Thrombin-specific inactivation of endothelial cell derived plasminogen activator

Journal Article · Wed Mar 05 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6798439

Highsmith, R F; Gallaher, M J

Although thrombin (T) has diverse functions in the overall hemostatic mechanism, relatively little is known about its direct effect on components of the fibrinolytic enzyme system. The authors have investigated the interaction of T with plasminogen activators (PA) derived from bovine aortic endothelial cells (EC) in culture (2-5th passage, preconfluent monolayers). Varying concentrations of purified bovine or human thrombin were added to EC-conditioned media (CM). CM + T mixtures were assayed at various times for PA activity using purified plasminogen and a sensitive /sup 125/I-fibrinogenolytic or caseinolytic assay. T (5 nM), but not plasmin or trypsin at equivalent concentrations, resulted in a time-dependent inhibition of the PA activity in CM. T had no effect on the PA activity of urokinase, streptokinase or preformed plasmin. The ability of T to inactivate the EC-derived PA was abolished by prior treatment of T with active site-directed reagents. SDS-PAGE and zymography with copolymerized fibrinogen and plasminogen revealed further specificity in that only one of the multiple-molecular weight forms of PA present in EC-CM was inactivated by T. The authors conclude that in a highly specific fashion, T inactivates the predominant PA present in EC-CM by limited proteolysis. Thus, another potentially important function of T is suggested which may have particular significance in the temporal regulation of coagulation and fibrinolysis at the blood-endothelium interface.

• Research Organization: Univ. of Cincinnati College of Medicine, OH
• OSTI ID: 6798439
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
AORTA
ARTERIES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL FUNCTIONS
BLOOD COAGULATION
BLOOD VESSELS
BODY
CARDIOVASCULAR SYSTEM
CATTLE
CHEMICAL REACTIONS
COAGULANTS
CULTURE MEDIA
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DOMESTIC ANIMALS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENDOTHELIUM
ENZYMES
FIBRINOLYTIC AGENTS
FUNCTIONS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
INHIBITION
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
PEPTIDE HYDROLASES
PLASMINOGEN
PROTEOLYSIS
RADIOISOTOPES
REACTION KINETICS
RUMINANTS
SERINE PROTEINASES
THROMBIN
TIME DEPENDENCE
TISSUES
TRACER TECHNIQUES
VERTEBRATES