Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PLASMINOGEN”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,783 records · Page 99Linked to original sources
PubMed2000

Endoluminal arterial injury in plasminogen-deficient mice.

BACKGROUND: Vascular remodeling following arterial injury is characterized by an initial inflammatory reaction. Prior experiments using peritoneal inflammatory models have shown that the plasminogen system plays a role in the intensity of the inflammatory response. This study was undertaken to test the hypothesis that an absence of plasminogen would lead to a decrease in vascular remodeling. METHODS: A left carotid artery injury was created with a flexible guidewire in both wild-type [Plg(+/+)] and plasminogen deficient [Plg(-/-)] mice. The right carotid artery was uninjured and used as a control. Three weeks postinjury, the mice were sacrificed and perfusion fixed, and the bilateral carotid arteries were sectioned for histological examination and collection of morphometric data. RESULTS: After arterial injury, electron microscopy of the acutely injured artery revealed that the endothelium was denuded, that there were breaks in the internal elastic membrane, and that there was disruption of the medial layer of smooth muscle cells. The intimal and medial areas were significantly increased between the uninjured and injured carotid arteries of both Plg(+/+) (+80% intimal, +41% medial, P < 0. 05) and Plg(-/-) [+48% intimal, +24% medial, P < 0.05) mice. However, although there was a significant increase in the adventitial area of Plg(+/+) mice (+18%, P < 0.05), there was no difference in Plg(-/-) mice (-6%). Interestingly, even after 3 weeks, four of six injured arteries in Plg(-/-) mice had persistent thrombus within the medial layer, whereas this was not found in any of the nine Plg(+/+) mouse arteries. DISCUSSION: Plasminogen deficiency inhibited the increase in adventitial area seen after injury in Plg(+/+) mice, but not the increase in intimal or medial areas. Not surprisingly, plasminogen-deficient mice also demonstrated a severe alteration in intramural thrombus clearance. Thus, specific aspects of the vascular remodeling response are dependent on plasminogen.

Animals↗
PubMed2000

Modes of evolution in the protease and kringle domains of the plasminogen-prothrombin family.

Phylogenetic analysis of protease domains of the vertebrate plasminogen-prothrombin family revealed two major subfamilies: (1) a subfamily containing macrophage-stimulating protein (MSP), hepatocyte growth factor (HGF), plasminogen, and apolipoprotein(a) (APOA); and (2) a subfamily containing prothrombin, HGF activator, and plasminogen activators. There was evidence that these two subfamilies diverged prior to the divergence of amphibians and amniotes. The phylogeny indicated a close relationship of APOA from the European hedgehog, rhesus monkey, and human with plasminogen. Phylogenetic analysis of repeated kringle domains supported the hypothesis that APOA evolved independently in hedgehog and primates through numerous duplications of different kringle domains of the ancestral plasminogen. Phylogenies of kringle domains revealed two modes of evolution: (1) a conservative mode, whereby duplication of kringle domains occurred prior to cladogenesis and the same kringle structure has been maintained in different lineages (exemplified by plasminogen and prothrombin); and (2) a concerted mode, whereby kringle domains have duplicated since cladogenesis and thus orthologous relationships do not exist between kringles of different lineages (exemplified by APOA).

Animals↗
PubMedDate not supplied

Secretion of plasminogen activators by human colorectal and gastric tumor explants.

Conditioned media from explants of human colorectal and gastric tumors in short-term organ culture were analysed for plasminogen activator activity, activity toward the synthetic urokinase substrate, Spectrozyme-UK, and for the presence of urokinase antigen using monospecific goat antibody, by enzyme-linked immunosorbent assay. Comparisons were made between primary tumors, adjacent normal mucosa and metastatic lesions. These analyses were carried out on unfractionated culture fluids and on fractions obtained by fast protein liquid chromatography separation using Superose 6 gels. Plasminogen activator activity, tested by azocaseinolysis in the presence of added plasminogen, was restricted to peaks of 55 kD and 155 kD. These were of the urokinase type as shown by specific immunoinhibition and by absorption by an antiurokinase antibody-Affigel 10 column. Spectrozyme-UK, in addition to these peaks, detected a series of higher molecular weight activities, the largest of which appeared in the void volume, and were therefore of greater than 10(6) molecular weight. These activities were greatly increased by inclusion of trace plasmin indicating that these components were mostly in their proenzyme forms. The characteristics of these very large enzymes were similar to those isolated earlier from a human lung cancer cell line. Comparison of the primary and metastatic tumors confirmed earlier observations showing that urokinase secretion by the metastatic tumors was greatly reduced in comparison with the primary tumors: in the colon carcinomas it was 10 per cent of the value for the primary, in the gastric tumors 3 per cent, whether means or medians were compared (P less than 0.0001). This large difference was characteristic only of plasminogen activator secretion assayable by azocaseinolysis; activities toward Spectrozyme-UK, and antigen reacting with anti-urokinase antibody, were considerably less different in the two groups. In individual tissues, no correlation was found between the amount of extractable plasminogen activator and amounts secreted, or between the latter and the amount of lactic acid released. It is postulated that the greatly reduced plasminogen activator secretion by explants of metastatic tumors may be a phenotypic characteristic of distinct advantage for cancer cells destined to initiate metastatic foci, and may contribute to the ability of circulating cancer cells to lodge in the blood vessels of the target organ.

Chromatography, Liquid↗
PubMed1990

Secretion of plasminogen activator inhibitor by normal rat pleural leukocytes in culture.

The normal balance between coagulation and fibrinolysis in the pleural cavity is poorly understood despite the critical role of the pleura in the movement of the lungs. To determine the fibrinolytic activity and the interaction between plasminogen activators and their inhibitors in the normal pleural space, we tested normal rat pleural leukocytes, principally macrophages and mast cells, and their supernatants, for activity in an [125I]fibrin degradation assay. It was found that pleural leukocytes did not release plasminogen activator, but the leukocytes and their supernatants inhibited the plasminogen-dependent fibrinolysis caused by both alveolar leukocytes and mesothelial cells. Further experiments demonstrated that pleural leukocytes produce a protein inhibitor primarily against urokinase-induced fibrinolysis in culture and that macrophages are the main source of the inhibitor. The lysate of mast cell-enriched population exhibited high plasminogen activator activity while no such activity could be determined in macrophage-enriched lysate. These data show that normal rat pleural leukocytes contain plasminogen activator inside the cells and synthesize a urokinase-type plasminogen activator inhibitor in culture that may be important in the fibrinolysis/coagulation balance in the pleural space.

Animals↗
PubMed2002

Interaction of different Leishmania mexicana morphotypes with plasminogen.

The interaction of plasminogen with Leishmania mexicana promastigotes was found, using immunoperoxidase assays, to occur with a specific morphotype. In in vitro cultured promastigotes, the morphotype that possessed the plasminogen binding capacity had round to ovoid cell bodies. In contrast, neither slender nor metacyclic promastigotes showed this property. In vivo plasminogen immunofluorescence assays showed deposits of plasminogen exclusively on the cell surface of promastigotes. This was observed as intense patches spread around the cell, with higher intensities towards the flagellar pocket. Plasminogen binding capacity detected by plasmin activity increased with the age of the promastigote culture, at pH 7.2 and pH 5.5, as well as after heat shock. The total amastigote population, freshly isolated from a hamster lesion, also bound plasminogen in a lysine-dependent manner as detected by immunoperoxidase studies.

Animals↗
PubMed1991

Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model.

Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route.

Analysis of Variance↗
PubMed1993

Comparison of lipoprotein(a) assay methods in serum and in a plasminogen-free fraction.

We compared five immunoassays for lipoprotein(a) (Lp(a)) determination (end-point immunonephelometry, two-site IRMA and three different ELISA methods) in order to verify their agreement. Since it has been demonstrated that human apo(a) structure is closely similar to that of plasminogen, cross-reactivity of apo(a) antibodies with plasminogen represents an important technical problem in serum Lp(a) quantification. On this account we used a plasminogen-free fraction obtained by one-step ultracentrifugation at a density of 1.125 g/ml, in which no plasminogen activity was found. A satisfactory correlation between serum and plasminogen-free fraction Lp(a) values was found for all the methods; the limits of agreement were too high, however, to use serum and fraction interchangeably. Furthermore, it emerged that the different assays were more comparable and individual Lp(a) differences between methods were less spread when plasminogen-free fraction was used instead of serum.

Analysis of Variance↗
PubMed1992

Production and secretion of plasminogen in cultured rat brain microglia.

The production and secretion of plasminogen in cultured rat brain microglia was investigated. Urokinase-dependent caseinolytic activity was detected by zymography in microglial conditioned medium with a molecular weight of about 90 kDa. The 90-kDa protein was also detected by Western blotting with anti-rat plasminogen antiserum in the non-reducing condition. Immunoprecipitation with plasminogen antiserum following [35S]methionine labelling revealed that the plasminogen detected in microglial conditioned medium is synthesized in microglia. The amount of plasminogen in the conditioned medium was increased by stimulation with lipopolysaccharide. These results show that cultured microglia produce plasminogen and secrete it into the culture medium.

Animals↗
PubMed1984

Successive study on the production of plasminogen activator in cultured endothelial cells by phytosterol.

In a previous study(1), it was demonstrated that one of phytosterols, sitosterol, has an ability to increase the intracellular and extracellular activities of plasminogen activator in cultured endothelial cells and that other steroids including cholesterol, 5-androsten-3 beta-ol, stigmasterol, 20(R)-propyl-5-pregnen-3 beta-ol and 20(R)-heptyl-5-pregnen-3 beta-ol have no ability. Once-stimulated cells went back to normal states by removal of sitosterol. The similar lines of research for plasminogen activators were reported by several groups which were cited in a previous paper(l). In the present communication, we found that fucosterol, which is present mainly in brown algae, Phaeophyta, enhances the production of plasminogen activator in endothelial cells, as well as sitosterol. A similar enhancement was not observed for other steroids and sex hormones including androsterone, testosterone, estrone and estradiol. Synthesis of plasminogen activator induced with fucosterol or sitosterol was inhibited by protein synthesis inhibitor, cycloheximide. The plasminogen activators produced in cells were, in the present study, classified into urokinase-type activators with molecular weights of 31,000 and 55,000 and tissue-type ones with molecular weights of 81,000 and 130,000, which were identified with respective antibodies. The synthesis of each type of plasminogen activator in endothelial cells was stimulated by sitosterol or by fucosterol.

Animals↗
PubMed1985

The activation of Glu- and Lys-plasminogens by streptokinase: effects of fibrin, fibrinogen and their degradation products.

Studies were performed on the activation of a native form of human plasminogen (Glu-plg) or its degraded form (Lys-plg) by streptokinase (SK) in the presence of fibrin, fibrinogen, SK-potentiator, fragment D or E. When Glu-plg (0.1 microM) was activated by 0.5 u/ml of SK in the presence of 100 micrograms of S-2251 and 0.1 microM of fibrin, fibrinogen or their degradation products (potentiating agents), fibrin enhanced the rate of the hydrolysis of S-2251 to the largest extent. Fragments D and E only slightly enhanced it. The order of effectiveness of enhancement was fibrin greater than SK-potentiator greater than fibrinogen greater than D greater than E. When Lys-plg (0.1 microM) was activated by 0.5 u/ml of SK in the presence of potentiating agents, SK-potentiator enhanced the hydrolysis of S-2251 to the largest extent. The enhancement was far less in comparison to the enhancement of the hydrolysis by Glu-plg and SK. The measurement of delta OD405/min at the time of 50% hydrolysis of the substrate was performed in order to compare the effects of concentrations of potentiating agents. The maximum enhancement was obtained at almost an equimolar ratio of plasminogen and fibrin. Fifty percent enhancement was obtained at 0.05 microM for SK-potentiator, 0.072 microM for fibrinogen, 0.21 microM for D and 0.35 microM for E. Fibrin caused the largest extent of enhancement among other potentiating agents. These results may indicate that a trimolecular complex between SK, plasminogen and potentiating agents hydrolyzes S-2251 more effectively than SK-plasminogen complex, thus a trimolecular complex being a better activator than SK-plasminogen complex. Although D and E enhanced only slightly the rate of hydrolysis of S-2251 at equimolar ratio to plasminogen, increase in their concentration resulted in the same extent of enhancement as shown in the presence of fibrinogen or SK-potentiator.

Fibrin↗
PubMed1989

Evidence for regulation of endothelial plasminogen-activating system by polymorphonuclear leukocyte elastase.

Incubation of unstimulated polymorphonuclear leukocytes with cultured bovine pulmonary artery endothelial cells increased the activity of endothelial plasminogen activator. On the other hand, polymorphonuclear leukocytes stimulated by serum-opsonized zymosan decreased the plasminogen activator activity. A specific elastase inhibitor increased the enhancing effect of the unstimulated polymorphonuclear leukocytes and reversed the suppressing effect of the stimulated polymorphonuclear leukocytes. Catalytically active elastase suppressed the plasminogen activator activity and increased the activity of plasminogen activator inhibitor. In contrast, inactivated elastase enhanced the activity of plasminogen activator. Both, active and inactive forms of elastase bound to the endothelial cells. These findings suggest that elastase modulates the endothelial plasminogen-activating system, apparently by binding to the endothelial cells.

Animals↗
PubMed1976

Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm.

We have surveyed the early stages in the development and differentiation of cultured mouse embryos for plasminogen activator production. This enzyme is first detectable by the sixth equivalent gestation day. Thereafter, cultured blastocysts produce plasminogen activator with a biphasic time course: in the first phase, enzyme secretion rises to a maximum at about the eighth day and then decreases; a second phase, during which more enzyme accumulates, begins somewhat later and continues to at least the fifteenth day. By fractionating the blastocyst into its constituent cell types, we have identified the trophoblast as the cells responsible for the first phase of enzyme synthesis. The pattern of enzyme production by the trophoblast is closely correlated with the invasive period of these cells in vivo and implies that plasminogen activator is involved in embryo implantation. The second phase of plasminogen activator production is due to parietal endoderm, which initiates enzyme synthesis upon differentiation from the inner cell mass. The properties of the parietal endoderm suggest that plasminogen activator may participate in the migration of these cells and/or in the metabolism of Reichert's membrane which accompanies embryo growth. These results are consistent with the concept, deveolped from work on other cell types, that plasminogen activator may represent a generalized mechanism for tissue remodeling and cell migration.

Animals↗
PubMed1994

Conformations and stabilities of human Glu1- and Lys78-plasminogen and of the fragments mini- and microplasminogen, analysed by circular dichroism and differential scanning calorimetry.

The conformations and stabilities of two forms of human plasminogen, Glu1-plasminogen (Glu1-HPg, Glu1-Asn791) and Lys78-plasminogen (Lys78-HPg, Lys78-Asn791), and two enzymatically derived plasminogen fragments, miniplasminogen (mini-HPg, Val443-Asn791) and microplasminogen (micro-HPg, Lys531-Asn791) were analysed by circular dichroism and differential scanning calorimetry. The two plasminogen forms differ by the lack of 77 N-terminal amino acids in Lys78-HPg in comparison to Glu1-HPg. Mini-HPg is composed of kringle 5 and the protease domain of HPg whereas micro-HPg is built from the protease domain of HPg and a stretch of about 15 amino acids from kringle 5. Differential scanning calorimetric measurements of Glu1-HPg and Lys78-HPg reveal seven thermal transitions for both plasminogen forms. The results obtained for Lys78-HPg largely agree with recently published data (Novokhatny, V. V., Kudinov, S. A. and Privalov, P. L. J. Mol. Biol. 1984, 179, 215). Three thermal transitions corresponding to kringle 5 and to two subdomains of the C-terminal protease region were identified for mini-HPg. In micro-HPg, the two thermal transitions of the protease region were found but one of the protease subdomains was modified and its stability was much higher than in any of the other studied proteins. According to the microcalorimetric data obtained for mini-HPg and micro-HPg, transitions 5 and 6 of Glu1-HPg and Lys78-HPg were reassigned to kringle 5 and to a subdomain of the protease region, respectively, in contrast to literature data.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗
PubMed1994

Effects of plasminogen and interleukin-1 beta on bone resorption in vitro.

Inflammatory bone resorption, a characteristic feature of periodontal disease and rheumatoid arthritis, appears to be mediated by interleukin-1 beta (IL-1 beta). IL-1 beta has been shown to stimulate a wide range of proteolytic enzymes, including collagenases and plasminogen activators, in particular chondrocytes, synovial cells, and isolated osteoblasts. In this study, we have examined the hypothesis that IL-1 beta may stimulate bone loss by inducing the activity of plasminogen activators (PAs) in bone cultures. The latter would convert plasminogen to plasmin, which in turn can activate precursor procollagenase to collagenase. Active collagenase would then break down the bone collagen matrix. In the present study, release of 45Ca from fetal rat long bones in culture was studied in the presence of plasminogen and IL-1 beta. Plasminogen and IL-1 beta separately enhance resorption of fetal rat long bones in vitro. When plasminogen and IL-1 beta are added together at suboptimal levels, mainly additive effects are observed. The presence of heat-inactivated serum does not alter these results. These data tend to indicate that IL-1 beta is stimulating bone resorption through both PA-dependent and PA-independent pathways.

Animals↗
PubMed1994

Modulatory effect of plasminogen on NMDA-induced increase in intracellular free calcium concentration in rat cultured hippocampal neurons.

The effect of plasminogen on the intracellular Ca2+ concentration ([Ca]i) was examined in cultured rat hippocampal neurons. Plasminogen (100 nM) did not increase [Ca]i in the presence of tetrodotoxin (TTX, 3 microM) but increased [Ca]i in the absence of TTX. In all the cells which responded to plasminogen (100 nM), NMDA (5 microM) also increased [Ca]i in the presence of TTX. Furthermore, plasminogen (100 nM) enhanced the NMDA-evoked [Ca]i increase, and the potentiation by plasminogen was blocked by an NMDA receptor blocker, 2-amino-phosphonovalerate (APV). These data suggest that plasminogen enhances glutamate-evoked [Ca]i increase through modulation of NMDA receptor in hippocampal neurons.

2-Amino-5-phosphonovalerate↗
PubMed1982

Production of plasminogen activator by synchronized normal and Rous sarcoma virus-transformed chicken fibroblasts in culture.

We studied intracellular activity of the plasminogen activator within the cell cycle of chemically synchronized normal and RSV-transformed chick fibroblasts in culture. Consideration has also been given to the relationship between the plasminogen activator activity and cycles of DNA synthesis or mitosis in cycling fibroblasts after viral infection. The plasminogen activator activity of the cell lysates was assayed on [125I]fibrin-coated Petri dishes and was expressed as the radioactivity released from the plates. Normal fibroblasts produced detectable levels of plasminogen activator in the S-phase and late G2-phase or mitosis of the cell cycle. In contrast, RSV-transformed cells produced high levels of this activator throughout the entire cell cycle although this activity fluctuated and reached a maximum in the G2-M periods. We also found that the level of plasminogen activator activity in the transformed fibroblasts is influenced by the cycles of DNA synthesis and that cell division is required for the appearance of plasminogen activator activity in the 'de novo' virus-infected cultures.

Animals↗
PubMed1990

Plasminogen receptors in the mediation of pericellular proteolysis.

A wide variety of cells bind plasminogen with very high capacity, with similar affinity and recognize the same structural features within the plasminogen molecule. As a consequence of binding to cell surfaces, plasminogen is more readily activated to plasmin. Plasmin remains cell-bound where it can degrade matrix constituents and is protected from inactivation by alpha 2-antiplasmin. Thus, the functional consequence of plasminogen binding to cells is pericellular proteolysis, permitting cell migration. Both proteins and nonprotein cell-surface constituents function as plasminogen binding sites. Gangliosides exhibit the appropriate properties of the non-protein plasminogen receptors.

Binding Sites↗
PubMed2006

Acute sensorineural hearing loss and vertigo in a young adult with congenital plasminogen disorder.

A 19-year-old Japanese man exhibiting acute right sensorineural hearing loss and vertigo was referred to the Jichi Medical School Hospital in June 1994. Although he had no history of recurrent thrombosis and no family history of thrombosis, he had undergone reconstruction of a right foot joint fracture 4 months earlier. Screening studies for plasminogen activity demonstrated 10% of normal plasminogen activity and his plasminogen was diagnosed as "plasminogen Tochigi" by the gene analysis using restriction enzyme Fnu4HI. The patient's hearing returned to normal with administration of heparin, and he was prescribed warfarin for the prevention of thrombosis until October 1995. There was no recurrence of hearing loss during seven years of follow-up. The cause of this patient's hearing loss is believed to be associated with consumption of the already low levels of plasminogen as a result of his surgery as well as congenital plasminogen disorder.

Acute Disease↗