Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat adrenal glands were stained immunocytochemically using antibodies against plasminogen activators of the tissue-type (t-PA) and urokinase-type (u-PA). A subpopulation of the cells in the adrenal medulla showed intense cytoplasmic t-PA immunoreactivity, while no u-PA immunoreactivity was detected in any adrenal cells. Fluorescence microscopy of adjacent sections demonstrated that the cells stained for t-PA contained noradrenaline. Analysis with a histochemical fibrin slide technique demonstrated a plasminogen-dependent fibrinolysis in the adrenal medulla. SDS-PAGE of adrenal gland extracts followed by zymography established the molecular weight of this plasminogen activator to be similar to that of rat t-PA. In addition SDS-PAGE followed by immunoblotting with anti-t-PA IgG of adrenal gland extracts revealed one band with an electrophoretic mobility indistinguishable from that found in the zymography. When tissue-sections and immunoblots were incubated with antibodies absorbed with highly purified t-PA no staining was found. In view of the previous finding of t-PA in growth hormone-containing cells of the pituitary gland, these findings substantiate that t-PA can be found in the intact normal organism outside endothelial cells, and further point to t-PA having a function in endocrine cells.
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PMID:Tissue-type plasminogen activator in rat adrenal medulla. 309 16

The release of plasminogen activators (PA) from human isolated glomeruli has been studied by a sensitive radioenzymatic assay using 125I-fibrin coated tubes and plasminogen. The glomerular fibrinolytic activity (GFA) was detectable after 15 minutes of incubation. Then it increased with time, the glomerular protein concentration, and with the plasminogen concentration (P less than 0.001 for all). CaCl2 (1 mM) increased the GFA (9.7 +/- 0.9 versus 4.9 +/- 0.4 micrograms fibrin/mg/30 min, P less than 0.05). The GFA was also enhanced when pH increased. Arachidonic acid (AA, 1 to 20 micrograms/ml) increased the GFA in a saturable manner. Inhibitors of cyclooxygenase (aspirin) or of lipoxygenase (nordihydroguaiaretic acid) did not modify the basal and AA-stimulated GFA. Other polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), eicosatrienoic acid (ETA), eicosatetraynoic acid (ETYA), or dihomo-gamma-linoleic acid (DHL), also stimulated the GFA whereas linoleic acid and oleic acid did not. Polyunsaturated fatty acids also stimulated the fibrinolytic activity of glomerular supernatants. Specific antibodies to t-PA, and to a lesser extent to u-PA, decreased this fibrinolytic activity whether or not AA was added. Furthermore, AA and EPA were found to increase the activity of purified u-PA and t-PA. We conclude that human glomeruli release both t-PA and u-PA, and that this release is increased by calcium and alkaline pH. The polyunsaturated fatty acids enhanced the GFA, mainly by a stimulatory effect of PA activity rather than an increased release of PA from glomerular cells.
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PMID:Polyunsaturated fatty acids increase fibrinolytic activity of human isolated glomeruli. 309 75

Biopsies of involved and uninvolved skin from psoriatic patients and of normal skin were stained immunocytochemically with monoclonal antibodies against urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activator using a multilayer peroxidase technique. Epidermis from psoriatic lesions showed focal staining for u-PA in and between the basal keratinocytes in the suprapapillary epidermal areas, while t-PA was found in the superficial keratinizing cells, including both stratum spinosum and the parakeratotic layer. No staining of keratinocytes was observed in uninvolved and normal skin. The specificity of the staining was supported by the finding that 3 different monoclonal antibodies and polyclonal antibodies against each of the plasminogen activators gave identical staining, while monoclonal antibodies of irrelevant specificity gave no staining. The present findings suggest abnormalities in the regulation of both types of plasminogen activators in psoriatic epidermis.
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PMID:Immunohistochemical localization of urokinase- and tissue-type plasminogen activators in psoriatic skin. 309 60

Interleukin 1, derived from human placenta, stimulates plasminogen activator activity in human articular chondrocytes. The stimulation of plasminogen activator activity can be abolished by preincubation of placental interleukin 1 with an antiserum to homogeneous 22K factor, a species of interleukin 1 beta, indicating that the stimulation of plasminogen activator activity is due to interleukin 1 and not contaminating factors. Chondrocytes produce three species of plasminogen activator, with apparent Mr approximately 50,000, 65,000 and 100,000 as determined after sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis with gels containing casein and plasminogen. Both placental interleukin 1 and 22K factor enhance the production of the species of Mr approximately 65,000 and 100,000. Comparison of the mobility of the plasminogen activator species on SDS-polyacrylamide gel electrophoresis with human urokinase (u-PA) and human melanoma tissue-type plasminogen activator (t-PA) and studies with antibodies to these enzymes indicate that the Mr approximately 50,000 species is a u-PA and the Mr approximately 65,000 a t-PA. The Mr approximately 100,000 species is possibly an enzyme-inhibitor complex. Interleukin 1 therefore appears to enhance the production of t-PA and a putative enzyme-inhibitor complex. Abolition of plasminogen activator activity in the fibrin plate assay with antibodies to t-PA and u-PA also confirms enhanced t-PA production on interleukin 1 stimulation, though there is also evidence for increased cell-associated production of u-PA.
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PMID:Interleukin 1 preferentially stimulates the production of tissue-type plasminogen activator by human articular chondrocytes. 310 96

We have studied the mechanism of a transforming growth factor-beta (TGF-beta)-stimulated production of type-1 plasminogen activator inhibitor (PAI-1) in WI-38 human lung fibroblasts. TGF-beta causes an early increase in the PAI-1 mRNA level which reaches a maximal 50-fold enhancement after 8 h. Blocking of protein synthesis with cycloheximide causes an equally strong increase in the level of PAI-1 mRNA. Quantitative studies of the effect of TGF-beta on PAI-1 protein levels in cell extracts and culture media by using monoclonal antibodies are consistent with the effect on PAI-1 mRNA. The results suggest a primary effect of TGF-beta on PAI-1 gene transcription, and also suggest the possibility that the transcription of this gene in non-induced cells may be suppressed by a short-lived negatively regulating protein. Urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activators are decreased in the culture media of TGF-beta-treated cells concomitantly with the increase in PAI-1 accumulation. These findings show that a primary and important biological effect of TGF-beta may be an overall decreased extracellular proteolytic activity, and give an insight into the molecular mechanisms underlying TGF-beta action at the genetic level.
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PMID:Transforming growth factor-beta is a strong and fast acting positive regulator of the level of type-1 plasminogen activator inhibitor mRNA in WI-38 human lung fibroblasts. 311 44

Two-chain tissue plasminogen activator (t-PA) was found to be inactive in a coupled colorimetric assay for plasminogen activators, but a high level of activity was obtained in the presence of poly-D-lysine. This stimulated activity was strongly inhibited by minactivin, a urokinase inhibitor, but unstimulated enzyme could be shown to be unaffected by minactivin. In the presence of poly-D-lysine minactivin was a very successful competitive inhibitor of t-PA with respect to the substrate, plasminogen. The Ki for minactivin determined by the Henderson method was 2.5 X 10(-12) M, compared to the Km for plasminogen determined as 0.6 X 10(-6) M. The value of Ki for minactivin with u-PA, determined under the same conditions, was 1.6 X 10(-11) M.
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PMID:Poly-D-lysine dependent inactivation of tissue plasminogen activator by a class PAI-2 inhibitor (minactivin). 311 9

The effect of hemodialysis on components of the fibrinolytic system was measured in 22 patients. Plasma levels of t-PA antigen, t-PA activity, u-PA antigen and plasminogen activator inhibitor were determined by means of immunological and functional assays. During hemodialysis, 11 patients exhibited an increase in t-PA antigen within the first hour to about three times the starting values (P less than 0.05), followed by a decrease to about double of the initial values until the end of the treatment. Eleven patients showed a continuous increase up to 200% of the starting values until the end of hemodialysis. u-PA levels did not change significantly during the time of investigation (P greater than 0.5).
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PMID:Enhanced fibrinolysis caused by tissue plasminogen activator release in hemodialysis. 311 19

The distribution of tissue plasminogen activator (t-PA) and urokinase (u-PA) was investigated immunohistochemically in squamous epithelium of the uterine cervix, in normal and dysplastic conditions as well as in preinvasive and invasive carcinomas. Normal epithelium showed presence of both t-PA and u-PA immunoreactivity only in the superficial cellular layer, whereas in preinvasive lesions they were present in all layers. In sections of normal specimens as well as preinvasive lesions the UK immunoreactivity was weaker compared to that of t-PA. Invasive lesions showed a patchy distribution of t-PA and u-PA immunoreactivity. Furthermore, it could be demonstrated that stromal cells close to the infiltrating malignant squamous epithelium contained t-PA immunoreactivity and also u-PA immunoreactivity. Further immunohistochemical studies disclosed that these cells were macrophages.
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PMID:Tissue plasminogen activator and urokinase in normal, dysplastic and cancerous squamous epithelium of the uterine cervix. 312 84

The occurrence of plasminogen activators of the urokinase-type (u-PA) and tissue-type (t-PA) at various stages of the epithelial cycle was studied immunohistochemically in rat seminiferous tubule segments. u-PA immunoreactivity was detected exclusively at stages VII and VIII in Sertoli cells, displaying a distinct granular cytoplasmic staining. t-PA immunoreactivity was found during mid- and late pachytene and diakinesis (stages VII-XIII) in spermatogenic cells, displaying a granular cytoplasmic staining with maximal intensity in stages IX-XIII. The specificity of the stainings was supported by staining controls, including absorption of the antibodies with purified preparations of the activators. It was also supported by zymographic studies of the occurrence of u-PA and t-PA in extracts of tubular segments at different stages of the cycle, isolated by transillumination-assisted microdissection. The possible functions of the two types of plasminogen activators in the seminiferous epithelium are discussed.
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PMID:Immunohistochemical localization of urokinase-type plasminogen activator in Sertoli cells and tissue-type plasminogen activator in spermatogenic cells in the rat seminiferous epithelium. 312 78

Constitutive gene expression of four components of plasminogen activating enzyme system, urinary and tissue-type plasminogen activator (u-PA and t-PA), plasminogen activator inhibitor 1 (PAI-1) and PAI-2 in HT-1080 human fibrosarcoma cells, was modulated by the synthetic glucocorticoid dexamethasone (Dex, 10(-7) M). More than 90% of u-PA, t-PA and PAI-1 antigen was found in conditioned medium, whereas PAI-2 was mainly cell associated. In 48-h culture supernatants (expressed per 10(6) cells) PAI-1 antigen increased from 350 to 3,300 ng and t-PA from 19 to 38 ng. u-PA and PAI-2 in the same samples decreased from 380 to 46 ng and from 3.5 to 1.8 ng, respectively. Northern blot hybridization and nuclear "Run-on" transcription assays demonstrated that the increase of t-PA and PAI-1 and the decrease of u-PA were associated with equivalent changes of gene template activity. Modulation of u-PA, t-PA and PAI-1 gene expression by Dex was completely blocked by the glucocorticoid antagonist RU 38486, suggesting that all effects were mediated through the glucocorticoid receptor. Cycloheximide, an inhibitor of protein biosynthesis induced a rapid transient increase of t-PA, u-PA and PAI-1 mRNA and a sustained increase of PAI-2 mRNA, but blocked the more long term effects of Dex, suggesting that both constitutive and hormonally regulated maintenance of mRNA steady state levels required protein biosynthesis.
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PMID:Glucocorticoid-modulated gene expression of tissue- and urinary-type plasminogen activator and plasminogen activator inhibitor 1 and 2. 312 94


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