Tissue Plasminogen Activator in Nervous System Function and Dysfunction

2001 ◽  
Vol 86 (07) ◽  
pp. 138-143 ◽  
Author(s):  
Sidney Strickland
Keyword(s):  
Nervous System ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
In Vivo Models ◽  
Knock Out ◽  
Tissue Plasminogen ◽  
Culture Models ◽  
Nervous System Function ◽  
Knock Out Mice

SummaryThe extracellular protease tissue plasminogen activator (tPA) has been implicated in various normal and pathological situations in the mammalian nervous system. The availability of (i) transgenic and knock-out mice in which the expression level of tPA can be widely varied, (ii) in vivo models for studying function and disease, and (iii) culture models for examining cell behavior, has allowed a detailed evaluation of many of these proposed functions. This chapter summarizes the current state of knowledge of possible roles for the tPA/plasminogen system in neuronal function and dysfunction.

Endothelial Binding of Recombinant Tissue Plasminogen Activator: Quantification In Vivo Using a Recirculatory Model

2003 ◽  
Vol 30 (1) ◽  
pp. 3-22 ◽  
Author(s):  
Michiel J. B. Kemme ◽  
Rik C. Schoemaker ◽  
Jacobus Burggraaf ◽  
Monique van der Linden ◽  
Marina Noordzij ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Tissue Plasminogen ◽  
Recirculatory Model

Transcription factor Sp1 is important for retinoic acid-induced expression of the tissue plasminogen activator gene during F9 teratocarcinoma cell differentiation

1990 ◽  
Vol 10 (11) ◽  
pp. 5883-5893
Author(s):  
A L Darrow ◽  
R J Rickles ◽  
L T Pecorino ◽  
S Strickland
Keyword(s):  
Transcription Factor ◽  
Retinoic Acid ◽  
Cyclic Amp ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Differentiated Cells ◽  
Cell Extracts ◽  
Transcription Factor Sp1 ◽  
Tissue Plasminogen

The induced differentiation of F9 cells by retinoic acid (RA) and cyclic AMP (cAMP) activated transcription of the tissue plasminogen activator (t-PA) gene. This differentiation-responsive regulation of the t-PA promoter was also observed in transient assays. Multiple sequence elements within 243 bp of t-PA DNA contributed to the high level of transcription in retinoic acid- and cyclic AMP-differentiated cells. To investigate the factors involved in controlling t-PA transcription upon differentiation, we used F9 cell extracts to examine proteins that bind two proximal promoter elements. These elements (boxes 4 and 5) are homologous to GC boxes that are known binding sites for transcription factor Sp1. Mobility shift assays in the presence and absence of anti-Sp1 antibodies demonstrated that the proteins which bound to this region were immunologically related to human Sp1. The proteins also had a DNA-binding specificity similar to that of a truncated form of Sp1. Mutations of the GC motif within boxes 4 and 5 that interfered with Sp1 binding reduced in parallel the binding of the F9 cellular factors and lowered transcription in vitro as well as in vivo. Although this proximal region of the t-PA promoter was active in vivo only in differentiated cells, the Sp1-like binding proteins were present in equal concentrations and had similar properties in extracts of both stem and differentiated cells. These data suggest that other cellular elements participate with this Sp1-like factor in controlling differentiation-specific expression.

In vivo ultrasound-activated delivery of recombinant tissue plasminogen activator from the cavity of sub-micrometric capsules

2019 ◽  
Vol 308 ◽  
pp. 162-171 ◽  
Author(s):  
Clara Correa-Paz ◽  
María F. Navarro Poupard ◽  
Ester Polo ◽  
Manuel Rodríguez-Pérez ◽  
Pablo Taboada ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Recombinant Tissue Plasminogen Activator ◽  
Tissue Plasminogen

Tissue Plasminogen Activator Expression in Endothelial Cells Exposed to Cyclic Strain in Vitro

1992 ◽  
Vol 1 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Toshiaki Iba ◽  
Bauer E. Sumpio
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Cyclic Strain ◽  
Neutral Position ◽  
Messenger Ribonucleic Acid ◽  
Tissue Plasminogen ◽  
Pai 1

The effects of cyclic strain on the production of tissue plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI-1) by cultured endothelial cells (EC) were examined. Human saphenous vein EC were seeded in selective areas of culture plates with flexible membrane bottoms (corresponding to specific strain regions) and grown to confluence. Membranes were deformed by vacuum (-20 kPa) at 60 cycles/min (0.5 s strain alternating with 0.5 s relaxation in the neutral position) for 5 days. EC grown in the periphery were subjected to 7-24% strain, while cells grown in the center experienced less than 7% strain. The results show a significant increase in immunoreactive tPA production on days 1, 3 and 5 compared to day 0 in EC subjected to more than 7% cyclic strain. There was no significant elevation of tPA in the medium of EC subjected to less than 7% strain. tPA activity could only be detected in the medium of EC subjected to more than 7% cyclic strain. PAI-1 levels in the medium were not significantly different in either group. In addition, immunocytochemical detection of intracellular tPA and messenger ribonucleic acid (mRNA) expression of tPA (assessed by the reverse transcriptase polymerase chain reaction utilizing tPA specific sense and antisense primers) was significantly increased in EC subjected to more than 7% cyclic strain. We conclude that a 60 cycles/min regimen of strain that is greater than 7% can selectively stimulate tPA production by EC in vitro and may contribute to the relative nonthrombogenicity of the endothelium in vivo.

scholarly journals The tissue plasminogen activator and urokinase response in vivo during natural resolution of venous thrombus

1995 ◽  
Vol 22 (5) ◽  
pp. 573-579 ◽  
Author(s):  
Andrew D.R. Northeast ◽  
Kenneth S. Soo ◽  
Linda G. Bobrow ◽  
Patrick J. Gaffney ◽  
Kevin G. Burnand
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Venous Thrombus ◽  
Tissue Plasminogen

In vivo clearance of tissue plasminogen activator: The complex role of sites of glycosylation and level of sialylation

1993 ◽  
Vol 7 (1) ◽  
pp. 15-22 ◽  
Author(s):  
E.S. Cole ◽  
E.H. Nichols ◽  
L. Poisson ◽  
M.L. Harnois ◽  
D.J. Livingston
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Tissue Plasminogen

Effect of PAI-1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-1 complex in plasma

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 930-937 ◽  
Author(s):  
WL Chandler ◽  
SL Trimble ◽  
SC Loo ◽  
D Mornin
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Molar Ratio ◽  
Molar Activity ◽  
Activity Measurements ◽  
Tissue Plasminogen ◽  
Activator Inhibitor Type ◽  
Pai 1

We determined the in vivo molar concentrations of active tissue plasminogen activator (t-PA), active plasminogen activator inhibitor type 1 (PAI-1), and t-PA/PAI-1 complex. t-PA activity was measured in plasma stabilized by immediate acidification. PAI-1 activity and t- PA/PAI-1 complex antigen were measured in citrated plasma; these measurements were corrected for the loss in PAI-1 activity and increase in complex that occurs in unacidified plasma samples due to the continued reaction between t-PA and PAI-1 after the sample was drawn. To convert t-PA and PAI-1 activity measurements into molar concentrations we determined the specific molar activity of t-PA and PAI-1 in vivo: 4.48 x 10(13) IU/mol. Of 72 subjects studied, 13 had less than 150 pmol/L active PAI-1; in these individuals 33% +/- 21% of their t-PA was active and the molar ratio of active t-PA to active PAI- 1 was 0.20 +/- 0.13. In the 11 subjects with greater than 500 pmol/L active PAI-1, 1.5% = 1.1% of the t-PA was active and the molar ratio of active t-PA to active PAI-1 was 0.0043 +/- 0.0036. Overall, the fraction of active t-PA declined exponentially as a function of the active PAI-1 concentration. During the day, the percentage of total t- PA that was active increased from 12% at 8:00 AM to 31% at 8:00 PM, while the molar ratio of active t-PA to active PAI-1 increased from 0.05 to 0.22 from morning to evening (n = 12).

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