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 in vitro effects of mercuric chloride and vanadate were examined on two functions of mouse peritoneal macrophages, i.e., the superoxide anion production and the plasminogen activator (PA) activity. Vanadate, at concentrations which do not affect the viability of the cells, does not seriously alter any of these functions. High concentrations of mercury depress the respiratory burst; this effect results from loss of the reducing properties of cellular NADPH. Low concentrations of mercury stimulate the effect of phorbol 12-myristate 13-acetate on PA activity. The mechanism of this stimulation does not involve the protein kinase C system. It is hypothesized that mercury could enhance the synthesis of PA, its translocation to the cell surface, or its binding to the membrane receptors.
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PMID:In vitro effect of mercury and vanadium on superoxide anion production and plasminogen activator activity of mouse peritoneal macrophages. 282 91

Phospholipases (PL) A-2 and C stimulated the outputs of prostaglandin (PG) F-2 alpha, PGE-2 and 6-keto-PGF-1 alpha from the Day-7 and Day-15 guinea-pig uterus superfused in vitro. PLC had a more pronounced effect than PLA-2, particularly on the output of PGE-2. The ratios of the outputs of PGF-2 alpha and PGE-2 were similar after stimulation by A23187 and PLA-2, but this ratio was lower after stimulation by PLC. It appears that the stimulation of endometrial PGF-2 alpha synthesis by Ca2+ is via activation of PLA-2 rather than via activation of PLC, although the PLC used was of bacterial origin (which uses phosphatidylcholine as substrate) rather than of mammalian origin (which uses phosphatidylcholine as substrate). Forskolin (which increased endometrial and myometrial cyclic AMP levels) and phorbol 12-myristate-13-acetate had no effect on uterine PG output, indicating that cyclic AMP and protein kinase C are not involved in the stimulation of endometrial PGF-2 alpha synthesis in the guinea-pig. Uterine PG output was not stimulated by 54 mM-KCl, which shows that the pulsatile nature of endometrial PGF-2 alpha synthesis and release is not due to an intermittent, synchronous depolarization of the endometrial cells.
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PMID:Effects of various factors on prostaglandin synthesis by the guinea-pig uterus. 311 14

FSH and GnRH both stimulate rat granulosa cells to produce tissue-type plasminogen activator (tPA). We have studied the molecular mechanisms involved in the action of these hormones by measuring tPA mRNA levels in primary cultures of rat granulosa cells. When granulosa cells were cultured in the presence of FSH or GnRH the level of tPA mRNA was increased 20- and 12-fold, respectively. The induction of tPA mRNA by FSH and GnRH was additive and the kinetics of induction differed. The effect of FSH could be mimicked by bromo-cAMP or forskolin, and was drastically enhanced by cotreatment with the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine. These findings are consistent with the notion that FSH mediates its effect through the protein kinase A pathway. GnRH is believed to augment phospholipid turnover in granulosa cells, leading to the activation of the protein kinase C pathway. Like GnRH, the protein kinase C activator phorbol myristate acetate also induced tPA mRNA in granulosa cells. In the presence of the protein synthesis inhibitor, cycloheximide, FSH-stimulated tPA message levels were enhanced by 30-fold, revealing superinduction of tPA mRNA levels by this pathway. In contrast the induction of tPA mRNA by GnRH was inhibited by cycloheximide indicating that the synthesis of an intermediate protein is required for the GnRH effect. Our data suggest that FSH and GnRH increase the tPA mRNA levels by two distinct pathways in cultured granulosa cells, providing a model system for studying the hormonal regulation of tPA gene expression.
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PMID:Hormonal regulation of tissue-type plasminogen activator messenger ribonucleic acid levels in rat granulosa cells: mechanisms of induction by follicle-stimulating hormone and gonadotropin releasing hormone. 313 93

The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.
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PMID:Role of non-TSH factors in thyroid cell growth. 347 6

Interleukin-1 (IL-1) is the name given to a family of related proteins showing a variety of activities. It was originally shown to be produced by monocytes and macrophages but is now known to be produced by numerous cell types, including synovial cells. From the point of view of arthritis, its most interesting activities are those on connective tissue cells in vitro. These include stimulation of production of prostaglandins, plasminogen activator and metalloproteinases such as collagenase and proteoglycanase. IL-1 is also mitogenic for synoviocytes and bone cells, and can alter rates of production of extracellular matrix constituents. The presence of IL-1 in synovial fluids from rheumatoid and osteoarthritic joints and its actions on connective tissues in vitro suggest that IL-1 may play an important role in the pathogenesis of arthritis. There are several potential cellular sources of IL-1 in the inflamed rheumatoid joint and interactions between these cells, T lymphocytes and plasma cells may continually induce IL-1 so contributing to the chronicity of the disease. The mechanism of action of IL-1 on connective tissue cells is at present uncertain though preliminary studies suggest that IL-1 may induce cellular responses by stimulating phosphoinositide turnover and possibly protein kinase C activity.
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PMID:The effect of interleukin-1 on connective tissue metabolism and its relevance to arthritis. 352 46

Tumor promoting phorbol esters and mezerein strongly induced plasminogen activator (urokinase, uPA) synthesis in porcine kidney cell cultures (LLC-PK1). Induction was due to increased uPA-mRNA levels which rose from 10 to 300 molecules/cell within 2 h of exposure to 16 nM phorbol myristate acetate. We have compared the action of tumor promoters with that of 8-bromo-cAMP, another potent inducer of uPA; the similarities between the two kinds of induction were: both involved transcriptional activation of the uPA gene; both were rapid in onset, changes in transcription rate being detectable within 10-20 min; the initial rates of transcription and uPA-mRNA accumulation were substantial and in the same order of magnitude; neither class of inducer required protein synthesis to stimulate uPA transcription. The main contrast between the two types of agents was that the uPA response to tumor promoters was transient whereas that to cAMP compounds was sustained: cultures rapidly lost their response to tumor promoters within 2 h after initial exposure while retaining responsiveness to cAMP-related agents. The cells developed a specific drug-induced desensitization which was slowly reversed after tumor promoters were removed from the culture medium. Since protein kinase C is now well established as the receptor for phorbol-derived and several other tumor promoters it will be of interest to determine whether desensitization occurs at the level of receptor.
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PMID:Induction and desensitization of plasminogen activator gene expression by tumor promoters. 386 68

We previously demonstrated that cultured human umbilical vein endothelial cells (HUVECs) overlaid with a fibrin clot induced a slight increase in tissue-type plasminogen activator (t-PA) secretion and marked reduction in plasminogen activator inhibitor-1 (PAI-1) secretion. In this study, the intracellular signal transduction after fibrin stimulation was further investigated by analyzing cyclic AMP (cAMP) and protein kinase C (PK-C). When HUVECs were stimulated by fibrin clots, t-PA mRNA increased to 130% but PAI-1 mRNA decreased to 42%. These changes concurred with the data on the protein levels of t-PA and PAI-1 as previously reported. The effect of fibrin on t-PA production in HUVECs was not significantly altered after the elevation of cAMP by either forskolin or dibutyryl cAMP. Furthermore, an effect of fibrin on t-PA production did not appear when the cells were treated by phorbol 12-myristate 13-acetate (PMA) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7). The suppressive effect of fibrin on PAI-1 secretion from HUVECs was not altered by elevation of cAMP. Regarding the activation of PK-C by PMA, PAI-1 secretion was enhanced, but was suppressed by fibrin stimulation. H-7 suppressed PAI-1 secretion and further stimulation by fibrin almost completely abolished PAI-1 secretion. These changes were well associated with mRNA levels of t-PA and PAI-1. These results suggested that fibrin on HUVECs preferably down-regulates PK-C resulting in a decrease of PAI-1 in both the protein and mRNA levels and that effect of fibrin on t-PA secretion is neither involved in PK-C nor cAMP pathway.
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PMID:Effects of fibrin on the secretion of plasminogen activator inhibitor-1 from endothelial cells and on protein kinase C. 767 18

Tissue-type plasminogen activator (tPA) secretion is a specific response of Sertoli cells to follicle-stimulating hormone (FSH), which is lower after preincubation of the cells with low FSH concentrations because of FSH receptor/Gs protein uncoupling. In this report, we present evidence that this desensitization induced by the lowest FSH concentrations is suppressed by specific peptidic inhibitors of endogenous PKA and PKC in permeabilized Sertoli cells. In contrast, desensitization promoted by slightly higher FSH concentrations is not mediated through PKA or PKC activation but is dependent on protein neosynthesis.
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PMID:Protein kinases and protein synthesis are involved in desensitization of the plasminogen activator response of rat Sertoli cells by follicle-stimulating hormone. 792 33

The plasminogen activator urokinase promotes tumor invasion by converting plasminogen into plasmin, which degrades several extracellular matrix components. Urokinase can bind to a specific cell surface receptor, which leads to accelerated plasmin production. While there is good evidence indicating a role for this binding site in tumor invasion/metastasis, there is little information concerning the regulation of urokinase receptor expression in invasive cancer. To address this question a series of colon cancer cell lines, which demonstrate either a high or low ability to invade an extracellular matrix-coated porous filter, was characterized for receptor expression at the transcriptional and post-transcriptional levels. The invasive cell lines possessed 10-fold more receptors than their non-invasive counterparts as shown by cross-linking experiments and by Western blotting. Northern blotting indicated that this disparity in receptor number could be largely accounted for by a different amount of steady-state mRNA encoding the binding site. However, neither gene amplification nor enhanced mRNA stability could account for the augmented receptor protein observed for the invasive colon cancer cell types. In contrast, nuclear run-on experiments with representative cell lines revealed that the 10-fold difference in receptor display between the invasive-competent and invasive-deficient cells could be largely accounted for by differences in transcription rates. Transcription of the u-PAR gene in the receptor-deficient GEO cells, but not in the receptor-rich RKO cells, could be augmented by protein kinase C stimulation. These findings provide a clear rationale for studies to determine if the urokinase receptor promoter in invasive colon cancer is activated in cis or in trans.
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PMID:Transcriptional activation of the urokinase receptor gene in invasive colon cancer. 807 48

A plasminogen activator (PA) system is involved in ovulation, implantation, tumor invasion and metastasis. In order to clarify the regulation of this PA system in endometrial cells, we examined which agent affecting cellular function altered tissue-type plasminogen activator (t-PA) secretion by endometrial carcinoma cell line (KLE cells) in vitro. Triiodothyronine, retinoic acid, insulin, 8-bromo-cAMP, PDGF, IGF-I, basic FGF or TNF-alpha did not alter t-PA secretion while the activator of protein kinase C, phorbol myristate acetate (PMA) stimulated t-PA secretion in a dose-dependent fashion (10(-10)-10(-8) M). The time required to give a statistically significant increase in t-PA over control was 3 hours, and the maximal increase was seen after 24 hours of exposure. Another active phorbol ester, PDD also stimulated t-PA secretion while inactive forms of phorbol ester, 4 alpha-PDD and phorbol did not alter it. Cholera toxin or 8-bromo-cAMP did not affect t-PA secretion, but enhanced PMA-stimulated t-PA secretion. Cycloheximide and actinomycin D completely abolished PMA-stimulated t-PA secretion. These results suggest that (1) t-PA secretion in the endometrial carcinoma cell is modulated by a protein kinase C system, (2) This effect is through new RNA production and protein synthesis. (3) There is a complicated relationship between protein the kinase C and protein kinase A system as to the regulation of t-PA secretion. This would be a suitable model to clarify the PA system in endometrial cells.
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PMID:[Effect of phorbol ester on tissue-type plasminogen activator (t-PA) secretion in endometrial carcinoma cell line in vitro]. 812 84


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