Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelial cell (EC) urokinase receptor plays an important role in the localization and receptor-mediated activation of EC-bound plasminogen and hence surface-localized fibrinolysis. Thrombin induced a rapid (< 5 minute), time- (0 to 30 minutes) and dose- (0.1 to 8 U/mL) dependent decrease in the specific binding of 125I-labeled two-chain urokinase-type plasminogen activator (tcu-PA) or diisopropylfluoro-phosphate-tcu-PA to urokinase-type plasminogen activator receptor (u-PAR) in cultured ECs from various sources (range, 21% to 50%). The thrombin receptor activation peptide but not control peptide showed a similar but reduced decrease in the specific binding of 125I-labeled tcu-PA to u-PAR. Incubation of thrombin-treated cultures (10 to 12 hours) in complete medium restored 125I-labeled tcu-PA ligand binding to normal levels. u-PAR mRNA levels rapidly (1 hour) increased and peaked 10 to 12 hours after thrombin treatment as analyzed by reverse transcriptase-polymerase chain reaction. Decreased thrombin-induced 125I-labeled tcu-PA binding correlated with the time-dependent decrease in surface-localized plasmin generation, as measured by the direct activation of 125I-labeled Glu-plasminogen and quantification of the 20-kD light chains of 125I-labeled plasmin. After incubation with thrombin, plasmin generation was decreased 50% to 56% (125 to 152 fmol/3 to 3.5 x 10(4) cells). Isolation of metabolically labeled 35S-labeled u-PAR from the media of thrombin and phospholipase C-treated human aortic cultures yielded approximately 10- and approximately 12-fold more 55-kD M(r) and approximately 6-fold more 35-kD M(r) 35S-labeled u-PAR forms than control cultures, respectively. The u-PAR antigen forms (M(r), 54 kD) and the glycosyl-phosphatidylinositol-anchored protein CD59 (M(r), 20 kD) were also simultaneously identified by immunoprecipitation in the media of thrombin-treated cultures. This suggests that thrombin may release u-PAR and decrease u-PA ligand binding through a common pathway involving phospholipase C. These results establish a novel interrelation between thrombin and EC fibrinolysis and suggest that thrombin may also have an additional regulatory role in the net expression of surface-localized EC fibrinolytic activity.
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PMID:Thrombin decreases the urokinase receptor and surface-localized fibrinolysis in cultured endothelial cells. 774 51

Rat glomerular epithelial cells were grown to confluency on semipermeable tissue culture inserts and the plasminogen system of these cells was analyzed using enzyme assays, Western analysis, zymography, and reverse transcriptase-PCR. The glomerular epithelial cells are capable of activating exogenous plasminogen to plasmin by endogenous plasminogen activators. The cells produce both tissue-plasminogen activator and urokinase-plasminogen activator with urokinase being the prominent activator. Both activators are present primarily on the basolateral side of the cells with urokinase found primarily at the cell surface presumably bound to its receptor and tissue-plasminogen activator found primarily in the matrix secreted by the cells on the semipermeable insert. The cells also produce plasminogen activator inhibitor-1 and urokinase-plasminogen activator receptor. Inhibition of plasminogen activation occurred with plasminogen activator inhibitor-1, anti-catalytic anti-tissue-plasminogen activator antibody, epsilon-aminocaproic acid, which inhibits the binding of plasminogen through its lysine binding sites, and amiloride, which specifically inhibits urokinase.
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PMID:Analysis of the plasminogen system on rat glomerular epithelial cells. 779 90

8701-BC is a recently characterized cell line isolated from a primary ductal infiltrating carcinoma of the breast (d.i.c.), showing some pleomorphism in cell microanatomy at an ultrastructural level. We have obtained different sublines of 8701-BC cells by cloning in soft agar at different concentrations (0.3% and 0.6%), and we have characterized the cloned lines by some morphological and growth parameters. 8701-BC cells and clones have been submitted to analysis by reverse transcriptase-linked polymerase chain reaction to detect mRNAs of various cytokines (transforming growth factor-beta s, tumour necrosis factors, interleukin 1s, interleukin 6, parathyroid hormone-related peptide, gamma interferon) and of urokinase, which are bioactive molecules commonly involved in cell-cell and cell-stroma interactions at primary and/or secondary sites of invasion. The aims of the present investigation were to determine: (a) if the corresponding genes are active in 8701-BC cell line and (b) if the sublines tested exhibit transcriptional heterogeneity. The results obtained show that 8701-BC cells express transcripts of transforming growth factor-beta s, urokinase and parathyroid hormone-related peptide (PTHrP), the latter product being responsible for the cancer-associated humoral hypercalcemic syndrome. Moreover, while the first two mRNAs are detectable in all the sublines tested, PTHrP is expressed almost uniquely by the clones isolated in 0.6% agar which exhibit a peculiar morphological appearance, a higher growth rate and a more active invasive behaviour in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor-beta 1, beta 2, and beta 3, urokinase and parathyroid hormone-related peptide expression in 8701-BC breast cancer cells and clones. 829 80

We examined mRNA expressions of urokinase-type plasminogen activator (u-PA), its specific receptor (u-PR), and plasminogen activator inhibitors (PAI-1 and PAI-2) in 50 human breast cancers by the reverse transcriptase-polymerase chain reaction method. The expressions of the genes are discussed in relation to the clinicopathological findings. In the overall population in breast cancers, a low level of PAI-2 expression was significantly associated with lymph node involvement (P < 0.0001). The u-PA, u-PR, and PAM expressions tended to be at high levels in such metastatic cancers. Also, positive expression of u-PA, u-PR, and PAI-1 was significantly correlated with negative expression of PAI-2. These results indicate that PAI-2 may play a critical role in the regulation of extracellular matrix degradation during tumor cell invasion and metastasis, and the expression of PAI-2 may be useful as a marker to evaluate the prognosis of breast cancers.
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PMID:Inverse correlation between mRNA expression of plasminogen activator inhibitor-2 and lymph node metastasis in human breast cancer. 864 85

Rat proximal tubular epithelial cells derived from Wistar-Kyoto and spontaneously hypertensive rats were grown to confluency on semipermeable tissue culture inserts, and the plasminogen system of these cells was analyzed using enzyme assays, Western analysis, zymography, and reverse transcriptase-polymerase chain reaction. The tubular epithelial cells are capable of activating exogenous plasminogen to plasmin by endogenous plasminogen activators. The cells produce tissue-plasminogen activator, urokinase-plasminogen activator, plasminogen activator inhibitor-1, and urokinase-plasminogen activator receptor. These cells also produce the Heymann nephritis autoantigen, gp330 (megalin), and an associated protein of 45 kd (RAP). Incubation with transforming growth factor-beta 1 resulted in a decrease in plasminogen activation, primarily because of an increase in plasminogen activator inhibitor-1 RNA and protein and a decrease in u-PA RNA as noted by quantitative reverse transcriptase-polymerase chain reaction, Western analysis, and zymography. Incubation of these cells with tumor necrosis factor-alpha resulted in an increase in plasminogen activating ability, presumably through an increase in urokinase. Gp330 and the associated 45-kd protein (RAP) RNA were decreased in cells treated with tumor necrosis factor-alpha. The data presented indicates that these transformed proximal tubular epithelial cells may be used to study changes that may occur during Heymann nephritis with respect to the plasminogen system and the autoantigen gp330.
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PMID:Effect of TGF-beta 1 and TNF-alpha on the plasminogen system of rat proximal tubular epithelial cells. 904 36

Scatter factor (SF), also known as hepatocyte growth factor, is angiogenic in systemic tissue, and SF titers correlate with the malignancy and metastatic phenotype of certain systemic cancers. Human gliomas express SF and its receptor c-met, but their role in the malignant progression of these tumors has not been defined. To examine this, 9L glioma cells that express c-met but not SF were transfected with human SF cDNA, and their behavior in vitro and in vivo was examined. SF gene expression was detected in conditioned medium of 9L-SF but not in control 9L-neo-transfected cell lines, by reverse transcriptase-PCR, immunoblot, ELISA, and scatter activity assays. Gliomas derived from 9L-SF and control 9L-neo cell lines implanted in the caudate/putamen of Fisher 344 rats (intracranially) and in the flanks of SCID/Beige mice (subcutaneously) were examined. Extracts from intracranial (i.c.) gliomas contained elevated levels of SF protein as determined by ELISA (1 to 5.5 ng SF/mg protein), whereas no SF was detected in control tumors. Reverse transcriptase-PCR of RNA from i.c. gliomas revealed that only 9L-SF gliomas expressed SF and both 9L-neo and 9L-SF gliomas expressed the c-met SF receptor. By postimplantation Day 14, 9L-SF i.c. gliomas were approximately 5-fold larger than 9L-neo control tumors (p < 0.001). Subcutaneous 9L-SF glioma growth was also greater than that in controls, although the differences were more variable. SF-producing i.c. gliomas contained elevated levels of 48-kd urokinase (3.5-fold) and 92-kd type IV collagenase (2.8-fold), both enzymes that correlate with the malignant progression of human gliomas (p < 0.001). SF-producing and control 9L cell lines did not differ in rates of proliferation, thymidine incorporation, or adhesion-independent growth in vitro. Conditioned medium from 9L-SF cells stimulated thymidine incorporation into microvessel brain endothelial cells 3- to 4-fold higher than did CM from 9L-neo controls (p < 0.001). Intracranial 9L-SF gliomas were more angiogenic than controls based on elevated peak (2.25-fold; p < 0.005) and mean (1.7-fold; p < 0.008) blood vessel densities. These results suggest that SF production by glioma cells enhances glioma malignancy in vivo, in part, by paracrine mechanisms involving glioma-associated angiogenesis.
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PMID:Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo. 911 17

We reported previously that NO is responsible for the angiogenesis produced by endothelium-dependent vasodilating peptides. To investigate the mechanisms by which NO controls angiogenesis, NO was assessed for the ability to affect cell proliferation and upregulation of urokinase-type plasminogen activator (uPA) induced by basic fibroblast growth factor (bFGF) when added exogenously to or when produced endogenously by coronary venular endothelial cells (CVECs). The treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA upregulation and cell proliferation, which were prevented by anti-bFGF antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA. SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine. We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP. This signaling paradigm may provide an important link between shear rate, NO, bFGF, and coronary angiogenesis.
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PMID:Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF. 916 87

Clinical studies suggest that moderate alcohol consumption may decrease the risk for coronary artery disease and myocardial infarction. This effect may be attributed, in part, to the alcohol-mediated increase in endothelial cell (EC)-mediated fibrinolytic activity mediated by the increase in synthesis and/or activity of tissue-type plasminogen activators (t-PAs) and/or urokinase-type PA (u-PAs). To determine whether low alcohol levels (0.01 to 0.1%, v/v) induced the expression of these proteins, cultured human saphenous vein ECs (HSVECs) were preincubated in the absence/presence of ethanol for 5 to 120 min at 37 degrees C, washed, refed, and further incubated for 8 and 24 hr without alcohol. PA mRNA (reverse transcriptase-polymerase chain reaction) and secreted antigen (ELISA) levels were analyzed after incubation for 8 and 24 hr and the net expression of (sustained) endogenous PA-mediated surface-localized HSVEC fibrinolytic activity (plasmin generation) quantitated by activation of 125I-Glu-plasminogen after incubation for 24 hr. A brief 5 to 30 min preincubation (induction) of both t-PA and u-PA antigen increased approximately 3-fold (t-PA control, 14.2 +/- 1.7, plus alcohol, 25.4 +/- 5 ng/ml; u-PA control, 15 +/- 0.8, plus alcohol, 46.4 +/- 1.3 ng/ml) and mRNA levels approximately 2-fold, as compared with controls. Increased PA expression was associated with a significant concomitant approximately 2-fold increase in surface-localized fibrinolytic activity (control, 96 +/- 2.8, plus alcohol, 255 +/- 42 fmol/ well). These combined results indicate that a brief exposure (<30 min) to low levels of alcohol can induce synthesis of EC-produced t-PA and u-PA resulting in an increased expression of HSVEC surface-localized fibrinolytic activity and may account, in part, for the apparent cardioprotective benefit associated with moderate alcohol consumption.
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PMID:Alcohol-induced upregulation of plasminogen activators and fibrinolytic activity in cultured human endothelial cells. 958 43

The expression of urokinase-type plasminogen activator (u-PA), u-PA receptor (u-PAR) and plasminogen activator inhibitor (PAI) 1 and 2 was examined in 105 cases of primary lung cancer tissue using immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. The expression of u-PA, u-PAR and PAI-1 was detected in approximately 80% of primary lung cancers, whereas detectable PAI-2 expression was observed only in half of the overall cases. We assessed the relationships between the expression pattern and clinicopathological findings and found that a diminished expression level of PAI-2 was significantly correlated with lymph node metastasis and a poor prognosis. These results indicate that PAI-2 may play a critical role in the regulation of extracellular matrix degradation during tumour cell invasion and metastasis, and the expression of PAI-2 may be useful as a marker for evaluating the prognosis of lung cancer.
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PMID:Significance of plasminogen activator inhibitor 2 as a prognostic marker in primary lung cancer: association of decreased plasminogen activator inhibitor 2 with lymph node metastasis. 974 10

The plasmin activation system plays a key role in extracellular matrix degradation in many malignant tumors. Because no data are available on the involvement of the plasmin activation system in matrix degradation by thyroid carcinoma, the present study was performed using follicular thyroid carcinoma cell lines obtained from a primary tumor (FTC-133) and metastases (FTC-236 and FTC-238) of one patient. Matrix degradation by these cell lines was studied assessing the release of radioactivity from S35-methionine labeled extracellular matrix coated onto plastic. The involvement of constituents of the plasmin activation system as well as matrix metalloproteinases (MMPs), another class of proteolytic enzymes, which can be activated by plasmin, were assessed by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and zymography. In the matrix degradation experiment, S35 release by FTC-133 was significantly higher than FTC-236 and FTC-238. S35 degradation could be inhibited by the plasmin inhibitor aprotinin and by anti-human urokinase-type plasminogen activator (uPA) antibody, indicating the involvement of the plasmin activation system. Matrix degradation could also be inhibited by the MMP inhibitor marimastat, thus demonstrating the involvement of MMPs in matrix degradation by these cell lines. Zymographic assays revealed activity of uPA in all cell lines. However, in contrast with FTC-236 and FTC-238, no plasminogen activator inhibitor (PAI) or PAI1 mRNA were found in FTC-133. Therefore, the differences in PAI activity as observed between the cell lines may originate from differences in PAI1 gene transcription. Differences in PAI1 expression did not affect the attachment of these cell lines to vitronectin. We conclude that the plasmin activation system is involved in extracellular matrix degradation by these metastatic follicular thyroid carcinoma cell lines. Differences in extracellular matrix degradation between the cell lines correspond with differences in PAI1 gene expression, indicating the significance of PAI1 in extracellular matrix degradation by metastatic follicular thyroid carcinoma.
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PMID:Degradation of extracellular matrix by metastatic follicular thyroid carcinoma cell lines: role of the plasmin activation system. 1052 70


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