Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of HTC rat hepatoma cells with the synthetic glucocorticoid dexamethasone rapidly inhibits plasminogen activator (PA) activity and reveals the presence of a specific PA inhibitor (PAI-1). To determine whether the hormonal inhibition of PA activity reflects a decrease in the amount of PA or an increased amount of the inhibitor, or both, we have assayed PA and PAI-1 immunologically. HTC PA was determined to be entirely of the tissue type (tPA), and both free and complexed antigen was quantified by a RIA using rabbit antirat tPA, with rat insulinoma tPA as tracer and standard. PAI-1 was quantified by a Western blot assay using rabbit anti-HTC PAI-1 antibody and purified HTC PAI-1 as standard. Under conditions in which dexamethasone inhibited PA activity by 90%, there was no decrease in the cellular content of tPA antigen. Paradoxically, dexamethasone increased tPA antigen approximately 1.5-fold. Under these same conditions, dexamethasone increased PAI-1 antigen 4- to 5-fold. We conclude that the glucocorticoid inhibition of tPA activity in HTC cells is not secondary to a decrease in the amount of tPA but is secondary to the induction of a specific PA inhibitor.
 ...
PMID:Dexamethasone inhibition of tissue-type plasminogen activator (tPA) activity: paradoxical induction of both tPA antigen and plasminogen activator inhibitor. 313 52

The total plasminogen activator (PA) activity and the activities of urokinase type (uPA) and tissue type (tPA) plasminogen activators were measured in 43 primary human breast cancer homogenates. The majority of the PA activity was found in the 100,000 X g crude membrane pellets (log mean of 490 milli-IU/mg of protein, +1169, -346), and little PA activity was present in the cytosolic supernatant (log mean of 19 milli-IU/mg of protein, +168, -17). The activities of total PA and of each type of PA were compared to the estrogen receptor (ER) and epidermal growth factor receptor (EGFR) status of the tumors and to their histological grade. Total PA activity and uPA activity were not significantly different in any group of tumors stratified according to receptor status or tumor grade. Tissue type PA levels, however, were significantly lower in ER-negative compared with ER-positive tumors and in EGFR-positive compared with EGFR-negative tumors (P less than 0.01 and less than 0.05, respectively). The tPA activity was also related to grade, decreasing with worsening differentiation (P = 0.04). The ER-negative tumors were further stratified into EGFR-positive and -negative subgroups. Only the ER-negative tumors possessing EGFR had significantly lower tPA levels than the ER-positive tumors (P less than 0.01). Low tPA levels in breast cancers were, therefore, associated with ER negativity combined with EGFR positivity and may be an indication of poorer differentiation and prognosis.
 ...
PMID:Relationship of membrane-bound tissue type and urokinase type plasminogen activators in human breast cancers to estrogen and epidermal growth factor receptors. 314 Oct 47

Since plasminogen is the proenzyme of plasmin most acquired defects of plasminogen are associated with situations with an increased fibrinolytic activity. Congenital defects also have been described both such associated with thrombotic disease and such that are not. An increased fibrinolytic activity leading to an acquired plasminogen defect is seen 1) in situations complicated with a free proteolytic activity most often involving both the fibrinolytic and the coagulation systems, 2) as a result of locally increased fibrinolytic activity (angiomas), 3) during thrombolytic therapy using plasminogen activators (SK, UK, tPA). A congenital plasminogen defect characterized by 1) a low protein level as well as one with 2) a normal plasminogen protein level in plasma but a defect activation pattern has been reported. Plasminogen can be determined immunochemically, a method which does not differentiate between functionally active plasminogen/plasmin and complexes between these proteins and inhibitors. Plasminogen activity is measured in a chromogenic method using the chromogenic substrate S2251 (Kabi Diagnostica, Stockholm). In this latter method SK is used as a plasminogen activator and the total plasmin formed is measured amidolytically. Using both the immunochemical and the amidolytical methods it has been possible to identify congenital plasminogen defects characterized by a defective activation of plasminogen into plasmin, a defect that has been associated with thromboembolic disease. Another congenital plasminogen defect seems to be caused by a decreased synthesis of a normal plasminogen molecule. Such a defect may not be associated with thrombotic disease. In situations complicated with an increased fibrinolytic activity, decreased plasminogen levels (in both types of assay) are of diagnostic help. Values down to below 50% or even lower may be seen.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Characterizing hereditary and acquired defects of plasminogen. 328 Apr 27

Endothelial cell-derived proteases can be classified according to their physiological role. The proteases involved in extracellular matrix degradation are important in endothelial cell migration and thereby in angiogenesis. They include the urokinase-type plasminogen activator (uPA) and the metalloproteases, collagenases, gelatinases and stromelysin. uPA secreted from endothelial cells remains associated with the cell membrane, on specific receptors localized in the vicinity of the receptors for plasminogen. This favours the local activation of plasminogen into plasmin. Plasmin, generated on the cell surface, is fully active as it is not inhibited by alpha 2-antiplasmin. Plasmin acts directly by degrading some components of the extracellular matrix and indirectly by activating the prometalloproteases. Secretion of PAI by migrating cells is generally stimulated by the same factors that induce uPA secretion, limiting the degradation of the matrix to the pericellular path. The degradation of the fibrin clot involves the tissue-type plasminogen activator tPA, which like the uPA activates plasminogen to plasmin. This system is also regulated by two different mechanisms. On the one hand, fibrin itself favours its own degradation by formation of a ternary complex, fibrin-plasminogen-tPA, in which the affinity of tPA for plasminogen is markedly increased, as compared to the affinity of unbound tPA. In addition, plasmin generated on the clot is protected from inhibition by alpha 2-antiplasmin. On the other hand, as for uPA, tPA is inhibited by PAI-1. The importance of the regulation of this system is illustrated by the thrombotic risk observed when there is either a decrease in tPA or an increase in PAI-1, and inversely by haemorrhages in the case of increase in tPA.
 ...
PMID:Endothelial cell proteases: physiological role and regulation. 751 36

Cultured keratinocytes resemble migrating keratinocytes under conditions of reepithelialization during wound healing. Such keratinocytes express urokinase-type plasminogen activator (uPA) and its specific receptor (uPA receptor). Receptor-bound uPA activates plasminogen, thus providing plasmin for pericellular proteolysis. uPA is regulated by the plasminogen activator inhibitors PAI-1 and PAI-2. As indicated by immunohistology, neither uPA nor uPA receptor is expressed in normal epidermis. Thus, the down-regulation of uPA and uPA-receptor expression in keratinocytes appears to be an important event in epidermal healing and restoration of a normal epidermal tissue architecture. We have addressed this matter by using a culture and differentiation system for keratinocytes in vitro. Keratinocytes were grown in organotypic cocultures for 4, 7, and 14 days. Frozen sections were analyzed with indirect immunofluorescence staining and overlay zymography, the latter detecting activity of plasminogen activators. While tPA and PAI-1 stainings were consistently negative over the entire observation period, uPA and uPA receptor were expressed by basal keratinocytes at Days 4 and 7, but not at Day 14. Accordingly, overlay zymography revealed uPA activity at Days 4 and 7. PAI-2 was found throughout the entire observation period, but with varying distribution: at Days 4 and 7 all suprabasal keratinocytes stained positive for PAI-2. At Day 14, PAI-2-specific stainings were confined to the uppermost cells of the stratum spinosum. Our data demonstrate that uPA and uPA receptor, which are up-regulated in cultured keratinocytes, are down-regulated upon restoration of an epidermis-like structure. The distribution of PAI-2 varied over the observation period and at Day 14 resembled the distribution of PAI-2 in normal epidermis. Taken together, keratinocytes in organotypic coculture behave like keratinocytes in healing wounds in vivo with respect to the expression of the plasminogen activator system.
 ...
PMID:Differential expression of urokinase-type plasminogen activator (uPA), its receptor (uPA-R), and inhibitor type-2 (PAI-2) during differentiation of keratinocytes in an organotypic coculture system. 755 51

The distributions of urokinase and tissue plasminogen activators (uPA, tPA), uPA receptor (uPAR), and plasminogen activator inhibitors (PAI-1, PAI-2) were studied immunohistochemically in two subsets of colorectal adenocarcinomas with low and high aggressiveness, respectively: nine Dukes' stage A tumors with additional other good prognostic markers and 13 Duke's stage C tumors with also other poor prognostic markers (referred to as Dukes' stage A and Dukes' stage C tumors). The results showed that these components of the tissue destructive plasminogen activation system were accumulated at the invading front of the tumors. Both tumor groups showed accumulations of uPA, uPAR, and PAI-1 at the tumor-host interface compared with the location within the tumor epithelium and the adjacent normal mucosa and muscularis propria (all P < .05). However, the uPA level at the tumor-host interface in the Dukes' stage C tumors was twice the level in the Dukes' stage A tumors (P < .05). The uPAR level was also significantly higher in the Dukes' stage C tumors (P < .05), whereas the PAI-1 level was not significantly higher. This may indicate that uPA in more aggressive tumors exceeds the inhibitory capacity represented by PAIs, resulting in enhanced tissue destructive potential that promotes tumor invasion. uPA and uPAR antigen levels and the uPA/PAI-1 ratio at the tumor-host interface appeared to be related to tumor aggressiveness in colorectal cancer.
 ...
PMID:Antigen levels of urokinase plasminogen activator and its receptor at the tumor-host interface of colorectal adenocarcinomas are related to tumor aggressiveness. 755 47

Four group of age- and sex-matched patients were studied: 1. nondiabetic subjects (n = 20) with a body mass index (BMI) < 25 Kg/m2 (lean control subjects); 2. obese non diabetic subjects (n = 22) with a BMI > 30 Kg/m2 (obese control subjects); 3. lean NIDDM subjects (n = 22); and 4. obese NIDDM subjects (n = 24). We determined: total cholesterol, triglycerides, HDL-cholesterol, blood glucose, Apolipoproteins A1 and B, insulin, Lp(a), Factor VII, fibrinogen, plasminogen, t-PA(Ag) pre and post venous occlusion (VO) and PAI activity pre and post VO. In addition to metabolic abnormalities obese non diabetic subjects and lean and obese NIDDM patients displayed significantly higher levels of fibrinogen, Factor VII, plasminogen, PAI pre and post VO and tPA(Ag) pre VO and significantly lower levels of t-PA(Ag) post VO. Our findings demonstrate an impairment of the haemostatic and fibrinolytic mechanisms which may be a key role in the pathogenesis of atherosclerotic vascular complications in obesity and in NIDDM.
 ...
PMID:Blood coagulation and fibrinolysis in obese NIDDM patients. 764 83

A one-step enzyme immunoassay (EIA) has been developed for plasminogen activator inhibitor-1 (PAI-1) antigen. The assay is based on polyclonal antibodies, which were found to be slightly more reactive with tissue-type plasminogen activator (t-PA)/PAI-1 complexes and latent PAI-1 than with active PAI-1. To correct this, active PAI-1 is converted to t-PA/PAI-1 complexes. Latent PAI-1 and tPA/PAI-1 complexes were equally reactive. The EIA is specific (PAI-2 and PAI-3 are not detected), precise (CVs range from 1.8% to 11.1%, depending on the PAI-1 concentration), fast (assay time less than 3 h), and easy to perform. It is compatible with the use of Stabilyte plasma. The assay is calibrated against the putative international standard of the National Institute of Biological Standards and Control (NIBSC; lot 87/512). The normal ranges found with this EIA were 13.2-88 ng/ml; one apparently normal donor had a value of 100 ng/ml.
 ...
PMID:A one-step enzyme immunoassay for total plasminogen activator inhibitor-1 antigen in human plasma. 765 40

The human colon carcinoma cell lines Co112 and Co115 are both invasive in nude mice following intraperitoneal implantation. Co115 cells only exhibit metastasis capacity under this condition. Characterization of the plasminogen activation system demonstrates that Co112 cells express the urinary-type plasminogen activator (uPA) and Co115 cells the tissue-type (tPA), exclusively. Immunocytochemical analyses revealed that the in vitro plasminogen-dependent lysis of exogenous basement membrane laminin induced by Co112 cells displayed a gradient-like pattern, whereas, in the case of Co115 cells, it was sharply confined to the pericellular area. Double-labeling experiments showed that uPA on Co112 and tPA on Co115 cells are cell-surface-associated constituents. The cellular distribution of laminin expressed by tumor cells themselves appears to be distributed homogeneously in the cytoplasm of both cell types. We suggest that the extracellular matrix degradation induced by tumor cell surface-associated plasmin implies two different mechanisms which are specifically related to uPA or to tPA, both contributing to matrix degradation and malignant invasion.
 ...
PMID:Laminin degradation by human colon carcinoma cells: a role for urinary and tissue plasminogen activators. 765 15

Altered coronary artery expression of plasminogen activator (PA) system components may predispose to thrombosis and modulate the vascular response to injury. By immunohistochemistry, we studied the expression of PAs (tPA and uPA), their major physiological inhibitor (PAI-1), and a receptor for uPA (uPAR) in human coronary arteries with either pure fibrointimal proliferation (n = 15) or developed atherosclerotic plaques (n = 10). Overall, the degree of staining showed the following rank order: PAI-1 > tPA > uPAR > uPA. A similar pattern was seen in two normal coronary arteries. There were no significant differences in the extent of staining in any vascular compartment between atherosclerotic arteries and those with only fibrointimal proliferation. However, the ratio of intimal to medial expression of tPA (P = .001) and uPAR (P = .004) was significantly increased in atherosclerotic arteries, with a similar trend for uPA (P = .069) but not for PAI-1 (P = .73). Four of 10 atherosclerotic arteries had higher uPAR expression in the intima than in the media, whereas none of the 15 arteries with only fibrointimal proliferation had this pattern (P < .01). Dual labeling studies demonstrated colocalization of all four PA system components in endothelial cells, smooth muscle cells, and macrophages, with a predominance of PAI-1. Thus, coronary arteries with a wide range of vascular pathology express an abundance of antifibrinolytic potential with enhanced local expression of profibrinolytic proteins, mainly within atherosclerotic plaques.
 ...
PMID:Plasminogen activator system in human coronary atherosclerosis. 767 Sep 59


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