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

It is demonstrated that i) theca-interstitial compartment synthesizes the majority of plasminogen activator inhibitor type 1 (PAI-1) in the ovary before ovulation, and the follicular wall may therefore serve as a specific barrier with the presence of PAI-1 activity to prevent the secretion of tPA into the extrafollicular compartments; ii) granulosa cells secrete only a small amount of ovarian PAI-1, but synthesize the most of tissue-type plasminogen activator tPA involved in the processes leading to ovulation; iii) since only matured cumulus-oocyte complexes secrete a large amount of tPA and PAI-1, both tPA and PAI-1 activity in the conditioned medium may be used as reliable markers for evaluating oocyte quality for in vitro fertilization.
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PMID:Secretion of plasminogen activator inhibitor type 1 by cultured ovarian cells obtained from gonadotropin-treated immature rats. 799 78

Osteoblasts have been reported to produce tissue-type (t) plasminogen activator (PA), which may be involved in the initiation of bone resorption via plasmin-metalloproteinase degradation of adjacent extracellular matrix. To investigate this cAMP-activated gene, we characterized the PTH regulation of tPA messenger RNA (mRNA) in neonatal rat osteoblast cultures before and after differentiation in vitro. RNA was purified from cultures at confluence or after treatment with glucocorticoid for 1 week and BGJ/ascorbic acid/beta-glycerophosphate for a second week. Northern blots of total or poly(A)+ RNA were hybridized simultaneously with an oligonucleotide or complementary RNA probe for rat tPA and an oligomeric DNA probe for cyclophilin (CYP), an abundant control gene. Differentiation was monitored by expression of rat osteocalcin mRNA and protein. Both bovine PTH1-34 and forskolin caused an increase in tPA/CYP ratio in the presence of phosphodiesterase inhibitor (IBMX) and cycloheximide (CHX). The effect was maximal (16- to 21-fold increase in tPA mRNA and 6- to 8-fold increase in tPA/CYP ratio) with 25 nM hormone for 6 h and was half-maximally stimulated by 0.75-2.5 nM PTH. The tPA response to PTH was present in first passage osteoblast cultures at confluence and after 1 to 2 weeks of glucocorticoid treatment. Exposure of the differentiated cultures of 1,25-dihydroxyvitamin D (10 nM) for 2 days markedly stimulated osteocalcin mRNA while having no effect on tPA. In Northern blots of poly(A)+ RNA from cultures not treated with CHX, IBMX and PTH (2.5 h) independently stimulated tPA mRNA with no significant effect on CYP mRNA levels. The tPA/CYP ratio increased in five consecutive experiments and the effect of IBMX and PTH were additive. These data indicate that PTH acts via cAMP to stimulate tPA expression by a mechanism that is independent of protein synthesis. The enhancement of PTH action by CHX is compatible with feedback inhibition of tPA transcription by a hormone-activated repressor (which has been proposed to occur in granulosa cells) but effects of CHX on tPA mRNA stability may also occur. Expression of tPA mRNA before and after differentiation may indicate that the enzyme has more than one function.
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PMID:Increased expression of tissue plasminogen activator messenger ribonucleic acid is an immediate response to parathyroid hormone in neonatal rat osteoblasts. 811 83

The tissue (tPA) and urokinase (uPA) types of plasminogen activator and the plasminogen activator inhibitor 1 (PAI-1) are enzymatic proteins that may play an important role in the degradation of the extracellular matrix in physiologic and neoplastic conditions. In particular, urokinase may underlie key properties of malignant cells, such as invasiveness and dissemination. We have studied the immunohistochemical distribution of tPA, uPA, and PAI-1 in 24 human gliomas, including seven well-differentiated astrocytomas, three oligodendrogliomas, six anaplastic astrocytomas, and eight glioblastomas multiforme. All anaplastic astrocytomas and glioblastomas showed numerous neoplastic cells immunoreactive for uPA, but not for tPA. In contrast, low-grade gliomas were negative for uPA, but contained some tPA-immunoreactive cells. Endothelial cells of vessels in non-neoplastic and neoplastic brain were immunoreactive for tPA, but not for uPA or PAI-1. Non-neoplastic glia were unreactive for tPA, uPA, and PAI-1. Small anaplastic cells present in three glioblastomas showed immunoreactivity for PAI-1. The presence of a large number of uPA-immunoreactive neoplastic cells in high-grade gliomas suggest that this fibrinolytic protein plays a significant role in the invasive properties of these neoplasms.
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PMID:Plasminogen activators and inhibitors in gliomas: an immunohistochemical study. 815 59

Since the serine protease inhibitor, protein C inhibitor (PCI), is present in seminal plasma at approximately 3 microM, complexes of PCI with urokinase (uPA) and tissue type (tPA) plasminogen activator were quantitated using sandwich enzyme-linked immunosorbent assays (ELISA's). Seminal plasma (N = 10) collected in the absence of extrinsic inhibitors had a mean of 25 +/- 5 ng/ml uPA:PCI, 76 +/- 23 ng/ml tPA:PCI, and 4 +/- 2 ng/ml of tPA complexes with plasminogen activator inhibitor-1 (tPA:PAI-1). 93% of the uPA and 17% of the tPA antigen in seminal plasma was in complex with PCI and, when complexation was inhibited by collecting semen into an 1,10-phenanthrolinium solution, 33% of the uPA and 7% of the tPA was complexed to PCI. Urine (N = 10) contained 4 +/- 1 ng/ml uPA:PCI. In purified system, complexation of uPA and tPA to PCI paralleled the inhibition of the enzymes. In vitro studies in blood and seminal plasma showed that heparin stimulated complexation of uPA and tPA with PCI, suggesting that negatively charged glycosaminoglycans in blood vessels and in the reproductive system may regulate PCI reactions with uPA and tPA. These results suggest that PCI is a physiologic regulator of uPA and tPA in male reproductive tissues and raises questions about a potential role of PCI in human fertility and in uPA-dependent cell invasiveness.
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PMID:Evidence for the regulation of urokinase and tissue type plasminogen activators by the serpin, protein C inhibitor, in semen and blood plasma. 816 23

Tissue injury is followed by formation of a provisional, fibrin-containing matrix. It is later on replaced by granulation tissue. Replacement involves extracellular proteolysis by fibrinolytic enzymes. Plasmin is a fibrinolytic proteinase and is generated from ubiquitous plasminogen by cell-derived urokinase-type (uPA) or tissue-type (tPA) plasminogen activator. To explore the cells and components involved in plasminogen activation, we have performed a combined immunohistological and zymographic study on human skin wounds produced iatrogenically by debridement. The fibrin(ogen)-specific staining indicated the progressive removal of a fibrin-containing provisional matrix. Plasmin(ogen) was present over the entire observation period. It was diffusely distributed and also displayed a conspicuous association with cells of the granulation tissue, in particular with monocytes/macrophages and fibroblasts. Also, uPA was associated with monocytes/macrophages and fibroblasts, whereas the uPA-receptor (uPA-R) was stained in monocytes/macrophages only. The uPA was potentially active as indicated by zymography. No tPA-specific staining was found. The findings point at the importance of monocytes/macrophages and fibroblasts in uPA-mediated plasminogen activation in healing human skin wounds.
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PMID:Plasminogen activation in healing human wounds. 820 66

The plasminogen activator (PA) system is present in the ovary and appears to be involved both in follicular growth and ovulation. Similarly, the growth hormone (GH) has been demonstrated to positively affect some ovarian activities. Interestingly, GH appears not only as a mediator of gonadotropin effects, but also as having an independent action of its own on the ovary. In the present study we wanted to investigate if GH could affect ovarian plasminogen activator (PA) activity and steroidogenesis. Granulosa cells from immature rats, injected with pregnant mare serum gonadotropin (PMSG) for inducing follicular growth, were cultured for 24 h with increasing concentrations of GH. A significant dose-dependent increase in tPA activity was observed in the GH-treated cells. This effect was exerted at the mRNA level and the use of cycloheximide, a protein synthesis inhibitor, suggested that GH did not require any other intermediary protein for inducing tPA-mRNA. Furthermore, cAMP levels were not affected by GH treatment. Finally, GH was found to increase progesterone (P) synthesis by granulosa cells. The correlation between the PA system and ovulation and the importance of a normal steroidogenesis for the ovarian physiology claim for a key role of GH in the ovarian activities.
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PMID:Growth hormone induction of rat granulosa cell tissue-plasminogen activator expression and progesterone synthesis. 820 22

Osteoblasts secrete transforming growth factor beta (TGF beta) as a biologically inert, latent complex that must be dissociated before the growth factor can exert its effects. We have examined the production and proteolytic activation of latent TGF beta (LTGF beta) by clonal UMR 106-01 rat osteosarcoma cells and neonatal mouse calvarial (MC) osteoblast-like cells in vitro. Synthetic bPTH-(1-34) increased the activity of tissue-type (tPA) and urokinase-type (uPA) plasminogen activators (PA) in cell lysates (CL) of UMR 106-01 cells. The concentration of active TGF beta in serum-free CM from cultures treated with bPTH-(1-34) and plasminogen was significantly greater than in CM from untreated controls and cultures treated with either bPTH-(1-34) or plasminogen alone. This effect occurred at concentrations of PTH-(1-34) that increased PA activity and was prevented by aprotinin, an inhibitor of plasmin activity. Treatment with bPTH-(1-34) had no effect on the concentration of TGF beta in acid-activated samples of CM. Functional consequences of proteolytically activated TGF beta was examined in primary cultures of neonatal MC osteoblast-like cells. Human platelet TGF beta 1 caused a dose-dependent increase in the migration of these cells in an in vitro wound healing assay. Cell migration was also stimulated in cultures treated with bPTH-(1-34) and plasminogen together. This effect was blocked by an anti-TGF beta 1 antibody. The results of these studies demonstrate that (1) LTGF beta secreted by osteoblasts in vitro is activated under conditions where the plasmin activity in the cultures is increased, and (2) the TGF beta generated by plasmin-mediated proteolysis is biologically active. We suggest that the local concentration of TGF beta in bone may be controlled by the osteoblast-associated plasminogen activator/plasmin system. Furthermore, since several calciotropic factors influence osteoblast PA activity, this system may have an important role in mediating their anabolic and/or catabolic effects.
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PMID:Plasminogen-dependent activation of latent transforming growth factor beta (TGF beta) by growing cultures of osteoblast-like cells. 825 64

Pemphigus may be an idiopathic disease or a syndrome induced by drugs, mainly thiol drugs. Autoantibodies, always present in the idiopathic form but often lacking in the drug-induced one, may cause acantholysis by activating endogenous proteolytic enzymes. Pathogenesis of drug-induced pemphigus when antibodies are absent has not been elucidated yet. Extracts of skin tissues cultured for 4 days with penicillamine, captopril or thiopronine were assayed for the presence of plasminogen activator (PA) and plasminogen activator inhibitors (PAI) on agar fibrin plates. Moreover, uPA, tPA, and PAI-1 were identified in the extracts by immunoenzymatic assay. The results have shown progressively decreasing amounts of PAI-1 in penicillamine, thiopronine and captopril-cultured tissue extracts, respectively. This suggests that the acantholytic potential of thiol drugs is directly correlated to their capability of reducing PAI-1 in the epidermal cells leading to increased PA activity. This PA-PAI imbalance may be itself the cause of intraepidermal splitting.
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PMID:Imbalance between plasminogen activator and its inhibitors in thiol-induced acantholysis. 842 39

Tissue remodeling that accompanies ovarian follicular cell proliferation and migration during follicular maturation and ovulation involves enzymatic degradation of extracellular matrix by proteases such as plasminogen activator (PA). However, the potential role of interleukin-1 beta (IL-1 beta) in the regulation of the rat granulosa cell PA system during folliculogenesis is not known. In vitro treatment of both undifferentiated and differentiated granulosa cells with FSH (400 ng/ml) elicited a significant increase in secreted (PAs) and cell-associated (PAc) PA activities, which were inhibited by IL-1 beta (0.5-50 ng/ml) in a concentration- and time-dependent manner. Basal PAs and PAc activities were stimulated in cultures of undifferentiated granulosa cells by IL-1 beta but attenuated in differentiated ones. The inhibitory effect of IL-1 beta was accompanied by an increase in PA inhibitor (PAI) activity irrespective of the stage of follicular development. Both urokinase-type PA (uPA; 30 kDa) and tissue-type PA (tPA; 55 KDa) activities were present in cultures of undifferentiated granulosa cells, but only tPA was detectable in differentiated granulosa cell cultures. Activity of both enzymes was stimulated by FSH but inhibited by the cytokine in vitro. Whereas FSH-induced differentiation of granulosa cells as indicated by an increase in progesterone (P) secretion was attenuated by IL-1 beta irrespective of the cytodifferentiative state of granulosa cells, the inhibitory effect of gonadotropin on DNA synthesis was reversed by the cytokine at both stages of follicular maturation. These findings suggest that during ovarian folliculogenesis, IL-1 beta may modulate the progression of granulosa cells from a proliferative to a differentiated state and may play a control role in determining the fate of the follicle (i.e., ovulation vs. atresia).
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PMID:Regulation of rat granulosa cell plasminogen activator system: influence of interleukin-1 beta and ovarian follicular development. 856 85

High-performance anion-exchange chromatography (HPAEC) with pulsed-amperometric detection was used to monitor the consistency of the oligosaccharides released from several partially purified preparations of a tissue-type plasminogen activator mutant (TNK-tPA). Differences in the oligosaccharide map were observed, primarily in the neutral carbohydrate region of the separation. Subsequent investigations using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF/MS) identified the neutral oligosaccharides to be primarily asialo-diantennary complex-type glycans with 2, 1, or 0 galactose residues. Additional asialo-triantennary and asialo-tetrantennary structures were also observed with varying amounts of galactose. Hydrolysis of the chromogenic substrate 4-methyl umbelliferyl-beta-galactoside confirmed that host-cell lysosomal beta-galactosidase is present at the first step in the purification process and is the cause of the observed glycan degradation. Subsequent steps in the purification process quantitatively remove this enzyme. Comparison of HPAEC and MALDI/TOF/MS analysis of time-course samples revealed quite similar rates of degradation and demonstrates the quantitative utility of these methods. HPAEC did not reveal significant changes in the sialylated structures as evidenced by nearly identical profiles for the sialic acid-containing structures.
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PMID:The use of high-performance anion-exchange chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to monitor and identify oligosaccharide degradation. 866 Jun 30


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