Iwg. Bobbink et al., GLYCATED PROTEINS MODULATE TISSUE-PLASMINOGEN ACTIVATOR-CATALYZED PLASMINOGEN ACTIVATION, Biochemical and biophysical research communications, 240(3), 1997, pp. 595-601
Plasminogen activation by tissue-plasminogen activator (t-PA) is accel
erated by the presence of a macromolecular surface, which acts as a te
mplate that brings enzyme and substrate in close proximity. Modificati
on of lysine residues, which are important for this template function,
occurs in diabetic patients as a consequence of glycation of proteins
. In this study, we investigated the effects of glycation of fibrin an
d other proteins in t-PA-catalyzed plasmin formation. Plasminogen acti
vation on glycated fibrin(ogen) was increased compared to non-glycated
fibrin(ogen), which could fully be attributed to an increased affinit
y of t-PA for glycated fibrin(ogen). Binding of plasminogen to glycate
d fibrin was increased, but did not contribute to increased plasminoge
n activation. Both plasminogen activator inhibitor-1 (PAI-1) binding a
nd activity were increased on glycated fibrin. Induction of template f
unction in plasminogen activation was also observed on immobilized gly
cated bovine serum albumin (BSA) and human gamma-globulins (IgG). Incr
eased plasmin generation at sites of deposition of glycated proteins m
ay lead to increased extracellular matrix breakdown and thereby affect
the integrity of the endothelial monolayer. Moreover, soluble glycate
d BSA and glycated IgG call inhibit t-PA binding to immobilized glycat
ed fibrin and interfere with fibrinolysis in diabetic patients. (C) 19
97 Academic Press.