Endothelin-1 promotes proteolytic activity of ovarian carcinoma

2002 ◽  
Vol 103 (s2002) ◽  
pp. 306S-309S ◽  
Author(s):  
Laura ROSANÒ ◽  
Debora SALANI ◽  
Valeriana DI CASTRO ◽  
Francesca SPINELLA ◽  
Pier Giorgio NATALI ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Angiogenic Factor ◽  
Dependent Manner ◽  
Direct Role ◽  
Gelatinase Activity ◽  
Endothelin 1 ◽  
High Concentrations ◽  
Activator Inhibitor Type

Endothelin-1 (ET-1) is a potent mitogenic and angiogenic factor for ovarian carcinoma cell lines, which acts selectively through the ETA receptor (ETAR). A previous study demonstrated that ET-1 is present at high concentrations in ovarian cancer ascites, indicating a direct role in the progression and metastasis of ovarian carcinoma. In this study, we investigated whether ET-1 could induce production and activation of tumour-associated proteinases in ovarian carcinoma cells. As demonstrated by ELISA, we found that the secretion of matrix metalloproteinase (MMP)-2 and MMP-9, urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 and -2 was upregulated by ET-1 in a dose-dependent manner in the HEY cell line. In addition, the MMPs in ET-1-treated cells are consistently active, as shown by MMP gelatinase activity assay. Finally, we demonstrated that BQ-123, an antagonist of ETAR, inhibited the ET-1-induced tumour protease secretion and activity, suggesting that ET-1/ETAR may play an important role in the progression and metastasis of ovarian carcinoma, activating multiple proteinase cascades.

scholarly journals Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X

Blood ◽  
1989 ◽  
Vol 73 (8) ◽  
pp. 2188-2195 ◽  
Author(s):  
BS Schwartz ◽  
MC Monroe ◽  
JD Bradshaw
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Lipid A ◽  
Mononuclear Cells ◽  
Plasminogen Activator Inhibitor ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

Abstract Peripheral blood mononuclear cells (PBMs) produce both tissue factor and plasminogen activator inhibitor type 2 (PAI-2) in response to gram- negative bacterial lipopolysaccharide (LPS). The cellular roles in the tissue factor response have been previously elucidated, and we now report those roles in PAI-2 production. Monocytes are the only cells among LPS-stimulated PBMs that produce PAI-2 as assessed by measurement of PAI-2 activity and antigen. Concomitant immunohistochemistry demonstrated that monocytes contain PAI-2, with a greater number staining positively and more intensely after exposure to LPS. LPS- stimulated monocytes produced increased amounts of PAI-2 with or without addition of lymphocytes. Lymphocytes prestimulated with LPS and then washed did not induce PAI-2 production in monocytes to which they were added. Lipid X, a precursor in the biosynthetic pathway of lipid A and LPS, was able to inhibit LPS induction of monocyte PAI-2 in a dose- dependent manner. This inhibition was not due to cellular toxicity, the phospholipidlike nature of lipid X, interference with the PAI-2 assay, or monocyte production of a substance interfering with PAI-2. Lipid X was an effective inhibitor of PAI-2 production even when added up to 30 minutes after LPS.

scholarly journals Antithrombotic and Antiplatelet Activities of New Isohopane Triterpene From the Roots of Rubia akane

2019 ◽  
Vol 14 (7) ◽  
pp. 1934578X1986291
Author(s):  
InWha Park ◽  
Wonhwa Lee ◽  
Hyelim Kim ◽  
Khong Trong Quan ◽  
DaYoung Kim ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Umbilical Vein ◽  
Plasminogen Activator Inhibitor ◽  
Tissue Type ◽  
Molecular Formula ◽  
Dependent Manner ◽  
Factor X ◽  
Rubia Akane ◽  
Activator Inhibitor Type ◽  
Pai 1

A new isohopane triterpenoid (1) and two known triterpenoids (2-3) were isolated from the roots of Rubia akane (Rubiaceae). The molecular formula C30H46O4 of 1 was determined by HRESIMS. Detailed NMR spectroscopic data analysis suggested that compound 1 is a new isohopane triterpenoid with a ketone moiety at C-16. Based on the key NOE correlations of H-3/H-5 and H-21/H3-28, compound 1 was determined as 3β-hydroxy-16-oxo-21β-isohop-22(29)-en-24-oic acid. The anticoagulant activities of new isohopane 1 were evaluated by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin (Factor IIa, FIIa) and activated factor X (FXa). The effects of 1 on expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated in tumor necrosis factor-α activated human umbilical vein endothelial cells. Treatment with 1 (200 μM) resulted in the prolongation of aPTT and PT and the inhibition of relative thrombin (28%) and FXa (29%) activities. In addition, 1 inhibited thrombin-catalyzed fibrin polymerization (18% inhibition at 100 μM) and platelet aggregation (21.8% inhibition at 100 μM). Compound 1 also elicited anticoagulant effects in mice in a dose-dependent manner ranging from 18.8 to 94.0 μg/mouse. In addition, treatment with 1 resulted in significant reduction of the PAI-1 to t-PA ratio (25% decreased). Collectively, the new isohopane triterpenoid 1 possesses antithrombotic activities and offers a basis for the development of a new anticoagulant agent.

scholarly journals Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X

Blood ◽  
1989 ◽  
Vol 73 (8) ◽  
pp. 2188-2195
Author(s):  
BS Schwartz ◽  
MC Monroe ◽  
JD Bradshaw
Keyword(s):  
Tissue Factor ◽  
Plasminogen Activator ◽  
Lipid A ◽  
Mononuclear Cells ◽  
Plasminogen Activator Inhibitor ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor

Peripheral blood mononuclear cells (PBMs) produce both tissue factor and plasminogen activator inhibitor type 2 (PAI-2) in response to gram- negative bacterial lipopolysaccharide (LPS). The cellular roles in the tissue factor response have been previously elucidated, and we now report those roles in PAI-2 production. Monocytes are the only cells among LPS-stimulated PBMs that produce PAI-2 as assessed by measurement of PAI-2 activity and antigen. Concomitant immunohistochemistry demonstrated that monocytes contain PAI-2, with a greater number staining positively and more intensely after exposure to LPS. LPS- stimulated monocytes produced increased amounts of PAI-2 with or without addition of lymphocytes. Lymphocytes prestimulated with LPS and then washed did not induce PAI-2 production in monocytes to which they were added. Lipid X, a precursor in the biosynthetic pathway of lipid A and LPS, was able to inhibit LPS induction of monocyte PAI-2 in a dose- dependent manner. This inhibition was not due to cellular toxicity, the phospholipidlike nature of lipid X, interference with the PAI-2 assay, or monocyte production of a substance interfering with PAI-2. Lipid X was an effective inhibitor of PAI-2 production even when added up to 30 minutes after LPS.

Raised Plasma Homocysteine: An Emerging Risk Factor for Ischaemic Heart Disease

1970 ◽  
Vol 19 (2) ◽  
pp. 87-93
Author(s):  
MS Kabir ◽  
AAS Majumder ◽  
AW Chowdhury ◽  
SA Haque ◽  
AQM Reza ◽  
...  
Keyword(s):  
Risk Factor ◽  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Plasminogen Activator ◽  
Research Work ◽  
Vascular Diseases ◽  
Plasminogen Activator Inhibitor ◽  
Plasma Homocysteine ◽  
Type I ◽  
Activator Inhibitor Type

Only one half to two thirds of atherosclerotic vascular diseases can be explained by classical risk factors like smoking, diabetes mellitus, hypertension, dyslipidaemia, family history of premature atherosclerotic vascular diseases, physical inactivity, obesity etc. Some other variables appear to contribute to the development of atherosclerotic vascular diseases which include estrogen deficiency, lipoprotein (a), plasma fibrinogen, plasminogen-activator inhibitor type I, endogenous tissue plasminogen activator (tPA), C-reactive protein and homocysteine. Over the last several years, investigators undertook extensive research work, in home and abroad, to determine the contribution of plasma homocysteine in the pathogenesis of atherosclerotic vascular diseases. So far the research work indicates, raised plasma homocysteine appears to be a potential risk factor for ischaemic heart disease.   doi: 10.3329/taj.v19i2.3158 TAJ 2006; 19(2): 87-93

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