人组织型纤溶酶原激活剂重链和轻链多肽链在大鼠体内的清除率
Clearance of the heavy and light polypeptide chains of human tissue-type plasminogen activator in rats.
作者信息
Rijken D C, Emeis J J
出版信息
Biochem J. 1986 Sep 15;238(3):643-6. doi: 10.1042/bj2380643.
Abstract
In order to assess which part of the tissue-type plasminogen activator (t-PA) molecule should be (genetically) modified to obtain more-slowly-clearing mutants, two-chain t-PA and its isolated heavy and light chains were radiolabelled and injected into rats. The vast majority of t-PA and the heavy chain disappeared from the blood circulation with half-lives of 2.3 and 1.0 min respectively. The clearance of the light chain was biphasic, owing to complex-formation with plasma proteinase inhibitors. The disappearance of di-isopropylphospho-light chain, which has a blocked active site, was nearly monophasic, with a half-life of 5.7 min. Organ distribution studies showed that hepatic clearance constituted the major pathway in all cases. These results strongly suggest that t-PA is recognized by the liver primarily through the heavy chain.
摘要
为了评估组织型纤溶酶原激活剂（t-PA）分子的哪一部分应该（通过基因）改造以获得清除更慢的突变体，对双链t-PA及其分离的重链和轻链进行放射性标记，并注射到大鼠体内。绝大多数t-PA和重链分别以2.3分钟和1.0分钟的半衰期从血液循环中消失。轻链的清除是双相的，这是由于与血浆蛋白酶抑制剂形成复合物。具有封闭活性位点的二异丙基磷酸轻链的消失几乎是单相的，半衰期为5.7分钟。器官分布研究表明，在所有情况下，肝脏清除都是主要途径。这些结果有力地表明，肝脏主要通过重链识别t-PA。
相似文献
1
Clearance of the heavy and light polypeptide chains of human tissue-type plasminogen activator in rats.人组织型纤溶酶原激活剂重链和轻链多肽链在大鼠体内的清除率
Biochem J. 1986 Sep 15;238(3):643-6. doi: 10.1042/bj2380643.
2
Two receptor systems are involved in the plasma clearance of tissue-type plasminogen activator (t-PA) in vivo.体内组织型纤溶酶原激活物（t-PA）的血浆清除涉及两个受体系统。
J Clin Invest. 1995 Aug;96(2):1164-8. doi: 10.1172/JCI118105.
3
Hepatic clearance of tissue-type plasminogen activator in rats.
Thromb Haemost. 1985 Oct 30;54(3):661-4.
4
Interaction of mutants of tissue-type plasminogen activator with liver cells: effect of domain deletions.组织型纤溶酶原激活剂突变体与肝细胞的相互作用：结构域缺失的影响。
Biochem J. 1996 Feb 1;313 ( Pt 3)(Pt 3):775-80. doi: 10.1042/bj3130775.
5
Investigation by HPLC of the catabolism of recombinant tissue plasminogen activator in the rat.
Thromb Haemost. 1988 Aug 30;60(1):107-12.
6
39-kD protein inhibits tissue-type plasminogen activator clearance in vivo.39-kD蛋白在体内抑制组织型纤溶酶原激活物的清除。
J Clin Invest. 1993 Aug;92(2):937-44. doi: 10.1172/JCI116669.
7
8
Clearance of t-PA, PAI-1, and t-PA-PAI-1 complex in an isolated perfused rat liver system.
J Lab Clin Med. 1991 Feb;117(2):109-14.
9
Isolation and functional characterization of the heavy and light chains of human tissue-type plasminogen activator.
J Biol Chem. 1986 Mar 5;261(7):3098-102.
引用本文的文献
1
Viral cirrhosis: an overview of haemostatic alterations and clinical consequences.病毒性肝硬化：止血改变及其临床后果概述。
Mediterr J Hematol Infect Dis. 2009 Dec 30;1(3):e2009033. doi: 10.4084/MJHID.2009.033.
2
Interaction of mutants of tissue-type plasminogen activator with liver cells: effect of domain deletions.组织型纤溶酶原激活剂突变体与肝细胞的相互作用：结构域缺失的影响。
Biochem J. 1996 Feb 1;313 ( Pt 3)(Pt 3):775-80. doi: 10.1042/bj3130775.
3
39-kD protein inhibits tissue-type plasminogen activator clearance in vivo.39-kD蛋白在体内抑制组织型纤溶酶原激活物的清除。
J Clin Invest. 1993 Aug;92(2):937-44. doi: 10.1172/JCI116669.
4
alpha-Fucose-mediated binding and degradation of tissue-type plasminogen activator by HepG2 cells.α-岩藻糖介导的HepG2细胞对组织型纤溶酶原激活物的结合与降解
J Clin Invest. 1994 Feb;93(2):703-10. doi: 10.1172/JCI117023.
5
New strategies in the development of thrombolytic agents.溶栓药物开发的新策略。
Blut. 1988 Oct;57(4):147-62. doi: 10.1007/BF00319543.
6
Reagents for reversible coupling of proteins to the active centres of trypsin-like serine proteinases.用于蛋白质与类胰蛋白酶丝氨酸蛋白酶活性中心可逆偶联的试剂。
Biochem J. 1987 Dec 1;248(2):409-13. doi: 10.1042/bj2480409.
7
Tissue-type plasminogen activator. A review of its pharmacology and therapeutic use as a thrombolytic agent.组织型纤溶酶原激活剂。其药理学及作为溶栓剂的治疗用途综述。
Drugs. 1989 Sep;38(3):346-88. doi: 10.2165/00003495-198938030-00003.
8
Binding of tissue plasminogen activator to human aortic endothelial cells.组织型纤溶酶原激活剂与人主动脉内皮细胞的结合。
Biochem J. 1990 Jul 15;269(2):475-82. doi: 10.1042/bj2690475.
9
Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator.低密度脂蛋白受体相关蛋白/α2-巨球蛋白受体是组织型纤溶酶原激活物的肝脏受体。
Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7427-31. doi: 10.1073/pnas.89.16.7427.
10
Characterization of the interaction both in vitro and in vivo of tissue-type plasminogen activator (t-PA) with rat liver cells. Effects of monoclonal antibodies to t-PA.组织型纤溶酶原激活剂（t-PA）与大鼠肝细胞在体外和体内相互作用的特性。抗t-PA单克隆抗体的作用。
Biochem J. 1992 Jun 1;284 ( Pt 2)(Pt 2):545-50. doi: 10.1042/bj2840545.
本文引用的文献
1
Fluid endocytosis by rat liver and spleen. Experiments with 125I-labelled poly(vinylpyrrolidone) in vivo.大鼠肝脏和脾脏的液体胞吞作用。体内用125I标记的聚（乙烯基吡咯烷酮）进行的实验。
Biochem J. 1980 Nov 15;192(2):613-21. doi: 10.1042/bj1920613.
2
Turnover of human extrinsic (tissue-type) plasminogen activator in rabbits.人外源性（组织型）纤溶酶原激活剂在兔体内的周转率。
Thromb Haemost. 1981 Oct;46(3):658-61.
3
Thrombolysis by human tissue plasminogen activator and urokinase in rabbits with experimental pulmonary embolus.用人组织纤溶酶原激活剂和尿激酶对实验性肺栓塞兔进行溶栓治疗。
Nature. 1981 Jun 18;291(5816):590-1. doi: 10.1038/291590a0.
4
Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture.培养的人黑色素瘤细胞分泌的纤溶酶原激活物的纯化及特性分析
J Biol Chem. 1981 Jul 10;256(13):7035-41.
5
Purification and characterization of a melanoma cell plasminogen activator.一种黑色素瘤细胞纤溶酶原激活剂的纯化与特性分析
Eur J Biochem. 1983 May 16;132(3):681-6. doi: 10.1111/j.1432-1033.1983.tb07418.x.
6
New approaches to thrombolytic therapy.溶栓治疗的新方法。
Arteriosclerosis. 1984 Nov-Dec;4(6):579-85. doi: 10.1161/01.atv.4.6.579.
7
In vivo metabolism of human tissue-type plasminogen activator.
Scand J Haematol. 1984 Jul;33(1):49-53. doi: 10.1111/j.1600-0609.1984.tb02209.x.
8
Tissue plasminogen activator: chemical and physiological aspects.组织型纤溶酶原激活剂：化学与生理学方面
Semin Thromb Hemost. 1984 Jan;10(1):6-17. doi: 10.1055/s-2007-1004403.
9
Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli.人组织型纤溶酶原激活剂cDNA在大肠杆菌中的克隆与表达。
Nature. 1983 Jan 20;301(5897):214-21. doi: 10.1038/301214a0.
10
Pharmacokinetics and systemic fibrinogenolytic effects of recombinant human tissue-type plasminogen activator (rt-PA) in humans.重组人组织型纤溶酶原激活剂（rt-PA）在人体内的药代动力学及全身纤维蛋白溶解作用
J Pharmacol Exp Ther. 1985 Nov;235(2):506-12.
Zotero 插件