Plasmin and the regulation of tissue-type plasminogen activator biosynthesis in human endothelial cells.
Plasmin inhibited the biosynthesis of tissue-type plasminogen activator (tPA) antigen by human umbilical vein endothelial cells (HUVEC) in a dose-dependent manner. The amount of tPA antigen found in the 24-h conditioned medium of cells treated with 100 nM plasmin for 1 h was 20-30% of that in the control group. However, in contrast to tPA, such treatment led to a 3-fold increase in plasminogen activator inhibitor (PAI) activity, whereas the amount of PAI type 1 antigen was unchanged. The effects of plasmin on HUVEC were binding- and catalytic activity-dependent and were specifically blocked by epsilon-aminocaproic acid. Microplasmin, which has no kringle domains, was less effective in reducing tPA antigen biosynthesis or enhancing PAI activity in HUVEC. Kringle domains of plasmin affected neither tPA antigen nor PAI activity of the cells. Other proteases including chymotrypsin, trypsin, and collagenase at comparable concentrations did not have a significant effect on the biosynthesis of tPA antigen or PAI activity of HUVEC. Thrombin stimulated the biosynthesis of tPA and PAI-1 antigens by HUVEC. Thrombin also stimulated an increase in the protein kinase activity in HUVEC, whereas plasmin inhibited the protein kinase activity of the cells. It is possible that plasmin regulates the biosynthesis of tPA in HUVEC through the signal transduction pathway involving protein kinase.
Shi
G Y
GY
Department of Biochemistry, Medical College, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Hau
J S
JS
Wang
S J
SJ
Wu
I S
IS
Chang
B I
BI
Lin
M T
MT
Chow
Y H
YH
Chang
W C
WC
Wing
L Y
LY
Jen
C J
CJ
D015119:Aminocaproic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D010450:Endopeptidases / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015849:Plasminogen Inactivators / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D010750:Phosphoproteins; D015849:Plasminogen Inactivators; D010450:Endopeptidases; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D015119:Aminocaproic Acid