Stimulation of plasmin activity by oleic acid.
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.
Higazi
A A
AA
Department of Clinical Biochemistry, Hadassah Medical Center, Jerusalem, Israel.
Finci-Yeheskel
Z
Z
Samara
A A
AA
Aziza
R
R
Mayer
M
M
D015119:Aminocaproic Acid / Q000494:pharmacology; D004347:Drug Interactions; D004586:Electrophoresis; D005341:Fibrinolysin / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010958:Plasminogen / Q000378:metabolism; D013268:Stimulation, Chemical; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology
D009829:Oleic Acids; D019301:Oleic Acid; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D015119:Aminocaproic Acid