Stimulation of plasmin activity by oleic acid

Abstract

The amidolytic activity of plasmin with the chromogenic substrate H-D-valyl-L-leucyl-L-lysine p-nitroanilide (S-2251) is stimulated by oleic acid in a dose-dependent and saturable fashion. The activity of plasmin on S-2251 in the presence of oleic acid followed a sigmoidal kinetic pattern, with an almost 4-fold stimulation of activity at 60 microM-oleic acid. Half-maximal stimulation occurred at an oleic acid level of 19.5 microM. The amino acid analogue 6-aminohexanoic acid (AHA), which is known to bind to lysine-binding sites in plasmin, suppressed the stimulatory effect of oleic acid in a concentration-dependent manner; at 0.3 mM-AHA, about 70% of the oleic acid-dependent enhancement of plasmin activity was abolished. The l/v versus 1/[S] plot for plasmin changed in the presence of oleic acid from a linear to a non-linear curve, suggesting positive co-operativity. 14C-labelled oleic acid bound to plasmin, and the bound ligand was displaced by an excess of unlabelled oleic acid. Oleic acid also produced a marked (40-fold) stimulation of the plasminogen-dependent cleavage of S-2251 by urokinase. A half-maximal effect on plasminogen activation was obtained at 40 microM-oleic acid. The present findings suggest that the ability of oleic acid to stimulate plasmin activity and to enhance the conversion of plasminogen to plasmin depends on the interaction of oleic acid with specific lysine-binding sites in plasmin.

The fibrinolytic mechanism of defibrotide: effect of defibrotide on plasmin activity

“…The phenomenon is similar to that induced by other ligands which bind to LBS in the plasmin, such as aspirin [36] and oleic acid [37].…”

Indigenous enzymes in milk: A synopsis of future research requirements

“…It has been reported that plasmin can act on the MFGM (e.g., via proteolysis of butyrophilin; Montagne, Girardet, & Humbert, 1999). It has also been reported that plasmin activity and the activation of plasminogen can be stimulated by oleic acid (Higazi, Finci-Yeheskel, Samara, Aziza, & Mayer, 1992) but it is not clear if this indicates a link between proteolysis and lipolysis in milk, as these observations were not studied in that medium. Furthermore, products of lipid oxidation may influence the activity of plasmin in milk, either by reacting directly with the enzyme molecule or by modification of the casein substrate (e.g., by forming Schiff's bases).…”

Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids

“…The presence of FN-II modules allows gelatinases A and B to bind and degrade insoluble elastin, a highly hydrophobic extracellular matrix macromolecule (16,39). Binding of long-chain fatty acids to kringles was found to modulate plasmin activity toward both synthetic substrate and fibrinogen (20,21). The involvement of the FN-II modules of gelatinase A in its inhibition by fatty acids was therefore investigated.…”

“…They bind to serine proteinases such as neutrophil elastase (18,19) and plasmin (20,21) and modulate their catalytic activities. Studies by Suzuki et al (22) show that oleic acid, 18-carbon fatty acid with one double carbon bond in the cis position, partially inhibits the formation of lung metastases from subcutaneous implantation of colon carcinoma cells in athymic mice.…”