FUNCTIONS OF TISSUE PLASMINOGEN ACTIVATOR

组织纤溶酶原激活剂，存在于所有被检查的组织中，还 释放到体液中，产生纤溶酶，这是一种广泛的特异性 在生理pH条件下有活性的蛋白酶。非常重要的是，它不会激活 纤溶酶原显着增加，除非存在第三种蛋白 作为调节信号的成分；测定纤维蛋白凝块的日期， 正如我们观察到的，异常蛋白质起到这种刺激作用， 防止蛋白质在全身不分青红皂白地分解。最密集的 在纤维蛋白凝块部位产生纤溶酶的研究似乎有助于 消化病理性内部凝块(血栓)。我们的努力集中在 主要是关于在存在的情况下选择性产生纤溶酶 许多类型的错误折叠(变性或化学修饰)的蛋白质， 相信这种选择性能力可以清除不健康的蛋白质 而不是消化健康的组织。纤维蛋白凝块可以被认为是 此一般角色的子案例。在体外的蛋白质状态 组织激活剂的“辅因子”(促进纤溶酶的产生 高达800倍)是纤维蛋白凝块；被酸、碱、 加热、尿素、奎尼丁或许多化学修饰；烧伤组织， 培养细胞(直接来自组织的天然细胞不是“辅因子”)； 以及暴露在氧化不饱和脂肪中的蛋白质。不确定的人 这些自我诱导的异常消化的生理相关性 蛋白质，除了纤维蛋白凝块，是未知的，并构成我们的 长期目标。激活剂在老年人选择性分解代谢中的作用 蛋白质(蛋白质周转)、受损组织、异常(癌变？)组织 新合成但错误折叠的蛋白质是可能的考虑因素。 由于测试组织激活剂可能参与的直接实验 在这些职能方面目前非常困难，我们立即提出建议 仅限于生化反应机制的表征 激活剂对异常(变性和化学修饰)蛋白质的影响 体外培养。这些研究与纤溶有关，这是一种被广泛接受的作用 组织激活剂，以及上面简要列出的更具投机性的角色。如果 这种机制是可以阐明的，而且有很多技术原因 它可能不能用纤维蛋白凝块来解释，这个问题 生理角色可能更容易接近。

Tissue plasminogen activator, present in all tissues examined and also released into the body fluids, generates plasmin, a broad specificity protease active at physiological pH. Very importantly it does not activate plasminogen significantly except in the presence of a third protein component which acts as a regulatory signal; to date the fibrin clot and, as we observe, abnormal proteins serve this stimulatory function, preventing indiscriminate proteolysis throughout the body. The intensively studied generation of plasmin at the site of a fibrin clot appears to serve to digest pathological internal clots (thrombi). Our efforts focus primarily on the selective generation of plasmin in the presence of misfolded (denatured or chemically modified) proteins of many types, with the belief that this selective ability serves to scavenge unhealthy protein while not digesting healthy tissue. The fibrin clot may be considered a sub-case of this general role. Protein states which are in vitro "cofactors" of tissue activator (the enhancement in plasmin generation is up to 800-fold) are the fibrin clot; proteins denatured by acid, base, heat, urea, quanidine or many chemical modifications; burned tissue, cultured cells (native cells directly form tissues are not "cofactors"); and protein exposed to oxidizing unsaturated fats. The uncertain physiological relavance of these self-induced digestions of abnormal proteins, except the fibrin clot, are not known and constitute our long-term objectives. Roles of activator in selective catabolism of aged proteins (protein turnover), damaged tissue, abnormal (cancerous?) tissue and newly synthesized but misfolded proteins are possible considerations. Since direct experiments to test possible involvement of tissue activator in these functions is very difficult at present, our immediate proposals are restricted to biochemical characterization of the mechanism of response of activator to abnormal (denatured and chemically modified) proteins in vitro. These studies relate to fibrinolysis, a widely accepted role of tissue activator, and the more speculative roles briefly listed above. If the mechanism can be elucidated, and there are many technical reasons why it probably cannot be elucidated using the fibrin clot, the issue of physiological roles may be more readily approached.