HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stringer, H. A. Articles by Pannekoek, H. Search for Related Content PubMed PubMed Citation Articles by Stringer, H. A. Articles by Pannekoek, H. Social Bookmarking                      What's this?

JBC, Vol. 270, Issue 19, 11205-11208, May, 1995

The significance of fibrin binding by plasminogen activator inhibitor 1 for the mechanism of tissue-type plasminogen activator-mediated fibrinolysis

HA Stringer and H Pannekoek
Department of Biochemistry, University of Amsterdam, The Netherlands.

The specific, reversible interaction between plasminogen activator inhibitor 1 (PAI-1) and intact fibrin polymers was studied using both purified components and isolated activated platelets as a source of PAI- 1. A key reagent in these experiments is a PAI-1 mutant, having its P1 reactive center residue arginine replaced by methionine (PAI-1 R346M). The second-order association rate of PAI-1 R346M with tissue-type plasminogen activator is over 10,000-fold lower than that of wild-type PAI-1, whereas the ability of the variant to bind to fibrin is unaltered. Competition experiments demonstrated that PAI-1 R346M is equally effective as wild-type PAI-1 in displacing 125I-labeled PAI-1 from fibrin. Fibrinolysis, mediated by tissue-type plasminogen activator, is inhibited in a dose-dependent manner by purified PAI-1. The inhibition can be relieved in a dose-dependent manner by PAI-1 R346M, presumably due to displacement of wild-type PAI-1 by PAI-1 R346M. Perfusion studies, using platelet-rich clots, revealed that the incorporation of PAI-1 R346M dose dependently decreased the 50% clot lysis time. These data indicate that PAI-1 R346M displaces fibrin- bound, endogenous PAI-1 released from activated platelets. Implications to manipulate PAI-1 activity for the management of clinical complications, in particular reocclusion after thrombolytic therapy, are discussed.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. Smolarczyk, J. Boncela, J. Szymanski, A. Gils, and C. S. Cierniewski Fibrinogen Contains Cryptic PAI-1 Binding Sites That Are Exposed on Binding to Solid Surfaces or Limited Proteolysis Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2679 - 2684. [Abstract] [Full Text] [PDF]

				A. N. Butte, A. K. Houng, I.-K. Jang, and G. L. Reed {alpha}2-Antiplasmin Causes Thrombi to Resist Fibrinolysis Induced by Tissue Plasminogen Activator in Experimental Pulmonary Embolism Circulation, April 1, 1997; 95(7): 1886 - 1891. [Abstract] [Full Text]

				I. M. Lang and R. R. Schleef Calcium-dependent Stabilization of Type I Plasminogen Activator Inhibitor within Platelet alpha-Granules J. Biol. Chem., February 2, 1996; 271(5): 2754 - 2761. [Abstract] [Full Text] [PDF]

				J. Boncela, I. Papiewska, I. Fijalkowska, B. Walkowiak, and C. S. Cierniewski Acute Phase Protein alpha 1-Acid Glycoprotein Interacts with Plasminogen Activator Inhibitor Type 1 and Stabilizes Its Inhibitory Activity J. Biol. Chem., September 14, 2001; 276(38): 35305 - 35311. [Abstract] [Full Text] [PDF]

				T. J. Podor, C. B. Peterson, D. A. Lawrence, S. Stefansson, S. G. Shaughnessy, D. M. Foulon, M. Butcher, and J. I. Weitz Type 1 Plasminogen Activator Inhibitor Binds to Fibrin via Vitronectin J. Biol. Chem., June 23, 2000; 275(26): 19788 - 19794. [Abstract] [Full Text] [PDF]