IDENTIFICATION OF AN ENDOTHELIAL-CELL COFACTOR FOR THROMBIN-CATALYZED ACTIVATION OF PROTEIN-C
IDENTIFICATION OF AN ENDOTHELIAL-CELL COFACTOR FOR THROMBIN-CATALYZED ACTIVATION OF PROTEIN-C
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DOI：
10.1073/pnas.78.4.2249
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
OWEN, WG
中科院分区：
文献类型：
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作者：
ESMON, CT;OWEN, WG
在凝血酶（EC 3.4.21.5）的存在下用蛋白C灌注心肌可激发有效的抗凝活性，其基于合成底物水解和抗凝性质被鉴定为活化蛋白C。在通过心肌转运期间，活化蛋白C形成的速率至少是灌注溶液中凝血酶催化的蛋白C活化的速率的20，000倍。当凝血酶存在于灌注液中时，心脏激活蛋白C的能力维持至少1小时，但衰减（半衰期约为10小时）。30分钟）。添加二异丙基磷酸凝血酶使这种衰减速率增加10倍以上。二异丙基磷酸凝血酶与活性凝血酶的共灌注降低了心肌中蛋白C活化的量。培养的人内皮细胞单层可提高凝血酶催化的蛋白C活化的速率。与心肌一样，培养基中含有二异丙基磷酸凝血酶可抑制激活速率。血管内皮表面显然提供了一种辅助因子，可提高凝血酶激活蛋白C的速率。
Perfusion of the myocardium with protein C in the presence of thrombin (EC 3.4.21.5) elicits a potent anticoagulant activity, which is identified as activated protein C on the basis of synthetic substrate hydrolysis and anticoagulant properties. The rate of activated protein C formation during the transit through the myocardium is at least 20,000 times that of thrombin-catalyzed activation of protein C in the perfusion solution. The capacity of the heart to activate protein C is maintained for at least 1 h when thrombin is present in the perfusate, but decays (half-life .apprxeq. 30 min) once thrombin is omitted. Addition of diisopropylphospho-thrombin increases this decay rate more than 10-fold. Coperfusing diisopropylphospho-thrombin with active thrombin lowers the amount of protein C activation in the myocardium. Cultured monolayers of human endothelium enhance the rate of thrombin-catalyzed protein C activation. As with myocardium, the activation rate is inhibited by including diisopropylphospho-thrombin in the medium. The surface of vascular endothelium apparently provides a cofactor that enhances the rate of protein C activation by thrombin.