scholarly journals Human tissue-type plasminogen activator

2014 ◽  
Vol 112 (08) ◽  
pp. 243-254 ◽  
Author(s):  
Egbert K. O. Kruithof ◽  
Sylvie Dunoyer-Geindre

SummaryTissue-type plasminogen activator (t-PA ) plays an important role in the removal of intravascular fibrin deposits and has several physiological roles and pathological activities in the brain. Its production by many other cell types suggests that t-PA has additional functions outside the vascular and central nervous system. Activity of t-PA is regulated at the level of its gene transcription, its mRNA stability and translation, its storage and regulated release, its interaction with cofactors that enhance its activity, its inhibition by inhibitors such as plasminogen activator inhibitor type 1 or neuroserpin, and its removal by clearance receptors. Gene transcription of t-PA is modulated by a large number of hormones, growth factors, cytokines or drugs and t-PA gene responses may be tissue-specific. The aim of this review is to summarise current knowledge on t-PA function and regulation of its pericellular activity, with an emphasis on regulation of its gene expression.

1986 ◽  
Vol 56 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Raymond R Schleef ◽  
Nancy V Wagner ◽  
Manjula Sinha ◽  
David J Loskutoff

SummaryHybridoma clones specific for tissue-type plasminogen activator (tPA) were screened in solid-phase radioimmunoassays for their reactivity toward free tPA and tPA complexed to the endothelial cell-derived, (3-migrating plasminogen activator inhibitor (β-PAI). Two monoclonal antibodies (MABs) were identified with quite distinct properties. The first, MAB LI72D1, bound to free tPA but did not recognize tPA complexed to the β-PAI, whereas the second, MAB HI72C1, bound both to free tPA and to tPA in complex with β-PAI. These properties were maintained when the MABs were immobilized to plastic micro- titer wells, thus permitting the development of immunoradiometric assays (IRMAs) to quantitate free tPA and total tPA antigen in various samples. The IRMAs were employed to analyze the tPA in media conditioned by several human cell types. The results indicate that in some cases, tPA may be present entirely as a free and active enzyme, while in others it apparently exists entirely in complex with β-PAI. Interestingly, some cells appear to contain both forms of tPA.


1990 ◽  
Vol 63 (03) ◽  
pp. 345-348 ◽  
Author(s):  
J Veenastra ◽  
C Kluft ◽  
Th Ockhuizen ◽  
H v d Pol ◽  
M Wedel ◽  
...  

SummaryShort-term effects of moderate alcohol consumption on platelet function, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were studied in two age groups of volunteers (20–30 and 45–55 years), each consisting of eight healthy males. The alcohol (30 g in red port and wine) was consumed during a standard dinner. Two blood samples were drawn: one in the postprandial phase, and one the next morning after fasting overnight. Alcohol consumption tended to increase platelet aggregation and production of hydroxy fatty acids, reduced plasma t-PA activity and increased PAI activity in the postprandial phase. After the overnight fast the effects on t-PA and PAI had disappeared whereas at that time alcohol consumption tended to decrease platelet function. The effects of alcohol on t-PA and PAI activity appeared mainly in the older age group, whereas the t-PA activity in this group was already much lower, irrespective of alcohol consumption.


2007 ◽  
Vol 53 (3) ◽  
pp. 399-404 ◽  
Author(s):  
Yuditiya Purwosunu ◽  
Akihiko Sekizawa ◽  
Keiko Koide ◽  
Antonio Farina ◽  
Noroyono Wibowo ◽  
...  

Abstract Background: Detection of placental mRNA in maternal plasma has been reported in high-risk pregnancies. We attempted to investigate the concentrations of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) mRNA in maternal plasma in preeclampsia. Methods: Peripheral blood samples were obtained from healthy pregnant women before and after delivery and also from women with or without preeclampsia. Plasma was isolated from these samples, and RNA was extracted. Plasma PAI-1 and tPA mRNA concentrations were then measured by use of reverse transcription PCR assays. The concentrations were converted into multiples of the median (MoM) of the controls adjusted for gestational age. Data were stratified and analyzed according to the clinical severity of preeclampsia and quantitative distribution of blood pressure and proteinuria. Results: The median (minimum–maximum) PAI-1 mRNA MoM values for women with preeclampsia and controls were 2.48 (0.82–8.53) and 1.00 (0.41–2.33), respectively, whereas the median (minimum–maximum) tPA mRNA MoM values were 3.33 (1.01–10.58) and 1.00 (0.95–1.20), respectively. The concentrations of both PAI-1 and tPA mRNA were significantly increased in cases of preeclampsia, compared with controls (P <0.0001). The MoM values of both mRNA species were directly correlated with the severity of preeclampsia and were greatest among a subgroup of hemolysis, increased liver enzymes, and low platelets pregnancies. Conclusion: Maternal plasma PAI-1 and tPA mRNAs are significantly increased in patients with preeclampsia and are positively correlated with the severity of preeclampsia.


Sign in / Sign up

Export Citation Format

Share Document