title: Heparin and heparan sulfate enhancement of the inhibitory activity of plasminogen activator inhibitor type 1 toward urokinase type plasminogen activator.
abstract: To study effects of glycosaminoglycan on the interaction between two chain urokinase type plasminogen activator (tcu-PA) (EC 3.4.21.31) and plasminogen activator inhibitor type 1 (PAI-1) the second order rate constant (k1) between high molecular weight tcu-PA and active recombinant prokaryotic PAI-1 (rpPAI-1) was determined employing a continuous method using chromogenic substrate S-2444 either in the presence or absence of various kinds of glycosaminoglycans. k1 was (5.9 +/- 1.6).10(6)/mol per s in the absence of effector molecule, and following addition of heparin (1.0 U/ml) k1 was enhanced to (3.22 +/- 0.73).10(7). A significant enhancement of k1 was also obtained by heparan sulfate (1.87 +/- 0.25).10(7). Dermatan sulfate or chondroitin sulfate did not show a significant effect on k1 although a slight decrease was obtained by mono-dextran sulfate (4.2 +/- 1.2).10(6). The intrinsic fluorescence of rpPAI-1 was shown to be slightly increased following addition of heparin (1.49 +/- 0.22%, n = 6), suggesting that heparin may enhance the inhibitory activity of PAI-1 toward tcu-PA both by a template mechanism and by a modification of PAI-1 structure.
authors.affiliation: Department of Physiology, Hamamatsu University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Urano
authors.forename: K
authors.initials: K
authors.lastname: Serizawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: T
authors.initials: T
authors.lastname: Ny
authors.forename: A
authors.initials: A
authors.lastname: Takada
mesh_terms: D002021:Buffers; D004347:Drug Interactions; D006493:Heparin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000494:pharmacology*; D007700:Kinetics; D017395:Plasminogen Activator Inhibitor 1 / Q000302:isolation & purification / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000302:isolation & purification; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
chemical_list: D002021:Buffers; D006493:Heparin; D006497:Heparan Sulfate; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D014568:Urokinase-Type Plasminogen Activator