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)

Since serine protease in involved in histamine release from mast cells, we attempted to prepare new protease inhibitors, trans-4-(guanidinomethyl)cyclohexanecarboxylic acid (GmcHX-CO2H) esters, and examined their inhibitory effects on typical serine proteases and on histamine release induced by compound 48/80. We compared their effects with those of trans-4-(aminomethyl)cyclohexanecarboxylic acid (AmcHx-CO2H) esters. AmcHxCO2H and GmcHxCO2H esters inhibited the esterolytic activity of trypsin, but GmcHx-CO2H esters had little or no inhibitory effect on caseinolytic activity whereas AmcHxCO2H esters strongly inhibited the latter. AmcHCO2H esters strongly inhibited plasmin but had no effect on chymotrypsin. GmcHxCO2H esters strongly inhibited the esterolytic activity of chymotrypsin, but had no effect on chymotrypsin-induced caseinolysis. Both GmcHxCO2H an AmcHxCO2H esters inhibited urokinase. Of the esters of AmcHxCO2H and GmcHxCO2H tested, only GmcHxCO2H p-tert-butylphenyl ester (GmcHxCOOPhBut) at low concentration (27 microM) strongly inhibited histamine release from rat mast cells induced by compound 48/80. GmcHxCOOPhBut was effective in preventing active systemic anaphylaxis and passively sensitized guinea pigs. Its effectiveness in preventing anaphylactic phenomena might be due to its strong inhibitory effects on histamine release from mast cells.
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PMID:Inhibitory effects of aryl trans-4-(aminomethyl)cyclohexanecarboxylate and aryl trans-4-(guanidinomethyl)cyclohexanecarboxylate on serine proteases, and their antiallergic effects. 617 16

Stimulation of Lys-plasminogen (Lys-Pg) and Glu-plasminogen (Glu-Pg) activation under the action of staphylokinase and Glu-Pg activation under the action of preformed plasmin-staphylokinase activator complex (Pm-STA) by low concentrations and inhibition by high concentrations of omega-amino acids (>90-140 mM) were found. Maximal stimulation of the activation was observed at concentrations of L-lysine, 6-aminohexanoic acid (6-AHA), and trans-(4-aminomethyl)cyclohexanecarboxylic acid 8.0, 2.0, and 0.8 mM, respectively. In contrast, the Lys-Pg activation rate by Pm-STA complex sharply decreased when concentrations of omega-amino acids exceeded the above-mentioned values. It was found that formation of Pm-STA complex from a mixture of equimolar concentrations of staphylokinase and Glu-Pg or Lys-Pg is stimulated by low concentrations (maximal at 10 mM) of 6-AHA. Negligible increase in the specific activities of plasmin and Pm-STA complex was detected at higher concentrations of 6-AHA (to maximal at 70 and 50 mM, respectively). Inhibitory effects of omega-amino acids on the rate of fibrinolysis induced by staphylokinase, Pm-STA complex, and plasmin were compared. It was found that inhibition of staphylokinase-induced fibrinolysis by omega-amino acids includes blocking of the reactions of Pm-STA complex formation, plasminogen activation by this complex, and lysis of fibrin by forming plasmin as a result of displacement of plasminogen and plasmin from the fibrin surface. Thus, the slow stage of Pm-STA complex formation plays an important role in the mechanism of action of omega-amino acids on Glu-Pg activation and fibrinolysis induced by staphylokinase. In addition to alpha-->beta change of Glu-Pg conformation, stimulation of Pm-STA complex formation leads to increase in Glu-Pg activation rate in the presence of low concentrations of omega-amino acids. Inhibition of Pm-STA complex formation on fibrin surface by omega-amino acids is responsible for appearance of long lag phases on curves of fibrinolysis induced by staphylokinase.
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PMID:Mechanism of action of omega-amino acids on plasminogen activation and fibrinolysis induced by staphylokinase. 1768 Jul 62

We have previously shown that intracerebroventricular (i.c.v.) administration of cysteine protease inhibitors suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of dynorphin degradation (see (Tan-No, K., Sato, T., Shimoda, M., Nakagawasai, O., Niijima, F., Kawamura, S., Furuta, S., Sato, T., Satoh, S., Silberring, J., Terenius, L., Tadano, T., 2010. Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice. Neuropeptides 44, 279-283)). In the present study, we examined the effect of phenylmethanesulfonyl fluoride (PMSF), a serine protease inhibitor, on naloxone-precipitated withdrawal jumping in morphine-dependent mice. The doses of morphine (mg/kg per injection) were subcutaneously given twice daily for 2 days [day 1 (30) and day 2 (60)]. On day 3, naloxone (8 mg/kg) was intraperitoneally administered 3h after the final injection of morphine (60 mg/kg), and the number of jumps was immediately recorded for 20 min. Naloxone-precipitated withdrawal jumping was significantly suppressed by i.c.v. administration of PMSF (4 nmol), given 5 min before each morphine treatment during the induction phase, with none given on the test day. The expression of tissue plasminogen activator (tPA), a serine protease that converts plasminogen to plasmin, in the prefrontal cortex was significantly increased in morphine-dependent and -withdrawal mice, as compared with saline-treated mice. Moreover, trans-4-(aminomethyl)-cyclohexanecarboxylic acid (300 pmol), an antiplasmin agent, and (Tyr(1))-thrombin receptor activating peptide 7 (0.45 and 2 nmol), an antagonist of protease activated receptor-1 (PAR-1), significantly suppressed naloxone-precipitated withdrawal jumping. The present results suggest that PMSF suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of activities of tPA and plasmin belonging to the serine proteases family, which subsequently activates PAR-1.
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PMID:Phenylmethanesulfonyl fluoride, a serine protease inhibitor, suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice. 2329 May 39

To date, there have been no treatments developed to ameliorate nonmelanoma skin cancer induced by long-term exposure to ultraviolet A (UVA) irradiation. In this study, we examined the effects of tranexamic acid (trans-4-aminomethyl cyclohexanecarboxylic acid) on long-term UVA-induced skin cancer. We exposed the dorsal skin of male hairless mice to UVA at a dose of 110 kJ m-2 using an FL20SBLB-A lamp three times weekly for 15 weeks after application of 7,12-dimethylbenz [a] anthracene (DMBA). During the experimental period, the mice were administered tranexamic acid (750 mg kg-1 day-1 ) three times weekly. We found that cancer development was ameliorated by administration of tranexamic acid. Furthermore, tranexamic acid treatment was observed to suppress increases in the plasma levels of matrix metalloproteinase-9 and interleukin (IL)-6, and skin expression of plasmin, CC chemokine 2, macrophages, signal transducer and activator of transcription (STAT)3, cyclin D and vascular endothelial growth factor (VEGF)-A that occurred in mice subjected to long-term UVA irradiation. These results indicated that the nonmelanoma skin cancer induced by DMBA+UVA long-term irradiation is ameliorated by tranexamic acid through regulation of the plasmin/macrophage/IL-6/STAT3/cyclin D signal transmission pathway. In addition, this ameliorative effect against skin cancer may be mediated via inhibition of the IL-6-induced expression of VEGF-A.
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PMID:Tranexamic Acid Ameliorates Nonmelanoma Skin Cancer Induced by Long-term Ultraviolet A Irradiation. 3026 77