Regulation of plasminogen activator inhibitor activity by plasmin in endothelial cells.
The fibrinolytic activity in endothelial cells was regulated by balance of plasminogen activators and plasminogen activator inhibitors. Plasmin can specifically inhibit the biosynthesis of tissue-type plasminogen activator (t-PA), but not plasminogen activator inhibitor, type 1 (PAI-1) in endothelial cells. The PAI activity in the conditioned medium of endothelial cells was low and remained constant in 24 hours. However, the PAI activity in the conditioned medium of the plasmin-pretreated cells increased linearly in 24 hours. Pretreatment with protein kinase C inhibitors, H-7 or staurosporine, partially suppressed the PAI activity induced by plasmin. Pretreatment of endothelial cells with a G-protein inhibitor pertussis toxin resulted in an inhibition of the plasmin-induced PAI activity. The phospholipase A2 inhibitor mepacrine specifically eliminated the effect of plasmin stimulation on PAI activity. Cyclooxygenase and lipoxygenase inhibitors also partially inhibited the plasmin-stimulated PAI activity in endothelial cells. All these inhibitors did not affect the biosynthesis of the PAI-1 antigen in the presence or absence of plasmin. The results indicate that plasmin increased the PAI activity of endothelial cells via pathways in which protein kinase C, G protein, and phospholipase A2 may be involved.
Shi
G Y
GY
Department of Biochemistry, Medical College, National Cheng Kung University, Tainan, Taiwan, R.O.C.
Wang
S J
SJ
Chang
B
B
Tasi
C F
CF
Lin
M T
MT
Chang
W C
WC
Wing
L Y
LY
Jen
C J
CJ
Wu
H L
HL
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005341:Fibrinolysin / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010879:Piperazines / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011796:Quinacrine / Q000494:pharmacology; D019311:Staurosporine; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D014471:Umbilical Veins; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D016859:Lipoxygenase Inhibitors; D010879:Piperazines; D017395:Plasminogen Activator Inhibitor 1; D010566:Virulence Factors, Bordetella; D009637:Masoprocol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D019204:GTP-Binding Proteins; D011796:Quinacrine; D019311:Staurosporine; D001241:Aspirin; D007213:Indomethacin