factor X Activation by Factor Xa-Tissue Factor Pathway Inhibitor
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因子 Xa-组织因子途径抑制剂对组织因子-因子 VIIa 催化的因子 X 激活的抑制

DOI:
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发表时间:
1999
影响因子:
4.8
通讯作者:
T. Lindhout
T. Lindhout
中科院分区:
生物学2区
文献类型:
--
作者:
I. Salemink;J. Franssen;G. Willems;H. Hemker;T. Lindhout

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组织因子(TF)·因子VIIa(FVIIa)的生理抑制剂,全长组织因子途径抑制剂(TFPIFL)与因子Xa(FXa)复合,对阴离子磷脂膜具有高亲和力。研究了阴离子磷脂在抑制TF·FVIIa催化的FX活化中的作用。在FXa·TFPIFL或FXa·TFPI1 - 161(TFPI缺少第三个Kunitz结构域和C末端)的预形成复合物存在下,在包埋有TF的旋转圆盘上测量FXa的产生,TF包埋在由纯磷脂酰胆碱(TF·PC)或25%磷脂酰丝氨酸和75%磷脂酰胆碱(TF·PSPC)组成的膜中。在TF·PC,FXa·TFPIFL和FXa·TFPI1 - 161显示出相似的抑制速率常数(分别为0.07 × 108 m − 1 s − 1和0.1 × 108 m − 1 s − 1)。磷脂酰丝氨酸存在时,FXa·TFPIFL的抑制速率常数增加3倍,而FXa·TFPI1 - 161的速率常数增加9倍。将TF·PSPC与FXa·TFPIFL在无FVIIa存在的情况下孵育,随后耗尽溶液FXa·TFPIFL,表明FXa·TFPIFL仍结合在膜上并继续其抑制活性。FXa·TFPI1 - 161或TF·PC膜均未观察到这种情况。这些数据表明,FXa·TFPIFL的膜结合池可能在TF·FVIIa活性的现场调节中具有生理重要性。
The physiological inhibitor of tissue factor (TF)·factor VIIa (FVIIa), full-length tissue factor pathway inhibitor (TFPIFL) in complex with factor Xa (FXa), has a high affinity for anionic phospholipid membranes. The role of anionic phospholipids in the inhibition of TF·FVIIa-catalyzed FX activation was investigated. FXa generation at a rotating disc coated with TF embedded in a membrane composed of pure phosphatidylcholine (TF·PC) or 25% phosphatidylserine and 75% phosphatidylcholine (TF·PSPC) was measured in the presence of preformed complexes of FXa·TFPIFL or FXa·TFPI1–161 (TFPI lacking the third Kunitz domain and C terminus). At TF·PC, FXa·TFPIFL and FXa·TFPI1–161 showed similar rate constants of inhibition (0.07 × 108 m −1 s−1 and 0.1 × 108 m −1 s−1, respectively). With phosphatidylserine present, the rate constant of inhibition for FXa·TFPIFL increased 3-fold compared with a 9-fold increase in the rate constant for FXa·TFPI1–161. Incubation of TF·PSPC with FXa·TFPIFL in the absence of FVIIa followed by depletion of solution FXa·TFPIFL showed that FXa·TFPIFL remained bound at the membrane and pursued its inhibitory activity. This was not observed with FXa·TFPI1–161 or at TF·PC membranes. These data suggest that the membrane-bound pool of FXa·TFPIFL may be of physiological importance in an on-site regulation of TF·FVIIa activity.
DOI: 10.1021/bi00107a001
发表时间: 1991-10-29
期刊: BIOCHEMISTRY
影响因子: 2.9
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DOI: --
发表时间: 1992
期刊: Blood
影响因子: 20.3
作者:
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DOI: --
发表时间: 1988
期刊: The Journal of biological chemistry
影响因子: --
作者:
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DOI: --
发表时间: 1993
期刊: The Journal of biological chemistry
影响因子: --
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