Takada A, Takada Y
Department of Physiology, Hamamatsu University, School of Medicine, Shizuoka-ken, Japan.
Haemostasis. 1988;18 Suppl 1:25-35. doi: 10.1159/000215834.
Plasminogen is said to be synthesized in many organs, but the major source of its production is considered to be the liver. The production of plasminogen is observed in fetal life, but its plasma level is low in new born infants, rising rapidly to attain adult levels in about 13 weeks. The plasma levels do not change much with age. Although the fibrinolytic enzyme system is influenced by many factors such as hormones, exercise, emotion, age, sex, nutritional states etc., the plasma levels of plasminogen are relatively stable. In this presentation we would like to discuss three important subjects related to the physiology of plasminogen. The first subject is the activation pathway of the native form of plasminogen (Glu-plg) by various activators in the plasma or clotted plasma. Glu-plg was not easily activated by activators such as urokinase (UK) or tissue plasminogen activator (t-PA), but activated very easily in the presence of fibrin clot. In the presence of purified clot, Glu-plg was partly activated by activators to Glu-plasmin, but also converted to Lys-plg by preformed plasmin, subsequently being activated to plasmin. Glu-plg I (containing two carbohydrate chains) changed conformation more easily upon interaction with fibrin than Glu-plg II (containing one carbohydrate chain) and Glu-plg I was also more easily activated by activators than Glu-plg II. Although Glu-plg was hardly activated by activators in the plasma, Glu-plg was activated easily in the presence of plasma clot. Results of immunoblotting experiments indicated that Glu-plg was mainly activated by activators directly to plasmin, not via Lys-plg in contrast to purified systems. The second subject is the degradation of plasminogen by elastase. Plasminogen may be degraded by proteolytic enzymes such as cathepsin or elastase. The degradation of plasminogen by elastase is shown to give rise to K1 to K3, K4, and mini-plg (containing K5). We have shown that the degradation rate to Glu-plg by elastase increased in the presence of tranexamic acid, indicating that the conformational change of Glu-plg in the presence of tranexamic acid resulted in the exposure of the hydrophobic regions connecting K3, K4 and K5, thus making them accessible to elastase. Consequently, Lys-plg or conformationally altered Glu-plg (possibly bound to fibrin or FDP) is more easily degraded in vivo. The last subject is relationship between plasma plasminogen levels and fibrinolytic activity in various ages. Although plasma plasminogen levels do not change with age, the fibrinolytic activity lowers.(ABSTRACT TRUNCATED AT 400 WORDS)
纤溶酶原据说在许多器官中合成，但其主要产生来源被认为是肝脏。在胎儿期可观察到纤溶酶原的产生，但其在新生儿中的血浆水平较低，在约13周时迅速上升至成人水平。血浆水平随年龄变化不大。尽管纤维蛋白溶解酶系统受许多因素影响，如激素、运动、情绪、年龄、性别、营养状况等，但纤溶酶原的血浆水平相对稳定。在本报告中，我们想讨论与纤溶酶原生理学相关的三个重要主题。第一个主题是血浆或凝血血浆中各种激活剂对天然形式的纤溶酶原（Glu-plg）的激活途径。Glu-plg不容易被诸如尿激酶（UK）或组织纤溶酶原激活剂（t-PA）等激活剂激活，但在纤维蛋白凝块存在时很容易被激活。在纯化凝块存在的情况下，Glu-plg被激活剂部分激活为Glu-纤溶酶，但也被预先形成的纤溶酶转化为Lys-plg，随后被激活为纤溶酶。与含有一条碳水化合物链的Glu-plg II相比，含有两条碳水化合物链的Glu-plg I在与纤维蛋白相互作用时更容易改变构象，并且Glu-plg I也比Glu-plg II更容易被激活剂激活。尽管Glu-plg在血浆中很难被激活剂激活，但在血浆凝块存在时Glu-plg很容易被激活。免疫印迹实验结果表明，与纯化系统不同，Glu-plg主要被激活剂直接激活为纤溶酶，而不是通过Lys-plg。第二个主题是弹性蛋白酶对纤溶酶原的降解。纤溶酶原可能被诸如组织蛋白酶或弹性蛋白酶等蛋白水解酶降解。弹性蛋白酶对纤溶酶原的降解会产生K1至K3片段、K4片段和微型纤溶酶原（含有K5片段）。我们已经表明，在氨甲环酸存在下，弹性蛋白酶对Glu-plg的降解速率增加，这表明氨甲环酸存在时Glu-plg的构象变化导致连接K3、K4和K5的疏水区域暴露，从而使它们易被弹性蛋白酶作用。因此，Lys-plg或构象改变的Glu-plg（可能与纤维蛋白或纤维蛋白降解产物结合）在体内更容易被降解。最后一个主题是不同年龄段血浆纤溶酶原水平与纤维蛋白溶解活性之间的关系。尽管血浆纤溶酶原水平不随年龄变化，但纤维蛋白溶解活性会降低。（摘要截断于400字）
