Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of oleic acid to modulate fibrinolysis was measured by following the urokinase-mediated and plasminogen-dependent cleavage of 125I-labelled fibrin clots. Oleic acid levels within the physiological range exerted a concentration-dependent inhibition of urokinase-mediated fibrinolytic activity. SDS/PAGE revealed that oleic acid enhances urokinase activity but simultaneously increases the autolytic cleavage of the newly formed low-molecular-mass subunit of plasmin. Oleic acid-induced cleavage of this subunit containing the catalytic site of plasmin was suppressed by the plasmin substrate H-D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251) and was prevented by alpha 2-antiplasmin. A concentration-dependent inhibition of the activity of purified plasmin on 125I-labelled fibrin clot was also observed; 93% and 50% inhibition was noted with 150 microM and 32 microM oleic acid respectively. Oleic acid at 200 microM also effectively displaced plasmin prebound to a polylysine-Sepharose column. Examination of the fatty acid specificity showed that a minimal chain length of 16 carbon atoms and the presence of at least one double bond, preferably in a cis configuration, were required for inhibition of the fibrinolytic activity of plasmin. Oleic acid at a concentration that produced only a minimal inhibition of plasmin activity induced a marked inhibition by palmitic acid, while palmitic acid alone is ineffective. The findings suggest that oleic acid stimulates plasminogen activation and modulates the fibrinolytic and autolytic activities of plasmin.
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PMID:Regulation of fibrinolysis by non-esterified fatty acids. 819 42

Fibrinogen (Fbg) leakage and intra-alveolar fibrin accumulation are commonly noticed in adult respiratory distress syndrome and interstitial lung diseases. Activation of the extrinsic coagulation pathway and elevation of antiplasmin- and plasminogen-activator inhibitor levels are assumed to favor alveolar clot formation and to inhibit fibrinolysis under these conditions. We investigated the influence of synthetic surfactants on the plasmic cleavage of fibrinogen in vitro. Fibrinogenolysis was quantified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with densitometric evaluation and fragment E enzyme-linked immunosorbent assay. A synthetic phospholipid mixture (PLM) (dipalmitoyl-DL-alpha-phosphatidylcholine:L-alpha-phosphatidyl-DL-gly cer ol: palmitic acid 68.5:22.5:9) caused a dose-dependent inhibition of fibrinogenolysis in a concentration range between 0.1 and 2 mg/ml. This inhibitory capacity was markedly amplified upon reconstitution of PLM with natural and recombinant surfactant protein (SP)-C as well as natural SP-B. Natural SP-A and recombinant SP-A were far less effective in this respect. In the absence of phospholipids, the hydrophobic apoproteins revealed only moderate plasmin inhibitory capacity (recombinant SP-C > natural SP-C and SP-B). Natural calf lung surfactant extract displayed comparable inhibitory capacity on plasmic Fbg cleavage as PLM. We conclude that hydrophobic surfactant material may suppress plasmin activity and thus may contribute to the finding of delayed alveolar fibrin clearance in inflammatory lung diseases with Fbg leakage.
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PMID:Apoprotein-based synthetic surfactants inhibit plasmic cleavage of fibrinogen in vitro. 836 28

Derivatives of benzisothiazolinone 1,1-dioxide (saccharin) N-acetylated with aliphatic and aromatic substituted aliphatic acyl groups were prepared. The inhibitory activity of the compounds was assayed against human leucocyte elastase (EC 3.4.21.37) and several other proteases. The IC50 values for inhibition of the human leucocyte elastase decreased with increasing length of the acyl residue, and reached a minimum value at C16 (2 microM). This phenomenon and the decrease of the inhibition by surfactants or by saturation of the enzyme with palmitic acid, indicates that in addition to acylation, hydrophobic interactions are also involved in the inhibition of this proteinase by compounds substituted with acyl groups containing at least 12 carbon atoms. The inhibitory activity of N-palmitoyl-benzisothiazolinone 1,1-dioxide (palmitoyl-saccharin) is about 14 times higher toward human leucocyte elastase than for thrombin (EC 3.4.21.5), and several hundred times, compared to porcine pancreatic elastase (EC 3.4.21.36) and to plasmin (EC 3.4.21.7). Fatty acylated saccharin derivatives were seen to bind in a saturable fashion to insoluble elastin, and decreased the susceptibility of this protein to hydrolysis by human leucocyte elastase.
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PMID:Inhibition of human leucocyte elastase by fatty acyl-benzisothiazolinone, 1,1-dioxide conjugates (fatty acyl-saccharins). 849 48