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)

Hormonal regulation in the production of a plasminogen activator (PA) was studied in rat hepatocytes in primary culture. Insulin and epidermal growth factor had no effect on the hepatic PA activity. However, glucagon and epinephrine augmented the activity, whereas dexamethasone suppressed it by lowering the production of hepatic PA rather than by inducing plasmin inhibitors or a plasminogen activator inhibitor (PAI). Dibutyryl cAMP, an analogue of cAMP, also augmented hepatic PA activity. The augmented activity level was lowered by either H-8, cycloheximide, or actinomycin D, suggesting that A-kinase and protein biosynthesis are closely associated with the augmentation. Glucocorticoid and hormones that act to raise the intracellular cAMP level may participate in hepatic PA production by the liver.
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PMID:Hormonal regulation of plasminogen activator production by rat hepatocytes in primary culture. 238 27

Sertoli cells (SC), plated onto an extracellular matrix-coated membrane mounted in a two-chambered assembly, secrete both transferrin and plasminogen activator (PA) into each chamber. Although transferrin concentrations are greatest in the inner chamber, concentrations of PA activities in the outer chamber are equal to or higher than those in the inner chamber. These data indicate that transferrin and PA are preferentially secreted in different directions. The addition of FSH or cAMP derivatives stimulates the formation and secretion of tissue-type PA. Addition of FSH enhances the polarized secretion of PA into the outer chamber, as measured by elevated ratios of outer to inner compartment PA concentrations. Ratios of PA to transferrin concentrations in the outer compartment are also increased in FSH-treated preparations, demonstrating that the differential secretion of the two products is enhanced by FSH. We interpret these data to indicate that polarized SC preferentially secrete transferrin apically while preferentially secreting PA basally, and that FSH augments this polarity of SC maintained in the two-chamber assembly. The addition of peritubular cells to the system results in decreased levels of total PA activity, with greatest diminution evident in the outer compartment. Data are consistent with previous observations that peritubular cells decrease PA activity by secreting a specific inhibitor of PA. Measurements of relative amounts of transferrin and PA secreted into inner and outer chambers, respectively, provide a means to evaluate the tightness of the seminiferous tubule barrier in the model system and the extent of polarized secretion by SC in the two-chambered assembly.
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PMID:Control of levels of plasminogen activator activity secreted by Sertoli cells maintained in a two-chamber assembly. 245 45

Recent studies conducted in our laboratory have demonstrated that plasminogen activator (PA) is present in granulosa cells collected from the largest preovulatory follicle in the ovary of the domestic hen, and that its activity can be modulated by a variety of hormones in vitro. The present study was conducted to evaluate the intracellular mechanisms involved in the control of hen granulosa cell PA activity through the use of physiological and pharmacological agents. Treatment of granulosa cells with increasing doses (1, 10, and 50 ng/tube) of ovine LH resulted in a significant reduction of PA activity, which was accompanied by an increase in intracellular levels of cAMP. Furthermore, the effects of LH were potentiated by cotreatment with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 mM). Exposure of cells to increasing concentrations of the adenylyl cyclase activator forskolin (0.005, 0.01, 0.05, and 0.1 mM) resulted in a significant reduction in PA activity at all doses given. Similarly, the presence of the cAMP analog 8-bromo-cAMP (0.005, 0.01, 0.05, 0.1, 0.5, 1.5, and 10 mM) caused a dose-dependent inhibition of PA activity from 0.005 to 1.0 mM, further suggesting the involvement of cAMP in the inhibitory regulation of hen granulosa cell PA activity. The induction of intracellular calcium mobilization through the use of the calcium ionophore A23187 (0.1, 0.5, 1, and 2 microM) resulted in a dose-dependent suppression of PA activity. By contrast, treatment of granulosa cells with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA; 0.5, 5, 10, 25, and 50 micrograms/tube), a compound that activates protein kinase-C, stimulated PA activity in a dose-dependent fashion; a non-tumor-promoting phorbol ester (phorbol 13-monoacetate; 0.5, 10, and 50 ng/tube) was without effect. Coincubation of granulosa cells with a submaximal dose of PMA (5 ng/tube) and low concentrations of A23187 (0.001, 0.005, 0.01, and 0.05 microM) could not significantly enhance the stimulatory effects of PMA on PA activity; however, higher concentrations of the ionophore (0.1, 0.5, and 1.0 microM) completely abolished PMA-stimulated PA activity. The stimulatory effects of PMA could also be eliminated by cotreatment with a protein kinase-C inhibitor (H-7; 100 microM), a mRNA transcription blocker (actinomycin-D; 5 micrograms/tube), or a protein synthesis inhibitor (cycloheximide; 50 micrograms/tube).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of a phorbol ester, a calcium ionophore, and 3',5'-adenosine monophosphate production on hen granulosa cell plasminogen activator activity. 245 14

F9 teratocarcinoma cells secrete the serine protease, tissue plasminogen activator (t-PA), upon differentiation induced in vitro by retinoic acid (RA) or RA and dibutyryl cAMP (RA/dbcAMP). A recombinant plasmid capable of directing the production of t-PA anti-sense RNA was constructed and transfected into F9 stem cells in an attempt to create a hypomorphic phenotype for t-PA synthesis. Several colonies were isolated which contained anti-sense RNA and which showed greater than a 50% reduction in t-PA activity upon differentiation. One such colony, 3b4, exhibited a 75% reduction in t-PA activity and was analyzed further. Large quantities of t-PA anti-sense transcript were expressed in the stem cells which are characterized by the absence of t-PA gene expression. In the induced cells, which normally express t-PA, the amount of detectable anti-sense transcript was significantly decreased. The amount of t-PA mRNA in differentiated cells containing t-PA anti-sense RNA was comparable to that in differentiated control cells. Subcellular localization of the mRNA in induced 3b4 cells appeared to be the same as induced control cells. Expression of collagen type IV, another marker of differentiation, was also monitored and was unaffected by the presence of t-PA anti-sense RNA in RA/dbcAMP-treated cells. The inhibition of differentiation-specific gene expression by anti-sense RNA may be useful for further studies of developmentally regulated genes.
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PMID:Anti-sense inhibition of tissue plasminogen activator production in differentiated F9 teratocarcinoma cells. 245 88

Factors have been identified that influence the integrity of the barrier generated by Sertoli cells (SC) in culture in a two-chambered assembly. The permeability of the barrier was assessed by determining rates of equilibration of [3H]methoxyinulin or [86Rb]Cl across the Sertoli cell monolayer. The complete system consisted of a confluent monolayer of SC maintained on an extracellular matrix (Matrigel)-coated filter together with peritubular cells on the opposite side of the filter. In confirmation of previous results, levels of plasminogen activator (PA) activity secreted were increased by treatment of SC with FSH or with cAMP derivatives [(Bu)2cAMP (dbcAMP)]. PA levels in the culture medium were inversely related to times required for 50% equilibration of [3H]methoxyinulin across the SC monolayer. Thus, elevated PA levels, elicited by stimulation with FSH or dbcAMP, were associated with a decreased integrity of the barrier generated by SC preparations maintained in serum-free medium in the complete system. The increase in permeability of the barrier in SC elicited by FSH dbcAMP could be prevented, however, by the addition of various antiproteases. FSH actions on barrier function were complex. Effects of FSH that favored barrier integrity were most readily detected when proteolytic activity was inhibited. The addition of intact serum increased the integrity of the barrier, but acid-treated serum depleted of antiproteases had no such effect. We advance the hypothesis that proteases are implicated in modulation of the formation and maintenance of the seminiferous tubule barrier by SC.
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PMID:Influences of follicle-stimulating hormone, proteases, and antiproteases on permeability of the barrier generated by Sertoli cells in a two-chambered assembly. 246 39

Pro-opiomelanocortin-derived peptides, alpha-MSH and beta-endorphin, are synthesized and secreted by Leydig cells, and are believed to have paracrine effects on Sertoli cells in the testis. Peptides with MSH activity stimulate adenylate cyclase and cAMP accumulation in Sertoli cell-enriched cultures. The purpose of the present study was to determine whether such peptides would affect Sertoli cell parameters, such as aromatase and plasminogen activator activities, that are known to be regulated by cAMP. alpha-MSH stimulated aromatase activity in Sertoli cell-enriched cultures prepared from 10-day-old rats and this effect was potentiated by methyl isobutylxanthine (MIX). The combination of alpha-MSH plus MIX was not as potent as FSH. alpha-MSH, des-acetyl-alpha-MSH, beta-MSH, ACTH(1-13), and ACTH(1-24) stimulated aromatase activity to a similar extent, suggesting that Sertoli cells do not distinguish between the activities of these peptides. alpha-MSH potentiated the action of dbcAMP and forskolin on Sertoli cell aromatase, but unexpectedly had no effect on the action of either half-maximal or maximal doses of FSH. The regulation of plasminogen activator was examined next; urokinase was markedly suppressed by FSH in 10-day-old Sertoli cells. Although neither alpha-MSH nor MIX alone had an effect on urokinase secretion, in combination they were as effective as FSH. In 10-day-old Sertoli cells each of these peptides had little or no effect on tissue plasminogen activator.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Estradiol and plasminogen activator secretion by cultured rat Sertoli cells in response to melanocyte-stimulating hormones. 247 57

Primary cultures of rat hepatocytes produce tissue-type plasminogen activator (tPA) and plasminogen activator-inhibitor type 1 (PAI-1). Incubation of hepatocytes with 50 microM 8-(4-chlorophenylthio)cAMP (CPT-cAMP) results in a 4-fold increase in tPA activity, whereas the synthetic glucocorticoid dexamethasone (1 microM) causes a more than 90% decrease. In combination, dexamethasone completely overcomes the CPT-cAMP effect and markedly decreases PA activity. PAI-1 is induced by both CPT-cAMP and dexamethasone, and the effects of these agents are additive. Accumulation of tPA mRNA is increased more than 4-fold by CPT-cAMP and is greatly decreased by incubation with dexamethasone. Dexamethasone in combination with CPT-cAMP totally blocks this cAMP effect. The protein synthesis inhibitor cycloheximide does not prevent either the dexamethasone-induced decrease or the CPT-cAMP-induced increase in tPA message and, in fact, augments the cAMP-induced increase in tPA mRNA. Hepatocyte PAI-1 mRNA levels are increased 2-fold by incubation with either CPT-cAMP or dexamethasone; in combination, these effectors cause a 4-fold increase in PAI-1 mRNA. Cycloheximide alone causes a marked increase in PAI-1 mRNA, but does not block the induction by either CPT-cAMP or dexamethasone. We conclude that incubation of hepatocytes with CPT-cAMP induces tPA activity by increasing tPA mRNA accumulation and that dexamethasone causes a decrease in tPA activity by both decreasing tPA mRNA and increasing PAI-1 mRNA and activity. Concomitant protein synthesis is not required for the regulation of tPA or PAI-1 mRNA by either CPT-cAMP or dexamethasone, indicating a primary effect of these agents on gene transcription or mRNA stability.
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PMID:Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor gene expression in primary cultures of rat hepatocytes. 253 89

The fibrinolytic enzyme profile of SMS-KAN human neuroblastoma cells was found to vary dramatically during the differentiation process. Five maturational agents--retinoic acid, dibutyryl cAMP, 5-bromodeoxyuridine, sodium butyrate and phorbol myristate acetate were tested for their effects on cellular morphology, DNA synthesis, plasminogen activator (PA) and PA inhibitor (PAI) activity. SMS-KAN cells secrete urokinase (UK) and tissue PA (tPA) as well as a possibly unique PAI. Treatment of cells with 1 microM RA resulted in an inhibition of proliferation, extension of neurite-like processes indicative of differentiation, as well as a switch from secretion of UK to tPA and a reduction in PAI secretion. Other agents which caused neural process formation and decreased cell proliferation also induced alterations in PA/PAI while agents which had no detectable effect on cell growth induced little change in the fibrinolytic enzyme profile.
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PMID:Alterations in plasminogen activator and inhibitor activity during the differentiation of a human neuroblastoma cell line, SMS-KAN. 253 81

Recent reports suggest that epidermal growth factor (EGF) or related peptides may act as local hormones to regulate granulosa cell differentiation. While FSH and GnRH are known to stimulate accumulation of tissue-type plasminogen activator (tPA) mRNA in granulosa cells, studies using nonovarian cells have shown stimulation of tPA by EGF. In this study, the effect of EGF and its structural analog transforming growth factor-alpha (TGF alpha) on ovarian tPA mRNA and activity was investigated. Granulosa cells obtained from immature estrogen-treated rats were cultured with FSH or increasing doses of EGF or TGF alpha before analysis of tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by a fibrin overlay technique. Like FSH and GnRH, EGF and TGF alpha stimulated the secretion of tPA activity in a dose- and time-dependent manner (onset, 12 h; maximum, 48 h). Northern blot hybridization of total RNA using a rat cRNA probe for tPA showed the accumulation of a 22S species mRNA in cells treated with EGF or TGF alpha, but not with nerve growth factor, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells confirmed a time-dependent increase in tPA mRNA preceding that in enzyme activity. Cotreatment of a saturating dose of EGF with phorbol myristate acetate (PMA) or GnRH resulted in additive increases in both tPA enzyme activity and mRNA levels. In addition, pretreatment with PMA desensitized the cells to subsequent treatment with PMA or GnRH, but did not diminish EGF-induced tPA mRNA, suggesting that EGF acts through a pathway independent of protein kinase-C. Also, extracellular cAMP levels did not increase with EGF treatment in the presence or absence of a phosphodiesterase inhibitor, suggesting the lack of involvement of the protein kinase-A pathway. Suppression of protein synthesis by cycloheximide inhibited the induction of tPA mRNA by EGF, whereas similar treatment resulted in the superinduction of tPA mRNA in FSH-treated cells, suggesting that EGF and FSH do not share the same pathway. These results suggest that EGF and TGF alpha induce tPA mRNA and activity in granulosa cells through a pathway independent of protein kinases-A (FSH) and -C (GnRH and phorbol ester), providing an interesting model for future elucidation of the molecular mechanism involved in tPA gene expression.
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PMID:Epidermal growth factor stimulates tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells: mediation by pathways independent of protein kinases-A and -C. 254 97

The sequence of events within the ovary during the process of ovulation discussed in this review is schematically represented in Fig. 1. It is obvious that LH, perhaps with some contribution from FSH, is the normal physiological trigger for the ovulatory sequence of events, and it appears from the available information that the effects of LH are mainly mediated via adenylate cyclase and increased cAMP levels. The cAMP in turn, via cAMP-dependent protein kinase, influences at least three distinct steps in the ovulatory process which seem to be of crucial importance, namely 1) the stimulation of steroidogenesis; 2) the stimulation of cyclooxygenase/lipooxygenase leading to increased prostaglandin/leukotriene synthesis; and 3) the stimulation of plasminogen activator which catalyzes the conversion of plasminogen to plasmin. A fourth crucial step in the ovulatory mechanism is the LH-induced increase in latent collagenase, but it remains to be determined if this step is mediated via cAMP. Concomitant with the increase in latent collagenase, there also appears to be an LH-dependent increase in collagenase inhibitors. The latent collagenase is then activated, and it appears that leukotrienes and prostaglandins, as well as plasmin, may be involved in this process. The active collagenase causes a digestion of the collagen in the follicle wall, and plasmin, as well as possibly other proteolytic enzymes such as proteoglycanases, may cause a further dissociation of the follicular wall. These processes of digestion of collagen and dissociation of the collagen fibers result in an opening in the follicular wall with the formation of the stigma and rupture. While the weakening of the follicular wall takes place throughout the entire wall, rupture remains for the most part a localized process at the apex of the follicle. This localization of the rupture may be explained on the basis of mechanical factors operating when the follicle wall thins and weakens. While it is clear that prostaglandins and leukotrienes can influence smooth muscle by causing contractions and that these compounds can cause vascular changes such as increased permeability, vasodilation, and vasoconstriction, it is not clear what the exact role of these latter processes are in ovulation. It appears that progesterone and not estrogen play an important role in the mechanism of LH-induced follicular rupture, but the locus of action of progesterone and its mechanism of action remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mechanism of mammalian ovulation. 255 97

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