UNIPROT:P00750 - FACTA Search

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Query: UNIPROT:P00750 (PLA)
16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The preovulatory surge of gonadotropins causes resumption of oocyte meiosis, rupture of follicle wall and release of a fertilizable ovum, and luteinization. In the present lecture, current studies of the biochemical mechanism of follicle rupture are discussed. Over the past decade the cyclooxygenase pathway of arachidonic acid metabolism, namely prostaglandins (PGs), has received considerable attention in ovulation studies. We studied the changes in ovarian levels of eicosanoids during ovulation and the effects of indomethacin or lipoxygenase inhibitors on ovulation and ovarian eicosanoids in PMSG/hCG primed immature rats. Our data demonstrate that lipoxygenase products, especially 15-hydroxyeicosatetraenoic acid (HETE), is more essential for the ovulatory process than PGs. Ovarian steroidogenesis shifts from estradiol to progesterone after LH surge. It is not yet clarified how progesterone participates in the ovulatory process. We studied the effects of epostane and RU486 on ovulation rate, ovarian levels of steroids and eicosanoids, ovarian 3 beta-HSD activity, and ovarian proteolytic enzymes (collagenase, plasminogen activator and kallikrein) activities in the rats. The results show that progesterone plays an important role in the initial 4 hours of the ovulatory process by regulating proteolytic enzyme activities, and that an autocrine regulation may take place in progesterone production during ovulation. Morphological studies have demonstrated dilation and increased permeability of follicle vasculature during ovulation. We investigated the relation between ovarian blood volume and progesterone, and the role of active oxygen in ovarian vascular permeability by using SM-SOD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Control mechanism of ovarian function]. 165 26

Proteose peptone (p.peptone) had an ability to induce tissue plasminogen activator (t-PA) production by human embryonic lung fibroblast, IMR-90 cells. We previously demonstrated that the induction was closely related to the activation of phospholipase A2 in the cells stimulated by p.peptone. In this report, we describe the involvement of arachidonate metabolism in the induction. The induction was inhibited in a dose-dependent manner by 5,8,11,14-eicosatetraenoic acid (ETYA), an inhibitor of both cycloxygenase and lypoxygenase, and also by nordihydroguaiaretic acid (NDGA), which in low concentrations selectively inhibits lipoxygenase. However, indomethacin, a specific inhibitor of cycloxygenase, had no effect on the induction. 5-hydroxyeicosatetraenoic acid (5-HETE), which is an arachidonate metabolite derived from lipoxygenase pathway, had an inductive effect, but prostaglandin E1 (PGE1), which is a metabolite from cycloxygenase pathway, had no effect on t-PA production by the cells. These results suggest that arachidonate metabolism is involved in the induction of t-PA production in IMR-90 cells by p.peptone, and that arachidonate metabolite(s) from lipoxygenase pathway is responsible for the induction.
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PMID:Possible roles of arachidonic acid and its metabolites in induction of tissue plasminogen activator (t-PA) production in human fibroblast, IMR-90 cells by proteose peptone. 173 58

The metabolism in vitro of exogenous and endogenous arachidonic acid was studied in circulating blood monocytes obtained from control (control group) and cholesterol (0.5%)-fed (cholesterol group) rabbits. The production of superoxide anion (O2-), tissue plasminogen activator (t-PA) and adherence of monocytes were assessed in both groups of animals. The amounts of cyclooxygenase and lipoxygenase products derived from exogenously added [1-14C]AA were not significantly different in monocytes collected from both groups of animals. However, the amounts of PGD2, TXB2 and PGE2 formed from endogenous substrate were decreased significantly in monocytes obtained from the cholesterol group compared to those from the control group. The production of immunoreactive LTB4 was not suppressed significantly in monocytes collected from the cholesterol group. The production of O2- and t-PA was suppressed significantly in monocytes obtained from the cholesterol group and these cells adhered onto glass surfaces more efficiently than control cells. Since the formation of prostanoids from endogenous but not exogenous substrate is reduced, an effect of cholesterol on the liberation of AA from phospholipid pools is implicated.
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PMID:Influence of cholesterol feeding on the production of eicosanoids, tissue plasminogen activator and superoxide anion (O2-) by rabbit blood monocytes. 301 60

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

P388D1 is a murine macrophage cell line which spontaneously secretes plasminogen activator (PA; activated function) and lysozyme (LYS; constitutive function). Compounds which decrease PA secretion without affecting LYS secretion have potential as "down-regulators" of macrophage function and, hence, of the immune system. Glucocorticoids (e.g., dexamethasone, IC50 less than 0.01 microM) and auranofin (IC50 = 1 microM) are positive in this model. In contrast, cyclooxygenase inhibitors (indomethacin, ibuprofen and piroxicam, all at 1 microM) boost PA secretion; lipoxygenase inhibitors (REV-5901, NDGA and piriprost, all at 10 microM) have little or no effect. Dexamethasone, but not auranofin, induces a urokinase-inhibitory activity which elutes between 0.13 and 0.19 M NaCl upon anion exchange HPLC (TSK-DEAE-5-PW). Fibrin overlay following SDS-PAGE of the HPLC peak reveals a urokinase-inhibitory band at approximately 90 Kd.
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PMID:Pharmacological modulation of plasminogen activator secretion by P388D1 cell line. 312 May 14

The long-acting antianginal drug molsidomine has been shown experimentally to reduce myocardial infarct size when administered prior to or after cardiac insult. This is due to several drug actions. Dilation of postcapillary capacitance vessels diminishes venous return, preload, heart dimensions, and myocardial oxygen consumption. Relaxation of stenosed conductive coronary arteries increases the perfusion of myocardial areas at risk of infarction due to enhanced collateral circulation. Increased regional blood supply nourishes predominantly subendocardial cardiac muscles as a result of reduction of extravascular coronary pressure, and resistance. The stable heart rate and cardiac contractility favor improved heart performance. The inhibition of platelet aggregation in vivo by molsidomine or its active metabolites, SIN-1 and SIN-1A, is linked to the stimulation of prostacyclin synthesis, inhibition of thromboxane release with induction of thrombosis and vasoconstriction, and enhanced concentrations of cyclic guanosine monophosphate. Dilation of coronary arteries after intracoronary administration of SIN-1, with inhibition of platelet aggregation by restrained release of adenosine diphosphate and stabilization of platelet membranes, facilitates the recanalization of stenosed arteries and reduces coronary muscle tone at the site of thrombosis. Activation of the human fibrinolytic system and drug-induced release of a plasminogen activator favor dysaggregatory effects. The drug's inhibiting actions on lipoxygenase products of arachidonate (e.g., 12-hydroperoxy-eicosatetraenoic acid and leukotrienes) may shift prostaglandin catabolism to cyclooxygenase products (e.g., prostacyclin) that protect against the expansion of ischemia and the induction of coronary spasm. Experimentally, the hemodynamic effectiveness of molsidomine can be antagonized by catecholamines (afterload effects) and dihydroergotamine (preload and afterload effects) respectively. Further clinical investigations will clarify the application of these mechanisms for the therapeutic success of the drug in human myocardial infarction.
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PMID:Molsidomine: alternative approaches to treat myocardial ischemia. 355 58

Production of plasminogen activator (PA) by granulosa cells (GC) and its stimulation by gonadotropins led to the suggestion that PA is involved in ovulation. However, whereas only LH may be regarded as the ovulation-inducing hormone in the rat, FSH was found to be much more potent than LH in enhancing PA production by GC. Assuming that the entire follicular wall, rather than isolated GC, is involved in follicular rupture, we have examined activity of PA in intact follicles. LH (NIH-LH-S23) was 5-fold more potent than FSH (NIH-FSH-S14), and purified ovine LH and FSH were equally potent in enhancing follicular PA activity. Furthermore, injection into the ovarian bursa of proestrous rats of epsilon-amino-caproic acid and benzamidine (0.05-0.25 mmol), inhibitors of serine proteases, including PA and plasmin, resulted in a dose-dependent inhibition of ovulation without causing changes discernible by histological examinations of the ovaries. Whereas steroids did not change basal follicular PA production in culture, addition of estradiol-17 beta [(E2) 1 microgram/ml] but not progesterone or testosterone, further enhanced LH-stimulated PA. Aminoglutethimide phosphate (10(-3) M) and 17 beta-formamidoandrost-4-en-3-one inhibited LH-induced increase in follicular PA and this inhibition was reversed by addition of E2. Intrabursal injection of indomethacin, an inhibitor of cyclooxygenase, and of nordihydroguaiaretic acid, an inhibitor of lipoxygenase pathway of arachidonic acid metabolism at doses which effectively blocked ovulation (0.3 mg/bursa) had no effect on PA content of the follicles. Likewise, indomethacin (10 microM) and nordihydroguaiaretic acid (100 microM) did not affect LH-stimulated PA in vitro. In conclusion, LH, the physiological trigger of ovulation is, at least, as potent as FSH in stimulating follicular PA activity. The role of serine proteases, most probably of PA and plasmin, in ovulation is further corroborated by a pharmacological approach. LH stimulation of follicular PA appears to be enhanced by E2 but is not mediated by arachidonic acid metabolites.
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PMID:Follicular plasminogen activator: involvement in ovulation. 391 2

Platelet-activating factor (PAF-acether; 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) induced the release of plasminogen activator in rat, both in vivo and in perfused hind legs. The released plasminogen activator was shown by immunologic and functional criteria to be tissue-type plasminogen activator (t-PA). Release of t-PA by PAF-acether could be inhibited by phospholipase inhibitors and by lipoxygenase inhibitors, but not by cyclooxygenase inhibitors. It is suggested that PAF-acether induces the release of t-PA from vascular endothelial cells by the (calcium-dependent) activation of a phospholipase-lipoxygenase pathway.
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PMID:PAF-acether-induced release of tissue-type plasminogen activator from vessel walls. 392 44

HeLa cells incubated with 12-O-tetradecanoylphorbol-13-acetate (TPA), and rat basophilic leukemia (RBL-1) cells incubated with calcium ionophore, showed increased levels of the protease plasminogen activator. These treatments have previously been shown to stimulate the cellular metabolism of arachidonic acid. The induction of plasminogen activator in both cell types was inhibited in a dose-dependent manner by 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid, two compounds known to inhibit arachidonate metabolism via lipoxygenases. In contrast, indomethacin, which selectively inhibits arachidonate metabolism via cyclooxygenase, was inactive. The levels of four enzyme markers in HeLa cells were unchanged by treatment with TPA plus the lipoxygenase inhibitors, indicating that the inhibitors did not exert their effects on plasminogen activator via general cell toxicity. HeLa cells preincubated with [3H]arachidonate and subsequently challenged with TPA produced small amounts of material with the chromatographic mobilities and resistance to indomethacin expected of hydroxylated fatty acids derived via lipoxygenase. RBL-1 cells have been shown previously to produce leukotrienes and other lipoxygenase metabolites when treated with calcium ionophore. Plasminogen activator in HeLa cells was stimulated by up to 2.5-fold by incubation with 0.5-2 micrograms/ml 5-hydroxyeicosatetraenoic acid. Our results suggest that the induction of plasminogen activator in HeLa and RBL-1 cells is not mediated by prostaglandins or thromboxanes, but may be mediated or modulated by arachidonate metabolites derived via a lipoxygenase pathway.
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PMID:Induction of plasminogen activator by 12-O-tetradecanoylphorbol-13-acetate and calcium ionophore. Suppression by inhibitors of fatty acid lipoxygenase. 640 51

Ovulation, recurring every midcycle of the mammalian female and triggered by a surge of luteinizing hormone (LH) released from the pituitary, is an essential prerequisite for fertilization and subsequent embryonic development. Here we shall describe two of the biological components of the ovulatory response, cumulus expansion (frequently denoted as cumulus maturation) and the rupture of follicular wall, both crucial for the release of a fertilizable ovum. The role of a proteolytic cascade and its regulation by eicosanoids will be emphasized in relation to follicle rupture. The new data implicating cumulus maturation as an essential step for the release of the ovum and the apparent mediatory role of interleukin-1 in this process will be presented. LH/hCG stimulates, in the preovulatory follicles, a cascade of proteolytic enzymes, including plasminogen activator (PA), plasmin and matrix metalloproteinase 1 (MMP-1). These enzymes bring about the degradation of perifollicular matrix and, most notably, the decomposition of the meshwork of collagen fibers which provides the strength to follicular wall. Furthermore, pharmacological blockage of any of these enzymes resulted in inhibition of follicle rupture. LH/hCG stimulates, in addition, an increase in ovarian production of eicosanoids. These include prostaglandins, obtained from arachidonic acid via the cyclooxygenase pathway and leukotrienes, the products of lipoxygenase. Previous studies from our and other laboratories have demonstrated the ability of inhibitors of cyclooxygenase and of lipoxygenases to suppress ovulation in several mammalian species. MK-886, which inhibits the translocation of 5-lipoxygenase (5-LO) from the cytosol and its binding to the membranal 5-LO activating enzyme, suppressed dose-dependently follicular rupture from the treated ovary. Zymographic analysis of ovarian extracts from PMSG/hCG-stimulated rats revealed a band of collagenolytic activity at 52kD, corresponding to human MMP-1 and at 72kD, corresponding to human MMP-2. Both activities were markedly stimulated by administration of hCG and were significantly inhibited by indomethacin, NDGA or MK-886. Thus, eicosanoids seem to mediate LH stimulation of follicular collagenase. Interleukin-1 (IL-1) has been recently implicated in ovulation. The ability of an IL-1 receptor antagonist (ra) to block ovulation in vivo and in vitro has been demonstrated recently. Morphological examination of the ovulatory follicles failing to ovulate suggests that this effect is exerted by inhibiting cumulus oophorus expansion and detachment from mural granulosa cells. In vitro, IL-1ra attenuated the action of hCG and FSH on cumulus expansion and follicular hyaluronic acid synthesis. Thus, IL-1 seems to mediate and/or facilitate gonadotropin action on cumulus expansion, and hence on ovulation.
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PMID:Ovulation as a tissue remodelling process. Proteolysis and cumulus expansion. 748 19

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