RSS-Feed abonnieren
DOI: 10.1055/s-0038-1646895
Stability of Plasminogen Activator Inhibitor 1 (PAI-1)
Publikationsverlauf
Received 30. Januar 1989
Accepted after revision 28. April 1989
Publikationsdatum:
30. Juni 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/198902/lookinside/thumbnails/10-1055-s-0038-1646895-1.jpg)
Summary
The stability of PAI-activity has been studied at different conditions. The inactivation followed first order kinetics. Lowering the temperature and decreasing the pH both, increased the stability of PAI-1 dramatically. Addition of the PAI-1 binding protein, vitronectin, to reactivated PAI-1, about doubled the halflife of PAI-1 at all conditions studied. In the presence of chloramine T, the inactivation of reactivated PAI-1 was very rapid. In this case the protective effect of purified vitronectin, human plasma or fetal calf serum, but not of bovine serum albumin, was pronounced. The stability of the spontaneously active high Mr form of PAI-1 (partially purified or in plasma), constituting a complex between PAI-1 and vitronectin, was quite similar to reactivated PAI-1 in the presence of vitronectin. Addition of pure vitronectin, human plasma or fetal calf serum to such material had no further stabilizing effect. Reactivated PAI-1, which was inactivated by incubation at physiological conditions could again be fully reactivated, in contrast to chloramine T-oxidized PAI-1, which was irreversibly inactivated.
-
References
- 1 Wiman B, Ljungberg B, Chmielewska J, Urden G, Blombäck M, Johnsson H. The role of the fibrinolytic system in deep vein thrombosis. J Lab Clin Med 1985; 105: 265-270
- 2 Nilsson IM, Ljungner H, Tengbom L. Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: Low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor. Br Med J 1985; 290: 1453-1455
- 3 Hamsten A, Wiman B, de Faire U, Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminogen activator in young survivors of myocardial infarction. N Engl J Med 1985; 313: 1557-1563
- 4 Hamsten A, Walldius G, Szamosi A, Blombäck M, de Faire U, Dahlén G, Wiman B. Plasminogen activator inhibitor in plasma: Risk factor for recurrent myocardial infarction. Lancet 1987; ii: 3-9
- 5 Urdén G, Hamsten A, Wiman B. Comparison of plasminogen activator inhibitor activity and antigen in plasma samples. Clin Chim Acta 1987; 169: 189-196
- 6 Sprengers ED, Princen HM G, Kooistra T, van Hinsbergh VW M. Inhibition of plasminogen activators by conditioned medium of human hepatocytes and hepatoma cell line Hep G2. J Lab Clin Med 1985; 105: 751-758
- 7 Chmielewska J, Carlsson T, Urdén G, Wiman B. On the relationship between different molecular forms of the fast inhibitor of tissue plasminogen activator. Fibrinolysis 1987; 1: 67-73
- 8 Levin EG. Quantitation and properties of the active and latent plasminogen activator inhibitors in cultures of human endothelial cells. Blood 1986; 67: 1309-1313
- 9 Loskutoff DJ, van Mourik JA, Erickson LA, Lawrence D. Detection of an unusually stable fibrinolytic inhibitor produced by bovine endothelial cells. Proc Natl Acad Sci 1983; 80: 2956-2960
- 10 Nielsen LS, Andreasen PA, Grøndahl-Hansen J, Huan JY, Kristensen P, Danø K. Monoclonal antibodies to human 54,000 molecular weight plasminogen activator inhibitor from fibrosarcoma cells - inhibitor neutralization and one-step affinity purification. Tromb Haemostas 1986; 55: 206-212
- 11 van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. J Biol Chem 1984; 259: 14914-14921
- 12 Ericksson LA, Hekman CM, Loskutoff DJ. The primary plasminogen-activator inhibitors in endothelial cells, platelets, serum and plasma are immunologically related. Proc Nactl Acad Sci 1985; 82: 8710-8714
- 13 Wiman B, Lindahl T, Almqvist Å. Evidence for a discrete binding protein of plasminogen activator inhibitor in plasma. Thromb Haemostas 1988; 59: 392-395
- 14 Wiman B, Chmielewska J, Rånby M. Inactivation of tissue plasminogen activator in plasma. Demonstration of a complex with a new rapid inhibitor. J Biol Chem 1984; 259: 3644-3647
- 15 Wiman B, Almquist Å, Sigurdardottir O, Lindahl T. Plasminogen activator inhibitor 1 (PAI) is bound to vitronectin in plasma. FEBS Lett 1988; 242: 125-128
- 16 Declerck PJ, de Mol M, Baudner S, Paques EP, Preissner KT, Miiller-Berghaus G, Collen D. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. Identification as a multimeric form of S protein (vitronectin). J Biol Chem 1988; 263: 15454-15461
- 17 Lindahl T, Wiman B. Purification of high and low Mr plasminogen activator inhibitor 1 (PAI) from fibrosarcoma cell-line HT1080 conditioned medium. Biochim Biophys Acta 1989; 994: 253-257
- 18 Dahlbäck B, Podack ER. Characterization of human S protein, an inhibitor of the membrane attack complex of complement. Demonstration of a free reactive thiol group. Biochemistry 1985; 24: 2368-2374
- 19 Chmielewska J, Wiman B. Determination of tissue plasminogen activator and its “fast” inhibitor in plasma. Clin Chem 1986; 32: 482-485
- 20 Hekman CM, Loskutoff DJ. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 1985; 260: 11581-11587
- 21 Kooistra T, Sprengers ED, van Hinsbergh VW M. Rapid inactivation of the plasminogen-activator inhibitor upon secretion from human endothelial cells. Biochem J 1986; 239: 497-503
- 22 Mimuro J, Schleef RR, Loskutoff DJ. Extracellular matrix of cultured bovine aortic endothelial cells contains functionally active type 1 plasminogen activator inhibitor. Blood 1987; 70: 721-728
- 23 Wiman B. Demonstration of a plasminogen activator inhibitor (PAI) binding protein in plasma/serum. XII Congr Int Soc Hematol. Milan, Italy: 1988. Abstract SYM-M-2-3 3
- 24 Lawrence DA, Loskutoff DJ. Inactivation of plasminogen activator inhibitor by oxidants. Biochemistry 1986; 25: 6351-6355
- 25 Chmielewska J, Rånby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res 1983; 31: 427-436
- 26 Knudsen BS, Harpel PC, Nachman RL. Plasminogen activator inhibitor is associated with the extracellular matrix of cultured bovine smooth muscle cell. J Clin Invest 1987; 80: 1082-1089
- 27 Ruoslahti E, Shintaro S, Hayman EG, Charles RI, Pierschbacher MD. Purification and characterization of vitronectin. Methods Enzymol 1987; 144: 430-437