Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of plasminogen activator (PAs) are present in human endometrium, and their contents vary with the different phases of menstrual cycle, i.e. high in the proliferative phase and low in the secretory phase. In the present study by immunohistochemical technique, both uPA and tPA antigens were demonstrated in the stromal and glandular cells of the endometrium. In cell culture, tPA was released only from stromal cells and uPA only from glandular cells as determined by SDS-PAGE followed by fibrin overlay technique, but PA inhibitor type-1 (PAI-1) was secreted by both stromal and glandular cells. Furthermore, secretion of PAs from endometrial cells was enhanced by adding estradiol and markedly inhibited by progesterone in a dose dependent manner, while the PAI reacted just in the opposite way. The effect of the peptide hormones, hCG, GnRH, PRL, as well as cAMP in cell culture on the secretion of PAs and PAI was similar to that of estradiol, while forskolin demonstrated definitely more stimulative effect on tPA than uPA. Taking into account of the finding of the present study, it appears that, under hormonal control, a balance between PAs and PAI in the endometrium exists. The physiological roles of the PAs and PAI in the endometrium were discussed.
 ...
PMID:[Plasminogen activators and plasminogen activator inhibitor type-1 in human endometrium]. 129 66

The immunocharacterization of a metalloproteinase isolated from rat glioma cell conditioned medium is described and confirms that the enzyme is identical to type IV collagenase. Free, active plasminogen activator (PA) and PA-PAI complexes were identified as being secreted by the same cells. Using affinity-purified metalloproteinase we demonstrate that the enzyme can be partially activated by u-PA but not by plasmin in vitro. On the basis of these findings and previous published work we propose a scheme for the proteolytic degradation of normal brain tissue during tumour invasion.
 ...
PMID:Invasion of brain tissue by primary glioma: evidence for the involvement of urokinase-type plasminogen activator as an activator of type IV collagenase. 132 8

The concentrations of tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA) and plasminogen activator inhibitor (PAI-1) have been determined in endometrial curettings obtained from 46 subfertile women during proliferative, early or late secretory phases of the menstrual cycle. t-PA activity and antigen concentrations was significantly higher (P < 0.001) in late secretory endometrium than in proliferative or early secretory endometrium. Higher concentrations of PAI-1 antigen (P < 0.05) were also noted in late secretory phase than in proliferative and early secretory endometrium. However, u-PA concentration was not significantly different and no PAI activity could be demonstrated in the menstrual phases studied. Zymography studies confirmed the presence of both t-PA and u-PA in the endometrium. Ovarian hormonal patterns may therefore influence the activity of plasminogen activators especially of t-PA in the endometrium during various phases of the menstrual cycle.
 ...
PMID:Concentration of plasminogen activators and inhibitor in the human endometrium at different phases of the menstrual cycle. 133 23

In this study, we determined the effect of 80% deacetylated chitin (DAC-80) membrane on postsurgical bleeding after visceral and parietal peritoneal abrasion. Japanese white rabbits underwent a midline laparotomy followed either by a bilateral peritoneal sidewall abrasion (4 x 4 cm) or an abrasion of liver surface (3 x 2 cm). The injured surface was then covered with a 0.2 mm thick DAC-80 membrane. On postsurgical day 2, the rabbits were sacrificed and the amounts of postsurgical bleeding was determined by quantitating the number of red blood cells recovered in 50 ml peritoneal lavage fluid. The DAC-80 membrane was found to reduce postsurgical bleeding after the abrasion of liver surface (treated with DAC-80 membrane: 2.9 +/- 0.8; control: 24.6 +/- 5.9 x 10(8) cells/peritoneal cavity, P less than 0.005). This same hemostatic activity was not observed after application in the peritoneal sidewall abrasion model. We also measured plasminogen activator activity (PA) and urokinase inhibitory (PAI) activity in the spent culture media of macrophages recovered from the postsurgical peritoneal exudate. The DAC-80 membrane reduced the PA secretion from postsurgical macrophages after liver surface abrasion (treated with DAC-80: 2.8 +/- 0.7; control: 3.9 +/- 0.9 mPU/ml). The DAC-80 membrane also showed similar effects on PA secretion after peritoneal sidewall abrasion. No significant effects were found in the secretion of PAI by postsurgical macrophages in both surgical models. These findings suggest that the DAC-80 membrane may have hemostatic activity through the modulation of fibrinolytic activity of peritoneal exudative macrophages.
 ...
PMID:The hemostatic effect of deacetylated chitin membrane on peritoneal injury in rabbit model. 139 45

Previous studies have shown that the fibrinolytic activity of peritoneum is depressed in local inflammation. We measured fibrinolytic parameters in peritoneal fluid and in plasma of 10 women with pelvic inflammatory disease (PID). Nine women, in whom laparoscopy for sterilisation was performed, served as a control group. In the peritoneal fluid of women with PID, PAI-Ag, t-PA-Ag and u-PA-Ag were many times higher than in the control group. In contrast to the antigens which may be present in inert complexes, the potentially active compounds, measured as t-PA activity and plasmin-activable scu-PA, were not significantly different in the two groups, and in none of the samples was the active enzyme tcu-PA detectable. Nevertheless, the mean peritoneal fluid TDP and FbDP concentrations were about twenty times higher in the PID group than in the control group. In plasma of PID patients, none of the parameters except u-PA-Ag differed from those in the control group. The difference between control and patient plasma u-PA-Ag was statistically significant, but too small to attach any relevance to the observation. Our data suggest that, in contrast to the classical concept of decreased fibrinolytic activity as a cause of adhesion formation, intraperitoneal fibrinolysis is enhanced in peritoneal inflammation through stimulation of the local production of t-PA and u-PA. Despite concomitant production of PAI, fibrinolysis occurs at a high rate, resulting in high levels of fibrin degradation products. Since this activated fibrinolysis does not meet the demand, therapeutic enhancement should be considered to prevent adhesions.
 ...
PMID:Peritoneal fluid and plasma fibrinolytic activity in women with pelvic inflammatory disease. 141 51

Fibrin gels form within the alveolar and interstitial compartments of the injured lung, and fibroblasts invade and facilitate organization of these transitional gels. We studied the effects of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) on fibrinolytic and procoagulant activities of human lung fibroblasts (HLF) to determine their capacity to regulate pulmonary fibrin deposition. Fibrinolytic activity of cell lysates and media (n = 6 HLF cultures) were uniformly depressed by TGF-beta or TNF-alpha. In dose and time-course studies, HLF plasminogen activator inhibitor-1 (PAI-1) was increased by TGF-beta, whereas TNF-alpha induced release of PAI-1 into the media. HLF and media urokinase concentrations were depressed by TGF-beta, whereas urokinase was unchanged or increased by TNF-alpha. Tissue plasminogen activator was mainly cell associated and unchanged by TGF-beta or TNF-alpha. HLF antiplasmin activity was not detected. Plasma recalcification times of HLF media were decreased by TNF-alpha but unchanged by TGF-beta. These studies suggest that TGF-beta and TNF-alpha impair the ability of HLF to degrade fibrin by disturbing the balance of HLF plasminogen activators and PAI and that these cytokines concurrently leave unchanged or increase the capacity of HLF to initiate fibrin formation. Cytokines likely to occur in the injured lung induce abnormalities of fibrinolysis in HLF from adults; such abnormalities favor extravascular fibrin deposition, a characteristic feature of alveolitis.
 ...
PMID:Mechanisms of fibrin formation and lysis by human lung fibroblasts: influence of TGF-beta and TNF-alpha. 141 27

Oral contraceptives caused increased fibrinogen, FVII, FX, and fibrinolysis. The latter was associated with elevated FXII and PKK, while C1-INH was decreased, ATIII and alpha 2M were unchanged; it could not be accounted for by changes in t-PA, u-PA, PAI, plasminogen, alpha 2-AP, proteins C or S. HCII and alpha 1-PI were increased and may regulate the availability of thrombin and FXIa. The increased FXII/PKK dependent fibrinolytic potential and HCII may offset any increase in thrombin generation, while alpha 1-PI limits intrinsic coagulation.
 ...
PMID:Procoagulant changes induced by oral contraceptives are balanced by an increased fibrinolytic tendency. 146 38

To characterize the activation state of monocytes during human immunodeficiency virus (HIV) infection, peripheral blood monocytes (PBMs) from patients with acquired immunodeficiency syndrome (n = 10) and from healthy controls (n = 10) were cultured for 4 days. Monocyte culture supernatant (MCS) was collected daily, and levels of urokinase (UK) inhibitor PAI-II, a product of activated monocytes, released into MCS were determined (fibrin plate assay). To examine the activation state of PBMs independently, expression of GM1 ganglioside on PBMs from patients with AIDS (n = 9), patients with AIDS-related complex (ARC) (n = 8), HIV+ asymptomatic patients (n = 6), and HIV- healthy controls (n = 11) was determined (flow cytometry; living cells in suspension). Data are expressed as percent inhibition of UK, or as percent total cells. Patients' MCS collected on days 1-4 of culture contained similar levels of PAI-II because it inhibited UK in similar fashion (70-90%). In contrast, MCS from healthy controls, collected after 2 days, had decreased ability to inhibit UK (15-50%) and thus contained lower levels of PAI-II. Monocyte activation, measured by increased expression of GM1 ganglioside on PBM surfaces, directly correlated with the progression of HIV infection into the development of AIDS, since the order of magnitude of GM1 ganglioside expression on PBMs was AIDS greater than ARC greater than HIV+ asymptomatic = healthy controls. Our data indicate that PBMs from patients with AIDS are constitutively activated and suggest that activation directly correlates with disease progression.
 ...
PMID:Constitutive production of PAI-II and increased surface expression of GM1 ganglioside by peripheral blood monocytes from patients with AIDS: evidence of monocyte activation in vivo. 152 87

The plasminogen activator (PA) activity in various cell lines is suppressed by glucocorticoids. These phenomena are attributed to either a suppression of PA biosynthesis, to an increase of PA inhibitor or to a combination of both. The regulation of urokinase (UK) production in a human pre-B cell lymphoma line, RC-K8, by dexamethasone (Dex) and phorbol myristate acetate (PMA) was investigated. RC-K8 is a cell line which is consistently producing a high molecular weight UK in the conditioned medium (Kubonishi, I., et al: Jpn. J. Cancer Res. 76, 12-15, 1985). The cells were cultured in RPMI-1640 with Dex or PMA for 1-4 days. UK activity was measured using a chromogenic substrate S-2444 and the antigen by an ELISA kit. PAI-1 and PAI-2 antigens were also measured by ELISA kits and the complex between PA and PAI was examined by SDS-PAGE fibrin-zymography. The UK secretion in RC-K8 cells was inhibited by cycloheximide and actinomycin D. PMA at 0.16-1.6 uM up-regulated the UK activity approximately two-fold, parallel with the antigen, whereas Dex at 1-10 uM decreased the UK expression approximately half. These were verified by SDS-PAGE fibrin-zymography. Neither PAI-1, PAI-2 nor PA/PAI complex was detected in the conditioned medium and in the cell lysate. These data suggest that PMA up-regulates the UK secretion without inducing PAIs and the down-regulation of the UK secretion by Dex results from the inhibition of the expression of UK itself but not from the induction of PAIs.
 ...
PMID:Down-regulation of urokinase secretion from a human lymphoma cell line RC-K8 by dexamethasone without inducing plasminogen activator inhibitors. 163 98

As cells progress through the multistep process of neoplastic transformation, they eventually acquire the property of invasive behavior. Although both plasminogen activators (PA) and their inhibitors (PAI) contribute to this process, their regulation in normal and transformed cells remains poorly defined. Because somatic cell hybrids provide useful tools for examining the transformation pathway, tumorigenic and invasive HeLa cells were fused with human normal vascular smooth muscle cells and tested for invasion-related parameters, including the expression of PA and PAI genes, and matrix degradation. Both parental cell lines produced large amounts of PAI activities with no detectable PA in either cellular or secreted form. Opposite findings were obtained with the hybrid cell lines, which demonstrated the presence of receptor-bound and secreted PA but absence of enzymatically measurable PAI activities. Both urokinase-type and tissue-type PA were found in cell-associated and secreted form in the hybrid cells. In addition, expression of the urokinase-type PA receptor gene was found in the three hybrid cells and the vascular smooth muscle cells but not in the HeLa cells. Expression of active, receptor-bound and secreted PA provided the nontumorigenic hybrid cells with the enzymatic tools to degrade extracellular proteins in a plasminogen-dependent manner. Thus, the hybrid cells lost tumorigenicity while retaining the tissue-degrading capability of HeLa cells. These hybrid cell lines should prove to be important reagents for investigating the complex regulatory control of PA and PAI gene expression.
 ...
PMID:Complex expression of the genes coding for plasminogen activators and their inhibitors in HeLa-smooth muscle cell hybrids. 163 10


1 2 3 4 5 6 7 8 9 10 Next >>