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纤溶酶原激活物抑制剂1(PAI-1)在体外血浆中阻止单链尿激酶型纤溶酶原激活物(scu-PA)转化为双链尿激酶型纤溶酶原激活物(tcu-PA)的重要性。

Importance of plasminogen activator inhibitor type 1 (PAI-1) for preventing single chain urokinase plasminogen activator (scu-PA) conversion into two chain urokinase plasminogen activator (tcu-PA) in plasma in vitro.

作者信息

Dosne A M, Dubor F, Samama M

机构信息

Lab. Immunopharmacologie exp., UPR 405 CNRS, Paris, France.

出版信息

Thromb Res. 1991 Sep 1;63(5):531-9. doi: 10.1016/0049-3848(91)90178-y.

DOI:10.1016/0049-3848(91)90178-y
PMID:1755005
Abstract

We have studied the effects of PAI-1 on the conversion of scu-PA into tcu-PA in vitro in plasma containing or not a 125I-fibrin clot by determining tcu-PA activity on S2444. Two preparations of PAI-1 have been used, a fraction of medium conditioned with the monkey Vero cells (Vero-Prep), the antiurokinase activity of which is inhibited at 83% by anti PAI-1 IgG, or purified human PAI-1 from HT 1080 fibrosarcoma cells. Scu-PA purified from human kidney cells has been treated with diisopropylfluorophosphate before use. In plasma, conversion of scu-PA into the tc form is accelerated by addition of anti PAI-1 IgG. In plasma containing a clot, generation of tcu-PA, is considerably delayed after addition of the Vero-Prep or human PAI-1. Clot lysis is also decreased but to a lesser extent than it would be expected from the level of tcu-PA activity. Addition of anti PAI-1 antibodies shortens the lag phase before tcu-PA appears and moderatly accelerates clot lysis. These results demonstrate the importance of PAI-1 for the stability of scu-PA in plasma in vitro by delaying its conversion into tcu-PA.

摘要

我们通过测定S2444上的tcu-PA活性,研究了纤溶酶原激活物抑制剂-1(PAI-1)在含有或不含有125I-纤维蛋白凝块的血浆中对单链尿激酶型纤溶酶原激活剂(scu-PA)转化为双链尿激酶型纤溶酶原激活剂(tcu-PA)的体外影响。使用了两种PAI-1制剂,一种是用猴Vero细胞培养的培养基上清(Vero-Prep),其抗尿激酶活性被抗PAI-1 IgG抑制83%,另一种是从HT 1080纤维肉瘤细胞中纯化的人PAI-1。从人肾细胞中纯化的scu-PA在使用前用二异丙基氟磷酸处理。在血浆中,添加抗PAI-1 IgG可加速scu-PA向tc形式的转化。在含有凝块的血浆中,添加Vero-Prep或人PAI-1后,tcu-PA的生成显著延迟。凝块溶解也减少,但程度小于根据tcu-PA活性水平预期的程度。添加抗PAI-1抗体可缩短tcu-PA出现前的延迟期,并适度加速凝块溶解。这些结果表明,PAI-1通过延迟scu-PA转化为tcu-PA,对体外血浆中scu-PA的稳定性具有重要作用。

相似文献

1
Importance of plasminogen activator inhibitor type 1 (PAI-1) for preventing single chain urokinase plasminogen activator (scu-PA) conversion into two chain urokinase plasminogen activator (tcu-PA) in plasma in vitro.纤溶酶原激活物抑制剂1(PAI-1)在体外血浆中阻止单链尿激酶型纤溶酶原激活物(scu-PA)转化为双链尿激酶型纤溶酶原激活物(tcu-PA)的重要性。
Thromb Res. 1991 Sep 1;63(5):531-9. doi: 10.1016/0049-3848(91)90178-y.
2
Effect of standard heparin and a low molecular weight heparin on thrombolytic and fibrinolytic activity of single-chain urokinase plasminogen activator in vitro.标准肝素和低分子量肝素对单链尿激酶型纤溶酶原激活剂体外溶栓和纤溶活性的影响。
Thromb Haemost. 1989 Nov 24;62(3):923-6.
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Mechanism of the enhanced intrinsic activity of single-chain urokinase-type plasminogen activator during ongoing fibrinolysis.持续纤溶过程中单链尿激酶型纤溶酶原激活剂内在活性增强的机制。
J Biol Chem. 1993 Sep 5;268(25):18554-9.
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Characterization of a fusion protein consisting of amino acids 1 to 263 of tissue-type plasminogen activator and amino acids 144 to 411 of urokinase-type plasminogen activator.一种融合蛋白的特性分析,该融合蛋白由组织型纤溶酶原激活剂的第1至263个氨基酸和尿激酶型纤溶酶原激活剂的第144至411个氨基酸组成。
J Biol Chem. 1987 Aug 5;262(22):10855-62.
5
Pro-urokinase: a study of its stability in plasma and of a mechanism for its selective fibrinolytic effect.尿激酶原:其在血浆中的稳定性及选择性纤溶作用机制的研究
Blood. 1986 May;67(5):1215-23.
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Activation with plasmin of tow-chain urokinase-type plasminogen activator derived from single-chain urokinase-type plasminogen activator by treatment with thrombin.
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Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects.
J Lab Clin Med. 1999 Aug;134(2):161-7. doi: 10.1016/s0022-2143(99)90121-x.
8
Absence of synergism between tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scu-PA) and urokinase on clot lysis in a plasma milieu in vitro.组织型纤溶酶原激活剂(t-PA)、单链尿激酶型纤溶酶原激活剂(scu-PA)和尿激酶在体外血浆环境中对血凝块溶解不存在协同作用。
Thromb Haemost. 1986 Aug 20;56(1):35-9.
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A sensitive bioimmunoassay for thrombin-cleaved two-chain urokinase-type plasminogen activator in human body fluids.一种用于检测人体体液中凝血酶裂解的双链尿激酶型纤溶酶原激活剂的灵敏生物免疫测定法。
Thromb Haemost. 1996 Jun;75(6):908-14.
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Characterization of a chimeric plasminogen activator consisting of amino acids 1 to 274 of tissue-type plasminogen activator and amino acids 138 to 411 of single-chain urokinase-type plasminogen activator.一种嵌合型纤溶酶原激活剂的特性,该激活剂由组织型纤溶酶原激活剂的1至274个氨基酸和单链尿激酶型纤溶酶原激活剂的138至411个氨基酸组成。
J Biol Chem. 1988 Dec 15;263(35):19083-91.

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Plasmin-dependent elimination of the growth-factor-like domain in urokinase causes its rapid cellular uptake and degradation.纤溶酶介导的尿激酶中生长因子样结构域的消除导致其快速的细胞摄取和降解。
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