HEPARIN AND HEPARAN-SULFATE ENHANCEMENT OF THE INHIBITORY ACTIVITY OFPLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 TOWARD UROKINASE-TYPE PLASMINOGEN-ACTIVATOR
T. Urano et al., HEPARIN AND HEPARAN-SULFATE ENHANCEMENT OF THE INHIBITORY ACTIVITY OFPLASMINOGEN-ACTIVATOR INHIBITOR TYPE-1 TOWARD UROKINASE-TYPE PLASMINOGEN-ACTIVATOR, Biochimica et biophysica acta (G). General subjects, 1201(2), 1994, pp. 217-222
To study effects of glycosaminoglycan on the interaction between two c
hain urokinase type plasminogen activator (tcu-PA) (EC 3.4.21.31) and
plasminogen activator inhibitor type 1 (PAI-I) the second order rate c
onstant (k(1)) between high molecular weight tcu-PA and active recombi
nant prokaryotic PAI-1 (rpPAI-1) was determined employing a continuous
method using chromogenic substrate S-2444 either in the presence or a
bsence of various kinds of glycosaminoglycans. k(1) was (5.9 +/- 1.6)
10(6)/mol per s in the absence of effector molecule, and following add
ition of heparin (1.0 U/ml) k(1) was enhanced to (3.22 +/- 0.73).10(7)
. A significant enhancement of k(1) was also obtained by heparan sulfa
te (1.87 +/- 0.25).10(7). Dermatan sulfate or chondroitin sulfate did
not show a significant effect on k(1) although a slight decrease was o
btained by mono-dextran sulfate (4.2 +/- 1.2).10(6). The intrinsic flu
orescence of rpPAI-1 was shown to be slightly increased following addi
tion of heparin (1.49 +/- 0.22%, n = 6), suggesting that heparin may e
nhance the inhibitory activity of PAI-1 toward tcu-PA both by a templa
te mechanism and by a modification of PAI-1 structure.