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

Several angiogenic preparations that have been shown to stimulate plasminogen activator (PA) and collagenase production by cultured bovine capillary endothelial (BCE) cells were tested for their ability to stimulate BCE cell motility in the phagokinetic track assay. Bovine retinal extract, medium conditioned by 3T3-F442A differentiated mouse adipocytes, SK HEP-1 human hepatoma cell lysate, mouse sarcoma 180 cell lysate, and medium conditioned by mouse sarcoma 180 cells stimulated motility 68.7%, 48.5%, 140.9%, 56.5%, and 102.1%, respectively, relative to untreated cells. The motility-stimulating activity of these preparations was dose dependent and linear over the 16-h assay period. Several hormones and growth factors were tested for BCE cell motility-stimulating activity, including insulin, vasopressin, fibroblast growth factor, and a partially purified preparation of sarcoma growth factor, and were found to be ineffective. 12-0-tetradecanoyl-phorbol-acetate (TPA), a potent stimulator of both PA and collagenase activities in BCE cells, also did not stimulate motility, indicating that protease production is not sufficient to stimulate BCE cell motility in this assay. Neither SK HEP-1 hepatoma cell lysate nor TPA was effective in stimulating motility in bovine aortic endothelial (BAE) cells. The inability of SK HEP-1 hepatoma cell lysate to stimulate movement in BAE cells is consistent with the observation that angiogenesis occurs by sprouting of capillaries, not large vessels.
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PMID:Stimulation of motility in cultured bovine capillary endothelial cells by angiogenic preparations. 632 76

Activity of secreted plasminogen activator (PA) by ZR-75-1 human breast cancer cells in culture is shown to be altered by the addition of physiologically relevant concentrations of the hormones 17 beta-estradiol (E2), insulin, and dexamethasone. After 48 h, E2 stimulated PA activity 6-fold at concentrations as low as 10(-12) M. This stimulation was prevented by the addition of actinomycin D and cycloheximide. The antiestrogen tamoxifen reduced estrogen stimulation of PA, but had slight stimulatory effects on PA secretion by itself. Insulin (5 X 10(-10) M) induced a 2-fold increase in PA activity. Effects of insulin and E2 were additive, suggesting independent sites of control of PA production. Dexamethasone (10(-8) M) decreased PA activity by 20%, but did not inhibit cell growth at the concentration tested. These data suggest that secreted PA activity is differentially regulated by hormones and that effects of PA and growth do not occur in parallel.
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PMID:Hormonal control of plasminogen activator secretion in ZR-75-1 human breast cancer cells in culture. 637 Jun 66

We have previously demonstrated that a short period of normoglycaemia obtained through an artificial pancreas in uncontrolled insulin-dependent diabetics improves parameters of the functional microangiopathy such as erythrocyte deformability and platelet aggregation. Because recently an immunoradiometric assay for tissue plasminogen activator (t-PA) was developed we measured t-PA levels in 18 uncontrolled insulin-dependent diabetics before and after 24 hr of normoglycaemia induced by insulin to look for a modification of endothelial cells function. After 24 hr of strict control, plasma free insulin levels rose significantly, total t-PA R-Ag, its active fibrin binding fraction and euglobulin fibrinolytic activity were significantly decreased. These results suggest a responsibility for insulin in the decrease in t-PA blood level and could explain at least partially the relation between hyperinsulinism, thrombosis and atherogenesis.
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PMID:Effect of 24 hours of normoglycaemia on tissue-type plasminogen activator plasma levels in insulin-dependent diabetes. 637 55

Changes in plasma growth hormone (GH), factor VIII related antigen (VIIIR:Ag), and plasminogen activator activity (PAA) during exercise were evaluated in 50 insulin-dependent diabetics. In patients with a short to moderately long duration of diabetes (5-19 years, mean 11), GH increased only in those with retinopathy. VIIIR:Ag and PAA increased most pronouncedly in retinopathy patients as well. In diabetics with long duration of the disease (21-49 years, mean 35), GH, VIIIR:Ag and PAA increased almost equally in those with and without retinopathy.
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PMID:Growth hormone and endothelial function during exercise in diabetics with and without retinopathy. 642 Oct 91

Islets of Langerhans isolated from rat pancreas contain and secrete plasminogen activator (PA). Production of PA is increased up to 15-fold by culture in the presence of high concentrations of glucose, and the dose-response curves for the effect of glucose on secretion of PA and on insulin are superimposable. Alloxan, a diabetogenic agent that is selectively cytotoxic for beta cells, abolishes the PA response to glucose. Various agents and hormones that affect beta-cell function affect the secretion of PA in a manner parallel to their modulation of insulin secretion. These observations suggest that PA is produced by beta cells and that enzyme synthesis and secretion are regulated in concert with those of the hormone. The potential role of PA and of plasmin in the physiology of the islets is considered. In particular, because plasmin cleaves proinsulin to a product that is electrophoretically indistinguishable from insulin, it is suggested that the PA/plasmin system may play a part in the conversion of proinsulin to the active hormone.
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PMID:Plasminogen activator of islets of Langerhans: modulation by glucose and correlation with insulin production. 644 26

In primary cultures of ovine thyroid cells, a high level of plasminogen activator (PA) activity was detected in the culture media. This level is much higher than in primary cultures of Sertoli cells, granulosa cells, and pituitary cells. PA activity increased with time in culture and was regulated by TSH and insulin. Activity gel analysis of the culture media revealed a major band of 43,000 daltons and a minor one of 70,000 daltons, suggesting the presence of both of the urokinase-type and the tissue-type PA in the media.
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PMID:Thyrotropin regulation of plasminogen activator activity in primary cultures of ovine thyroid cells. 654 81

Two unrelated multipotent embryonal carcinoma cell lines, OC-15S1 and 1003, have been cultured in hormone-supplemented defined media in order to identify the signals that influence their differentiation. Previous studies have shown that F9 embryonal carcinoma cells can be grown for many generations in the defined medium, EM-3, which contains fibronectin, insulin, and transferrin in place of serum. F9 cells, which only differentiate into a few cell types, undergo little or no differentiation in EM-3 unless an inducer is present (A. Rizzino and C. Crowley, 1980, Proc. Nat. Acad. Sci. USA 77, 457-461). This report demonstrates that, in contrast to F9, OC-15S1 and 1003 embryonal carcinoma cells do not proliferate in EM-3. Instead, the cells differentiate. However, the differentiated cells do not survive in EM-3 unless it is supplemented with factors such as purified serum lipoproteins. In EM-3 containing high-density lipoprotein, a population of differentiated cells, devoid of embryonal carcinoma cells, is formed. The differentiated cells that appear exhibit an epitheloid morphology throughout the culture. These cells also secrete plasminogen activator and two different criteria argue that it is the type released by parietal endoderm. This suggests that, under the influence of the defined medium, both multipotent embryonal carcinoma cell lines differentiate at high frequency into parietal endoderm. It was also determined that fibronectin promotes the differentiation of OC-15S1 and 1003 in serum-containing media, and this suggests that fibronectin is at least partly responsible for the differentiation observed in EM-3 plus high-density lipoprotein. In light of these findings, it is suggested that fibronectin may directly influence cellular differentiation during early mammalian development.
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PMID:Two multipotent embryonal carcinoma cell lines irreversibly differentiate in defined media. 668 83

A low plasminogen activator response to venous occlusion is frequently found in diabetes. The aims of this investigation were to study any relationships between plasminogen activator activity and autonomic neuropathy (AN), and between abnormal toe temperature reactions and AN. Asymptomatic AN is frequently found in insulin dependent diabetics. The results might be an abnormal balance between the parasympathetic and sympathetic innervation of the vessels, which in turn will lead to a change of the reaction to cooling of the feet followed by indirect heating. In this study 52 insulin dependent diabetics were examined with a combination of tests for AN and blood flow measurements as well as plasminogen activator activities of the blood and vascular walls. In patients with a short duration of diabetes (mean 11 years) the prevalence of AN was high in those with abnormally slow increase in toe temperature after cooling followed by indirect heating. The mechanism behind appeared to be a functional vasospasm. In diabetics of short as well as of long duration (mean 35 years), an abnormally low plasminogen activator activity of the blood during venous occlusion was found in those without AN, while those with AN showed a normal activity. Thus, AN might influence the deterioration of the circulation in diabetes.
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PMID:Endothelial factors, toe temperature and leg circulation in diabetics with and without autonomic neuropathy. 681 Apr 94

This paper describes a method for obtaining cultures of rat ventral prostate epithelial cells. The prostate is first perfused with a collagenase solution before removal from the animal; subsequent mincing and incubation in vitro produces a suspension of alveolar cell clumps. Upon incubation, these clumps attach to the surface of the culture dish and spread into discrete epithelial cell colonies, which both retain differentiated morphology, and secrete a species of plasminogen activator that is characteristic of prostatic tissue. These properties were not observed in cultures prepared from single cell suspensions of the same organ. Maintenance of epithelial colony integrity and secretory activity specifically required the continued presence of stromal cells, glucocorticoids and insulin. Androgenic steroids were much less effective than glucocorticoids in stimulating plasminogen activator secretion and in maintaining colony integrity, in spite of the well-established androgen dependence of prostatic tissue morphology in vivo and in organ culture. Furthermore, no effects of prolactin were observed, either when this hormone was tested alone or in conjunction with steroid hormones. Of 3 retinoids tested, retinal was highly cytotoxic at concentrations in the range of 1 microM, whereas retinol and retinoic acid were without detectable effect.
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PMID:The culture of hormone-dependent epithelial cells from the rat ventral prostate. 699 12

The effect of the antiestrogens tamoxifen and nafoxidine on the growth of the human breast cancer cell line MCF-7 is modified by both serum and insulin. Tamoxifen inhibition of the growth of MCF-7 cells in culture is reduced as the concentration of serum in the medium is increased from 0.1% to 5 to 10%. Estradiol does not stimulate cell growth over the same range of serum levels. Insulin changes the sensitivity of MCF-7 cells to both estrogen and antiestrogens. Cells growing in media containing insulin are less sensitive to inhibition by either tamoxifen or nafoxidine than are cells growing in its absence. In addition, higher concentrations of estradiol are required to stimulate the production of plasminogen activator when cells are grown in media containing insulin. This effect of insulin can be accounted for by the finding that insulin lowers the level of estrogen receptor in MCF-7 cells without altering the binding constant for the hormone. Cells grown with insulin have an average of 21,000 +/- 4,700 (S.D.) estrogen binding sites/cell compared to 62,000 +/- 9,700 sites/cell in cells grown in the absence of insulin. This difference in receptor level is sufficient to account for the difference in the concentration of estradiol needed for equivalent induction of plasminogen activator in cultures with or without insulin. These results indicate that the level of estrogen receptor in breast cancer cells can be changed and that the sensitivity of such cells, both to estrogen and to antiestrogens, is altered by changes in the level of estrogen receptor. They also have implications concerning the mechanism by which antiestrogens act to inhibit the growth of mammary tumor cells.
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PMID:Effects of serum and insulin on the sensitivity of the human breast cancer cell line MCF-7 to estrogen and antiestrogens. 700 31


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