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)

The secretion of plasminogen activator by seminiferous tubules at defined stages of the epithelial cycle is influenced both by neighboring spermatogenic cells and by hormones. We have used cRNA probes for urokinase-type (uPA) and tissue-type (tPA) plasminogen activators to analyze their mRNA levels in different stages of the epithelial cycle. Urokinase-type PA mRNA was most abundant in stages VII-VIII, while tPA mRNA levels showed smaller variations between the different stages. Both FSH and (Bu)2cAMP increased the steady-state level of tPA mRNA and tPA production without affecting those of uPA in stages VII-IX in vitro, whereas retinoic acid treatment selectively increased the concentration uPA mRNA and uPA production in stages II-VI. The results show that the expression of the uPA and tPA genes is differentially regulated in specific stages of the rat seminiferous epithelium.
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PMID:Regulation of urokinase- and tissue-type plasminogen activator gene expression in the rat seminiferous epithelium. 253 92

The relationship between plasminogen activator (PA)/plasminogen activator inhibitor (PAI) activity and morphological differentiation was investigated in human neuroblastoma (NB) cells treated with retinoic acid (RA). Conditioned medium from nine NB cell lines and one closely related neuroepithelioma line was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and zymography. All NB cell lines were shown to secrete urokinase (UK)-type PA (mol. wt., 52 kDa), and all except two produced tissue PA (mol. wt., 65 kDa). Identification of the PAs was made based on molecular weight and sensitivity to inhibition by anti-UK and anti-tPA antibodies. Several cell lines expressed PA inhibitory molecules; two molecular-weight forms were observed (35 and 40 kDa) in different cell lines. Complex formation with [125]I-labelled proteases revealed specific binding with UK and trypsin but not thrombin, plasmin, or kallikrein. After treatment for 6 days with 1 microM RA, six of the cell lines exhibited an increase in cell-associated and/or secreted tPA activity, corresponding to morphological differentiation of the cells as manifested by extensive neurite outgrowth. A decrease in UK and UK-complex secretion was observed in several of these cell lines. Three cell lines exhibiting no detectable morphological alterations with RA treatment also showed no dramatic changes in PA/PAI activity. These results suggest that morphological differentiation of NB cells may be associated with alterations in the regulation of PA activity.
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PMID:Effect of retinoic acid on human neuroblastoma: correlation between morphological differentiation and changes in plasminogen activator and inhibitor activity. 259 Sep 98

The urokinase-type and tissue-type plasminogen activators are the two enzymes found in mammals, which specifically convert the zymogen plasminogen to plasmin. Using cDNA probes, we have assayed for the presence of the two types of plasminogen activator mRNAs in murine tissues. We demonstrate that tissue-type plasminogen activator mRNA can be detected in a wide variety of tissues. In contrast, the accumulation of urokinase-type plasminogen activator mRNA is observed in only a few of the tissues analyzed. Using an S1 nuclease assay, we demonstrate that the tPA mRNA detected contains the complete sequences encoding the non-protease finger, growth-factor and kringle domains.
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PMID:Tissue plasminogen activator mRNA in murine tissues. 283 Oct 81

The effect of a low molecular weight heparin CY 222 (Choay) on t-PA induced thrombolysis was investigated in the rabbit jugular thrombosis model. The compound CY 222 was administered as 1.4 mg/kg (group A) by IV injection immediately after start of t-PA infusion (0.125 and 0.250 mg/kg) and then hourly during the 4 hours of infusion of the thrombolytic; results were compared with those obtained in the absence of CY 222 (group B). A significant increase in percent thrombolysis was noted in the presence of CY 222: A versus B = 31 +/- 1/22 +/- 2 (p less than 0.02) (tPA = 0.125 mg/kg; 72 +/- 4/36 +/- 3 (p less than 0.01) (tPA = 0.250 mg/kg). Anti-Xa activity 60 minutes after 1.2 u/ml IV of CY 222 was comparable with that observed in patients with venous thrombosis treated with high-dose CY 222. The conclusion is reached of the interest of CY 222 in combination with t-PA, the CY 222 acting not only on coagulation by also on thrombolysis by potentiating the effect of t-PA.
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PMID:[Low molecular weight heparin CY 222 (Choay) potentiates the thrombolytic effect of 1-PA in rabbits with experimental thrombosis of the jugular vein]. 283 93

Neutrophils (PMN) are important in the cellular phase of blood fibrino lytic activity (FA). The contribution of monocytes (MC), which have FA, is unclear. To determine the relative roles of these cells to activity in normal blood, we examined, by solid phase radiofibrin assay, FA of normal blood and plasma, and of purified PMN and MC, with and without plasminogen (PLG), mini-plasminogen (mPLG), the other major elastase fragment of PLG, or autologous plasma. PMN alone (0.5 x 10(6)/ml) had striking activity (292 +/- 25 SEM ng fibrin lysed/h; n = 10 normal subjects) while MC alone (0.5 x 10(6)/ml) had mean FA of 32 +/- 4 ng/h, which could be accounted for by contaminating PMN (36 +/- 8 ng/h). Thus, in a 1 h assay (when cellular FA accounts for 70-80% of FA in whole blood), normal numbers of MC (0.5 x 10(6)/ml) had no detectable FA when assayed with PLG or normal plasma. With longer assay times (2-6 h), PLG-dependent (plasminogen activator, PA) activity was demonstrated with mixtures of MC and PLG or plasma. This PA activity was released into the medium and required prior contact of MC and an intact, soluble PLG molecule for PA activity to be detected in medium (suggesting a PLG-MC triggering mechanism), since activity was reduced or absent when MC were exposed to mPLG, the other major elastase fragment of PLG, or solid phase PLG. Exposure of MC to solid phase fibrin did not result in PA release. MC PA activity was little affected by cycloheximide pretreatment, indicating preformed rather than newly synthesized PA. By SDS-PAGE and fibrin zymography, MC extracts revealed a single PA band with features of pro-urokinase (single chain urinary-type PA): Mr 55,000, inhibition by antiurokinase antibody (but not by anti-tPA), and resistance to inhibition by DFP. By ELISA assay, approximate normal monocyte content of this PA (as Mr 55,000 urokinase) was 0.03 fg (3.3 x 10(8) molecules) per cell.
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PMID:Fibrinolytic activity of normal human blood monocytes. 292 5

A one-chain recombinant tissue-type plasminogen activator (EC 2.4.31.-) (tPA) analogue was constructed in which Arg-275 of the activation site was changed to Gly by site-directed mutagenesis. This analogue, tPA-Gly275, was very resistant to plasmin (EC 2.4.21.5) cleavage. It has been used to gain information about the activity of the uncleaved one-chain tPA form, also when plasmin is generated as a result of a plasminogen activation reaction. The amidolytic activity of tPA-Gly275 with less than Glu-Gly-Arg-pNA was investigated and compared to that of one-chain and two-chain wild-type recombinant tPA. A small but significant intrinsic amidolytic activity was observed with the analogue as well as the wild-type one-chain tPA form. However, it was much lower than that of two-chain tPA. Polymerised fibrin enhanced the amidolytic activity of both one-chain tPA forms but not of two-chain tPA. Measurements of the plasminogen activation kinetics in the absence of fibrin revealed that tPA-Gly275 possessed a significant intrinsic activity. However, it was 30-fold lower than that of two-chain tPA. Addition of polymerised fibrin profoundly enhanced the plasminogen activation rate of both tPA-Gly275 and wild-type one- and two-chain tPA to approximately the same maximal level. The results were interpreted to mean that fibrin binding can induce an activated state of the intact tPA one-chain form.
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PMID:The effect of polymerised fibrin on the catalytic activities of one-chain tissue-type plasminogen activator as revealed by an analogue resistant to plasmin cleavage. 296 43

The applicability of 4-methylumbelliferyl-p-guanidinobenzoate hydrochloride (MUGB) as active-site titrant for tissue-type plasminogen activator (t-PA) was studied in comparison to urokinase. Although t-PA was capable of cleaving MUGB, active-site titration of t-PA (one-chain form as well as two-chain form) with MUGB was not possible, whereas MUGB titration of urokinase could be performed. We therefore studied the kinetics of the interaction of these two plasminogen activators with MUGB. The equilibrium dissociation constant, KS, for the interaction between MUGB and urokinase was 2.9 X 10(-6) M, and for the interaction with t-PA 3.13 X 10(-5) M. However, one main requirement for active-site titration, namely a stable acyl enzyme intermediate (ES'), was only fulfilled for MUGB urokinase but not for MUGB t-PA. Whereas for the reaction of MUGB and urokinase the first-order acylation rate constant k2 was found to be about 10(6)-times higher than the first-order deacylation rate constant k3 (k2 = 3.76 X 10(-1) s-1, k3 = 3.7 X 10(-7) s-1), the k2/k3 ratio for the reaction of MUGB and t-PA (one- and two-chain form) was 0.77 to 3.85. Therefore, urokinase and t-PA differ in their reaction with this fluorogenic substrate and MUGB cannot be used for active-site titration of tPA.
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PMID:Tissue-type plasminogen activator and urokinase: differences in the reaction pattern with the active-site titrant 4-methylumbelliferyl-p-guanidinobenzoate hydrochloride. 310 86

Two types of plasminogen activator (tissue-type, tPA; urokinase-type, uPA) have been demonstrated in ovarian granulosa cells, but only tPA activity was found in denuded oocytes. Immature rats were treated subcutaneously with 20 IU pregnant mare's serum gonadotropin (PMSG) to stimulate follicle maturation, followed 2 days later by an injection of 10 IU human chorionic gonadotropin (hCG) to induce ovulation. Cellular plasminogen activator activities were determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis followed by a fibrin-overlay technique. Cumulus-oocyte complexes from rats before and after PMSG treatment contained low amounts of tPA, but not uPA, activity. After hCG treatment, tPA activity showed a time-dependent increase, reaching a maximum at 24 h after injection. At 12 and 24 h after hCG treatment, uPA activity was also detected. The appearance of high molecular weight lysis zones further suggested the formation of plasminogen activator-inhibitor complexes. Morphological analysis indicated that the increases in oocyte tPA activity were correlated with the extent of cumulus cell expansion and dispersion. In denuded oocytes, tPA activity also progressively increased during the periovulatory period to a maximum at 24 h after hCG treatment. In contrast, neither uPA activity nor activator-inhibitor complex was detected. Secretion of the proteases was measured in the conditioned media of cumulus-oocyte complexes cultured for 24 h in vitro. Substantial increases in tPA release were found in complexes obtained at 8 and 12 h after hCG injection, with lower secretion from complexes obtained at 24 h after hCG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasminogen activator activity in cumulus-oocyte complexes of gonadotropin-treated rats during the periovulatory period. 310 10

Vascular or tissue-type plasminogen activator (plasma t-PA) is the circulating physiological fibrinolytic enzyme of endothelial cell origin which function is regulated by fibrin and a specific inhibitor (PAI). To study the pattern of release of t-PA and the behavior of t-PA-PAI complexes in plasma we determined t-PA activity in 44 healthy subjects before and after 10 min of forearm venous occlusion using a new spectrophotometric solid-phase fibrin-tPA activity assay. The assay is based on 1) the high affinity binding of t-PA to fibrin, and 2) the detection of fibrin-bound t-PA by measuring the release of pNA from a chromogenic substrate in the presence of plasminogen. Values at rest were rather undetectable in plasma (0.05 +/- 0.03 IU/ml, in 23 out of 44 samples) but were positively detected in all the euglobulins: 0.88 +/- 0.68 IU/ml. After venous occlusion the majority of plasmas (36 out of 44) showed a slight increase in t-PA activity (0.65 +/- 0.63 IU/ml) as compared to the important level observed in all the euglobulins (9.78 +/- 9.58 IU/ml). So, the ratio plasma/euglobulin t-PA activity was very low (0.06) and remained identical in both pre- and postocclusion samples. However, when diluted plasmas were tested the inhibitory effect disappeared and t-PA activity increased indicating that although t-PA circulates in a neutralized state it can be available for fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Release pattern of the vascular plasminogen activator and its inhibitor in human postvenous occlusion plasma as assessed by a spectrophotometric solid-phase fibrin-tPA activity assay. 312 85

Ovarian follicles produce two types of plasminogen activator (tPA and uPA), and their inhibitor (PAI). We have examined the interaction and regulation of these factors in ovarian intact follicles as well as granulosa and theca-interstitial cells. The results show that only tPA, but not uPA, is regulated by the gonadotropins and reaches maximum prior to ovulation. PAI is secreted mainly by theca-interstitial cells and is stimulated also by the gonadotropins. The formation of complexes between PA and PAI completely blocks or decreases PA activity. It is suggested that the interaction between plasminogen activators and their inhibitor in the follicles may play a very important role in maintaining normal ovarian function and the machnism of ovulation.
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PMID:Interaction and regulation of plasminogen activators and their inhibitor in rat follicles during periovulatory periods. 313 65


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