Regulation of plasminogen activator inhibitor activity in endothelial cells by tissue-type plasminogen activator

G. Y. Shi, C. C. Hsu, B. I. Chang, C. F. Tsai, H. S. Han, M. D. Lai, M. T. Lin, W. C. Chang, L. Y C Wing, C. J. Jen, M. J. Tang, H. L. Wu

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3 Citations (Scopus)

Abstract

Tissue-type plasminogen activator (t-PA) may stimulate the expression of plasminogen activator inhibitor type 1 (PAI-1) mRNA in cultured human umbilical vein endothelial cells. The PAI-1 antigen in the conditioned medium of cells, pretreated with t-PA, was less than the control, probably due to the formation and degradation of the t-PA-PAI-1 complex. However, the PAI activity of the t-PA-pretreated cells reached the same level as control group, 24 h after the residual t-PA activity was rapidly neutralized by the newly synthesized PAI-1. To test the release of PAI-1 from the substratum of the endothelial cells, the cultured cells were metabolically prelabeled with 35S-methionine for 3 h and then treated with t-PA. The 35S-PAI-1 of 46 kDa was found in the substratum and culture medium of cultured endothelial cells as analyzed by the SDS-PAGE after immunoprecipitation. During the treatment of endothelial cells with t-PA, the PAI-1 of 46 kDa in the cell substratum disappeared, and the 110 kDa t-PA-PAI-1 complex, the 81 kDa degraded t-PA-PAI-1, and the 44 kDa degraded PAI-1 products concomitantly appeared in the conditioned medium instead. In summary, t-PA can regulate the fibrinolytic activity of endothelial cells by enhancing PAI-1 mRNA biosynthesis and release PAI-1 from the substratum to neutralize t-PA activity. The PAI-1 which released into the medium was immediately converted to the inactive latent form in the absence of active t-PA.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
JournalFibrinolysis
Volume10
Issue number3
Publication statusPublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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